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.

Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.
Infant, Newborn ; Humans ; Hair Cells, Auditory, Inner/physiology* ; Ear, Inner/physiology* ; Hair Cells, Auditory/physiology* ; Regeneration/genetics* ; Stem Cells

Objective:To establish an animal model of trans-sutural distraction osteogenesis in SD rats.Methods:A self-designed V-shaped distraction device(distractor)was fabricated with the traction force(N)of 0,1.3,2.2,3.0,4.3 and 5.0 corresponding to the distraction length(mm)of 5,4,3,2,1 and 0 respectively,meeting the trans-sutural distraction osteogenesis requirements in skull of 5-week-old SD rats.The distractor was plased into the sagittal suture of 12 SD rats.Continuous sampling was conducted 1,3,5 and 7 days respectively(n=3)after operation.The tissue changes in the trans-sutural distraction area were observed by HE and Masson's trichrome staining.Inflammation levels were determined using Arg-1 immunofluorescence staining.The early angiogenesis was clarified through co-staining with CD31 and EMCN.Results:A stable trans-sutural distraction osteogenesis model was estab-lished,5 mm distraction osteogenesis width was observed completely within 7 days of distraction.Significant new bone formation was observed at 7 days after operation.Arg-1 expression increased and was concentrated at the bone margins,overlapping with the areas of new bone formation.EMCN expression gradually decreased,and by day 7 CD31 was predominant,indicating the basic maturation of blood vessels.Conclusion:This study successfully constructed a stable and effective trans-sutural distraction osteogenesis animal model,and provides an experimental basis for the investigation of its early continuous histological changes.

AIM:This study was performed to investigate the impact of neutrophil extracellular traps(NETs)on scar formation following urethral trauma.METHODS:(1)Clinical samples were derived from patients of Department of Urology,The First Affiliated Hospital of Fujian Medical University,from June 2021 to December 2022.Levels of NETs in the blood and urine were compared between patients with urethral trauma(n=20)and those without urethral trauma(controls,n=20).The relationship between NETs and scar formation was analyzed.(2)Urethral fibroblasts were isolated from urethral scar tissues,and neutrophils were induced to produce NETs in vitro.The urethral fibroblasts were treated with normal saline,0.5 mg/L NETs,or 1.5 mg/L NETs to investigate the effects of NETs on activation and collagen syn-thesis of urethral fibroblasts.Additionally,a rabbit model of urethral trauma was established and the animals were dioided into four groups to explore the therapeutic potential of deoxyribonuclease I(DNase I)in preventing urethral scar forma-tion:control,operation + transforming growth factor-β1(TGF-β1),operation + normal saline,and operation+DNase I.RESULTS:The level of NETs in urine increased after urethral trauma(P<0.05),but the level of NETs in blood did not change(P>0.05).In the animal models,the urethral scar became more severe as the level of NETs in the urine increased(P<0.05).At the cellular level,NETs promoted the viability,migration,and collagen synthesis of urethral fibroblasts(P<0.05)..Additionally,urethral injection of DNase I after trauma reduced the level of NETs and inhibited the formation of urethral scar tissue in the animal models(P<0.05).CONCLUSION:Infiltration of NETs promotes activation of urethral fibroblasts and scar formation after urethral trauma.

The lumbosacral transitional vertebra (LSTV) is a common lumbar vertebral variation characterized by unilateral or bilateral enlarged transverse processes. When the enlargement of the transverse processes alters the local biomechanics of LSTV, it may give rise to a series of clinical symptoms known as Bertolotti syndrome. The main manifestations include pain in the lumbosacral region, buttocks, outer side of the lower limbs, numbness, and symptoms related to the sciatic nerve. LSTV is often classified using the Castellvi classification. The presence of lumbosacralization and sacralization of vertebrae in LSTV makes it challenging to accurately locate and number LSTV. So various anatomical landmarks and spinal parameters have been proposed to assist in the localization and numbering of LSTV, but they all have a certain error rate. Even after the lumbar vertebrae is clearly numbered, there is often controversy over the baseline selection for preoperative spinal parameters. Currently, the horizontal level of S 1 is considered the optimal measurement baseline, but this conclusion needs further confirmation in a clinical context. The main basis for LSTV diagnosis is imaging signs, while the diagnosis of Bertolotti syndrome requires local injection of local anesthetics or corticosteroids into the pseudo-joint and the exclusion of other degenerative diseases of the lumbar spine. The treatment of Bertolotti syndrome includes conservative and surgical approaches. Common surgical procedures include fusion and decompression, both of which can achieve good short-term outcomes. However, due to the limited number of patients studied or a lack of direct comparisons, it is challenging to determine the superiority of these two methods in terms of medium to long-term effectiveness. This article provides a comprehensive review of the symptoms and causes of Bertolotti syndrome, preoperative localization and numbering of LSTV, baseline selection for preoperative spinal parameter measurements, and treatment methods.

Sj?gren′s syndrome is a chronic autoimmune inflammatory disease characterized by exocrine gland and extraglandular involvement. Cases of Sj?gren′s syndrome-associated aseptic meningitis (SS-AM) are relatively rare, and a case of recurrent aseptic meningitis with leukopenia and mild anemia associated with primary Sj?gren′s syndrome is reported, whose symptoms basically disappeared after treatment with prednison and hydroxychloroquine. The purpose of reporting this case is to raise awareness of SS-AM among fellow clinicians.

The Ehlers-Danlos syndrome(EDS)is a rare inherent connective tissue disorder.The prev-alence of EDS in the population is estimated at one out of ten thousand to one out of a hundred thousand.The vascular EDS(vEDS)are rare among the subtypes but are the worst in prognosis.The article reports a case of vEDS admitted to the hospital.The patient was a young man complaining of a sudden onset of aphasia in right hemiparalysis and severe left abdominal pain for unknown reasons.The diagnosis was made after the genetic testing.The patient suffered from vEDS.Then,the multi-disciplinary team(MDT)made a treatment plan tailored to this young patient.The complexity in classification and delusive presentations of the EDS make the correct diagnosis very challenging.This article hopes to report this case and to share the experiences to the bet-ter understanding of this disease.

Objective:To prepare hydroxyapatite(HA)coating on polyether ether ketone(PEEK)surface by magnetron sputtering technique and to study its biosafety.Methods:Sulfonated PEEK was used to increase the binding area and HA coating was constructed on it using magnetron sputtering technology.SEM and energy dispersive spectroscopy(EDAX)were used to detect the construction effect.Cell adhesion assay,cytoskeletal fluorescence staining and SEM validation were used to assess cytologrcal safety.In vivo safety tests were conducted in SD rats and golden hamsters.Results:HA coating with gradient morphology was successfully constructed on the PEEK surface using above technique.The coating promoted cell adhesion,extension and proliferation.No systemic toxicity and no sig-nificant influence in HE staining of the main infernal organs samples were observed.The coating alleviated the oral mucosal irritation caused by simple sulfonation to a certain extent.Conclusion:HA coating can be prepared stably with magnetron sputtering technology and can meet the biosafety needs for clinical applications.

Objective:To investigate the clinical outcomes of total knee arthroplasty (TKA) combined with the modified “overlap” technique in the treatment of end-stage knee osteoarthritis with fixed patellar dislocation.Methods:This is a retrospective case series study. Clinical data of 19 patients (22 knees) who underwent TKA combined with the modified “overlap” technique for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation from January 2011 to January 2022 in the Department of Orthopaedics, the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. The cohort included 5 males (6 knees) and 14 females (16 knees), with an age of (60.6±12.2) years (range:33 to 77 years) and a body mass index of (25.4±4.1) kg/m2 (range:20.0 to 33.0 kg/m2). Among them, 11 cases (12 knee) had valgus deformity, with Keblish classification showing mild in 2 cases (2 knees), moderate in 6 cases (6 knees), and severe in 4 cases (4 knees). All cases were treated using a medial parapatellar approach, with lateral retinaculum release combined with the “overlap” technique to restore the patellar trajectory. Knee function was evaluated using the American Knee Society (KSS) Score. Paired sample t tests were used for intergroup comparisons. Results:All patients successfully completed the surgery. Postoperatively, patellar dislocation, knee valgus deformity, flexion contracture deformity, and extensor lag were all corrected. All patients were followed up, with a follow-up duration of (63.8±35.2) months (range:24 to 136 months). One patient experienced periprosthetic infection 2 weeks postoperatively, 1 patient had recurrent patellar dislocation 2 months postoperatively, 1 patient developed knee stiffness 3 months postoperatively and underwent closed manipulation. No other patients exhibited signs of patellar dislocation or subluxation. At the last follow-up, the KSS clinical score improved from (36.4±12.7) points preoperatively to (83.4±6.3) points postoperatively ( t=-15.15, P<0.01), and the KSS functional score improved from (30.7±11.1) points preoperatively to (77.6±8.3) points postoperatively ( t=-14.37, P<0.01). The range of motion of the knee increased from 81.7°±19.6° preoperatively to 107.6°±12.5° postoperatively ( t=-4.85, P<0.01). Conclusion:TKA combined with the modified “overlap” technique is an effective surgical option for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation, demonstrating satisfactory clinical outcomes.

This study investigated the association between serum 25(OH)D 3 levels and cardiovascular risk-related indicators. 4 727 participants aged 20 and above from the National Health and Nutrition Examination Survey 2015-2018 database were enrolled. Body mass index, hypersensitive C-reactive protein, high density lipoprotein cholesterol, systolic blood pressure, waist-height ratio, and total cholesterol were selected as the research indicators. Weighted multiple linear regression models, subgroup analyses, smooth curve fitting, and saturation threshold effect analyses were employed to explore the relationship between serum 25(OH)D 3 and these indicators. The results showed that after full adjustment for covariates, every 1 nmol/L increase in serum 25(OH)D 3, the changes in β (95% CI) values for body mass index(BMI), hypersensitive C-reactive protein(hs-CRP), systolic blood pressure(SBP), waist-height ratio(WHtR), high density lipoprotein cholesterol(HDL-C), and total cholesterol(TC) were -0.05 (-0.06, -0.04) kg/m 2, -0.01 (-0.02, -0.01) mg/L, -0.02 (-0.04, -0.01) mmHg, -0.000 7 (-0.000 8, -0.000 6), 0.10 (0.08, 0.11) mg/dl, and 0.08 (0.04, 0.12) mg/dl, respectively. Female participants were more sensitive to changes in serum 25(OH)D 3, while participants aged 60 and above were relatively less sensitive. The relationship between serum 25(OH)D 3 and these indicators partially exhibited nonlinear patterns across different gender and age subgroups. The saturation threshold effect analysis revealed 8 meaningful inflection points. In summary, vitamin D has a close association with cardiovascular risk-related indicators.