Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.

ObjectiveTo investigate the induction of ferroptosis by polyphyllin Ⅱ （PPⅡ） in hepatocellular carcinoma HepG2 cells and its underlying mechanism. MethodThe effect of PPⅡ （0， 1.5， 3.0， 4.5， 6.0， 9.0， 18.0 mg·L^-1） on the in vitro proliferation of HepG2 cells was assessed using the methyl thiazolyl tetrazolium （MTT） assay. Colony formation ability of HepG2 cells was evaluated through a colony formation assay. Cell migration ability was assessed via a scratch assay. Lactate dehydrogenase （LDH） content in HepG2 cells was measured using a kit. Reactive oxygen species （ROS） levels in HepG2 cells were observed using a fluorescence inverted microscope. Malondialdehyde （MDA）， glutathione （GSH）， and free Fe²⁺ content in HepG2 cells were detected using respective kits. The mitochondrial ultrastructure in HepG2 cells was observed by transmission electron microscopy. The expression of ferroptosis-related proteins p53， solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， and transferrin receptor 1 （TFR1） in HepG2 cells was detected using Western blot. ResultCompared with the control group， the PPⅡ treatment groups showed significantly decreased survival rate of HepG2 cells in a dose-dependent manner （P<0.01）， significantly reduced number of cell colonies （P<0.01）， significantly shortened scratch healing distance， inverse correlation of the migration distance with drug concentration （P<0.01）， significantly increased LDH leakage in cells （P<0.01）， significantly enhanced relative fluorescence intensity of intracellular ROS， and significantly increased accumulation of lipid peroxide MDA （P<0.01）， decreased intracellular GSH content with increasing drug concentration （P<0.01）， and significantly enhanced fluorescence intensity of FeRhoNox-1 in cells （P<0.01）. Moreover， cells exhibited vacuolation， and mitochondria showed significant shrinkage with reduced or even disappeared cristae. Compared with the results in the control group， the expression of p53， ACSL4， and TFR1 proteins significantly increased， while the expression of SLC7A11 and GPX4 proteins significantly decreased in the PPⅡ treatment groups （P<0.05）. ConclusionIn summary， PPⅡ induces ferroptosis in HepG2 cells by regulating the p53/SLC7A11/GPX4 signaling axis， promoting ACSL4 expression and Fe³⁺ uptake， leading to an imbalance in the antioxidant system.

ObjectiveTo observe the effect of Cuscutae Semen total flavonoids combined with Tripterygium wilfordii polyglycoside tablets （TWPT） on ovarian germline stem cells of female physiological mice through neurogenic locus notch homolog （Notch） signaling pathway. MethodSixty female Kunming mice （5 weeks old） were randomly divided into normal group， Tripterygium wilfordii polyglycoside tablets low-， high-dose groups （13.65 mg·kg^-1·d^-1 and 27.3 mg·kg^-1·d^-1， 1 and 2 times clinical equivalent dose）， Cuscutae Semen total flavonoids low- and high-dose groups （150 mg·kg^-1·d^-1 and 300 mg·kg^-1·d^-1）， and combination group （13.65 mg·kg^-1·d^-1 TWPT and 150 mg·kg^-1·d^-1 Cuscutae Semen total flavonoids）， with 10 in each group. After 3 weeks of continuous administration， the uterus/brain and ovarian/brain indexes were calculated， and the pathological changes of ovarian tissue were observed under light microscope. The content of estradiol in serum was determined by enzyme linked immunosorbent assay （ELISA）. Immunofluorescence assay was performed to observe the expressions of germline stem cell markers in ovarian epithelium， including mouse vasa homologue （Mvh）， octamer-binding transcription factor 4 （Oct4）， tyrosine-protein kinase receptor （c-kit）， Nanog， Notch signaling pathway molecules， neurogenic locus notch homolog protein 1 （Notch1）， hes family BHLH transcription factor 1（Hes1）， and jagged canonical Notch ligand 1 （JAG1）. ResultCompared with the normal group， low and high doses of TWPT had no significant effect on the uterus/brain and ovary/brain indexes and the uterus and ovary morphologies of mice， while only the number of atretic follicles was increased （P<0.01）. The expressions of ovarian germline stem cell markers and Notch signaling pathway molecules had a decreasing trend in TWPT low-dose group， while the expressions of Mvh， c-kit， and Nanog were down-regulated （P<0.05， P<0.01） and the expressions of Notch1 and Hes1 were also reduced （P<0.01） in TWPT high-dose group. However， the above indexes were increased in Cuscutae Semen total flavonoids low-dose group （P<0.05， P<0.01）. Compared with the low does of TWPT group， the combination group had a decrease in the increased number of atretic follicles （P<0.01）， an improvement in the down-regulated expressions of Mvh and Nanog （P<0.01）， and an increase in the expressions of Notch1 and Hes1 （P<0.05， P<0.01）. ConclusionOvarian germline stem cells are the source target of the reproductive toxicity of TWPT. Cuscutae Semen total flavonoids participate in the regulation of the germline stem cell pathways to alleviate the reproductive toxicity caused by TWPT， and its mechanism of action may be related to the Notch signaling pathway.

ObjectiveTo study the constituents migrating to blood of Qingyan formula by serum pharmacochemistry， and investigate the binding energy between these constituents and estrogen receptor （ER）， so as to confirm the pharmacodynamic material basis of Qingyan formula in rats. MethodUltra-high performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry （UPLC-Q-Orbitrap-MS） was used to determine the constituents migrating to blood of Qingyan formula in rats by comparing the fingerprint differences of 70% ethanol extract of Qingyan formula， 70% ethanol extract of each single drug in this formula， blank serum and serum after administration of 70% ethanol extract of Qingyan formula， according to the retention time， relative molecular weight and the primary and secondary ion fragments provided by MS. Mobile phase was 0.1% formic acid aqueous solution （A）-acetonitrile（B） for gradient elution （0-5 min， 2%-20%B； 5-10 min； 20%-50%B； 10-15 min， 50%-80%B； 15-25 min， 80%-95%B； 25-26 min， 95%-2%B； 26-30 min， 2%B）， the flow rate was 0.3 mL·min^-1 and the injection volume was 5 μL， electrospray ionization was used with detection range of m/z 150-2 000， positive and negative ion scanning modes. Molecular docking technology was used to characterize the binding energy of constituents migrating to blood with ERα and ERβ， and to confirm the material basis of this formula. ResultAfter oral administration of Qingyan formula， 30 components were detected in serum， of which 9 were prototype components and 21 were metabolites. Nine prototype components were identified as monotropein， asperuloside， verbascoside， β-ecdysone， allantoin， deacetyl asperuloside acid， echinacoside， betaine and caffeic acid， 21 metabolites mainly included organic acids， amino acids， cholines and so on. The binding energies of the above 9 prototype components with ERα were -6.7， -8.9， -6.0， -5.7， -5.3， -4.9， -7.3， -3.3， -6.3 kcal·mol^-1 （1 kcal≈4 184 J）， and the binding energies of them with ERβ were -6.6， -7.2， -7.7， 8.0， -7.4， -5.5， -6.9， -3.6， -6.4 kcal·mol^-1， respectively. ConclusionThese nine prototype components into blood are the active ingredients of Qingyan formula that play estrogen-like role in the body， which can provide experimental basis for the formulation of quality standards and subsequent research and development of Qingyan formula.

The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.

Objective:To provide scientific evidence for infection prevention and control by analyzing the risk factors of surgical site infection, which can move forward the gateway of infection prevention and control.Methods:The surgery-related information of patients admitted to the Department of General Surgery and Department of Orthopedics, People's Hospital of Guangnan Hospital of Yunnan province from November 2016 to August 2019 was retrospectively analyzed. According to whether postoperative surgical site infection occurred, the patients were divided into an infection group and a non-infection group. Logistic regression model was used to analyze the risk factors of surgical site infection.Results:A total of 9 346 patients, consisting of 117 patients in the infection group and 9 229 patients in the non-infection group, were included for final analysis. In the infection group, the incidence of surgical site infection was 1.25%. Multivariate analysis showed that hypoproteinemia ( OR = 2.585), unclean incision ( OR = 3.243 and 5.125), and operation duration more than 3 hours ( OR = 2.315), blood transfusion ( OR = 2.239), drainage tube placement ( OR = 2.133) and indwelling catheter placement ( OR = 1.973) were the independent risk factors for surgical site infection, while prophylactic use of antibiotics was a protective factor ( OR = 0.383). Conclusion:Individual factors, operation-related factors, and treatment-related factors are closely related to the occurrence of surgical site infection. Much attention should be paid to the clinical issues like preoperative hypoproteinemia, perioperative prophylactic use of antibiotics and postoperative drainage tube and indwelling catheter placement.

Objective:To explore the value of dual-layer spectral detector CT in differentiating the diagnosis of lung cancer and inflammatory nodules.Methods:A total of 92 patients undergoing enhanced chest scan from March 2019 to September 2020 at Renji Hospital, School of Medicine, Shanghai Jiaotong University, were retrospectively enrolled in the study. The conventional CT parameters, spectral CT parameters were measured and the nodules′ morphological characteristics were analyzed. Later the factors with statistical significance were identified as independent variables in a logistic regression model to establish models for predicting malignant nodules. ROC curve was used to assess the diagnostic performance for the conventional CT model, spectral CT parameters and combined model, respectively. Differences in the area under the ROC curve (AUC) were analyzed by the DeLong test.Results:Lobulated sign (42 and 8, respectively, χ2=10.779, P=0.001), short burr sign (41 and 7, respectively, χ2=11.911, P=0.001), pleural indentation sign (45 and 9 respectively, χ2=11.705, P=0.001), vascular convergence sign (35 and 8, respectively, χ2=5.337, P=0.021) and the venous phase iodine concentrations (IC) value [(2.1±0.5) mg/ml, (2.3±0.5) mg/ml, t=-2.464, P=0.016], normalized iodine concentrations (NIC) value (0.40±0.06, 0.45±0.08, t=-6.943, P<0.001), and Z-effective (Z eff) values (8.38±0.21, 8.49±0.19, t=-2.122, P=0.037) were significantly different between the lung cancer group and the inflammatory group, while other CT signs and CT indicators were not significantly different between the lung cancer group and the inflammatory group ( P>0.05). The conventional CT model was established with lobulated sign, short burr sign, pleural indentation sign, vascular convergence sign, and the AUC for differential diagnosis of lung cancer and inflammatory nodules was 0.827. The spectral CT parameter model was established with venous phase IC, venous phase NIC, and venous phase Z eff value, and the AUC for differential diagnosis of lung cancer and inflammatory nodules was 0.899. The conventional CT model combined spectral CT parameter model was established with the significant factors in the univariate analysis, and the AUC for differential diagnosis of lung cancer and inflammatory nodules was 0.925. The AUC of the combined model showed no significant difference from that of the spectral CT parameter model ( Z=1.794, P=0.073). However, AUC of the combined model was significantly higher than that of evaluation based on conventional CT alone ( Z=2.156, P=0.031). Conclusion:Spectral CT parameters combined with conventional CT signs can improve the differential diagnosis efficiency between lung cancer and inflammatory nodules.

Objective:To investigate the feasibility of transplantation of neural stem cells (NSCs) modified by hypoxia-regulated nerve growth factor (NGF) gene to treat acute spinal cord injury (SCI) and observe the functional repair after SCI.Methods:Adeno-associated virus (AAV) was used as the vector to construct gene-modified NSCs. Three days after SCI attack on the animal model, the NSCs modified by hypoxia-regulated NGF were transplanted to the site of SCI as the NGF group. The GFP-modified neural stem cell group (GFP group), sham group, SCI group were set up. Hindlimb motor function was assessed by Basso-Beattie-Bresnahan (BBB) Locomotor Rating Scale, inclined plane tests and footprint analysis at 10 time points on day 1, 3, 7, 10, 14, 21, 28, 35, 42 and 60 after transplantation. The video cassette recorder (VCR) image and quantitative measurement of the height of the rat from the ground, the foot error and plantar steps were used to test the hindlimb support and flexibility of the rats. The degree of spinal cord injury in rats was roughly measured by observing the visual map of the spinal cord. The neuronal repair and morphological changes in SCI area were evaluated by Nissl staining, HE staining and immunofluorescence. CM-DiI was used to trace neural stem cells and to analyze the differentiation of NSCs by immunofluorescence.Results:Two months after transplantation of genetically modified NSCs, the BBB, inclined plane tests and footprint Analytical scores of NGF group rats were higher than those of SCI group and GFP group ( P<0.05); Through VCR image analysis, the hindlimb support and mobility of the rats in the NGF group were better than those in the SCI group and GFP group, and the difference was statistically significant ( P<0.05). Visual analysis showed that the spinal cord of the rats in each group was visually compared to the NGF group, and the spine did not show significant atrophy and color deepening, and the degree of injury was lower than that of the SCI group and GFP group; Through Nissl staining, HE staining and immunofluorescence detection, obviously positive in NeuN at the transplant site was noted at NGF group, and evidently regenerated neural structure can be seen at the morphological level. The cavity in SCI was obviously reduced, neurons and Nissl bodies were distinctly increased ( P<0.05). CM-DiI was used to track NSCs, NeuN was used to mark neurons, and GFAP was used to mark astrocytes. It was found that neural stem cells could differentiate into neurons and astrocytes. Neural stem cells in GFP group were more differentiated into astrocytes, and neural stem cells in NGF group were more differentiated into neurons. Conclusion:NSC transplantation with oxygen-regulated NGF gene mediated by adeno-associated virus can treat SCI, NSCs can differentiate into neural stem cells and astrocytes to fill the damaged cavity, NSCs secrete NGF as the carrier, playing the protective role on adjacent damaged nerve cells and reducing the death of neurons, which is expected to provide new ideas for the treatment of acute spinal cord injury, and at the same time make new attempts for the development of NGF protein drugs.

Endogenous adult neural stem cells are closely related to the normal physiological functions of the brain and many neurodegenerative diseases. Neurons are affected by factors such as extracellular microenvironment and intracellular signaling. In recent years, some specific signaling pathways have been found that affect the occurrence of neural stem cells in adult neural networks, including proliferation, differentiation, maturation, migration, and integration with host functions. In this paper, we summarize the signals and their molecular mechanisms, including the related signaling pathways, neurotrophic factors, neurotransmitters, intracellular transcription factors and epigenetic regulation of neuronal differentiation from both the extracellular and intracellular aspects, providing basic theoretical support for the treatment of central nervous system diseases through neural stem cells approach.