Since its establishment in 2016, the National Rare Diseases Registry System of China (NRDRS) has accumulated valuable case data and bio-specimen for basic and clinical research on rare diseases in China. However, the emerging challenges in clinical diagnosis and treatment of rare diseases make it unable for data and resource platform to fully meet the diversified needs. Under this backdrop, we have developed a protocol to optimize and upgrade the system based on the core functions of the NRDRS platform. The goal is to leverage intelligent digital technologies to transform NRDRS into a new platform integrating multimodal data and auxiliary diagnostic and treatment functions. It is specified as the development and construction of "one platform and four intelligent tools." Currently, we have upgraded and developed NRDRS platform, intelligent tool for genotype-phenotype analysis of rare diseases, AI-assisted diagnostic tool for rare diseases, remote multidisciplinary diagnosis and teaching tool for rare diseases, drug screening and validation tool for rare diseases. The next step will focus on the promotion of the application of these tools in clinical settings in order to address the issue of severe imbalance in the allocation of resources for the diagnosis and treatment of rare diseases. This article provides an overview of the digital and intelligent upgrades of the NRDRS, the trials in applications in clinical settings, and direction in the future.

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective:To investigate the efficacy, feasibility, and safety of task-oriented exercise training for hospitalized elderly diabetic patients.Methods:This study is a parallel randomized controlled trial with a positive control and a single-blinded assessor.From July 2020 to July 2021, we included 84 elderly patients with type 2 diabetes who were hospitalized in the Department of Endocrinology at Beijing Hospital.These patients were randomly divided into two groups: the task-oriented exercise training group(TOE group)and the regular exercise training group(regular group). The TOE group participants were trained using a task-oriented exercise program that was specifically developed by our research team.On the other hand, the regular group participants were trained using a classical program that comprised of all exercise modes.Each subject received individualized exercise training for 10 consecutive days while staying in the hospital.We evaluated the efficacy, feasibility, and safety of the training programs by measuring the physical fitness of the participants, assessing the feasibility of the program, and monitoring any exercise-related adverse events that occurred.Results:A total of 79 subjects completed the entire intervention and follow-up period, with 40 subjects in the TOE group and 39 subjects in the regular group.In terms of efficacy, both groups showed improvement in their physical fitness indexes after the intervention, with no significant differences in the degree of improvement between the two groups(all P>0.05). When considering feasibility, the TOE group had a higher proportion of prospective feasibility at 87.5%(35 out of 40)compared to the regular group at 71.8%(28 out of 39). Similarly, the TOE group had a higher proportion of practical feasibility at 75.0%(30 out of 40)compared to the regular group at 53.8%(21 out of 39). The TOE group showed a significant advantage in practical feasibility between the two groups( χ2=3.862, P=0.049). As for safety, there were no exercise-related adverse events during the intervention in either group. Conclusions:The efficacy and safety of the task-oriented exercise program for hospitalized elderly diabetic patients is comparable to that of the regular program.Additionally, the task-oriented program is more feasible than the regular program.

This paper summarizes the exploration process and academic significance of the academic thought of Zhou Zhongying,a master of traditional Chinese medicine,who took the creation of a new system of TCM pathogenesis theory as the core,and interprets its theoretical connotation.As a pioneer in the construction of higher education textbooks for traditional Chinese medicine,Professor Zhou Zhongying created the outline of TCM internal medicine viscera differentiation,persisted in carrying out innovative research on patho-genesis theory,achieved fruitful academic results,and enriched and developed the academic system of TCM theory.In the clinical di-agnosis and treatment of exogenous febrile diseases and acute and difficult internal injuries,he systematically created new pathogenesis theories such as stasis-heat theory and cancer toxicity theory.Based on this,the legislation of medication can improve the clinical effi-cacy,and it is realized that identifying the pathogenesis is the key link in syndrome differentiation and treatment.In his later years,Professor Zhou Zhongying,guided by the holistic view,proposed the"thirteen pathogenesis"and constructed a new system of TCM pathogenesis differentiation,highlighting the guiding value of complex pathogenesis and the causal chain of pathogenesis elements to complex clinical diseases and syndromes,forming a theory with the idea of"examining syndromes and seeking pathogenesis,activating syndrome differentiation"as its soul.This theory breaks through the rigid thinking of syndrome differentiation and treatment based on a single pathogenesis or fixed syndrome type,reconstructs the theoretical framework of TCM with the idea of holistic view,and is a major academic innovation in modern TCM.

Objective:To investigate the iodine nutritional status of children and the consumption condition of non-iodized salt in Henan Province after implementation of the new standard of "Definition and demarcation of water-borne iodine-excess areas and iodine-excess endemial areas" (GB/T 19380-2016, hereinafter referred to as new standard) for four years (2021), and to provide a basis for scientific adjustment of intervention strategies.Methods:In 2021, according to the requirements of the new standard and based on the results of the water iodine survey in Henan Province from 2017 to 2020, a survey was conducted on the iodine nutrition status of children in water-borne high iodine areas in 47 counties (cities, districts, hereinafter referred to as counties) with high iodine administrative village (neighborhood committee, hereinafter referred to as administrative village). In each county, 5 administrative villages with median water iodine > 100 μg/L were selected as the investigation villages, and water samples were collected to determine the water iodine value. Forty non-boarding students aged 8 - 10 (age balanced, half male and half female, age increased to 6 - 12 when less than 40) were selected from each village as investigation subjects. Salt samples from their homes and urine samples were collected to detect salt iodine and urine iodine content, and thyroid volume of children was measured. And the monitoring results of areas where the supply of iodized salt had been suspended for less than 4 years (in newly high iodine areas) and more than 10 years (in previously high iodine areas) were further compared and analyzed.Results:A total of 257 administrative villages in the province were monitored, and the range of water iodine was 1.6 - 609.5 μg/L, with a median of 132.5 μg/L. A total of 8 611 children were tested for salt iodine, urine iodine and thyroid volume. The non-iodized salt rate was 58.3% (5 017/8 611), and the median urine iodine was 342.2 μg/L, thyroid enlargement rate was 2.9% (250/8 611). The median water iodine (153.0 vs 118.4 μg/L), the median urine iodine in children (371.6 vs 287.7 μg/L) and the goiter rate [3.8% (211/5 537) vs 1.3% (39/3 074)] in the newly high iodine areas were higher than those in the previously high iodine areas, and the differences were statistically significant ( Z = 583.12, - 14.09, P < 0.001; χ 2 = 44.40, P < 0.001); the non-iodized salt rate was lower than that of the previously high iodine areas [37.2% (2 057/5 537) vs 96.3% (2 960/3 074)], and the difference was statistically significant (χ 2 = 2 841.37, P < 0.001). Conclusions:The iodine nutrition level of children in water-borne high iodine areas of Henan Province in 2021 is at an excess level, but the non-iodized salt rate in residential households is low. We should make every effort to ensure the precise supply of non-iodized salt in high iodine areas after implementation of the new standard, and strengthen iodine nutrition monitoring and health education for key populations to prevent the occurrence of high iodine hazards.

Objectives:To evaluate the valvular and cardiac function,cardiac reverse remodeling at 6-month after transcatheter edge-to-edge repair(TEER)for patients with functional and degenerative mitral valve regurgitation,and summarize the experience of echocardiography application. Methods:The clinical data of 93 patients with moderate to severe mitral regurgitation(MR)treated with TEER and completed 6-month follow-up in Yunnan Fuwai Cardiovascular Hospital from July 2022 to February 2023 were retrospectively analyzed.Patients were divided into functional mitral regurgitation(FMR)and degenerative mitral regurgitation(DMR)groups according to MR etiology.The valve characteristic parameters,as well as valvular function,chamber volume and cardiac functional parameters before and at 6 months after operation were compared.The key points of echocardiography application were summarized. Results:Among all patients,71 were FMR and 22 were DMR.There were differences in valve structure between the two groups.Mitral TEER were successfully accomplished and all patients completed 6-month follow-up.The key points of echocardiography application included:valve structure analysis,atrial septal puncture location,device delivery process monitoring and image optimization during clamping process.The mitral regurgitation grade and NYHA grade were significantly improved in all patients at 6 months after TEER(P<0.05),and the mean mitral valve pressure gradient was higher than that before operation(P<0.05).Left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV)and left atrial volume index in FMR group were significantly decreased(P<0.05),while left ventricular and left atrial volume in DMR group remained unchanged(P>0.05).There were no significant changes in left ventricular ejection fraction and left ventricular global strain in both groups during the observation period(P>0.05).The changes of LVEDV and LVESV before and after operation were more significant in FMR group than those in DMR group(P<0.05). Conclusions:Mitral TEER can reduce the degree of regurgitation and improve cardiac function in the early postoperative period for moderate and severe MR patients with different etiologies.There are differences in preoperative valve structure and postoperative cardiac reverse remodeling between FMR and DMR patients.Echocardiography is an important imaging technique for the evaluation and monitoring process before,during and post mitral TEER.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Evaluate the interventional effect of Lycium barbarum leaves extract on cataract rats and its effects on plasma and liver tissue metabolites. The ultimate goal is to explore the scientific connotation of Lycium barbarum leaves extract on vision improvement. All experiments were approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (202306A067). D-Galactose (D-gal) induced cataract model in rats was established. The lens opacity, lens and liver tissue pathology, level of oxidative stress and polyol metabolism regulation in the lens, level of oxidative stress in serum and liver tissue, and the content of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and liver tissue were analysed to evaluate the effect of Lycium barbarum leaves extract on cataract. The metabolite profiles of plasma and liver tissue of rats were analyzed by UPLC-QTOF-MS/MS. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to compare and analyze the metabolic data in control group and cataract group, and screen potential biomarkers. The related metabolic pathways were further constructed by KEGG database analysis. The results showed that lens and liver pathology of cataract rats were improved after being intervened by the leaves extract of Lycium barbarum. The contents of AR and Ca²⁺ were significantly decreased in lens, and the contents of SDH and GSH and the ability of CAT were significantly increased; the content of GSH and the ability of SOD were significantly improved in serum and liver tissue, the content of MDA, the abilities of ALT and AST and the level of inflammatory factors were significantly reduced. The metabolomics results showed that there were 15 different metabolites in plasma and liver tissue of cataract rats, and 9 different biomarkers including retinyl ester, stearic acid, and palmitic acid, were returned by Lycium barbarum leaves extract. As revealed by pathway enrichment in plasma and liver tissue, it was found that the retinol metabolic pathway was mainly regulated by Lycium barbarum leaves extract. In summary, Lycium barbarum leaves can effectively alleviate the pathological changes of cataract, inhibit inflammation and improve antioxidant capacity, which may relate to the retinol metabolic pathway. It provides scientific basis and support for revealing the scientific connotation of the effect of Lycium barbarum leaves on vision improvement.