To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine，the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13，2024，the 36^th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing，focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction （ED）. The conference brought together leading experts from traditional Chinese medicine，western medicine，and interdisciplinary fields，facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED，researching and developing new drugs of traditional Chinese medicine，and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs，it identified key directions for future scientific layout and scientific research tackling： （1） Standardization of syndrome differentiation system of traditional Chinese medicine for ED. （2） Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. （3） High-quality clinical research guided by evidence-based medicine. （4） In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. （5） Clinical translation and application promotion of new drugs of traditional Chinese medicine. （6） Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction，key focus areas，expected objectives，and clinical value were further refined，along with the establishment of a scientifically sound priority funding level evaluation system. Therefore，building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine，this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management，effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout， research and development decision-making in new drugs of traditional Chinese medicine，research topic planning，and clinical guideline formulation.

ObjectiveTo investigate the patterns of chronic disease comorbidity among permanent elderly residents in Xuhui District of Shanghai, and to analyze the impact of different comorbidity patterns on the elderly’s ability to perform activities of daily living. MethodsBased on data from the 2015 and 2021 Surveys on Health Status and Health Service Utilization among Permanent Residents in Xuhui District of Shanghai, the study included permanent residents who fully participated in both surveys, were aged 60 years or older at the 2015 survey, self-reported having a chronic disease, and reported no significant changes in their chronic disease status between the two surveys. A prospective cohort study design was adopted, using the 2015 data as the baseline and the 2021 survey data as follow-up data. Physical examinations and questionnaire surveys were conducted by the Shanghai Xuhui District Center for Disease Control and Prevention in the subdistricts and towns within the jurisdiction from April to July in both 2015 and 2021. Latent class analysis (LCA) was used to classify comorbidity patterns across 11 types of chronic diseases. The smaller the values of the Akaike information criterion (AIC), the Bayesian information criterion (BIC), and the sample-corrected Bayesian information criterion (aBIC), the better the model fits. The Barthel index (BI) and the Lawton and Brody Instrumental Activities of Daily Living Scale (LB-IADL) were used to assess the participants’ activities of daily living (ADL) and instrumental activities of daily living (IADL). Multiple linear regression and multivariate logistic regression models were used to analyze the association between different comorbidity patterns and ADL and IADL. ResultsA total of 1 608 study participants were enrolled. Among them, 671 (41.73%) self-reported having no chronic diseases. The prevalence of 11 types of chronic diseases was as follows: hypertension in 743 participants (46.21%), heart disease in 148 participants (9.20%), cerebrovascular disease in 37 participants (2.30%), diabetes or abnormal blood glucose in 310 participants (19.28%), other endocrine system diseases (non-diabetic) in 39 participants (2.43%), malignant tumors in 37 participants (2.30%), chronic lung disease in 16 participants (1.00%), gout in 8 participants (0.50%), musculoskeletal disorders in 34 participants (2.11%), gastric or digestive system diseases in 27 participants (1.68%), and dyslipidemia in 15 participants (0.93%). LCA was used to classify comorbidity patterns of chronic diseases among older adults into 1 to 9 latent category combinations. Model 5 (i.e., 5 latent categories) had the lowest BIC (7 112.69) and aBIC (6 909.38), with a relatively low AIC (6 768.20), indicating the best model fit; thus, five latent categories represented the optimal combination in this study. The five latent categories (and their respective proportions of study participants) were the healthy control group (41.73%), the hypertension group (31.28%), the diabetes-hypertension group (19.28%), the severe illness group (5.29%), and the other metabolic diseases group (2.43%). According to multiple linear regression analyses, compared with the healthy control group, the diabetes-hypertension group had significantly lower BI-20 scores (b=-0.952, 95%CI: -1.317‒ -0.587, P<0.001) and lower IADL scores (b=-0.744, 95%CI: -0.999‒ -0.489, P<0.001); the severe illness group (b=-0.644, 95%CI: -1.072‒ -0.217, P=0.003) and the hypertension group (b=-0.344, 95%CI: -0.562‒ -0.125, P=0.002) had lower IADL scores. According to multivariate logistic regression analyses, compared with the healthy control group, older adults in the diabetes-hypertension group had a higher risk of disability (OR=2.835, 95%CI: 1.392‒5.774), impaired ADL function (OR=2.470, 95%CI: 1.637‒3.726), and impaired IADL function (OR=1.739, 95%CI: 1.264‒2.392); older adults in the severe illness group had a higher risk of impaired ADL function (OR=2.206, 95%CI: 1.171‒4.155). ConclusionAmong the elderly participating in the Survey on Health Status and Health Service Utilization of Permanent Residents in Xuhui District of Shanghai, diabetes-hypertension is one of the key chronic disease comorbidity combinations and has adverse effects on both ADL and IADL. Community health management should prioritize the elderly with diabetes-hypertension comorbidity, and strengthen early screening and comprehensive interventions to slow the decline in ADL and IADL.

Objective:To investigate the clinical efficacy of moxibustion(Mox)combined with low-dose tadalafil(TAD)in the treatment of diabetes mellitus-induced erectile dysfunction(DMED)with the syndrome of Qi deficiency and blood stasis.Meth-ods:According to the inclusion and exclusion criteria,we selected 90 patients with DMED for this trial and equally randomized them into a Mox,a TAD,and a Mox combined with TAD(Mox+TAD)group to be treated by mild Mox applied to the acupoints Zusanli,Sanyinjiao and Yinlingquan qd alt,oral medication with low-dose TAD at 5 mg per dose qd,and combination of the above two thera-pies,respectively,all for 4 weeks.We obtained from the patients their IIEF-5 scores,traditional Chinese medicine(TCM)symptoms scores,Erectile Hardness Scale(EHS)scores,corpus cavernosal hemodynamic indexes,and the peak systolic velocity(PSV),end diastolic velocity(EDV)and resistance index(RI)of the corpus cavernosal arteries before and after treatment,and compared them among the three groups.Results:The total effectiveness rate was significantly higher in the Mox+TAD(90.0％)than in the Mox(46.7％)and TAD groups(60.0％)(P＜0.05).Compared with the baseline,the IIEF-5 and EHS scores were increased,while the TCM symptoms scores decreased in all the three groups after treatment,more significantly in the Mox+TAD group than in the other two(P＜0.05).And the PSV and RI were remarkably increased,while the EDV decreased(P＜0.05)in all the three groups(P＜0.05)after treatment,with PSV even higher in the Mox+TAD than in the Mox and TAD groups(P＜0.05).Conclusion:Moxi-bustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED,which can effectively improve the erectile function of the patients by increasing penile blood supply,benefiting qi and activating blood circulation.

Objective To develop dynamic prediction models based on multiple postnatal time points to support early diagnosis and individualized intervention for bronchopulmonary dysplasia(BPD)in preterm infants with gestational age<32 weeks.Methods Clinical data of 472 preterm infants with gestational age<32 weeks admitted to the Second Xiangya Hospital of Central South University between January 2016 and November 2020 were retrospectively analyzed.Multivariable logistic regression was applied to develop five independent prediction models at postnatal days 1,7,14,21,and 28.The performance of the models was assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Results Baseline characteristics such as gestational age and birth weight differed significantly between the BPD group(n=147)and the non-BPD group(n=325)(P<0.05).Predictors of BPD evolved across time points:on day 1,key predictors included gestational age,birth weight,Score for Neonatal Acute Physiology II(SNAP-II),invasive mechanical ventilation,and fraction of inspired oxygen>30%;by day 7,additional variables emerged,including fasting duration>2 days,mean feeding advancement rate<8.5 mL/(kg·d),neonatal respiratory distress syndrome,apnea of prematurity,and positive sputum culture;from day 14 onward,nutrition-and treatment-related indicators were incorporated additionally.The models demonstrated good discrimination at postnatal days 1,7,14,21,and 28,with AUCs of 0.917,0.927,0.939,0.944,and 0.968,respectively,and good calibration(Hosmer-Lemeshow P>0.05).Internal validation showed AUCs ranging from 0.899 to 0.958,indicating robust performance.Conclusions Dynamic postnatal prediction models incorporating indicators spanning perinatal factors,respiratory support,nutritional management,and therapeutic interventions demonstrate high predictive performance and facilitate dynamic risk assessment for BPD in preterm infants with gestational age<32 weeks.

Objective:To investigate the clinical efficacy of moxibustion(Mox)combined with low-dose tadalafil(TAD)in the treatment of diabetes mellitus-induced erectile dysfunction(DMED)with the syndrome of Qi deficiency and blood stasis.Meth-ods:According to the inclusion and exclusion criteria,we selected 90 patients with DMED for this trial and equally randomized them into a Mox,a TAD,and a Mox combined with TAD(Mox+TAD)group to be treated by mild Mox applied to the acupoints Zusanli,Sanyinjiao and Yinlingquan qd alt,oral medication with low-dose TAD at 5 mg per dose qd,and combination of the above two thera-pies,respectively,all for 4 weeks.We obtained from the patients their IIEF-5 scores,traditional Chinese medicine(TCM)symptoms scores,Erectile Hardness Scale(EHS)scores,corpus cavernosal hemodynamic indexes,and the peak systolic velocity(PSV),end diastolic velocity(EDV)and resistance index(RI)of the corpus cavernosal arteries before and after treatment,and compared them among the three groups.Results:The total effectiveness rate was significantly higher in the Mox+TAD(90.0％)than in the Mox(46.7％)and TAD groups(60.0％)(P＜0.05).Compared with the baseline,the IIEF-5 and EHS scores were increased,while the TCM symptoms scores decreased in all the three groups after treatment,more significantly in the Mox+TAD group than in the other two(P＜0.05).And the PSV and RI were remarkably increased,while the EDV decreased(P＜0.05)in all the three groups(P＜0.05)after treatment,with PSV even higher in the Mox+TAD than in the Mox and TAD groups(P＜0.05).Conclusion:Moxi-bustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED,which can effectively improve the erectile function of the patients by increasing penile blood supply,benefiting qi and activating blood circulation.

Objective To organize and summarize the medication rules of GU Nai-fang in treating skin diseases through real-world data.Methods We collected traditional Chinese medicine prescriptions for GU Nai-fang's treatment of skin diseases from the outpatient medical record system of Shanghai Traditional Chinese Medicine Hospital to establish a database.Statistical analysis of disease types,performance,and efficacy was conducted,and association rules and systematic clustering analysis were performed using SPSS Modeler 18.0 and SPSS 26.0 software,respectively.Results A total of 5 020 patients were included,and 5 020 prescriptions were collected,involving 241 traditional Chinese medicines with a total frequency of 85 758 uses.The frequency of using heat clearing drugs,deficiency tonifying drugs,blood activating and stasis removing drugs,surface clearing drugs,and wind and dampness dispelling drugs was relatively high;most drugs tended to be cold and warm,mainly targeting the heart,lungs,and colon meridians.The top 15 Chinese medicines with the highest frequency of use were Smilacis Glabrae Rhixoma,Cortex Moutan,Radix Paeoniae Rubra,Rehmanniae Radix,Scutellariae Radix,Cynanchi Paniculati Radix et Rhizoma,Schisandrae Chinensis Fructus,Violsse Herba,Mume Fructus,Herba Pyrolae,Hedyotis Diffusae Herba,Lonicerae Japonicae Flos,Cicadae Periostracum,Bombyx Batryticatus,Radix Salviae.Association rule analysis obtained 15 high-frequency combinations of 2 traditional Chinese medicines and 3 traditional Chinese medicines.Cluster analysis resulted in 7 clustered prescriptions.Conclusion GU Nai-fang commonly used heat clearing drugs,deficiency tonifying drugs,blood activating and stasis removing drugs,surface resolving drugs,and wind and dampness dispelling drugs in the treatment of skin diseases,and Smilacis Glabrae Rhixoma,Cortex Moutan,Radix Paeoniae Rubra,Rehmanniae Radix,and Scutellariae Radix were the most frequently used drugs.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Selenoproteins, as the active form of selenium, play an important role in various physiological and pathological processes, such as anti-oxidation, anti-tumor, immune response, metabolic regulation, reproduction and aging. Although the expression level of selenoproteins in adipose tissue is significantly influenced by dietary selenium intake, it is closely related to the homeostasis of adipose tissue. In this review, we summarized the role of selenoproteins in the physiological function of adipose tissue and the pathogenesis of obesity in recent years, in order to provide a rationale for developing potential therapeutic agents for the treatment of obesity and related metabolic diseases.
Selenoproteins/metabolism* ; Adipose Tissue/physiology* ; Obesity/metabolism* ; Humans ; Animals ; Selenium

This study aimed to explore the pharmacological mechanism of Yourenji Capsules(YRJ) in improving osteoporosis by combining network pharmacology and proteomics technologies. The SD rats were randomly divided into a blank control group and a 700 mg·kg~(-1) YRJ group. The rats were subjected to gavage administration with the corresponding drugs, and the blank serum, drug-containing serum, and YRJ samples were compared using ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) to analyze the main components absorbed into blood. Network pharmacology analysis was conducted based on the YRJ components absorbed into blood to obtain related targets of the components and target genes involved in osteoporosis, and Venn diagrams were used to identify the intersection of drug action targets and disease targets. The STRING database was used for protein-protein interaction(PPI) network analysis of potential target proteins to construct a PPI network. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed using Enrichr to investigate the potential mechanism of action of YRJ. Ovariectomy(OVX) was performed to establish a rat model of osteoporosis, and the rats were divided into a sham group, a model group, and a 700 mg·kg~(-1) YRJ group. The rats were given the corresponding drugs by gavage. The femurs of the rats were subjected to label-free proteomics analysis to detect differentially expressed proteins, and GO functional enrichment and KEGG pathway enrichment analyses were performed on the differentially expressed proteins. With the help of network pharmacology and proteomics results, the mechanism by which YRJ improves osteoporosis was predicted. The analysis of the YRJ components absorbed into blood revealed 23 bioactive components of YRJ, and network pharmacology results indicated that key targets involved include tumor necrosis factor(TNF), tumor protein p53(TP53), protein kinase(AKT1), and matrix metalloproteinase 9(MMP9). These targets are mainly involved in osteoclast differentiation, estrogen signaling pathways, and nuclear factor-kappa B(NF-κB) signaling pathways. Additionally, the proteomics analysis highlighted important pathways such as peroxisome proliferator-activated receptor(PPAR) signaling pathways, mitogen-activated protein kinase(MAPK) signaling pathways, and β-alanine metabolism. The combined approaches of network pharmacology and proteomics have revealed that the mechanism by which YRJ improves osteoporosis may be closely related to the regulation of inflammation, osteoblast, and osteoclast metabolic pathways. The main pathways involved include the NF-κB signaling pathways, MAPK signaling pathways, and PPAR signaling pathways, among others.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Osteoporosis/metabolism* ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Network Pharmacology ; Female ; Protein Interaction Maps/drug effects* ; Capsules ; Humans ; Signal Transduction/drug effects*