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 Build an evidence-based big data governance platform centered around intelligent Traditional Chi-nese Medicine(TCM),incorporating TCM characteristics,to promote the development of intelligent TCM healthcare,and en-hance the efficiency of medical research and practical applications..Methods We integrate hospital TCM diagnosis and treat-ment process data and other kinds of clinical data..And we employ artificial intelligence and big data technologies to effectively clean and standardize the data,among other data governance and data preparation tasks,in order to build a Chinese Medicine Clinical Data Center System.Results The platform has achieved the collection and governance of millions of real medical re-cords,providing strong support for health management and clinical research in TCM,particularly promoting research in TCM's syndrome differentiation and treatment,prescription research,and drug reactions.Conclusion By constructing a big data gov-ernance platform based on Traditional Chinese Medicine(TCM),we have achieved value-added effective management and utili-zation of TCM data,particularly enhancing the precision of TCM diagnosis and treatment and the speed of research output,thus driving the modernization process of TCM.

Objective:To summarize the clinical features associated with respiratory syncytial virus (RSV) infection in patients following the hematopoietic stem cell transplant (HSCT) and exploring the risk factors for death.Methods:Patients who had RSV infection after undergoing HSCT from October 2023 to January 2024 in the hematology department of Peking University People’s Hospital were enrolled in the study. The clinical characteristics of the participating patients were summarized. The clinical characteristics of the surviving and the dying patients were compared, and the risk factors of death were analyzed by binary logistic regression.Results:Among the 43 RSV-positive HSCT patients, 20 (46.5%) were hypoxemic, six (14.0%) were admitted to the ICU for further treatment, four (9.3%) required tracheal intubation assisted ventilation, and seven patients (16.3%) died. A comparison of the clinical features of the surviving patients and the deceased patients demonstrated that the deceased patients had a lower PLT when infected with RSV [74.5 (8.0-348.0) ×10 9/L vs 15.0 (10.0-62.0) ×10 9/L, P=0.003], a higher incidence of simultaneous bacterial infections (85.7% vs 41.7%, P=0.046), and a higher rate of hematological recurrence (71.4% vs 13.9%, P=0.004). Hematological recurrence ( OR=15.500, 95% CI 2.336-102.848, P=0.005), influenza A viral infection ( OR=14.000, 95% CI 1.064-184.182, P=0.045), and low PLT at the time of RSV infection ( OR=0.945, 95% CI 0.894-0.999, P=0.048) were the factors associated with death following HSCT. Conclusion:Patients infected with RSV after undergoing HSCT have a poor prognosis, and active prevention and treatment of RSV in the autumn and winter requires urgent attention.

FLT3 internal tandem duplication (ITD) mutations are common in acute myeloid leukemia and show an important significance in guiding prognostic stratification and targeted therapy. With the widespread application of high-throughput sequencing technology and the increased ability to analyze mutation sequences, it has been found that more than half of FLT3-ITD mutations are not just tandem duplications but are also accompanied by some complex situations such as the addition of non-template sequences. Recent studies have revealed the sequence characteristics, mutagenesis mechanisms and related clinical prognostic significance of FLT3 length mutations (FLT3-LM). FLT3-LM with added non-template sequences is formed by abnormally activated terminal deoxynucleotidyl transferase. These patients show different treatment responses and prognosis when treated with chemotherapy, targeted therapy, and allogeneic hematopoietic stem cell transplantation, which provides a new perspective to understand FLT3-LM mutations more accurately and provides proposals for FLT3-LM typing based on the mutagenesis mechanism. The new typing rules can better reflect the differences in biological characteristics of the disease and more accurately guide the prognostic stratification and development of individualized treatment for patients with FLT3-LM mutations.

Objective:To explore the efficacy of central combined peripheral dual-target magnetic stimulation on Parkinson disease (PD) patients with freezing of gait (FOG).Methods:A total of 39 patients with FOG diagnosed at the Parkinson disease clinic of the Affiliated Hospital of Nantong University were included in the study from July 2022 to September 2023.They were randomly divided into observation group ( n=20) and control group ( n=19) by the random number table method. The patients in control group were treated with repetitive transcranial magnetic stimulation (rTMS), while the patients in observation group were treated with additional repetitive peripheral magnetic stimulation(rPMS) on the affected tibialis anterior muscle on the basis of the control group. Other clinical medical treatments were the same for both groups of patients.The timed up and go test (TUGT), 10 meter walk test (10MWT), and motor evoked potentials (MEP) were used to evaluate the efficacy before and after 2 weeks of treatment.The SPSS 25.0 software was used for statistical analysis. Independent sample t-test was used for comparison between the two groups, and paired sample t-test was used for comparison before and after treatment within group. Results:Before treatment, there were no statistically significant difference in TUGT time, 10MWT speed and MEP amplitude between the two groups( t=0.659, 0.514, 0.345, all P>0.05).After treatment, the TUGT time((7.87±1.74) s vs (9.31±1.57)s)and MEP amplitude((41.59±14.81)mV vs (58.26±19.26) mV)of the observation group were lower than those of the control group( t=2.723, 3.039, P=0.010, 0.004), while the 10MWT speed of the observation group was higher than that of the control group ((1.21±0.20) m/s vs (1.01±0.17)m/s, t=3.173, P=0.003).After treatment, the TUGT time and MEP amplitude of patients in the observation group and control group were all lower than before treatment (observation group: t=13.512, 7.126, both P<0.001; control group: t=6.535, 3.094, both P<0.05). The 10MWT speeds of patients in the observation group and control group after treatment were both higher than before treatment ( t=25.665, 6.750, both P<0.001). Conclusion:The combination of central and peripheral dual-target magnetic stimulation may improve the FOG of PD patients, and it is worthy of clinical promotion.

Objective:To investigate the clinical characteristics and prognosis of human adenovirus (HAdV) infection in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:This is a retrospective case series study. Patients who received allo-HSCT and had symptoms of HAdV infection were tested in the Hematology Department at Perking University People′s Hospital from August 2015 to October 2019. Real-time quantitative PCR was used to detect HAdV DNA from 2 728 patients with potential infection. HAdV DNA-positive patients were defined as having HAdV infection. The clinical features of these patients were analyzed, and a case-pair method was used to select patients without HAdV infection as the control group in a 1∶3 ratio. The clinical results of the two groups were compared using Kaplan-Meier and Log-rank testing.Results:A total of 7 119 samples were tested for HAdV, of which 99 samples from 36 patients were positive. Of these patients, 22 developed HAdV viremia, and 24 patients had concurrent infection with another virus. Nineteen patients had fever (53%), 25 had gastrointestinal symptoms (69%), 11 had respiratory symptoms (31%), nine had reduced liver function (25%), and six had nervous system symptoms (17%). Twenty-three patients developed acute graft-versus-host disease of grade 2 or higher. Of all the patients with HAdV infection, nine were treated with cidofovir, seven of whom became HAdV negative and two had invalid treatment. The median follow-up time was 496 (216, 940) d post-HSCT. The overall survival at 5 years post HSCT was 48.4%±9.2% vs. 91.3%±3.5% ( χ2=65.03, P<0.001) in patients with and without HADV, respectively. The non-relapse mortality at 5 years post-HSCT was 40.8%±8.8% vs. 4.0%±2.0% ( χ2=34.17, P<0.001) in patients with and without HADV, respectively. Conclusions:After allo-HSCT, HAdV-infected patients are dominated by gastrointestinal and respiratory symptoms and have an increased risk of combined acute graft-versus-host disease of >2 degrees. Patients with HAdV infection have poor overall survival and high non-relapse mortality.

Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.
Anemia, Aplastic/genetics* ; Epigenesis, Genetic ; Fanconi Anemia/genetics* ; Germ Cells ; Hematologic Neoplasms/genetics* ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Retrospective Studies

Objective:To retrospectively analyze the incidence and clinical significance of platelet transfusion refractoriness (PTR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myelomonocytic leukemia (CMML) .Methods:A cohort of 55 CMML patients received allo-HSCT at Peking University Institute of Hematology during 2004-2021 were retrospectively assessed. The incidence of PTR within 30 days after allo-HSCT was retrospectively analyzed, and the impact on clinical outcomes and bleeding event were compared between patients with platelet transfusion refractoriness (PTR) or effective platelet transfusion (EPT) .Results:The incidence of PTR after allo-HSCT in CMML patients was 25.5% (14/55) . PTR patients had a lower rate of platelet engraftment than EPT patients (28.6% vs 100%) , and the median time of engraftment was 67 (33-144) days and 21 (9-157) days respectively ( P<0.010) . There was no significant difference between two groups in acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) ( P=0.183, P=0.455) . After following-up a median of 684 (24-3978) days, the 1-year overall survival (OS) and 1-year leukemia free survival (LFS) in PTR and EPT patients were (35.4±13.9) % vs (75.1±7.8) % ( P=0.037) and (28.1±13.3) % vs (65.3±8.2) % ( P=0.072) , respectively. The transplant-related mortality (TRM) were (48.2±2.4) % and (9.0±0.25) %, respectively ( P=0.009) . Bleeding events occurred in five patients (35.7%) of PTR and 2 patients (4.9%) of EPT ( P=0.009) . Conclusion:In CMML patients with allo-HSCT, the incidence of PTR is 25.5%, which was associated with delayed platelet engraftment, increased bleeding events, inferior OS and increased TRM.

OBJECTIVE: To detect fusion gene with pathological significance in a patient with refractory and relapsed acute B cell lymphoblastic leukemia (B-ALL) and to explore its laboratory and clinical characteristics. METHODS: Transcriptome sequencing was used to detect potential fusion transcripts. Other laboratory results and clinical data of the patient were also analyzed. RESULTS: The patient was found to harbor TCF3 exon 17-ZNF384 exon 7 in-frame fusion transcript. The minimal residual disease (MRD) has remained positive after multiple chemotherapy protocols including CD19-, CD22- targeted chimeric antigen receptor T cells immunotherapy. The patient eventually achieved complete remission and sustained MRD negativity after allogeneic hemopoietic stem cell transplantation (allo-HSCT). CONCLUSION Transcriptome sequencing can effectively detect potential fusion genes with clinical significance in leukemia. TCF3-ZNF384 positive B-ALL has unique laboratory and clinical characteristics, may not well respond to chemotherapy and immunotherapy, and is more likely to relapse. Timely allo-HSCT treatment may help such patients to achieve long-term disease-free survival. TCF3-ZNF384 positive B-ALL is not uncommon in pediatric patients but has not been effectively identified.
B-Lymphocytes ; Basic Helix-Loop-Helix Transcription Factors/genetics* ; Child ; Hematopoietic Stem Cell Transplantation ; Humans ; Laboratories ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Trans-Activators/genetics* ; Transcriptome

Objective:To investigate the incidences and risk factors of poor hematopoietic reconstitution (PHR) in patients with hematological diseases who underwent haploidentical allograft and were treated with rituximab for desensitization.Methods:Eight-three donor specific anti-HLA antibody (DSA, 2000 ≤MFI<10 000) positive patients who underwent haploidentical allograft were prospectively enrolled. Rituximab (375 mg/m 2) was used for desensitization day-3 of conditioning regimen. Incidence and factors associated with PHR, including primary poor graft function and prolonged thrombocytopenia, were investigated. Results:There were 22 males and 61 females with a median age of 39(range: 1-65) years. Kaplan-Meier analysis showed that the 100 day cumulative incidences of neutrophil and platelet engraftment were 93.0% and 90.7%, respectively. The incidences of PHR were 14.7%. The 3-year relapse rate, non-relapse mortality (NRM) rate, event-free survival (EFS), leukemia-free survival (DFS) and overall survival (OS) were 6.5%, 15.1%, 70.8%, 79.4% and 79.4%, respectively. Patients with DSA MFI<5 000 (group A, n=46) experienced lower PHR (4.4% vs. 27.5%, P=0.003), and higher 3-year EFS (79.5% vs. 59.8%, P=0.020) compared to those with DSA MFI≥5 000 (group B, n=37). Multivariate analysis showed that DSA MFI≥5 000 was correlated with PHR ( HR=6.101, P=0.021). PHR was associated with higher NRM ( HR=4.110, P=0.026), lower DFS ( HR=3.656, P=0.019) and OS ( HR=3.656, P=0.019). Conclusion:Our data suggest that high pre-transplant DSA level is a risk factor for PHR in patients with hematological diseases receiving haploidentical allograft and rituximab for desensitization.