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 analyse the prognosis and risk factors of lung cancer with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Tongchuan City, and to provide a theoretical basis for improving the prognosis of patients with lung cancer complicated with AECOPD. Methods A total of 280 patients with lung cancer combined with AECOPD admitted to Tongchuan People's Hospital from January 2021 to August 2022 were selected and divided into survival group and death group according to whether the patients survived during hospitalization. Serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1) and other tumor markers were compared between the two groups. Lung function was measured by lung function instruments, and the levels of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC and other lung function indicators were compared between the two groups. The patients' clinical data were collected from the medical record system, and univariate analysis and logistic regression were used to analyze the independent risk factors affecting the prognosis of patients with lung cancer complicated with AECOP. Results The values of FEV1, FVC and FEV1/FVC in the death group were significantly lower than those in the survival group (P<0.05). Serum CEA and CYFRA 21-1 levels in the death group were significantly higher than those in the survival group (P<0.05). Multiple logistic regression analysis showed that albumin level <35 g/L (OR=2.728), TNM stage III to IV (OR=2.416), multidrug-resistant bacterial infection (OR=2.982), and GOLD grade III to IV (OR=3.417) were independent risk factors for death in patients with lung cancer complicated with AECOPD in Tongchuan City (P<0.05). Conclusion Patients with lung cancer complicated with AECOPD in Tongchuan City have a high risk of death during hospitalization, especially patients with TNM stage III to IV and GOLD grade III to IV. Multi-drug resistant bacteria infection should be actively controlled to improve the albumin level of patients, which is conducive to the prognosis of patients.

This article combs and summarizes the entire process of rare disease selection and priority theme determination,including the application and preliminary review of rare diseases,standardization of disease theme information,the evaluation methods of evidence sorting and disease selection for priority se-lection of disease themes,and other aspects of the content were analyzed in depth.It is expected to provide reference for the subsequent selection of rare diseases,improve the fairness,rationality and scientificity of rare disease selection,and further promote research and decision-making in China's rare disease-related fields.

Objective To study the characteristics of a rat model of migraine with hyperactivity of liver-yang and blood stagnation,which was established by Fuzi Decoction combined with electrical stimulation of the trigeminal ganglion.Methods The 30 SD rats were divided into normal group,model group,and Zhengtian pill group(1.6 g·kg-1),with 10 rats in each group.Rats in the model group and Zhengtian pill group were fed with aconite decoction(2.00 g·kg-1)once a day for 28 day to establish the hyperthermia model;On the 15 day of intragastric administration,rats in the Zhengtai pill group were simultaneously given Zhengtai pill solution once a day for 14 day;At 29 day,the trigeminal ganglion was stimulated to create the migraine model of hyperliver and stasis.After 30 min of the last dose,the macroscopic signs and behaviors were observed,and the blood rheology was detected by blood visticometer.Positive substance P(SP)expression,mRNA and relative protein expression in the trigeminal cervical pulp complex(TCC)in rat mice by immunohistochemistry,RT-qPCR and Western blot analysis.Results Compared with the normal group,the model group has macro signs such as red eyes,irritability,cage fighting,dark tongue and stasis points;regular head positioning and frequent hair management;increased distance in the central area(P<0.05).The relative viscosity of whole blood,plasma viscosity,red blood cell aggregation index all increased(P<0.05),and the red blood cell variant index decreased(P<0.05);SP positive expression,mRNA and the relative protein expression increased in TCC(P<0.05).Compared with model group,Zhengtian pill group can improve macro representation and behavior significantly;can significantly reduce central distance(P<0.05);can reduce plasma viscosity,high-shear relative viscosity of whole blood,and red blood cell aggregation index(P<0.05);increase the Red blood cell variant index significantly(P<0.05);down-regulate SP positive expression,mRNA and relative protein expression in TCC(P<0.05,P<0.01).Conclusion SD rats were used for 4 weeks to construct a migraine model of hyperhepatic hyperactivity and stasis,which was basically consistent with the clinical manifestations.

To study the effects of nucleoside antiviral drug zidovudine (AZT) on the flexibility of global metabolism and liver glucolipid metabolic balance in mice, male ICR mice were given zidovudine intragastric administration for 12 weeks, and their water and food intake was recorded daily.Serum glucose (GLU) and triglyceride (TG) levels and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected after 12 weeks of administration.Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed.HE staining was used to observe the pathological changes of liver.The gene levels of glucose transporter (Glut2), carnitine palmitate transferase (Cpt1α), medium chain acyl-coa dehydrogenase (Mcad), phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6pase) were detected by RT-PCR.Western blot was used to detect the protein levels of insulin signaling Akt, P-Akt, Glut2, Mcad and Cpt1α in liver.The results showed that zidovudine significantly decreased lipid metabolism, impaired glucose tolerance, increased liver cell volume, significantly increased liver triglyceride (TG) and non-esterified fatty acid (NEFA) content, increased Glut2 gene expression, down-regulated fatty acid oxidative metabolism genes Cpt1α, Mcad and gluconeogenesis related genes after fasting, and down-regulated protein expression of Cpt1α.The results suggest that zidovudine can induce the disorder of glucose and lipid metabolism after fasting in a dose-dependent manner.

OBJECTIVE To expl ore the mechanism of effe ctive fractions from Xiongma decoction in the treatment of migraine with hyperactivity of liver-yang and blood stasis. METHODS Totally 70 male SD rats were randomly divided into normal group ， model group ，positive control group （Flunarizine hydrochloride capsules 0.9 mg/kg），low-dose and high-dose groups of Xiongma decoction effective fractions （ethyl acetate extract 0.87，3.46 g/kg，n-butanol extract 1.80，7.20 g/kg）. Except for normal group ， rats in other groups were given aconite decoction （2 g/kg），once a day ，for 4 consecutive weeks to establish the hyperactivity model of liver-yang. On the 15th day of modeling ，all administration groups were given corresponding drugs intragastrically at the same time ，once a day ，for 2 consecutive weeks. On the 29th day of modeling ，rats trigeminal ganglion was stimulated to establish the migraine model with hyperactivity of liver-yang and blood stasis ，then the medication was maintained for another time according to the above method. The macroscopic signs and behavior of the rats were observed ；positive expression ，mRNA and protein expression of transient receptor potential vanilloid 1 （TRPV1），calcitonin generelated peptide （CGRP），calcitonin receptor-like receptor （CRLR） and receptor-associated membrane proteins 1 （RAMP1） in trigeminal cervical spinal complex （TCC） were detected by immunohistochemistry ，RT-qPCR and Western blot assay. RESULTS Rats in model group showed macrophysical signs and behaviora l manifestations related to migraine with hyperactivity of liver-yang and blood stasis. Thirty minutes after last administration ，the above conditions of rats in Xiongma decoction effective fraction groups were improved significantly. Compared with normal group ， positive expression，mRNA and protein expression of TRPV 1，CGRP， CRLR and RAMP 1 in TCC of rats in the model group were significantly increased （P＜0.05）. Compared with model zengguirong@hnse.org group， most of above indicators in Xiongma decoction effective fraction groups were significantly decreased （P＜0.05）. CONCLUSIONS The mechanism of Xiongma decoction in preventing and treating migraine with hyperactivity of liver-yang and blood stasis may be related to inhibit the activity of TRPV1-CGRP/CGRP receptor signaling pathway in TCC.

OBJECTIVE To determ ine the contents of main active constituents in Gynura divaricata leaf with different drying methods and at different harvesting time ，so as to confirm the best drying method and harvesting time. METHODS G. divaricata leaf with different drying methods [drying in the shade ，drying in the sun ，oven drying （60℃，70℃，80℃），microwave drying and freeze drying] and different harvesting time （March to October ）were prepared. The content of water-soluble extract was determined by hot dip method. The contents of total flavonoids and polysaccharides were determined by ultraviolet-visible spectrophotometry. The content of astragalin was determined by HPLC. Analytic hierarchy process was used for comprehensive analysis. RESULTS The time of drying in the shade ，drying in the sun ，drying at 60 ℃，drying at 70 ℃，drying at 80 ℃， microwave drying and freeze drying were 7 d，5 d，8 h，5 h，3.5 h，6 min and 1 d respectively. The average contents of water-soluble extract in G. divaricata leaf were 55.98％，60.78％，52.33％，49.54％，46.87％，59.70％ and 58.24％；those of total flavonoids were 3.27％，3.22％，1.99％，1.70％，1.31％，3.92％ and 2.28％；those of polysaccharides were 4.70％，6.09％， 6.48％，5.45％，5.74％，5.76％ and 7.15％；those of astragalin were 0.48％，0.46％，0.24％，0.23％，0.20％，0.48％，0.29％. The comprehensive score of microwave drying was the highest ，being 0.996 3. The average contents of water-soluble extract from March to October were 41.50％，40.57％，39.16％，40.65％，40.68％，43.30％，45.19％ and 40.12％；those of total flavonoids were 2.24％，2.81％，3.87％，3.92％，3.82％，3.93％，3.66％ and 3.25％；those of polysaccharides were 4.41％，4.61％， 4.98％，5.26％，5.75％，5.94％，5.32％ and 4.47％；those of astragalin were 0.20％，0.21％，0.25％，0.26％，0.25％，0.24％， 0.25％ and 0.21％，respectively. The comprehensive scores of samples collected from May to September exceeded 0.92，and the comprehensive score in August was the highest （0.988 6）. CONCLUSIONS Microwave-dried Gynura divaricata leaf has the best quality ，and the best harvesting time is from May to September.

BACKGROUND: Feeding intolerance (FI) among intensive care unit (ICU) patients undergoing early continuous enteral nutrition (EN) is related to poor outcomes. This study aimed to explore the prevalence and risk factors of FI in ICU patients. METHODS: We retrospectively enrolled 1057 patients who received early continuous EN via a nasogastric tube between January 2014 and August 2019. The prevalence of FI during the first 7 days of ICU stay was calculated, and the risk factors were investigated using multivariate logistic regression analysis. RESULTS: The prevalence of FI during the first 7 days of ICU stay was 10.95%. FI occurred in 159 of 1057 (15.04%) patients on ICU day 2, 114 of 977 (11.67%) patients on ICU day 3, and 86 of 715 (12.03%) patients on ICU day 7. Mechanical ventilation (MV) (odds ratio [OR]: 1.928, 95% confidence interval [CI]: 1.064-3.493, P  = 0.03) was an independent risk factor for FI defined by a gastric residual volume (GRV) of 200 mL and/or vomiting, and acute renal failure (OR: 3.445, 95% CI: 1.115-10.707, P  = 0.032) was an independent risk factor of FI defined by a GRV of 500 mL and/or vomiting. Continuous renal replacement therapy (CRRT) was an independent predictor regardless of the FI defined by a GRV of 200 mL (OR: 2.064, 95% CI: 1.233-3.456, P  = 0.006) or 500 mL (OR: 6.199, 95% CI: 2.108-18.228, P  = 0.001) in the ICU patients. CONCLUSIONS FI occurs frequently in early ICU days, especially in patients receiving MV and CRRT. However, further investigation of a consensus definition of FI and risk factors is still warranted in future studies.
Critical Illness ; Enteral Nutrition/adverse effects* ; Humans ; Infant, Newborn ; Intensive Care Units ; Prevalence ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Vomiting/etiology*

ABSTRACT OBJECTIVE：To study the effects of the extract of Xiongmatang on 5-HT and CGRP in brain tissue of rats with liver-yang hyperactivity and blood stagnation migraine. METHODS：Fifty male spontaneously hypertension （SHR） rats were randomly divided into model control group，Zhengtian pill positive control group （1.6 g/kg），the extract of Xiongmatang low-dose，medium-dose and high-dose groups（4.5，9.0，18.0 g/kg，by crude drug），with 10 rats in each group. Another 10 normal rats were taken as normal control group. Administration group was given relevant medicine intragastrically，once a day，for consecutive 28 d. Normal control group and model control group were given equal volume normal saline intragastrically. After last administration，except for normal control group，other groups were used to stimulate trigeminal ganglia（10 min）to establish liver-yang hyperactivity and blood stagnation migraine model，and maintained the administration once more after making the model. 30 min later，general behavior and tongue quality of rats were observed，and the blood pressure was measured；the contents of 5-HT and CGRP in cerebral tissue of rats were determined by ELISA. The protein expression of CGRP in cerebral tissue of rats were determined by Western blot method. RESULTS： Compared with the normal control group， the rats in the model control group had behavioral symptoms，such as the color of conjunctiva deepened and reddened， excessive hairdressing，head flicking，and most of the rats had purple tongue；the systolic pressure and the content and protein expression of CGRP were all increased obviously（P＜0.05 or P＜0.01）， while the content of 5-HT in cerebral tissue was decreased obviously（P＜0.01）. Compared with model control group，general behavior and tongue quality of rats were improved significantly in administration groups. Systolic pressure，the content and the protein expression of CGRP in cerebral tissue of rats were decreased significantly in Zhengtian pill positive control group and the extract of Xiongmatang high-dose group （P＜0.05），while the content of 5-HT in cerebral tissue of rats were increased significantly in Zhengtian pill positive control group，the extract of Xiongmatang medium-dose and high-dose groups（P＜0.05）.CONCLUSIONS：The extract of Xiongmatang has obvious protective effect on liver-yang hyperactivity and blood stagnation migraine model rats，the mechanism of which may be associated with reducing the content of CGRP in cerebral tissue and raising the content of 5-HT in cerebral tissue

OBJECTIVETo detect potential mutations of fibrillin-1 (FBN1) gene in a child with Marfan syndrome (MFS) and explore its molecular pathogenesis.

METHODSThe 66 exons of the FBN1 gene were analyzed by direct sequencing. SIFT and PolyPhen-2 were used to predict the structural and functional changes at the protein level.

RESULTSA novel heterozygous mutation c.3998 G>A (p.Cys1333Tyr) was found in exon 32 in the child. The same mutation was not found among his unaffected family members and 683 healthy controls. Multiple sequence alignment showed that this novel mutation was located in a highly conserved region of the FBN1 protein across various species and may induce structural change to a functional domain.

CONCLUSIONThe novel c.3998G>A (p.Cys1333Tyr) mutation of the FBN1 gene probably predisposed the MFS in the child. Above finding has enriched the spectrum of FBN1 mutations.