The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.
Animals ; Mice ; Humans ; Ependymoglial Cells/metabolism* ; Hedgehog Proteins/metabolism* ; Ferrets/metabolism* ; Cerebral Cortex ; Neurogenesis ; Mammals/metabolism* ; Neuroglia/metabolism* ; Bone Morphogenetic Protein 7/metabolism*

【Objective】 To detect the anti-SARS-CoV-2 antibody levels in blood donors in Guangzhou, so as to provide laboratory data support for the collection and clinical use of convalescent plasma. 【Methods】 Anti-SARS-CoV-2 antibodies were measured by ELISA in qualified donors. Among them, 326 donors who gave blood in February 2023 were tested for IgG antibodies, 444 donors were tested for neutralizing antibodies. In July 2023, 398 donors were tested for IgG and IgM. 【Results】 399 of 724 blood samples diluted with normal saline (1∶160) were IgG reactive, with a reactive rate of 55.11%. Chi-square test showed that there was a significant difference in the reactive rate of IgG among samples collected at different times (25.46% in February vs 79.40% in July, χ²=210.74, P<0.01, 95%CI: 7.97, 15.98), but there was no significant difference in the reactive rate between different genders and different age groups. IgM was detected in 5 of 398 blood samples, with a reactive rate of 1.26%. The IgG test results of these five blood donors were all reactive, whereas the nucleic acid test results were negative. Neutralizing antibody was detected in 440 of 444 blood samples, with a reactive rate of 99.10%, and 71.59% of the reactive donors had a neutralizing antibody level of 10 μg/mL or more. 【Conclusion】 Blood donors in Guangzhou have a high level of SARS-CoV-2 antibody, which is sufficient to provide convalescent plasma for clinical treatment.

【Objective】 HLA-DRB1 * 11:01, as a class HLA-Ⅱ gene, was reported to be associated with spontaneous clearance of HCV in Han and Li population. Our study was to investigate the effects of viral selection pressure and CD4+T cell epitope on the natural outcome of HCV infection in HLA-DRB1 * 11:01 positive infected patients. 【Methods】 The positive selection sites and population growth of E1E2 and NS3 genes of common HCV 6a in HLA-DRB1 * 11:01 positive and negative groups in Guangdong were respectively analyzed. The peptide library covering the conserved regions of common HCV genotypes was used to stimulate HCV spontaneous clearance group and chronic infection group using ELISPOT method. Reactive peptides were obtained according to the number of spot-forming cells per well and the frequency of occurrence in different groups. 【Results】 The positive selection sites (PSSs) of E1E2 and NS3 of common HCV 6a in HLA-DRB1 * 11:01 negative group were greater than those in HLA-DRB1 * 11:01 positive group. Furthermore, the number of PPSs in CD4+T cell peptide in HLA-DRB1 * 11:01 negative group were also greater than those in HLA-DRB1 * 11:01 positive group; Both groups of HCV 6a had a population growth in Guangdong, and the expansion trend of HLA-DRB1 * 11:01 negative group was significantly higher than that of HLA-DRB1 * 11 :01 positive group. Compared to HCV chronic infection group, the response rate of HCV spontaneous clearance group to five peptides (C-52 E2691-707, C-119 NS31545-1560, C-134 NS4A1669-1684, C-154 NS4B1912-1927, C-159 NS4B1929-1944) was higher. However, the HCV chronic infection group showed a higher response rate to two of the peptides(C-111 NS31497-1512, C-130 NS31650-1665). When HLA-DRB1 * 11:01 typing was considered, there was no significant difference in HCV-specific immune response generated by PBMCs between HLA-DRB1 * 11:01 positive and HLA-DRB1 * 11:01 negative groups. 【Conclusion】 This study revealed the relationship between viral selection pressure of HLA-DRB1 * 11:01 HCV infected persons and CD4+T cell antigen epitopes. At the same time, CD4+ T cell antigen epitopes of HCV pan-genotype were obtained, providing basic data for the development of T cell vaccine suitable for HCV pan-genotype.

ObjectiveTo analyze the research hotspots and development trends of postpartum rehabilitation at home and abroad in the past ten years. MethodsCiteSpace 6.2.R2 was used to analyze the co-occurrence, cluster, and bursting of keywords of the relevant literature in the field of postpartum rehabilitation in CNKI and Web of Science (WOS) in the past ten years. ResultsTotally, 2 686 Chinese papaers were included in CNKI and 1 247 English papers were included in WOS. Both databases showed an increasing trend in the number of publications related to the field of postpartum rehabilitation, but the overall number of publications in CNKI grew faster and the total number of publications was more than that in WOS. For CNKI, there were 455 nodes, 1 102 links, with a density of 0.010 7; nine clusters were obtained; the bursting keywords showed that the diseases of concern shifted from breast distension and pain to pelvic floor diseases, and the hot spots of treatment methods shifted from Chinese medicine to electrical stimulation, biofeedback, and then pelvic floor training. For WOS, there were 463 nodes, 1 633 connected lines, with a density of 0.015 3; 14 clusters were obtained; the bursting keywords showed that the disease hotspots of concern shifted from anal prolapse and postpartum hemorrhage to organ prolapse, the hotspots of treatment methods shifted from analgesia to exercise, and the focus of research methods shifted from trial to qualitative research and meta-analysis. ConclusionDomestic postpartum rehabilitation started later than foreign countries. Although certain research results have been achieved, there is still a certain gap compared with the development of foreign postpartum rehabilitation.

Blood screening is essential for blood safety. Traditional methods are not very effective in unknown pathogen testing. The blood metagenomic analysis with high-throughput sequencing as the main method is not limited to a particular microbe but detects all microbes in the sample (total genome), which has advantages that traditional methods cannot compare with. With the increasingly maturation of technology and the gradual reduction of cost, metagenomic sequencing has been applied more and more widely. In this paper, the concept and research procedures of metagenomics, the current status and future prospect of metagenomics sequencing technology in the field of blood screening are reviewed.

Objective:To investigate and analyze the occurrence and the related risk factors of gastrointestinal polypectomy accompanied by bleeding in patients with liver cirrhosis.Methods:127 cases of gastrointestinal polyps with cirrhosis who had endoscopy at the Endoscopic Center of Tianjin Third Central Hospital between November 2017 and November 2020 were collected. At the same time, 127 cases of gastrointestinal polyps with non-cirrhosis that were treated by endoscopy were collected for comparison. The occurrence of hemorrhagic complications between the two groups was compared. The effects of age, sex, liver function, peripheral blood leukocytes, hemoglobin, platelets, blood glucose, the international normalized ratio (INR), polyp resection method, polyp location, size, number, endoscopic morphology, pathology, the presence or absence of diabetes, portal vein thrombosis, and esophageal varices on polypectomy bleeding in the cirrhosis group were analyzed. The measurement data between groups were compared using the t-test and rank sum test. The χ2 test or Fisher’s exact probability method, and multivariate logistic regression analysis were used for the comparison of categorical data between groups. Results:The number of polypectomy bleeding cases in the cirrhotic group was 21, with a bleeding rate of 16.5%. The number of bleeding cases in the non-cirrhotic group was 3, with a bleeding rate of 2.4%. The bleeding rate was higher in the cirrhosis group when polypectomy was performed ( χ2 = 14.909, P < 0.001). A univariate analysis of the risk factors for gastrointestinal polypectomy associated with bleeding in patients with liver cirrhosis showed that liver function grading, platelets, INR, hemoglobin, degree of esophageal and gastric varices, and the location, shape, size, and pathology of the polyps had a statistically significant impact on bleeding ( P < 0.05). Multivariate logistic regression analysis showed that liver function grade, degree of varicose veins, and polyp location were independent risk factors for bleeding. Patients with Child-Pugh B or C grade liver function were more likely to bleed than those with Child-Pugh A grade ( OR = 4.102, 95% CI 1.133 ~ 14.856), gastric polyps were more likely to bleed than colorectal polyps ( OR = 27.763, 95% CI 5.567 ~ 138.460), and severe esophagogastric varices were more likely to bleed than no varices or mild to moderate varices ( OR = 7.183, 95% CI 1.384 ~ 37.275). Conclusion:Cirrhotic population has higher risk of bleeding during endoscopic gastrointestinal polypectomy than the non-cirrhotic population. Cirrhotic patients with Child-Pugh grades B or C liver function, polyps located in the stomach, severe esophagogastric varices, and other high-risk factors should be listed as a relative contraindication for endoscopic polypectomy.

Objective : To study the guidance effects of fibroblast growth factor 3 ( FGF3) on the prethalamic γ⁃aminobutyric acid (GABA) inhibitory axons, and to explore the effect of FGF3 on the formation of thalamic axonal network. Methods : Expression and localization of FGF3 and prethalamic GABA marker gene in chicken embryonic diencephalon were detected by immunofluorescence. Early orientation of GABA axons was tracked by DiI. Three⁃dimensional gel co⁃culture experiment was carried out to investigate guidance effects of FGF3 on early prethalamic GABA inhibitory axons. Results : Prethalamic GABA cells were adjacent to the FGF3 + hypothalamas, located above the hypothalamus. DiI tracing experiments revealed that prethalamic GABA inhibitory axons had already extended into the thalamus at E6. Compared with the blank control group, FGF3 not only significantly promoted the growth of prethalamic GABA inhibitory nerve fibers in the prethalamus, but also repelled the newborn prethalamic axons to the dorsal thalamus. The number of prethalamic axons was significantly less in proximal section (towards FGF3 beads) than that in distal section (away from FGF3 beads) (P < 0. 01) . Moreover, the guidance effects of FGF3 on prethalamic axons could be blocked by the FGF pathway inhibitor SU5402. Conclusion FGF3, an axon guidance molecule expressed in hypothalamus, exerts guidance effects on the pathway selection of adjacent prethalamic GABA inhibitory nerve fibers.

【Objective】 To study the CD4 T cell epitopes in Core and NS3 protein of genotype 1(GT1) and 6(GT6) of hepatitis C virus(HCV). 【Methods】 A total of 298 overlapping peptides(16-mer) spanning Core and NS3 protein of GT1 and GT6 HCV were synthesized. Peripheral blood mononuclear cells(PBMCs) from 17 HCV+ and 7 healthy blood donors were stimulated by peptide pools, followed by evaluating T cell response by IFN-γ ELISPOT, by which 21 peptides with positive results were found. These peptides were further applied to individually stimulate 20 HCV+ and 18 healthy PBMCs. The differences of responsive frequencies to the 21 positive peptides between the two study groups were compared. 【Results】 Pooled and individual peptide stimulation tests showed that HCV+ PBMCs were responsive to the stimulation of 5 peptides(GT1 NS31273-1288 and NS31315-1330; GT6 NS31033-1048, NS31087-1102 and NS31351-1366), with a responsive frequency ranging 18.9%-27.0%. In contrast, healthy PBMCs were not or low responsive(0%-4.0%) to these five peptides. The responsive frequencies were statistically different between the two groups(P<0.05). No reported epitopes in IEDB were found identical with these 5 peptides via sequence alignment. 【Conclusion】 Our study identified novel CD4 T cell epitopes in NS3 protein of GT1 and GT6 HCV, which has potential application value for the research and development of HCV vaccine.

【Objective】 To learn the situation of the evolution process of HCV virus population and the selection pressure of HCV NS5B in intravenous drug users (IDUs) in Guangdong. 【Methods】 141 blood samples from hepatitis C virus (HCV) RNA-positive blood donors and 58 from HCV patients in Guangdong were randomly collected for HCV NS5B sequence amplification, combined with HCV NS5B sequences from blood donors and IDUs obtained by sequencing previously(between 2009 and 2011). Homology analysis was performed by Molecular Evolutionary Genetics Analysis (MEGA) software, evolutionary analysis were performed by Bayesian Evolutionary Analysis Sampling Trees (BEAST) software package. Selection pressure analysis was performed on sequences isolated from IDUs by Datamonkey online software package with Mixed Effects Model Evolution (MEME) method, and the population expansion of species were analyzed using Tajima and Fu neutrality test by Arlequin software. 【Results】 The comparison results of internal homology among different subtypes of IDUs in this group were as follows : HCV-3b had the highest homology (97%), followed by HCV-3a (96%), HCV-6a (95%) and HCV-1b (94%); HCV evolution rate analysis showed that HCV-1b had the fastest evolution rate [2.17E-03 substitutions/site/year (y/y/y)], followed by HCV-3b (2.12E-0 y/y/y), HCV-3a (1.58E-03 y/y/y) and HCV-6a (1.28E-03 y/y/y). The analysis on effective population of HCV: 1980~1990 was rapid growth period for HCV-6a, 1990~1995 period for HCV-1b, and 2000~2007 period for HCV-3a. HCV population genetic characteristics was as follows: HCV-1b, 3a, 3b and 6a experienced population expansion, among which 3a and 3b were the most obvious. As to the analysis of HCV selection pressure, two positive selection sites (235 and 243)were found in the 339 nucleotide fragment of the NS5B sequence in injecting drug users, but mutation only occurred at position 316 [mutation rate 1.24% (14/1 130)] among 5 direct antiviral drug (DAA) sites in this gene. 【Conclusion】 The evolution of HCV-3b in Guangdong has showed an obvious trend of population expansion, with a high proportion and homology especially in the local IDUs. HCV-3b should be the focus of HCV prevention and control in this region. Given that the positively selected sites of the HCV NS5B gene region of IDUs in Guangdong are non-DAA binding sites, DAA is expected to demonstrate a good effect on these patients.

【Objective】 To investigate the CMV-IgG positive yeild among blood donors in Guangzhou and explore the differences in the efficacy of three test reagents, aimed at improving blood safety and service capacity of blood centers. 【Methods】 A total of 630 blood samples from eligible blood donors from July to October 2020 in our center were randomly selected and screened for CMV-IgG by one ELISA reagent.Among them, 180 samples were tested in parallel using three reagents (two ELISA reagents and one ECLIA reagent), and those tested negative were conducted quantitative CMV-DNA detection.The test results of different reagents were compared and analyzed. 【Results】 Out of the 630 samples, a total of 598 positive samples were screened out, including 180 samples yielded by three reagents, 171 and 175 by the two ELISA reagents, respectively, and 175 by ECLIA.The results given by three reagents were consistent (Kappa>0.4), and no significant difference in the positive yeild by three reagents was found.In the 180 samples, 11 were negative, among which 3, 2 and 6 samples were negative by all three reagents, two reagents and one reagent (ELISA), respectively.All the 11 samples were tested negative for CMV-DNA. 【Conclusion】 The yeild of positive CMV-IgG in blood donors was 94.9% (598/630), suggesting a high prevalence of CMV in Guangzhou. CMV serologically negative blood should be considered when providing blood products to immunocompromised patients to improve the safety of recipients.The detection results of ELISA reagents and ECLIA reagent for CMV- IgG are consistent, but ECLIA reagent has better detection efficacy.