Objective To search for new biomarkers to predict prognosis in colorectal cancer (CRC) patients.Methods A prognostic model was developed for colorectal cancer with immune-related genes from the cancer ge-nome atlas (TCGA) database using one-way Cox regression analysis and least absolute shrinkage and selection op-erator (LASSO) regression analysis.Moreover, the immune infiltration characteristics of patients in high and low risk groups was compared by sstimation of stromal and immune cells in malignant tumor tissues using expression da-ta (ESTIMATE) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) .In addition, the expression levels of immune checkpoints were analyzed in patients from different risk groups.The sen-sitivity of patients in the two risk groups to chemotherapeutic agents was also compared based on genomics of drug sensitivity in cancer (GDSC).Results It was found that the prognostic model constructed based on immune genes could better predict the overall survival (OS) of CRC patients,and the results showed area under curve (AUC) values of 0.764 (95％ CI:0.751-0.793), 0.773 (95％ CI:0.761 -0.779), and 0.760 (95％ CI:0.742 -0.774) for 1-, 3-, and 5-year OS, respectively.Patients in the low-risk group had higher expression levels of im-mune checkpoints and more abundant immune cells such as T cells (P<0.001) , dendritic cells (P<0.001) , macrophages (P<0.001) , neutrophils (P<0.001) .Patients in the high-risk group might be more sensitive to some chemotherapeutic agents such as axitinib, imatinib, methotrexate, pazopanib, rapamycin, sunitinib and tasig-arnib.Conclusion A prognostic model based on 19 immune genes was effective in predicting the prognosis of CRC patients.The number and activity of immune cells in the immune microenvironment in different patients may be an important factor influencing their response to immunocheck inhibitors and chemotherapeutic agents.

ObjectiveTo observe the effect of Qinggan Jianpi Huoxue prescription（QGJPHXP） on the polarization of M1/M2 macrophages in rats with hepatic fibrosis induced by carbon tetrachloride（CCl₄）. MethodA rat hepatic fibrosis model was established by intraperitoneal injection of 40% CCl₄-olive oil suspension twice a week at the dosage of 2.0 mL·kg^-1 for 8 weeks. After the model was successfully established， these rats were randomly divided into the model group， QGJPHXP group（32.084 g·kg^-1） and Biejiajian pills（BJJP） group（0.925 5 g·kg^-1）， with 12 rats in each group. The blank group was injected intraperitoneally with the same amount of olive oil. The rats in the administration groups were given the corresponding solution according to the dose， and the blank and model groups were given the same dose of purified water， once a day. After 4 weeks of continuous administration， the liver tissues of rats were taken and stained with hematoxylin-eosin（HE） and Masson to observe the pathological changes. The serums were collected to detect the alanine aminotransferase（ALT） and aspartate aminotransferase（AST） levels. Interleukin（IL）-6， IL-12， IL-10， IL-1β， transforming growth factor-β₁（TGF-β₁） and tumor necrosis factor-α（TNF-α） levels in liver tissues were measured by enzyme-linked immunosorbent assay（ELISA）. The expression levels of CD86 and CD206 were detected by immunohistochemistry（IHC）. Western blot and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression levels of inducible nitric oxide synthase（iNOS）， arginase-1（Arg-1）， phosphorylated p38 mitogen-activated protein kinase（p-p38 MAPK）， nuclear transcription factor-κB p65（NF-κB p65） in liver tissues of rats. ResultCompared with the blank group， the hepatic cell plate was irregularly arranged, and local inflammatory cell infiltration and fibrous hyperplasia were observed， while the serum levels of ALT and AST were significantly increased in the model group（P<0.01）， and IL-1β， IL-6， IL-12， TGF-β₁， TNF-α， CD86， CD206， iNOS， p-p38 MAPK，p38 MAPK and NF-κB p65 levels in liver tissues were obviously increased（P<0.05， P<0.01）， while the levels of IL-10 and Arg-1 were obviously decreased（P<0.05， P<0.01）. Compared with the model group， QGJPHXP group reduced the degree of liver cell fibrosis，and serum levels of ALT and AST（P<0.01）， and IL-1β， IL-6， IL-12， TGF-β₁， TNF-α， CD86， iNOS， p-p38 MAPK， p38 MAPK， and NF-κB p65 levels in liver tissues were obviously decreased（P<0.05， P<0.01）， the levels of IL-10， CD206 and Arg-1 were obviously increased in the QGJPHXP group（P<0.05， P<0.01）. ConclusionQGJPHXP has ability to inhibit the activation of pro-inflammatory M1 macrophages， induce the secretion of anti-inflammatory cytokines by M2 macrophages， reduce the release of pro-fibrogenic cytokines， and promote the macrophage polarization of M1 to M2 in liver for tissue repair， thereby serving as an anti-inflammatory and anti-hepatic fibrosis drug.

Since the discovery of circulating hepatitis B virus (HBV) RNA in the peripheral blood of patients with chronic hepatitis B in 1996, a growing number of studies have focused on clarifying the biological characteristics and clinical application value of serum HBV RNA. This consensus mainly summarizes the research progress of serum HBV RNA existing profiles, quantitative detection methods, and current clinical applications. In order to better apply this indicator for the clinical management of patients with chronic HBV infection, recommendations on quantitative detection target regions, detection results, and clinical applications are put forward.

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective:To analyze the clinical features, genetic characteristics, treatment and follow-up results of patients with hydrocephalus caused by methylmalonic acidemia combined with homocysteinuria, and to discuss the optimal strategies for assessing and treating such patients.Methods:From January 1998 to December 2020, 76 patients with hydrocephalus due to methylmalonic acidemia combined with homocysteinuria in the Department of Pediatrics in 11 hospitals including Peking University First Hospital were diagnosed by biochemical, genetic analysis and brain imaging examination. The patients were divided into operation-group and non-operation-group according to whether they underwent ventriculoperitoneal shunt. The clinical features, laboratory examinations, genotype, and follow-up data were retrospectively analyzed. Data were compared between the two groups using rank sum test, and categorical data were compared using χ 2 test. Results:Among the 76 patients (51 male, 25 female), 5 were detected by newborn screening, while 71 were diagnosed after clinical onset, 68 cases (96%) had early-onset, 3 cases (4%) had late-onset. The most common clinical manifestations of 74 cases with complete data were psychomotor retardation in 74 cases (100%), visual impairment in 74 cases (100%), epilepsy in 44 cases (59%), anemia in 31 cases (42%), hypotonia or hypertonia in 21 cases (28%), feeding difficulties in 19 cases (26%) and disturbance of consciousness in 17 cases (23%). Genetic analysis was performed in 76 cases, all of whom had MMACHC gene variations, including 30 homozygous variations of MMACHC c.609G>A. The most common variations were c.609G>A (94, 62.7%), followed by c.658_660del (18, 12.0%), c.567dupT (9, 6.0%) and c.217C>T (8, 5.3%). Therapy including cobalamin intramuscular injection, L-carnitine and betaine were initiated immediately after diagnosis. A ventriculoperitoneal shunt operation was performed in 41 cases (operation group), and 31 patients improved after metabolic intervention (non-operation group). There was no significant difference in the age of onset, the age of diagnosis, the blood total homocysteine, methionine, and urinary methylmalonic acid concentration between the two groups (all P>0.05). The symptoms of psychomotor development, epilepsy, and visual impairments improved gradually after a long-term follow-up in the operation group. Conclusions:Hydrocephalus is a severe complication of methylmalonic acidemia combined with homocysteinuria. The most common clinical manifestations are psychomotor retardation, visual impairment, and epilepsy. It usually occurs in early-onset patients. Early diagnosis and etiological treatment are very important. Hydrocephalus may improve after metabolic intervention in some patients. For patients with severe ventricular dilatation, prompt surgical intervention can improve the prognosis.

Objective:To verify the ability of the newly developed ultra-high resolution CT (U-HRCT) for displaying the fine bony anatomy of temporal bone.Methods:The cone-beam CT architecture was used on U-HRCT. The focus size of X-ray generator was 0.27 mm × 0.29 mm, the rated tube voltage was 60-100 kV, and the unit size of flat panel detector was 0.074 8 mm×0.074 8 mm. From October to December 2019, 16 adult head specimens (32 temporal bones, provided by Huanghe University of Science and Technology) were imaged using U-HRCT. The scanning mode was small-field-of-view and high-resolution scanning for unilateral temporal bone. The scanning parameters were: voltage 100 kV, current 3.5 mA, rotation time 40 s, reconstructed field of view 65 mm×65 mm, voxel size 0.1 mm×0.1 mm×0.1 mm, layer number 370, slice thickness 0.1 mm, and slice interval 0.1 mm. The ultimate spatial resolution of the system was detected using a phantom with line pair card, after the scanning with the same parameters. Through multi-planar reconstruction and minimum intensity projection method, a total of 6 anatomical positions of 4 structures (stapes footplate, cochlear axis bottom, vestibular aqueduct internal orifice and isthmus, cochlear aqueduct internal orifice and auditory sac segment) were scored with 1-3 points. The Wilcoxon test was used to compare the difference of bilateral scores of each structure.Results:The phantom test results showed that the ultimate spatial resolution of the system was ≥4.0 lp/mm. The scores of stapes footplate, cochlear axis bottom and vestibular aqueduct internal orifice were ≥2 points, with a display rate of 100%. The display rates of vestibular aqueduct isthmus, cochlear aqueduct internal orifice and auditory sac segment were 87.5% (28/32), 71.9% (23/32) and 53.1% (17/32), respectively. There were no significant differences in left and right scores of all anatomical structures ( P>0.05). Conclusion:The newly developed U-HRCT has good display ability for fine bony anatomy of temporal bone and has great clinical application potential.

Objective To explore the functional properties of the brain's resting state networks in neonates with hypoxic ischemic encephalopathy.Methods Use the methods of functional MRI probabilistic tractography and graph theory to compare the global and local functional properties of the brain's resting state network between 12 cases of children with mild HIE and 14 cases of children with moderate/severe HIE.Results In terms of global topological properties,both the mild and moderate/severe group showed small-world properties.The γ and λ in the mild group were 2.450± 1.642 and 1.542±0.564 and in the moderate/severe group were 2.331± 1.554 and 1.353±0.672,respectively,which were in line with the characteristics of small-world properties (γ＞ 1 and λ ≈ 1).As far as local topological properties were concerned,the distribution of hub regions in the functional networks had smaller number of nodes in the moderate/severe group (8 nodes) than the mild group (14 nodes).The comparison of nodal efficiencies showed that the moderate/severe group had significantly reduced nodal efficiency in the left insula opercula,left supramarginal gyrus,left and right temporal pole and right middle temporal gyrus(the nodal efficiencies of the moderate/severe group:0.4089±0.0865,0.3377±0.1223,0.3842±0.0898,0.3508±0.1295,0.3564±0.0843;the nodal efficiencies of the mild group:0.4801±0.0762,0.4465±0.0898,0.4655 ±0.0812,0.4640±0.0690,0.4271±0.0636,all P＜0.05).Conclusion The topological structure of resting state functional network in children with moderate and severe hypoxic-ischemic encephalopathy is obviously backward than that in children with mild hypoxic-ischemic encephalopathy,which may be related to abnormal language,movement and cognitive function in the late stage.

Objective To investigate the characteristics of cognitive development of children with attention deficit hyperactivity disorder (ADHD) by using resting-state functional magnetic resonance imaging (fMRI) degree centrality (DC) from the view of neuro-imaging.Methods Forty-five ADHD children were diagnosed at specialist clinic of Changzhou Children's Hospital,Nantong University from June 2015 to December 2016,and they were divided into 3 groups according to their ages (children aged 7-8 years old,9-10 years old and 11-12 years old,15 children in each group) and received the resting-state fMRI scans.DC value was used to analyze fMRI data.Comparative analysis was done pairwise between the three groups.Results Compared with 7-8 years old group,9-10 years old group showed lower DC value in cerebellum posterior lobe (t =-4.36) and higher DC in inferior parietal lobe (t =-5.86),and the differences were statistically significant (all P ＜ 0.05,after correction).Compared with 7-8 years old group,11-12 years old group showed lower DC value in cerebellum posterior lobe (t =-4.99) and higher DC in left superior temporal gyrus (t =5.18) and superior frontal gyrus (t =4.58),and the differences were statistically significant (all P ＜ 0.05,after correction).Compared with 9-10 years old group,11-12 years old group showed lower DC value in inferior parietal lobe (t =-5.71) and higher DC value in left superior temporal gyrus (t =5.05) and superior frontal gyrus (t =4.36),and all the differences were statistically significant (all P ＜ 0.05,after correction).Conclusion Children with ADHD at different ages had different characteristics of brain regions of fMRI.It can offer objective evidence for early cognitive intervention of children with ADHD at different ages.

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.