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.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination

Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3⁺/CD4⁺/CD8⁺ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.
COVID-19 ; Clostridiales ; Gastrointestinal Microbiome ; Humans ; Immunity ; Leukocytes, Mononuclear ; SARS-CoV-2

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors. Brain metastasis, such as breast cancer and lung cancer, also leads to high mortality. The available medicines are limited due to blood-brain barrier. Abnormal activation of phosphatidylinositol 3-kinases (PI3K) signaling pathway is prevalent in glioblastoma and metastatic tumors. Here, we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3K inhibitor with excellent anti-tumor activity against human glioblastoma. XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3K signaling pathway, induced cell cycle arrest in G1 phase as well. Additionally, XH30 inhibited the migration of glioma cells and blocked the activation of PI3K pathway by interleukin-17A (IL-17A), which increased the migration of U87MG. Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models. XH30 also repressed tumor growth in brain metastasis models of lung cancers. Moreover, XH30 reduced IL-17A and its receptor IL-17RA in vivo. These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.

Objective:The aim of this study was to explore the associations of muscle size and density with handgrip strength(HGS)and the Timed Up and Go(TUG)test.Methods:Totally 301 participants living in the Xinjiekou community near Beijing Jishuitan Hospital were recruited for CT imaging of the hip and a 1-cm slice of the mid-thigh.The cross-sectional area and density of the gluteus maximus and the mid-thigh muscles were estimated by the Osirix viewer based on CT images.HGS and TUG were also performed in these subjects.Logistic regression analysis was used to evaluate the correlations of muscle density and size with TUG and grip strength.Results:In women, after adjustment for age and BMI, the density of the gluteus maximus was negatively correlated with TUG( P trend=0.0366), while the size of the gluteus maximus and the mid-thigh muscles was not correlated with TUG.In men, the density or size of these muscles was not correlated with TUG.After adjustment for age and BMI, the density of the gluteus maximus was positively correlated with grip strength( P trend=0.0334)and the size of the mid-thigh muscles was also positively correlated with grip strength( P trend=0.0155)in men, but they were not correlated with grip strength in women. Conclusions:There were sex differences in the relationship between muscle size or density and grip strength or timed up and go.The density of the gluteus maximus is associated with muscle strength and physical performance while the size of the mid-thigh muscles is correlated with muscle strength.

Objective:To understand the molecular transmission characteristics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome(AIDS) patients in the mountainous area of southwest Zhejiang Province(Lishui city).Methods:A total of 147 blood samples were collected from newly-diagnosed HIV-1 infected who received no antiviral therapy, and pol gene was amplified, followed by sequencing. MEGA6.0 software was used to construct phylogenetic tree and determine gene subtypes. HIVDB online was used to analyze drug resistance mutation, then the pairwise genetic distance(GD) was calculated and the opitimal threshold of GD was selected, finally the molecular transmission network was constructed by Cytoscape3.7.0 software. Chi-square or Fisher′s exact probability method was used for statistical analysis. Results:A total of 134 sequences were obtained successfully, and nine subtypes were detected. The dominant subtypes were CRF08_BC (34.33%, 46/134), CRF01_AE (29.85%, 40/134) and CRF07_BC (23.88%, 32/134). It also found that age, registered residence, education level and transmission route had significant differences in distribution of subtypes ( P<0.05). Nineteen drug resistance individuals were found, and the total drug resistance rate was 14.18% (19/134). The HIV-1 molecular transmission network was plotted based on 1.2% GD threshold. A total of 15 transmission clusters (cluster size ranging from 2 to 29) were found. The network access rate was 49.25% (66/134), mainly including male (75.76%, 50/66), heterosexual (81.82%, 54/66) and patientsrinfected with CRF08_ BC (50.00%, 33/66). A transmission cluster including two cases of female sex workers and seven cases of drug resistance was identified, in which the average age of the patients was 57.21 years old and the average degree value was 22.7, and the cases were mainly infected through heterosexual contact (96.55%, 28/29). The highest homology of the sequences in the cluster was in Yunnan. Conclusions:The HIV-1 subtypes were diverse in the mountainous area of southwest Zhejiang Province(Lishui city). Drug resistant transmission had reached a moderate epidemic level. There were molecular transmission clusters with the aggregation characteristics of elderly clients in specific regions. It was urgent to formulate and implement precise intervention strategies to curb the spread of HIV.

Objective:To explore the value of iterative decomposition of water and fat with asymmetry and least squares estimation-quantitative fat imaging (IDEAL-IQ) in quantitative evaluation of thigh muscle fat content and its correlation with muscle strength in middle-aged and elderly volunteers.Methods:From December 2020 to April 2021, 30 volunteers aged 45 to 70 were recruited prospectively, including 15 males and 15 females with 52.5 (49.0, 56.3) years old. All subjects were scanned at 3.0 T MR, including axial T 1WI, IDEAL-IQ and coronal T 2WI of the left thigh. The region of interest of the knee extensors (quadriceps femoris) and knee flexors (hamstrings) in the left mid-thigh were delineated, and muscle cross-sectional area (CSA), skeletal muscle index (SMI), intermuscular fat fraction (FF) and intramuscular FF were obtained. In addition, isokinetic muscle strength measurement was performed on the left knee joint of all subjects at angular speeds of 60°/s and 180°/s to obtain peak torque (PT) and total work (TW) of knee flexors and extensors. Independent sample t-test, paired t-test or Mann-Whitney U test were used to compare the differences of CSA, SMI, intermuscular FF, intramuscular FF, PT and TW between different genders and muscle groups. Pearson or Spearman correlation analysis, and multiple linear regression analysis were used to analyze the correlation between CSA, SMI, intermuscular FF, intramuscular FF and PT, TW of thigh muscles. Results:The CSA, PT and TW of thighs in males were higher than those in females ( P<0.05), while the intermuscular FF in males was lower than that in females ( P=0.005). The CSA, SMI and PT of the thigh extensors were higher than those of the flexors ( P<0.001), while the intramuscular FF and intermuscular FF were lower than those of the flexors ( P<0.001). Intramuscular FF of flexors and extensors were moderately negatively correlated with PT ( r=-0.635, P<0.001; r=-0.546, P<0.001), and highly, moderately negatively correlated with TW ( r=-0.718, P<0.001; r=-0.616, P<0.001). Intermuscular FF of flexors and extensors were moderately negatively correlated with PT ( r=-0.519, P=0.003; r=-0.443, P=0.014), and negatively correlated with TW ( r=-0.363, P=0.049; r=-0.552, P=0.002). There was no significant correlation between CSA, SMI and PT, TW in flexors and extensors of thigh ( P>0.05). Multiple linear regression analysis showed that intramuscular FF was still significantly correlated with PT and TW of flexors and extensors (flexors: R 2adj=0.505, P=0.001; R 2adj=0.540, P<0.001; extensors: R 2adj=0.351, P=0.006; R 2adj=0.470, P=0.002). Conclusion:FF based on IDEAL-IQ technology can accurately quantify the intramuscular and intermuscular fat content of thighs, and there are negative correlations between intramuscular FF, intermuscular FF and isokinetic muscle strength measurements including PT and TW. Among them, intramuscular FF is more significant.

Objective:To evaluate the short-term precision and accuracy of bone mineral density (BMD) measured with quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA) in multi-centre clinical research with a European spine phantom (ESP).Methods:From January 2016 to April 2020, totally 40 CT scanners (12 Siemens from Germany, 12 Philips from Netherlands, 9 GE from US, 5 Toshiba from Japan, 2 United Imaging from China) and 53 DXA instruments (34 GE Lunar from US, 14 Hologic from US, 5 Medlink from France) used in multi-centre in China were enrolled. The CT equipment came from 31 centers and DXA equipment from 32 centers.Using Mindways QCT software, the ESP was scanned 10 times on each instrument with repositioning using standardized spine protocols with QCT and DXA. The BMD value of the three lumbar vertebrae with low, medium, high density and the mean BMD value were measured. Accuracy was assessed by comparing BMD values measured on each device with the actual value of the phantom. Short-term precision was calculated as the root-mean-square standard deviation (RMS-SD) and root-mean-square standard deviation coefficient of variation (RMS-%CV) for the repeated measurements. The repeated measures variance analysis was used to compare the differences in BMD between different devices.Results:The differences in BMD values were statistically significant among different CT and DXA devices.The ranges of the accuracy measured by different QCT devices were 1.20% to 7.60% for Siemens, -1.83% to 0.20% for Philips, 1.18% to 13.20% for GE, -0.12% to 3.55% for Toshiba, -1.65% to 6.32% for United Imaging, 6.59% to 21.34% for GE Lunar, -6.65% to 5.45% for Hologic, and -6.97% to -0.68% for Medlink, respectively. The RMS-%CV of all vertebral BMD values measured by QCT and DXA ranged from 0.38% to 3.85%. The RMS-SD of QCT was 0.54 to 2.45 mg/cm 3, of DXA was 0.009 to 0.037 g/cm 2. The RMS-%CV values of each vertebral body measured by different QCT and DXA devices decreased with the increase of BMD, while the RMS-SD values showed the opposite tendency. Conclusions:Based on ESP, the QCT and DXA devices have significant differences in lumbar spine BMD measurement. Comparing the measurement results among different devices requires cross-calibration. Overall, the accuracy and short-term precision are within a reasonable range, which can be used for clinical follow-up observation. The short-term precision error and accuracy error range of QCT in evaluating the density of ESP were slightly smaller than those of DXA.

The ongoing pandemic of Coronavirus disease 19 (COVID-19) is caused by a newly discovered β Coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination. Here we examined, using ELISA, the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6-7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection. All samples were positive for IgGs against the S- and N-proteins of SARS-CoV-2. Notably, 14 samples available at 6-7 months post-infection all showed significant neutralizing activities in a pseudovirus assay, with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2. Furthermore, in 10 blood samples from cases at 6-7 months post-infection used for memory T-cell tests, we found that interferon γ-producing CD4
Adaptive Immunity/physiology* ; Adult ; Aged ; Antibodies, Neutralizing/blood* ; COVID-19/immunology* ; Cohort Studies ; Female ; Humans ; Immunoglobulin G/blood* ; Male ; Middle Aged ; SARS-CoV-2/immunology* ; T-Lymphocytes/physiology* ; Time Factors ; Viral Proteins/immunology*

Objective:By using array-based comparative genomic hybridzation (CGH), the karyotype of spontaneous abortion was detected to analyze the genetic background difference between initial abortion and recurrent abortion.Methods:From July 2016 to September 2019, patients diagnosed as spontaneous abortion in Dalian Women′s and Children′s Medical Center were collected continuously. The abortion tissue microarray was used to analyze.Results:A total of 618 cases were collected, 345 of whom met the inclusion criteria, 133 cases (38.55%) in spontaneous abortion group and 212 cases (61.45%) in recurrent abortion group. A total of 237 cases of abnormal chromosome were detected, among whom the incidence of trisomy 22 (10.14%), trisomy 16 (9.86%) and monosomy 19 (7.25%) was high. The abnormal rate of chromosome karyotype was lower in recurrent abortion group, but there was no significant statistical difference ( P>0.05). After analyzing different age and gestational age, there was no significant statistical difference between haplotype and trisomy ( P>0.05). Conclusions:Some abnormal karyotypes are more common in abortion tissues. In recurrent abortion, the abnormal rate of chromosome karyotype is lower, but there is no significant difference in genetic background between spontaneous abortion and recurrent abortion.