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.

The Shanghai-style pediatric Tuina(Chinese therapeutic massage)school,a renowned academic school of pediatric Tuina in China,was founded by Professor JIN Yicheng,a mentor of the National Senior Traditional Chinese Medicine(TCM)Experts'Clinical Experience Inheritance Class and a distinguished TCM practitioner in Shanghai.This academic school has now been perpetuated through four generations.Prof.JIN Yicheng,a pioneering leader in modern China's pediatric Tuina,has dedicated sixty years to medical practice with unwavering benevolence and adherence to"principled innovation".While delving into traditional and ancient teachings,he has also embraced contemporary advancements.Building upon the essence of traditional pediatric Tuina,he integrated distinctive techniques from various Tuina schools,including the Yi Zhi Chan Tuina school,rolling manipulation Tuina school,and Neigong Tuina school.He also assimilated the quintessence of historical pediatric Tuina literature,the experience of modern Shanghai-based pediatric Tuina masters,and folk techniques while incorporating his years of clinical insights.This synthesis finally led to the formulation of the academic thought of"reinforcing healthy Qi and unblocking regulation"in Shanghai-style pediatric Tuina that guides clinical practice.Specifically,he comprehensively applies techniques such as"unblocking regulation of Zang-Fu organs","unblocking regulation of the four seas","unblocking regulation of the water and fire",and"unblocking regulation of the back"to the prevention and treatment of pediatric diseases across internal medicine,external medicine,orthopedics,and otolaryngology,which has significantly enhanced clinical efficacy and expanded the applicable age range and scope of Tuina for pediatric health issues,more aligning with the characteristics of children and adolescents'health challenges and current clinical demands,and paving a new way in preserving and developing traditional pediatric Tuina.

Lirispirolides A-L (1-12), twelve novel sesquiterpene-monoterpene heterodimers featuring distinctive carbon skeletons, were isolated from the branches and leaves of Chinese tulip tree [Liriodendron chinense (L. chinense)], a rare medicinal and ornamental plant endemic to China. The structural elucidation was accomplished through comprehensive spectroscopic analyses, quantum-chemical calculations, and X-ray crystallography. These heterodimers exhibit a characteristic 2-oxaspiro[4.5]decan-1-one structural motif, biosynthetically formed through intermolecular [4 + 2]-cycloaddition between a germacrane-type sesquiterpene and an ocimene-type monoterpene. The majority of the isolated compounds demonstrated significant anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV-2 microglial cells by reducing the production of pro-inflammatory mediators, specifically tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Further investigation revealed that the lirispirolides' inhibition of NO release correlated with decreased messenger ribonucleic acid (mRNA) expression of inducible NO synthase (iNOS).
Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Animals ; Mice ; Tumor Necrosis Factor-alpha/genetics* ; Nitric Oxide/immunology* ; Microglia/immunology* ; Molecular Structure ; Liriodendron/chemistry* ; Monoterpenes/isolation & purification* ; Plants, Medicinal/chemistry* ; Cell Line ; Lipopolysaccharides ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; China

The Shanghai-style pediatric Tuina(Chinese therapeutic massage)school,a renowned academic school of pediatric Tuina in China,was founded by Professor JIN Yicheng,a mentor of the National Senior Traditional Chinese Medicine(TCM)Experts'Clinical Experience Inheritance Class and a distinguished TCM practitioner in Shanghai.This academic school has now been perpetuated through four generations.Prof.JIN Yicheng,a pioneering leader in modern China's pediatric Tuina,has dedicated sixty years to medical practice with unwavering benevolence and adherence to"principled innovation".While delving into traditional and ancient teachings,he has also embraced contemporary advancements.Building upon the essence of traditional pediatric Tuina,he integrated distinctive techniques from various Tuina schools,including the Yi Zhi Chan Tuina school,rolling manipulation Tuina school,and Neigong Tuina school.He also assimilated the quintessence of historical pediatric Tuina literature,the experience of modern Shanghai-based pediatric Tuina masters,and folk techniques while incorporating his years of clinical insights.This synthesis finally led to the formulation of the academic thought of"reinforcing healthy Qi and unblocking regulation"in Shanghai-style pediatric Tuina that guides clinical practice.Specifically,he comprehensively applies techniques such as"unblocking regulation of Zang-Fu organs","unblocking regulation of the four seas","unblocking regulation of the water and fire",and"unblocking regulation of the back"to the prevention and treatment of pediatric diseases across internal medicine,external medicine,orthopedics,and otolaryngology,which has significantly enhanced clinical efficacy and expanded the applicable age range and scope of Tuina for pediatric health issues,more aligning with the characteristics of children and adolescents'health challenges and current clinical demands,and paving a new way in preserving and developing traditional pediatric Tuina.

  Objective  To evaluate the clinical and paraclinical features of Chinese patients with anti- LGI1 encephalitis.  Methods  Patients with memory deficits, psychiatric symptoms, seizures or altered level of consciousness, suspicious of encephalitis, at presentation to Peking Union Medical College Hospital were recruited between July 2013 and January 2018, and tested for anti-LGI1 antibodies in their serum and/or cerebrospinal fluid(CSF) samples. Patients with anti-LGI1 antibodies were enrolled. The demographic characteristics, clinical manifestations, laboratory examination results, neuroimaging features, immunotherapy, follow-up practices and outcomes for included patients were registered and analyzed.  Results  The study enrolled 120 patients, of whom 66.7% were male. The median age was 61 years (interquartile range [IQR]: 49-66 years). Seizures(65.0%) were the most common initial symptoms. Most patients developed seizures (95.0%), including faciobrachial dystonic seizures (54.2%), memory deficits (92.5%), and psychiatric symptoms (69.1%). Brain MRI and ¹⁸F-FDG PET / CT showed that the lesions were mainly located in unilateral or bilateral medial temporal lobes, and (or) basal ganglia. Of the patients, 95.0% received intravenous immunoglobulin (IVIg) or corticosteroids, 47.5% received mycophenolate mofetil as long-term immunotherapy, and no one received second-line immunotherapy. The median follow-up was 34.2 months(IQR: 22.0-45.6 months). 91.2% had a good outcome (modified Rankin Scale score≤2 points). Residual mild memory deficits were present in 47.8% of the patients. Nine deaths were documented. Relapses occurred in 24.8% of the patients in the first year. In total, 24 (20%)cases were young patients(onset age ≤45 years).There were fewer males among the younger patients(37.5% vs. 74.0%, P < 0.01). Besides, there were fewer younger patients with psychiatric symptoms(50.0% vs. 74.0%, P=0.02), hyponatremia(33.3% vs. 68.8%, P < 0.01), and abnormalities on brain ¹⁸F-FDG PET/CT(20.8% vs. 47.9%, P=0.02). The relapse-free survival rate was significantly higher in the young patients.  Conclusions  Elderly males were predominant in patients with anti-LGI1 encephalitis. Most patients developed symptoms of limbic encephalitis and/or FDBS during the disease course. Several patients were young adults and lacked typical symptoms. Neuroimaging features were consistent with the involvement of limbic system or basal ganglia. Patients with anti-LGI1 encephalitis respond well to immunotherapy, irrespective of the age.

To date, there is no report on the genetic diversity of ticks in these regions. A total of 370 representative ticks from the south and east regions of Kazakhstan (SERK) and Xinjiang Uygur Autonomous Region (XUAR) were selected for molecular comparison. A fragment of the mitochondrial cytochrome c oxidase subunit I (cox1) gene, ranging from 631 bp to 889 bp, was used to analyze genetic diversity among these ticks. Phylogenetic analyses indicated 7 tick species including Hyalomma asiaticum, Hyalomma detritum, Hyalomma anatolicum, Dermacentor marginatus, Rhipicephalus sanguineus, Rhipicephalus turanicus and Haemaphysalis erinacei from the SERK clustered together with conspecific ticks from the XUAR. The network diagram of haplotypes showed that i) Hy. asiaticum from Almaty and Kyzylorda Oblasts together with that from Yuli County of XUAR constituted haplogroup H-2, and the lineage from Chimkent City of South Kazakhstan was newly evolved; and ii) the R. turanicus ticks sampled in Israel, Almaty, South Kazakhstan, Usu City, Ulugqat and Baicheng Counties of XUAR were derivated from an old lineage in Alataw City of XUAR. These findings indicate that: i) Hy. asiaticum, R. turanicus and Ha. erinacei shared genetic similarities between the SERK and XUAR; and ii) Hy. marginatum and D. reticulatus show differences in their evolution.

Objective: To evaluate possible effects of Gelctin-9 on acute graft versus host disease (aGVHD) development and clinical outcomes in patients before and afer allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood samples were obtained from 29 patients and 15 healthy volunteers with heparin anticoagulant tubes. Samples were analyzed using ELISA kits to measure the serum concentrations of Galectin-9. Results: Patients developing aGVHD had significantly lower level of Galectin-9 [ (7.96±1.18) μg/L] before allo-HSCT compared with those not developing aGVHD [ (12.37±0.97) μg/L, P<0.001]. And after allo-HSCT, the consentration of Galectin-9 increased markedly in patients developing aGVHD [ (17.78±1.78) μg/L] compared with those not developing aGVHD [ (9.45±0.80) μg/L, P<0.001]. Patients developing 3-4 grade aGVHD had significantly higher level of Galectin-9 [ (23.25±2.59) μg/L] compared with those developing 1-2 grade aGVHD [ (14.37±1.45) μg/L, P=0.008] and those without aGVHD [ (9.45±0.80) μg/L, P<0.001]. The patients with lower level of Galectin-9 after allo-HSCT (<13.61 μg/L) showed more favorable clinical outcomes compared with those with higher level of Galectin-9 (≥13.61 μg/L) . The 3-year overall survival rates were (100.00±6.05) % and (69.23±12.80) %, respectively (P=0.009) . The cumulative incidence of non-relapse mortality was significantly higher in high Galectin-9 group [ (23.08±11.69) %] in comparison with low Gaelctin-9 group [ (0.00±7.39) %] (P=0.023) . There was no significant difference between the two groups in terms of the cumulative incidence of relapse. The cumulative incidence of relapse at 3 years were (8.33±7.98) % and (12.50±8.27) % in high and low Galectin-9 groups, respectively (P=0.708) . Conclusions The serum concentration of Galectin-9 at the time of engraftment after allo-HSCT may be used as a predictor for the development and severity of aGVHD. Galectin-9 might be considered as a potential new approach to regulate transplant rejection to achieve desirable survival.

Cell death plays important roles in living organisms and is a hallmark of numerous disorders such as cardiovascular diseases, sepsis and acute pancreatitis. Moreover, cell death also plays a pivotal role in the treatment of certain diseases, for example, cancer. Noninvasive visualization of cell death contributes to gained insight into diseases, development of individualized treatment plans, evaluation of treatment responses, and prediction of patient prognosis. On the other hand, cell death can also be targeted for the treatment of diseases. Although there are many ways for a cell to die, only apoptosis and necrosis have been extensively studied in terms of cell death related theranostics. This review mainly focuses on molecular imaging and therapeutic strategies directed against necrosis. Necrosis shares common morphological characteristics including the rupture of cell membrane integrity and release of cellular contents, which provide potential biomarkers for visualization of necrosis and necrosis targeted therapy. In the present review, we summarize the updated joint efforts to develop molecular imaging probes and therapeutic strategies targeting the biomarkers exposed by necrotic cells. Moreover, we also discuss the challenges in developing necrosis imaging probes and propose several biomarkers of necrosis that deserve to be explored in future imaging and therapy research.

Objective To investigate the clinical,therapeutic and prognostic features of patients with lateral sinus stenosis and isolated intracranial hypertension,and further explore the possible mechanisms of their coexistence.Methods We retrospectively enrolled 16 patients with neurosurgery in our hospital from January 2009 to December 2016,who were clinically diagnosed as simple intracranial hypertension with bilateral or predominant lateral sinus stenosis and lateral stenting.These 16 patients were recorded surgical procedures and postoperative outcomes,and followed-up to understand the long-term prognosis of them.Results There were 14 females in the 16 patients,with an average age of (32.4 ± 10.1) years,a mean duration of (10.9 ± 7.3) months,and an average body mass index of (28.9 ± 3.6) kg/m2.In terms of clinical manifestions,majority of the patients presented with headache (n =15) and visual symptoms (n =14),and all with papilledema by fundus examination.The elevated opening cerebrospinal fluid (CSF) pressure was noticed:five cases between 25-33 cmH2O (1 cmH2O =0.098 kPa),11 cases more than 33 cmH2O.The mean pressure difference in the proximal and distal sinus of the anterior chamber was (36.3 ± 9.4) cmH2O in the range of 15-91 cmH2O.The pressure difference between the two ends of the stenosis disappeared immediately after the operation in 12 cases and the pressure difference less than 15 (2-12) cmH2O in four cases.Thirteen patients underwent lumbar puncture at one week after operation.The CSF pressure of them decreased significantly,of which eight were in the normal range.Six months after the operation,11 patients underwent DSA/MRV,none of which had serious surgical complications.With the average follow-up of (35.4 ± 9.8) months,the overall prognosis of these patients was good.Headaches in 14 of 15 patients were improved,out of which 12 were free of headache,two with only mild headache and a slight intracranial hypertension (19 and 23 cmH2O,respectively);visual complaints were reversed in nine out of 14 cases;10 patients underwent fundus examination,and nine of them were observed the improvement of papilledema.During the follow-up period,the symptoms of other patients were improved (headache relief and visual improvement) except one,the overall effective ratio being 15/16.Conclusions The interventional treatment of lateral sinus stenting is effective in patients with sinus stenosis associated with simple intracranial hypertension.The stenosis of the lateral sinus may be the main mechanism of increased intracranial pressure.

Objective To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in antileucine-rich glioma-inactivated 1 (LGI1) encephalitis by analyzing the clinical and immunologic data of patients treated with MMF in this prospective cohort of anti-LGI1 encephalitis.Methods Patients treated with MMF for more than one year in Peking Union Medical College Hospital were included in this study.MMF was given at a dosage of 1.5-3.0 g/d in the induction period (two to four months) and 0.75-2.00 g/d in the maintenance period.All the patients were followed up regularly.Modified Rankin Scale (mRS) score evaluation,serum IgG and peripheral CD19-positive B cells,CD4-positive T cells and CD8-positive T cells testing were performed every two months.Results Fifteen patients were included in this study who received first-line immunotherapy combined with MMF.No other second-line therapy including rituximab was used.Thirteen patients responded well to MMF combined with first-line immunotherapy (a decrease in mRS score of more than 1).All 15 patients had a good outcome (i.e.,a mRS score of 0-2),including nine patients without residual symptoms (a mRS score of 0).After 12 months of MMF treatment,CD19-positive B cells were significantly decreased (median 320 (227,628) × 106/L vs 152 (105,223) × 106/L;Z=-2.028,P=0.043),while serum IgG (9.07 (6.70,11.32) g/L vs 8.35 (6.63,10.69) g/L,P=0.144)),CD4-positive T cells (1 136 (736,1 432) × 106/L vs 1 055 (802,1 072) × 106/L,P =0.866) and CD8-positive T cells (627 (413,784) × 106/L vs 568 (393,743) × 106/L,P =0.735) were not significantly changed.Three patients relapsed and were treated with additional cycle of first-line immunotherapy and increased dosage of MMF (induction dosage) resulting in remission.CD19-positive B cells were tested to be increased during the patients' relapse.No serious adverse event was noted in all these patients.Conclusions MMF is safe and effective as a long-term immunotherapy in patients with anti-LGI1 encephalitis.MMF can be used as an add-on therapy to first-line immunotherapy for autoimmune encephalitis.CD19-positive B cell count should be monitored and used as a parameter to individualize dosage of MMF.