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.

Objective:To analyze the influential factors of blurred vision after general anesthesia.Methods:The clinical data of 997 patients who underwent elective general anesthesia at The No. 1 People's Hospital of Pinghu from September 2022 to May 2023 were retrospectively analyzed. The data collected included age, sex, body mass index, American Society of Anesthesiologists classification, history of hypertension, history of diabetes, operation duration (specifically whether it exceeded 3 hours), surgical position (whether the patient was in the supine position), operating room temperature, use of penehyclidine hydrochloride, use of muscle relaxant antagonists, use of atropine, blood pressure (specifically whether it was ≥ 30% of the baseline value), fluid input, blood loss, and use of pneumoperitoneum. Collinearity diagnosis and univariate logistic regression analysis were conducted to select factors with statistical significance. Subsequently, multivariate logistic regression analysis was performed.Results:Univariate and multivariate logistic regression analyses showed that age > 65 years ( OR = 1.47, 95% CI: 1.01-2.15, P = 0.043), surgical position (non-supine position) ( OR = 1.54, 95% CI: 1.06-2.25, P = 0.025), operation time exceeding 3 hours ( OR = 1.76, 95% CI: 1.05-2.94, P = 0.031), and the use of penehyclidine hydrochloride ( OR = 4.91, 95% CI: 3.35-7.21, P < 0.001) were identified as factors contributing to postoperative blurred vision in patients undergoing general anesthesia. Conclusion:Factors contributing to postoperative blurred vision in patients undergoing general anesthesia include age > 65 years, the use of penehyclidine hydrochloride during surgery, operation time exceeding 3 hours, and non-supine surgical position. Clinically, it is essential to implement early and effective preoperative education, enhance intraoperative nursing quality, and optimize preoperative medication for general anesthesia to reduce the incidence of blurred vision after surgery.

Objective:To explore the differential efficacies of conventional chemotherapy, autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for T lymphoblastic lymphoma (T-LBL) .Method:From January 2012 to December 2022, the relevant clinical data were retrospectively reviewed for 82 T-LBL patients hospitalized at Affiliated Tongji Hospital. According to different treatments, they were assigned into two groups of non-transplantation (49 cases) and transplantation (33 cases). The transplantation group was divided further into two groups of allo-HSCT (22 cases) and auto-HSCT (11 cases) according to different transplantation modes. In non-transplantation group, remission was induced mostly by cyclophosphamide+messosodium+doxorubicin+dexamethasone+vincrine/methotrexate+Hyper CAVD A/B. Six patients achieved remission based upon cyclophosphamide+cytarabine+6-mercaptopurine (CAT), etoposide+vincristine+doxorubicin+cyclophosphamide+cyclophosphamide+ prednisone (EPOCH), high-dose methotrexate+dexamethasone and vincristine+pirubicin+ cyclophosphamide+ pemasase+prednisone (VDCLP). The transplantation group underwent HSCT after multi-drug combination intensive induction therapy. Efficacy and survival were analyzed by observing the rates of overall survival (OS) and progression-free survival (PFS) .Result:There were 64 males and 18 females with a median age of 23 (11~74) year. Among them, 62 cases (75.61%) had clinical stage Ⅲ~Ⅳ. And 43 cases (53.44%) had systemic symptoms (B symptom) of fever, night sweats and weight loss at an onset of disease. Fifty cases (61.00%) had an involvement of bone marrow and 33 cases (80.5%) belonged to Ann Arbor stage Ⅲ and above. There were 65 cases (79.27%) with Eastern Cooperative Oncology Group (ECOG) score ≤2 and 17 cases (20.73%) with ECOG score >2. International Prognostic Index (IPI) was ≤3 (63 cases, 76.83%) and >3 (19 cases, 23.17%). Follow-up period was 27.5 (5~118) month. And 3-year OS and PFS were 53.64% (95% CI: 42.35%~64.62%) and 47.56% (95% CI: 36.53%~58.82%). Significant inter-group difference existed in 3-year OS[42.86% (95% CI: 29.12%~57.71%) vs 69.70% (95% CI: 51.13%~83.79%), P=0.014]and 3-year PFS was 38.76% (95% CI: 25.54%~53.76%) and 60.61% (95% CI: 42.24%~76.57%). And the difference was statistically significant ( P=0.032) . Conclusion:As a consolidation therapy, HSCT may improve the long-term outcomes of T-LBL patients as compared with chemotherapy alone.

Objective:To analyze the clinical characteristics and prognosis of patients with stiff-person syndrome (SPS) associated with glutamic acid decarboxylase (GAD) antibodies.Methods:A retrospective analysis was conducted on demographic characteristics, clinical manifestations, auxiliary examination results, treatment, and prognosis of patients with GAD antibody-related SPS treated at Peking Union Medical College Hospital from January 2015 to July 2023.Results:A total of 33 patients were included, comprising 26 females (78.8%) and 7 males (21.2%), with an onset age of (42±12) years and a disease duration of 24.0 (10.5, 37.5) months. Two cases (6.1%) were diagnosed with tumors, including 1 case with invasive thymoma and 1 case with small cell lung cancer. The majority of patients (87.9%, 29/33) presented with stiffness of trunk and proximal limb muscles, 42.4% (14/33) of patients exhibited episodic spasm, and 54.5% (18/33) of patients were triggered by stimuli such as sound and light. Babinski or Chaddock reflexes were elicited in 33.3% (11/33) of patients. Some patients (36.4%, 16/33) had concurrent limbic encephalitis/epilepsy or cerebellar ataxia (referred to as complex SPS). The median cerebrospinal fluid (CSF) white blood cell count was 2×10 6/L [quartile: 1×10 6/L, 6×10 6/L; range: (0-30)×10 6/L], with mild elevation in 28.0% (7/25) of patients. Multi-channel surface electromyography in 14 out of 21 cases (66.7%) suggested synchronous contraction of agonist and antagonist muscles in a relaxed state. The modified Rankin Scale (mRS) score during the acute phase was 4 (3, 4). All patients received treatment with benzodiazepines or baclofen. Thirty patients (90.9%, 30/33) received first-line immunotherapy, 3 patients (9.1%, 3/33) received second-line immunotherapy with rituximab, and 14 (42.4%, 14/33) received mycophenolate mofetil as long-term immunotherapy. The follow-up period was 16 (10, 42) months, with a median best mRS score of 2; 66.7% (22/33) of patients had a favorable functional prognosis (mRS score≤2), and the recurrence rate was 30.0% (9/30). At the last follow-up, the median mRS score was 2, and 53.3% (16/30) of patients had a favorable functional prognosis. Prognosis was not significantly correlated with gender, age, clinical type, or CSF white blood cell level (all P>0.05). Conclusions:SPS is one of the main clinical phenotypes of GAD antibody-related neuroimmune diseases, commonly observed in middle-aged women, and exhibits a chronic progressive course. Only a minority of patients have concomitant tumors. The diagnosis relies on typical symptoms, GAD antibody testing, and electromyography examination. The initial immune therapy yields good results, but the prognosis for recurrent patients is poor.

Objective:To explore the impact of intradialytic hypotension (IDH) on brain component volume, as well as its relationship with depression and cognitive function changes in maintenance hemodialysis patients.Method:It was a cross-sectional observational study. Clinical data of 119 patients under maintenance hemodialysis in Peking Union Medical College Hospital from July 2013 to July 2014 were collected, retrospectively. Patients were divided into IDH group and non-IDH group. 3.0T Magnetic resonance imaging examination of the head for all patients was completed and the results of volume analysis of each component of the brain were extracted. Cognitive function was assessed by the Chinese version of the simplified mental state examination scale (C-MMSE) and the Chinese version of the Montreal cognitive assessment scale (C-MoCA). Depressive status was assessed by the Hamilton depression scale 17 (HAMD_17) and living ability was assessed by the Alzheimer's disease collaborative study-daily living ability assessment questionnaire. In addition, the Philadelphia word learning test was used to measure memory, the Boston naming test to measure language, the connection test A and B to measure executive ability, and the Stroup test C to measure attention. The differences in brain component volume, cognitive function, emotion, and life ability between two groups of patients were compared, and the correlation between IDH and brain component volume was explored by regression analysis.Result:A total of 119 patients were included in this study, of whom 22 (18.5%) had hypotension during dialysis. The volumes of amygdala, cuneiform lobe, and posterior cingulate gyrus in IDH group were significantly smaller than those in the non-hypotension group [ (1.6±0.2) mm 3vs. (1.7±0.2) mm 3, t=2.674, P=0.009; (6.9±0.8) mm 3vs. (7.4±1.0) mm 3, t=2.187, P=0.031; (6.9±0.8) mm 3vs. (7.4±0.9) mm 3, t=2.252, P=0.024]. The differences of gray matter, white matter volume between the two groups showed a similar trend but did not reach statistical significance. And lacunar infarction and cerebral microbleeds were more common in IDH group. The daily living ability scores of the two groups were similar (65.51±11.52 vs. 65.71±11.53, Z=-0.456, P=0.648). The proportion of patients with cognitive abnormalities was higher in the IDH group, without statistical significance. The proportion of depression was similar. Univariate linear regression analysis showed that IDH was significantly negatively correlated with the volume of amygdala, cuneiform cortex, and posterior cingulate gyrus, which control emotions in the brain ( B=-0.117, 95% CI -0.203--0.030, P=0.009; B=-0.484, 95% CI -0.923--0.046, P=0.031; B=-0.485, 95% CI -0.911--0.058, P=0.026). After multivariate adjustment, decreased amygdala volume was still correlated with IDH ( B=-0.111, 95% CI -0.198--0.025, P=0.026). Conclusion:Recurrent IDH may lead to atrophy of various brain components, which may be one of the reasons for cognitive and emotional changes in maintenance hemodialysis patients.

Objective To investigate independent risk factors for unintended initial dissection of the posterior plane(UIDPP)during small incision lenticule extraction(SMILE)by surgeons with different qualifications.Methods A total of 1 600 patients(3 003 eyes)who underwent SMILE performed by three surgeons with different qualifications from April to September 2021 were selected as the research subjects,including 911 males and 689 females,with an average age of(21.82±3.55)years.The incidence of UIDPP in patients was recorded,along with a comprehensive summary of the age,gender,eyes,surgeons,surgical proficiency,subjective refraction,central corneal thickness,lenticule thickness,side cut angle,and peripheral lenticule thickness of the patients.Independent risk factors of UIDPP were analyzed using the binary logistic regression.Test level:α=0.05.Results In this study,the incidence of UIDPP was 6.56％(197/3 003),and the lenticule was successfully removed in all eyes.Multivariate logistic regression analysis demonstrated that surgeon(P=0.035),surgical proficiency(P=0.026),eyes(P=0.007),lenticule thickness(P＜0.001),and peripheral lenticule thick-ness(P＜0.001)were independent risk factors associated with the UIDPP during SMILE surgery.No significant differences were observed in other parameters(all P＞0.05).Conclusion Surgeons,surgical proficiency,eyes,lenticule thick-ness,and peripheral lenticule thickness are independent risk factors of UIDPP.

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.

BACKGROUND:The most prominent transcription factor activated by tumor stem cells in osteosarcoma is EZH2,and silencing of EZH2 has been reported to inhibit osteosarcoma cell growth.Studies have confirmed that bovine serum albumin-chitosan nanoparticles are a drug delivery vector with excellent biocompatibility and biodegradability,and the albumin carrier can provide tumor-targeted drug delivery function. OBJECTIVE:To investigate the effect and mechanism of bovine serum albumin-chitosan nanoparticles loaded with EPZ6438(EZH2 inhibitor)for the treatment of osteosarcoma. METHODS:(1)Bovine serum albumin-chitosan nanoparticles loaded with and without EPZ6438 were prepared.The drug encapsulation rate and drug release rate of serum albumin-chitosan nanoparticles loaded with EPZ6438 were detected.(2)MG-63 cells were divided into four groups and added with PBS(control group),serum albumin-chitosan nanoparticle extract solution(blank nanoparticle group),EPZ6438 solution(free drug group),and serum albumin-chitosan nanoparticle extract loaded with EPZ6438(drug-loaded nanoparticle group),respectively.After 3 days of culture,cell apoptosis was detected by flow cytometry and the expression of caspase-3 mRNA was detected by RT-PCR.(3)Twelve nude mice were selected and the subcutaneous tumor-bearing mouse model was established by injecting MG-63 cell suspension under the armpit.After successful modeling,the mice were randomly divided into four groups for intervention.Normal saline(control group),serum albumin-chitosan nanoparticle solution(blank nanoparticle group),EPZ6438 solution(free drug group)and serum albumin-chitosan nanoparticle solution loaded with EPZ6438(drug-loaded nanoparticle group)were injected into tumor tissues,with three animals in each group.After 7 days of injection,the tumor volume and frozen sections of tumor tissue were observed by TUNEL staining. RESULTS AND CONCLUSION:(1)The drug encapsulation rate of the nanoparticles was about 8.8%,and the nanoparticles had a good drug release effect in pure water.The drug release amount was(34.72±1.93)μg at 24 hours,(48.58±1.10)μg at 72 hours,(49.18±1.24)μg at 120 hours,and(50.25±1.13)μg at 168 hours.The drug release reached the plateau at 120 hours,and the release rate was about 97.9%.(2)After 3 days of cell culture with MG-63,the apoptotic rate in the control group and blank nanoparticle group was lower than that in the free drug group and drug-loaded nanoparticle group(P<0.001),and the expression of caspase 3 mRNA was lower than that in the free drug group and drug-loaded nanoparticle group(P<0.000 1).(3)After 7 days of injection,the tumor volume of nude mice in the drug-loaded nanoparticle group was smaller than that in the other three groups(P<0.05),and the percentage of TUNEL-positive cells in tumor tissue was higher than that in the other three groups(P<0.000 1).(4)The results verify that serum albumin-chitosan nanoparticles loaded with EPZ6438 can inhibit the growth of osteosarcoma by inducing apoptosis of tumor cells.

Objective:To explore the differences between the deep learning-based image reconstruction (DLIR) and the adaptive statistical iterative reconstruction V (ASiR-V) algorithms in the radiation dose and image quality of head and neck CT angiography (CTA).Methods:The data of 80 patients undergoing head and neck CTA due to vascular diseases in the head and neck were prospectively collected. These patients were randomly divided into groups A and B based on their examination sequence. The CTA images of group A were reconstructed based on ASiR-V 50%, with a tube voltage of 120 kV and a noise index of 11.0. In contrast, those of group B were reconstructed based on ASiR-V 50% (for group B1) and DLIR-H (for group B2), with a tube voltage of 80 kV and a noise index of 9.0. Then, the radiation doses and image quality of both groups were compared using the independent-sample t-test. The radiation doses, and both subjective and objective image quality of the two imaging method were compared through the Kruskal-Wallis test and the Wilcoxon rank-sum test. The independent- or paired-sample t-test was employed to measure inter-group vascular enhanced CT values, as well as signals and noise from regions of interest (ROIs), with signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) calculated. Results:The effective doses of groups A and B were (0.77±0.08) and (0.45±0.05) mSv, respectively, with a statistically significant difference ( t = 21.96, P < 0.001). The vascular enhanced CT values, SDs, SNRs, and CNRs in the arch of the aorta, the initial and bifurcation parts of the common carotid artery, and the M1 segment of the middle cerebral artery showed statistically significant differences among groups A, B1, and B2 ( F = 67.69, 68.50, 50.52, 74.10, 63.10, 91.22, 69.16, P < 0.001). Additionally, statistically significant differences were observed in the subjective scores of image quality among groups A, B1, and B2 ( Z = 71.06, P < 0.05). Conclusions:The DLIR algorithm can further reduce the radiation dose in head and neck CTA examination while significantly reducing image noise and ensuring image quality, thus demonstrating high clinical application value.

To explore the effectiveness of "near peer learning" (NPL) in the electromyography(EMG)teaching module for neurology residents.