BACKGROUND:Previously,a SENP1 gene-silenced human alveolar epithelial cell line was successfully constructed in vitro,and the role of SENP1 in hyperoxic lung injury was investigated at the cellular level.OBJECTIVE:To construct a mouse model of alveolar type II epithelial cell-specific knockout of SENP1 gene based on the Cre-loxP recombinase system.METHODS:SENP1flox/-mice were self-crossed to obtain SENP1flox/flox and SENP1flox/-mice;Sftpc-Cre+/+mice were crossed with wild-type mice to obtain more Sftpc-Cre+/-mice.Sftpc-Cre+/+or offspring Sftpc-Cre+/-mice were crossed with SENP1flox/-or offspring SENP1flox/flox mice to obtain SENP1flox/-Sftpc-Cre+/-double heterozygous mice.SENP1flox/-Sftpc-Cre+/-mice were then crossed with SENP1flox/flox mice to obtain SENP1flox/floxSftpc-Cre+/-mice.The genomic DNA was extracted by tail clipping and amplified by PCR.The amplified product was subjected to agarose gel electrophoresis to determine the mouse genotypes.Lung tissues of SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice were subjected to immunofluorescence double-labelling and western blot assay to verify the knockdown effect of SENP1 gene.Heart,liver,lung and kidney tissues of SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice were stained with hematoxylin-eosin to observe the histomorphology of each organ in the two groups of mice.RESULTS AND CONCLUSION:SENP1flox/floxSftpc-Cre+/-mice were correctly screened by agarose gel electrophoresis.Immunofluorescence double-labeling experiments showed that the mean fluorescence intensity of SENP1 was reduced in lung tissues of SENP1flox/floxSftpc-Cre+/-mice compared with that of SENP1flox/flox mice(P<0.01)and no significant co-localization of SENP1 and Sftpc was observed(P<0.01).Western blot results showed that SENP1 protein expression was reduced in lung tissues of SENP1flox/floxSftpc-Cre+/-mice compared with SENP1flox/flox mice(P<0.001).Hematoxylin-eosin staining showed no significant alterations in the histomorphology of heart,liver,lung and kidney tissues in SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice.This study successfully constructed alveolar type II epithelial cell-specific knockout SENP1 gene mice using the Cre-loxP recombinase system,which provides a good tool for the subsequent study of the role of SENP1 gene in lung diseases such as bronchopulmonary dysplasia and idiopathic pulmonary fibrosis,in which alveolar type II epithelial cells are the main damage cells.

Glioma is the most common primary malignant tumor of the central nervous system in adults. Despite the standard treatment of surgery combined with radiotherapy and chemotherapy, the prognosis for high-grade glioma patients remains poor, highlighting the urgent need to further explore its pathogenesis and develop new therapeutic strategies. This article reviews the research progress in the field of glioma in China in 2024, covering tumorigenesis mechanisms, tumor immune microenvironment composition, advances in imaging techniques and novel imaging agents, improvements in surgical approaches, mechanisms of radio- and chemoresistance, and explorations of new therapeutic modalities. These studies provide a solid theoretical foundation for advancing clinical diagnosis and treatment of gliomas and may offer new opportunities to improve patient outcomes.

Game-based psychological assessment utilizes game mechanisms and elements to enhance partic-ipants'motivation and improve measurement accuracy,but similar to traditional methods,it mainly focuses on static results.By integrating game-based psychological assessment with artificial intelligence technology,this paper propo-ses the paradigm of intelligent psychological assessment based on interactive environment.With analyzing dynamic process data within the game,this paradigm can accurately depict the participants'actions and results in the interac-tive context,more effectively representing individual psychological states and behavioral characteristics.This new paradigm demonstrates advancements and significant potential for development in terms of demand,data collection,and analysis techniques.

Game-based psychological assessment utilizes game mechanisms and elements to enhance partic-ipants'motivation and improve measurement accuracy,but similar to traditional methods,it mainly focuses on static results.By integrating game-based psychological assessment with artificial intelligence technology,this paper propo-ses the paradigm of intelligent psychological assessment based on interactive environment.With analyzing dynamic process data within the game,this paradigm can accurately depict the participants'actions and results in the interac-tive context,more effectively representing individual psychological states and behavioral characteristics.This new paradigm demonstrates advancements and significant potential for development in terms of demand,data collection,and analysis techniques.

BACKGROUND:Previously,a SENP1 gene-silenced human alveolar epithelial cell line was successfully constructed in vitro,and the role of SENP1 in hyperoxic lung injury was investigated at the cellular level.OBJECTIVE:To construct a mouse model of alveolar type II epithelial cell-specific knockout of SENP1 gene based on the Cre-loxP recombinase system.METHODS:SENP1flox/-mice were self-crossed to obtain SENP1flox/flox and SENP1flox/-mice;Sftpc-Cre+/+mice were crossed with wild-type mice to obtain more Sftpc-Cre+/-mice.Sftpc-Cre+/+or offspring Sftpc-Cre+/-mice were crossed with SENP1flox/-or offspring SENP1flox/flox mice to obtain SENP1flox/-Sftpc-Cre+/-double heterozygous mice.SENP1flox/-Sftpc-Cre+/-mice were then crossed with SENP1flox/flox mice to obtain SENP1flox/floxSftpc-Cre+/-mice.The genomic DNA was extracted by tail clipping and amplified by PCR.The amplified product was subjected to agarose gel electrophoresis to determine the mouse genotypes.Lung tissues of SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice were subjected to immunofluorescence double-labelling and western blot assay to verify the knockdown effect of SENP1 gene.Heart,liver,lung and kidney tissues of SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice were stained with hematoxylin-eosin to observe the histomorphology of each organ in the two groups of mice.RESULTS AND CONCLUSION:SENP1flox/floxSftpc-Cre+/-mice were correctly screened by agarose gel electrophoresis.Immunofluorescence double-labeling experiments showed that the mean fluorescence intensity of SENP1 was reduced in lung tissues of SENP1flox/floxSftpc-Cre+/-mice compared with that of SENP1flox/flox mice(P<0.01)and no significant co-localization of SENP1 and Sftpc was observed(P<0.01).Western blot results showed that SENP1 protein expression was reduced in lung tissues of SENP1flox/floxSftpc-Cre+/-mice compared with SENP1flox/flox mice(P<0.001).Hematoxylin-eosin staining showed no significant alterations in the histomorphology of heart,liver,lung and kidney tissues in SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice.This study successfully constructed alveolar type II epithelial cell-specific knockout SENP1 gene mice using the Cre-loxP recombinase system,which provides a good tool for the subsequent study of the role of SENP1 gene in lung diseases such as bronchopulmonary dysplasia and idiopathic pulmonary fibrosis,in which alveolar type II epithelial cells are the main damage cells.

Leptomeningeal metastasis(LM)is a serious late complication in patients with solid tumors,which is common in patients with lung cancer,breast cancer and melanoma.In recent years,due to the progress of diagnosis,the diagnosis rate of LM has gradually increased.The main goal of the therapy is to maintain neurological function,improve the quality of life and the overall survival rate,and prolong the progression-free survival time of patients.Intrathecal therapy is one of the main treatments for LM,which can deliver drugs directly to the subarachnoid space.The traditional intrathecal drugs are methotrexate,cytarabine and thiotepa.With the development of new research,a variety of chemotherapeutic drugs,targeted drugs and immune checkpoint inhibitors have also been used in intrathecal therapy.In addition,different ways of intrathecal administration also bring new hope to patients.This article reviewed the clinical research progress of intrathecal therapy in the treatment of LM.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective    To evaluate the changes of ascending aortic (AA) diameter after transcatheter aortic valve replacement (TAVR), and evaluate the safety and efficacy of TAVR in patients with AA dilation. Methods    We retrospectively included 87 patients who underwent TAVR at our center from 2016 to 2019. These patients were divided into 2 groups based on the preoperative AA diameter. There were 17 patients in the AA diameter≥45 mm group (including 10 males, aged 74.4±5.6 years), and 70 patients in the AA diameter<45 mm group (including 39 males, aged 75.9±7.0 years). Results     The baseline variables were similar between two groups (P>0.05). The overall device success rate was 97.7% (85/87). The median computed tomography (CT) follow-up time was 24.2±11.8 months in patients with AA diameter≥45 mm and 23.0±10.7 months in patients with AA diameter<45 mm, and the median annual dilation rate of AA were 0.36 mm/year and 0.00 mm/year, respectively. No statistical significance was observed between two groups (P>0.05). No adverse aortic events occurred during the follow-up period. Conclusion    TAVR is safe and effective in patients with preoperative AA diameter≥45 mm, and the AA diameter remains stable after the procedure. Patients with preoperative AA diameter≥45 mm and AA diameter<45 mm have similar annual dilation rates.

Objective:To revise the 2017 classification of irreducible intertrochanteric fractures and summarize reduction techniques of 2021 classification.Methods:A retrospective analysis was conducted of the 17 patients with irreducible intertrochanteric fracture who had been treated at Department of Orthopaedic Surgery, The Ninth People's Hospital of Shanghai, Shanghai Jiaotong University School of Medicine from January 2015 to December 2019. They were 7 males and 10 females, with an age of (73.2 ± 16.1) years. On the basis of 2017 classification, the irreducible intertrochanteric fractures were classified into 2 types in the present 2021 classification. Type Ⅰ were interlocking fractures which were further classified into 3 subtypes: type ⅠA were sagittal interlocking ones (7 cases), type ⅠB greater trochanter interlocking ones (one case) and type ⅠC lesser trochanter interlocking ones (one case). Type Ⅱ were separating fractures which were further classified into 4 subtypes: type ⅡA were sagittal separating ones (4 cases), type ⅡB coronal separating ones (one case), type ⅡC rotational separating ones(one case) and type ⅡD complete separating ones (2 cases). All patients were treated by closed reduction and intramedullary nailing with different reduction strategies corresponding to their fracture types (application of ejector rods, clamps or prying techniques, etc.). A total of 132 patients with reducible femoral intertrochanteric fracture who had been admitted during the same period were selected as the control group. The fracture reduction time, intraoperative blood loss and Harris hip score at the last follow-up were compared between the 2 groups.Results:The 2 groups were comparable because there was no significant difference in their preoperative general data ( P>0.05). Type ⅠA accounted for the highest proportion of irreducible intertrochanteric fractures [41.3% (7/17)], followed by type ⅡA [23.6% (4/17)]. The fracture reduction time [(44.6 ± 6.7) min] in the irreducible group was significantly longer than that in the control group [(39.2 ± 9.6) min] ( P<0.05). There was no significant difference in intraoperative blood loss or Harris hip score at the last follow-up between the 2 groups ( P>0.05). Conclusions:Compared with the "2017 classification" , the "2021 classification" is more concise and easy to remember, and can directly prompt the corresponding proper fracture reduction techniques. The patients with irreducible intertrochanteric fracture using proper reduction techniques can obtain functional recovery similar to that in the patients with reducible intertrochanteric fracture after reduction and fixation.

Objective    To compare the perioperative results of hybrid coronary revascularization (HCR), off-pump coronary artery bypass (OPCAB) and percutaneous coronary intervention (PCI) in elderly patients with three-vessel coronary artery disease involving left anterior descending (LAD) branch and explores the safety of surgery. Methods    We prospectively enrolled patients with coronary heart disease over 65 years who were admitted to General Hospital of People’s Liberation Army from January 2018 to September 2019. Coronary angiography results were all three-vessel lesions involving the anterior descending artery. After preoperative examination and assessment by the cardiovascular team, all patients were suitable for OPCAB or PCI treatment. According to the patient’s preference, HCR, OPCAB or PCI were performed. The preoperative baseline data and perioperative results were collected, and SPSS 22.0 was used for statistical analysis. Results    A total of 110 patients met the criteria and were included in the study, 28 in the HCR group, 45 in the OPCAB group, and 37 in the PCI group, with an average age of 71.4±5.6 years. There was no statistical difference in the preoperative baseline data of patients among the three groups. The intubation time (P=0.039), perioperative drainage volume (P<0.001), blood transfusion (P=0.021) in the HCR group were lower than those in the OPCAB group. There was no statistical difference in the main organ adverse events (MOAE, P=0.096) and in-hospital mortality (P=0.784) among the three groups of patients. The use of antibiotics in the PCI group was significantly lower than the other two groups (P<0.001). Conclusion    HCR combines the advantage of CABG and PCI including proved long-term patency rate with left internal mammary artery-LAD grafting, less trauma and superior long-term patency with PCI in non-LAD territory. Compared with OPCAB and PCI, there is no increase in perioperative major organ adverse events and in-hospital mortality. It is a safe and reliable minimally invasive myocardial revascularization technique for elderly patients with three-vessel coronary artery disease involving the anterior descending artery.