The diagnosis and treatment resources for rare diseases in China are highly imbalanced. The basic diagnosis and treatment capabilities are weak, the diagnosis period for patients is long, and the rates of missed diagnosis and misdiagnosis are relatively high. The establishment of a hierarchical diagnosis and treatment system is the inevitable approach to enhancing the diagnosis and treatment standards of rare diseases. Currently, the implementation of the domestic hierarchical diagnosis and treatment system for rare diseases still confronts numerous challenges, such as ambiguous referral standards and processes of primary medical institutions, and ineffective information interaction among institutions at all levels. Thus, it is essential to facilitate high-level information construction for the hierarchical diagnosis and treatment of rare diseases. This paper explores the process of constructing a multidisciplinary joint remote diagnosis and treatment platform and a health management platform through informatization, with the hope of establishing two closed loops of digital diagnosis and treatment services and health follow-up management for patients with rare diseases, as well as achieving timely diagnosis and lifelong health management for patients. It integrates and optimizes auxiliary diagnostic tools, promotes the rapid dissemination of rare disease diagnosis and treatment experiences to the grassroots, enhances the information construction level of the hierarchical diagnosis and treatment system, and endeavors to address the practical predicament of weak diagnosis and treatment capabilities of rare diseases in grassroots medical institutions. Additionally, this paper proposes an essential approach for multi-dimensional independent innovation to guide the popularization of efficient and high-quality rare disease diagnosis and treatment services. By encompassing innovating the rare disease diagnosis and treatment collaboration network and multidisciplinary diagnosis and treatment model, facilitating the application of the latest biomedical and informatics technologies to the grassroots, and constructing a national intelligent data platform for rare disease innovation, a new model for rare disease services with Chinese characteristics will be established. This will significantly enhance the medical treatment level of rare diseases in China and strive for more benefits for patients.

Objective:Age-related cataract is the most common type of adult cataract and a leading cause of blindness.Currently,there are few reports on the establishment of animal models for age-related cataract.During the experimental breeding of Microtus fortis(M.fortis),we first observed that M.fortis aged 12 to 15 months could naturally develop cataracts.This study aims to explore the possibility of developing them as an animal model for age-related cataract via identifing and analyzing spontaneous cataract in M.fortis. Methods:The 12-month-old healthy M.fortis were served as a control group and 12-month-old cataractous M.fortis were served as an experimental group.The lens transparency was observed using the slit-lamp biomicroscope.Hematoxylin and eosin staining was used to detect pathological changes in the lens.Biochemical detection methods were applied to detect blood routine,blood glucose levels,the serum activities of superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in both groups.Finally,real-time RT-PCR was used to detect the transcription levels of cataract-related genes in the lens of 2 groups. Results:Compared with the control group,the lens of cataract M.fortis showed severely visible opacity,the structure of lens was destroyed seriously,and some pathological damage,such as swelling,degeneration/necrosis,calcification,hyperplasia,and fiber liquefaction were found in lens epithelial cells(LECs).The fibrous structure was disorganized and irregularly distributed with morgagnian globules(MGs)aggregated in the degenerated lens fibers.There was no statistically significant difference in blood glucose levels between the experimental and control groups(P＞0.05).However,white blood cell(WBC)count(P＜0.05),lymphocyte count(P＜0.01),and lymphocyte ratio(P＜0.05)were significantly decreased,while neutrophil percentage(P＜0.05)and monocyte ratio(P＜0.01)were significantly increased.The serum activities of SOD and GSH-Px(both P＜0.05)were both reduced.The mRNAs of cataract-related genes,including CRYAA,CRYBA1,CRYBB3,Bsfp1,GJA3,CRYBA2,MIP,HspB1,DNase2B,and GJA8,were significantly downregultaed in the lenses of the experimental group(all P＜0.05). Conclusion:There are significant differences in lens pathological changes,peroxidase levels,and cataract-related gene expression between cataract and healthy M.fortis.The developed cataract spontaneously in M.fortis is closely related to age,the cataract M.fortis might be an ideal animal model for the research of age-related cataract.

Objective:To investigate the risk factors of postoperative recurrence of solid pseudopapillary neoplasms of the pancreas (SPN).Methods:Case-control studies on risk factors for postoperative recurrence in patients with SPN were conducted by searching in China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, Web of Science and Embase database from inception of these databases to November 2022. Two investigators screened the collected literatures independently according to the inclusion and exclusion criteria, extracted the data and evaluated the methodological quality, and then used Review Manager 5.4 for statistical analysis, odds ratio ( OR) was calculated with 95% confidence interval ( CI). Results:A total of 14 articles were included, including 1 409 patients with 67 cases in recurrence group and 1 342 cases in non-recurrence group. Twelve risk factors with predictive value for postoperative recurrence of SPN were extracted from the literatures. The analysis showed that the pooled OR and 95% CI of each risk factor were: gender ( OR=0.75, 95% CI: 0.35-1.59, P=0.450), age( OR=-2.08, 95% CI: -5.24-1.08, P=0.200), tumor diameter( OR=5.29, 95% CI: 4.71-5.87, P<0.001), tumor location( OR=0.56, 95% CI: 0.28-1.13, P=0.100), synchronous metastasis( OR=86.84, 95% CI: 22.64-333.05, P<0.001), lymph node metastasis ( OR=7.55, 95% CI: 2.58-22.06, P<0.001), perineural invasion ( OR=2.10, 95% CI: 0.98-4.48, P=0.060), positive margin( OR=7.00, 95% CI: 2.56-19.15, P<0.001), calcification( OR=0.49, 95% CI: 0.11-2.23, P=0.360), lymphovascular invasion( OR=11.22, 95% CI: 4.81-26.18, P<0.001), peripancreatic soft tissue invasion( OR=1.38, 95% CI: 0.48-4.00, P=0.550), capsular invasion( OR=1.72, 95% CI: 0.53-5.65, P=0.370). Conclusion:Large tumor diameter, synchronous metastasis, lymph node metastasis, positive margin, lymphovascular invasion increase the risk of recurrence of pancreatic SPN after resection, and patients with these characteristics should receive long-term follow-up.

Objective To compare the accuracy rate of talar osteochondral lesions between the small field of view (FOV) surface coil MR imaging and 2D FSE proton density weighted imaging (2D-FSE-PD),3D-SPACE sequences MR imaging with boot-shaped coil.Methods Totally 43 patients (45 ankles) underwent 3D-SPACE sequence after 2D-FSE-PD sequence scanning using the boot-shaped coil,then the PDWI sequence was scanning after the boot-shaped coil was replaced by the small FOV surface coil at 1.5T MRI.The results of the arthroscopic examinations was regarded as the standard for assessing the accuracy rate of the three methods.Results The accuracy rate of 2D-FSE-PD sequence with small FOV surface coil was 86.67％ (39/45),the accuracy rate of 2D-FSE-PD sequence with boot coil was 60.00％ (27/45),the accuracy rate of 3D-SPACE sequence with boot coil was 68.89％ (31/45).The accuracy rate of small FOV surface coil was higher than those of boot coil used 3D-SPACE sequence (x2 =4.114,P =0.002) and boot coil used 2D-FSE-PD sequence (x2 =8.182,P＜0.001).There was not significant difference between 3D-SPACE sequence using boot coil and 2D-FSE-PD sequence using boot coil (x2 =0.776,P=0.125).Conclusion Compared with the 2D-FSE-PD and 3D-SPACE sequences with boot-shaped coil,the small surface coil scanning with routine sequence can show talar osteochondral lesions better.

The present paper is aimed to explore the origins of Proteus mirabilis (PM) whorl swarming growth phenomenon. The whorl swarming growth phenomenon of PM was observed by changed bacterial culture inoculation time, humidity, vaccination practices, cultured flat placement, magnetic field, pH and other factors. Bacterial ring spiral direction of rotation is counterclockwise and the volatile growth process of PM was whorl swarming growth phenomenon. Spiro fluctuation phenomenon was of high frequency in the sealing tanks by cultured anytime inoculation, wherever inoculation technique applied or not, the presence or absence of the magnetic field, and wherever the dish position was. The experimental results showed that the whorl swarming growth phenomenon of PM requires specific pH environment, in which the facts may be relative to its genetic characteristics and the Earths rotation.
Cell Culture Techniques ; Hydrogen-Ion Concentration ; Magnetic Fields ; Proteus mirabilis ; growth & development

ObjectiveTo discusses the MSCT multiplanar reconstruction manifestation (MPR) of localized fat collection adjaction to subdiaphragmatic inferior vena cava (IVCfat).MethodsThe thoracic and abdominal MSCT scan data of 8246 patients were browsed,45 patients with presumed IVCfat on axial CT scans were further studied prospectively with MSCT MPR.The predisposing position of IVCfat and its relationship with IVC were observed.It was divided into two kinds of intraluminal type and extraluminal type according to the angle of IVCfat with respect of the wall of IVC.The other 50 patients without IVCfat were randomly selected as the control group.The sagittal inclination angle (SIA) and diameter ratio (DR) between supra- and sub-diaphragmatic IVC between the two groups were compared by using t test.Results The detection rate was 0.55％ (45/8246).Of which hepatic vein lacuna 8 patients,subdiaphragmatic gap medial to IVC 28 patients and IVC groove 9 patients.The shape of IVCfat showed mainly for the round,oval and crescents on axial CT scans,of 15 patients intraluminal type,4 showed target signs .The shape of IVCfat showed mainly for half-moon at MPR.The SIA and DR at IVCfat group were 21.62° ± 8.42°and 2.01 ±0.84 respectively,at control group were 16.75° ±7.82°(t =1.594,P ＞0.05) and 1.31 ±0.28(t =2.341,P ＜ 0.05 ) respectively.ConclusionThe round,oval or half of limited fat density shadow adjaction to subdiaphragmatic inferior vena cava which similar to in the lumen is the characteristic performance of IVCfat,it may be an anatomical variation.

Activation-induced cytidine deaminase (AID) is required for the generation of antibody diversity through initiating both somatic hypermutation (SHM) and class switch recombination. A few research groups have successfully used the feature of AID for generating mutant libraries in directed evolution of target proteins in B cells in vitro. B cells, cultured in suspension, are not convenient for transfection and cloning. In this study, we established an AID-based mutant accumulation and sorting system in adherent human cells. Mouse AID gene was first transfected into the human non-small cell lung carcinoma H1299 cells, and a stable cell clone (H1299-AID) was selected. Afterwards, anti-hTNF-α scFv (ATscFv) was transfected into H1299-AID cells and ATscFv was displayed on the surface of H1299-AID cells. By 4-round amplification/flow cytometric sorting for cells with the highest affinities to hTNF-alpha, two ATscFv mutant gene clones were isolated. Compared with the wild type ATscFv, the two mutants were much more efficient in neutralizing cytotoxicity of hTNF-alpha. The results indicate that directed evolution by somatic hypermutation can be carried out in adherent non-B cells, which makes directed evolution in mammalian cells easier and more efficient.
Animals ; Antibody Affinity ; Cells, Cultured ; Cytidine Deaminase ; genetics ; metabolism ; HEK293 Cells ; Humans ; Immunoglobulin Variable Region ; genetics ; immunology ; Mice ; Mutation ; Single-Chain Antibodies ; chemistry ; genetics ; immunology ; Somatic Hypermutation, Immunoglobulin ; genetics ; immunology ; Tumor Necrosis Factor-alpha ; immunology

Objective To evaluate the roles of multi-voxel proton magnetic resonance spectroscopy (1H-MRS) in the early diagnosis of vascular cognitive impairment no dementia (VCIND).Methods Seventy-eight out-patients and inpatients in Department of Neurology, the second Affiliated Hospital of Soochow University from December 2008 to September 2009 were recruited in this case-control study.Their cognitive functions were assessed with a wide range of neuropsychological battery of tests including Montreal cognitive assessment ( MoCA Beijing Version ), auditory verbal learning test ( AVLT), digital span test (DST), Rey-Osterrieth complex figure test (CFT) ,semantic and phonetic fluency tests, digit symbol coding subtest (DSCT), trail making test (TMT), clock drawing test (CDT) and the Stroop color-word test (SCWT).All patients were classified into vascular cognitive impairment no dementia (VCIND) group and cognitive normal control group based on the results of neuropsychological tests.Eighteen patients with VCIND and 18 gender-, age- and education-matched normal control were randomly selected for the following study.With multi-voxel 1H-MRS, the levels of N-acetylaspartartate (NAA), creatine (Cr) and choline (Cho) in gray matters of bilateral frontal lobe, temporal lobe, parietal lobe and thalamus were measured and the ratios of NAA/Cr, Cho/Cr were compared between the two groups.Meanwhile, the correlations between scores of MoCA and its sub-items and the ratios of NAA/Cr, Cho/Cr were analyzed in VCIND group.Informed consent was obtained from all participants and the study was approved by the Ethics Committee of the hospital.Results Compared with control group, the ratios of NAA/Cr were significantly decreased in bilateral gray matters of thalamus ( left, 1.56 ± 0.49 vs 1.89 ± 0.48, F = 11.222, P = 0.002; right,1.63± 0.45 vs 1.86 ± 0.33, F = 5.358, P = 0.027 ).No significant difference were found in NAA/Cr in gray matters of bilateral frontal lobe, temporal lobe, parietal lobe and Cho/Cr in all regions between two groups ( all P ＞ 0.05 ).In VCIND group, the decreased degree of NAA/Cr in bilateral gray matters of thalamus was significantly positively correlated with the MoCA total score ( r = 0.54, 0.44 ) as well as the sub-scores in tested items of memory ( r = 0.61, 0.49 ), attention ( r = 0.43, 0.36 ), language ( r = 0.39,0.31) and visuospatial or executive( r = 0.29 , 0.33, all P＜0.05 orP＜0.01).Conclusions Cognitive impairment in patients with VCIND maybe related to metabolic dysfunction of neurons in bilateral thalamic.Multi-voxel 1H-MRS plays an important role in early diagnosis and monitoring disease progression of VCIND.

the incidence of the complication.

Objective To investigate the regulative role of N-Acetyl-D-glucosamine(GlcNAc) on the stressed mice macrophages function.Methods The stressed mice model was established by electric footshock method.The mice were divided into 5 groups:normal control group,stressed mice model group,low dose Glc-NAc treatment group(0.25 ml 15% GlcNAc),medium-dose GlcNAc treatment group(0.5 ml 15% GlcNAc) and high-dose GlcNAc treatment group(1 ml 15% GlcNAc).GlcNAc was intragastrically injected to corresponding mice 2 h before the electrical stimulation.Peritoneal macrophage(PM?) phagocytosis capability was detected by phagocytosis saccharomycete assay,and PM? energy metabolism was detected by MTT assay.Results Compared with normal control group,stressed mice PM? phagocytosis capability was significantly lower(P