1.Standard operating procedure for endobronchial ultrasound guided laser multi-point ablation of mediastinal tumors
Dan LIU ; Nansheng WAN ; Jie WANG ; Guangsheng LI ; Wei XIE ; Yu TIAN ; Jing FENG
Tianjin Medical Journal 2024;52(1):80-83
The treatment of mediastinal tumor has always been a clinical difficulty due to its complex anatomical location and many important organs.Compared with traditional local treatment,endobronchial ultrasound guided laser multi-point ablation of mediastinal tumors has many advantages,including real-time monitoring of ablation range and effect,avoidance of damage to normal tissue and organs,few side effects and good tolerance.This article describes the standard operating procedure for endobronchial ultrasound guided laser multi-point ablation of mediastinal tumors.
2.Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity.
Yongshun ZHANG ; Lan YANG ; Yangsen OU ; Rui HU ; Guangsheng DU ; Shuang LUO ; Fuhua WU ; Hairui WANG ; Zhiqiang XIE ; Yu ZHANG ; Chunting HE ; Cheng MA ; Tao GONG ; Ling ZHANG ; Zhirong ZHANG ; Xun SUN
Acta Pharmaceutica Sinica B 2024;14(1):350-364
Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.
3.Isolated anterior cerebral artery territory infarction: etiology, clinical features, and outcome
Guangsheng WANG ; Junjie BAO ; Ting HU ; Yuanyuan TIAN ; Li HUANG
International Journal of Cerebrovascular Diseases 2024;32(6):414-420
Objective:To investigate the etiology, clinical features and outcome of isolated anterior cerebral artery (ACA) territory infarction.Methods:Patients with isolated ACA territory infarction admitted to the Affiliated Shuyang Hospital of Xuzhou Medical University from April 2019 to December 2023 were retrospectively included. The demographic and clinical data were collected. The etiology subtypes of stroke were divided into large artery atherosclerosis (LAA), cardioembolism (CE), small vessel occlusion (SVO), stroke of other determined etiology (SOE), and stroke of undetermined etiology (SUE). At 90 days after onset, the modified Rankin Scale was used to evaluate the outcome. 0~2 points were defined as good outcome, and >2 points were defined as poor outcome. Multivariate logistic regression analysis was used to identify independent risk factors for poor outcomes. Results:A total of 67 patients with isolated ACA territory infarction were enrolled, including 31 males (46.27%), aged 67.20±12.59 years. There were 26 patients (38.81%) of LAA type, 10 (14.93%) of CE type, 7 (10.45%) of SVO type, 12 (17.91%) of SOE type, and 12 (17.91%) of SUE type. Fifty-two patients (77.61%) had good outcome, while 15 (22.39%) had poor outcome. There were significant differences in gender, diabetes, atrial fibrillation, antithrombin-Ⅲ activity, urinary incontinence, cognitive impairment, and the baseline National Institutes of Health Stroke Scale (NIHSS) score among different etiological subtypes (all P<0.05). Multivariate logistic regression analysis showed that previous stroke history (odds ratio 17.995, 95% confidence interval 1.276-253.852; P=0.032) and high baseline NIHSS score (odds ratio 2.094, 95% confidence interval 1.333-3.292; P=0.001) were the independent risk factors for poor outcome. Conclusions:The most common etiology of isolated ACA territory infarction is LAA, and most patients have good outcome. Previous stroke history and high baseline NIHSS score are the independent risk factors for poor outcome.
4.Three-dimensional reconstruction and biomechanical analysis of calcaneal Micro CT data
Guangsheng TANG ; Kai WANG ; Yuefu DONG ; Jian XU ; Lu ZHOU
International Journal of Biomedical Engineering 2024;47(4):356-363
Objective:To construct a three-dimensional calcaneal finite element model and study its biomechanical distribution by finite element analysis.Methods:Four large calcaneal specimens were taken from the Department of Human Anatomy of Kangda College of Nanjing Medical University in the second semester of 2021—2022. Micro CT scans were performed to obtain the image data of these specimens, and then the three-dimensional calcaneal model was reconstructed using the Mimics and Geomagic Wrap software. The obtained data were imported into the finite element analysis software to perform the material assignments and mesh delineation to obtain the three-dimensional finite element model. The boundary constraints were set, and loads were applied to the calcaneal model to perform finite element analysis calculations, and the stresses and displacements of the finite element model were extracted.Results:The three-dimensional calcaneal model had a high simulation quality. The morphology and structure were complete and without defects, and the size was consistent with that of the real calcaneus, which restores the original bony morphology and structure. The geometric appearance of the three-dimensional calcaneal model after meshing was vivid and lifelike, and without defect. The reconstructed morphology and structure of the three-dimensional model were the same as those of the three-dimensional reconstruction, the size was the same, and the main structure was clearly visible. The meshes and nodes of each component of the three-dimensional calcaneal model were uniformly distributed, and their numbers were comparable to those of the real heel bone. The maximum stresses of the three-dimensional calcaneal model were in the cortical bone, and the maximum stresses were in the same position. These two positions were the lowest part of the anterior part of heel bones. The maximum displacements in the three-dimensional calcaneal model were all less than 0.10 mm.Conclusions:A high-precision three-dimensional finite element calcaneal model has been constructed, which is of good mechanical validity.
5.Biomechanical analysis of calcaneal sustentaculum tail sustentacular screw in treatment of Sanders type Ⅱ fractures
Guangsheng TANG ; Qi WANG ; Yao XU ; Bing WANG ; Jianning SUN ; Deguang WANG
International Journal of Biomedical Engineering 2024;47(5):449-456
Objective:To construct a finite element analysis model for the application of sustentaculum tail sustentacular screw in the treatment of calcaneal fracture of Sanders type Ⅱ. The finite element analysis method was used to study the effectiveness of the simulation treatment of Sanders type Ⅱ calcaneal fracture.Methods:A complete adult calcaneal specimen that was not affecting the normal quality of bone after teaching in the Department of Human Anatomy, Kangda College of Nanjing Medical University from 2021 to 2022 second semester was selected. A micro CT scan was performed to obtain data. The three-dimensional model of the calcaneus was reconstructed by the software of Mimics and Geomagic Wrap. The internal fixation and fracutre model were drawn using SolidWorks software. The obtained data were imported into the finite element analysis software for material assignment and meshing to obtain a three-dimensional finite element model. The load and boundary constraints were applied to each model to perform finite element analysis and calculation, and the stress and displacement of the model were extracted. Finally, the experimental screw placement of the calcaneus loading process was verified.Results:The three-dimensional model of calcaneal fracture had a high degree of appearance simulation, complete morphological structure, no defect, and was consistent with the size of the solid calcaneus. After surgical treatment, the anatomical reduction of each fracture model was good, the steel plate fit to the bone surface, and the screw did not protrude outside the model. There was no deformation or damage to the whole internal fixation, the grid division was clear, and the number was relatively uniform and consistent. The maximum stress in each type of calcaneal fracture model was in the internal fixation, and the overall stress was uniformly distributed in each component. The maximum displacement distance of each type of calcaneal fracture was less than 0.13 mm, and the angles and lengths of nails were accurate. The tip of the Kirschner wires was located in the sustentaculum tail. There was no rupture of the sustentaculum tali and no protrusion of the Kirschner wires.Conclusions:The internal fixation is an effective method to treat the Sanders type Ⅱ calcaneal fractures by using sustentaculum tail sustentacular screws.
6.A new diagnosis and ablation technique of lung isolated percutaneous transthoracic needle biopsy
Dan LIU ; Nansheng WAN ; Jie WANG ; Guangsheng LI ; Wei XIE ; Yu TIAN ; Jing FENG
Tianjin Medical Journal 2024;52(9):982-984
Pathological puncture biopsy is the key to early diagnosis and treatment of thoracic tumours,and percutaneous puncture biopsy(PTNB)technology has been widely used in clinical practice.Common complications of PTNB include pneumothorax,air embolism and pulmonary hemorrhage.In order to optimize traditional PTNB,our center has developed a new percutaneous puncture diagnosis and ablation technology for lung lesions,which greatly reduces the occurrence of complications,increases the accuracy of pathological biopsy.At the same time,it can bridge target lesion ablation.This article describes the standard operating procedure for diagnosis and ablation techniques of filling operation assisted percutaneous transthoracic needle biopsy under rigid endoscopy with regular frequency controlled ventilation during general anesthesia.
7.Application of multidisciplinary small-class teaching in general surgery residency training
Shuai WANG ; Guangsheng DU ; Dan BIAO ; Yujiao CAI ; Jie MEI ; Yuan QIU ; Weidong XIAO
Chinese Journal of Medical Education Research 2024;23(4):568-572
Objective:To investigate the effects of multidisciplinary small-class teaching on expertise and skill acquisition and learning experience in standardized residency training in general surgery.Methods:Sixty residents of grade 2021 rotating in general surgery from January to August 2023 were divided into multidisciplinary teaching group ( n=30) and traditional teaching group ( n=30, to receive tradition one-on-one teaching). All the residents underwent a theoretical examination and Mini-Clinical Evaluation Exercise (Mini-CEX) skill assessment before admission, and the scores were compared between the two groups. At the end of training, the two groups were compared in terms of theoretical and Mini-CEX skill assessment scores and the degree of satisfaction with teaching. Statistical analysis was conducted using SPSS 26.0. Results:There were no significant differences in the theoretical assessment and Mini-CEX skill assessment scores before admission between the two groups ( P>0.05). At the end of training, the multidisciplinary teaching group had a significantly higher theoretical examination score [(88.15±3.45) vs. (72.25±4.36), P<0.05] and a significantly higher Mini-CEX score [(86.35±2.24) vs. (76.28±3.92), P<0.05] compared with the traditional teaching group. According to the survey, the residents in the multidisciplinary teaching group were more satisfied with teaching and more likely to recognize the teaching effects. Conclusions:Multidisciplinary small-class teaching can help improve the quality of standardized general surgery residency training on gastrointestinal tumor treatment, which is a highly accepted and effective attempt at standardized residency training.
8.Laboratory and clinical characteristics of patients with different SF3B1 genotypes in myelodysplastic syndromes
Huimin JIN ; Liying ZHU ; Fei HUANG ; Zhongxun SHI ; Hairong QIU ; Yan WANG ; Hui JIN ; Zijuan WU ; Guangsheng HE ; Jianyong LI ; Wenyi SHEN ; Chun QIAO
Chinese Journal of Laboratory Medicine 2023;46(5):464-472
Objective:To analyze the distribution of different SF3B1 genotypes in patients with myelodysplastic syndromes (MDS) and its prognostic value.Methods:Totally, 377MDS patients who were initially diagnosed in the First Affiliated Hospital of Nanjing Medical University from January 2014 to January 2022 were included in the retrospective analysis.The patients were divided into three different groups according to mutation stcote of SF3B1, including 317 patients with SF3B1 wild type (SF3B1 WT) (214 males and 103 females, 63(49, 71) years old),39 patients with SF3B1 K700E mutation(SF3B1 K700E(17 males and 22 females, 65(52, 73)years old)) and 21 patients with SF3B1 non-K700E mutation(SF3B1 non-K700E)(13 males and 8 females, 67(63, 73) years old). MDS-related 20 gene mutations were detected using targeted sequencing technology; Survival curves were constructed by the Kaplan-Meier method; Cox proportional hazards model was established to evaluate different factors at diagnosis on survival by univariate and multivariate analyses.. Results:Compared with SF3B1 non-K700E patients, SF3B1 K700E patients had a higher median absolute neutrophil count ( P=0.002) and were likely to be in the low/int-1 International Prognostic Scoring System (IPSS) categories ( P=0.023). A 20-gene targeted sequencing analysis showed that, compared with SF3B1 WT patients, SF3B1 K700E patients were associated with lower frequency of ASXL1 and U2AF1 mutations ( P=0.018 and P=0.003); while compared with SF3B1 non-K700E patients, the frequency of ASXL1 mutation was significantly lower in SF3B1 K700E cases ( P=0.029). Patients with SF3B1 K700E had better overall survival (OS) in comparison with SF3B1 WT and SF3B1 non-K700E in MDS patients ( P<0.001 and P=0.045, respectively). In comparison with SF3B1 WT patients, SF3B1 MUT patients had more favorable OS and progression-free survival (PFS) in MDS without excess blasts ( P<0.001 and P<0.001, respectively), but no significant difference was found in MDS with excess blasts ( P>0.05). Compared with SF3B1 WT patients, SF3B1 K700E patients had superior OS and PFS in the int-1 IPSS category ( P=0.010 and P=0.013, respectively). By multivariable analysis, the presence of SF3B1 K700Ewas an independent predictor of superior OS ( HR=0.461,95% CI 0.262-0.811, P=0.007). Conclusion:SF3B1 K700E and SF3B1 non-K700E patients had significantly improved OS in comparison with SF3B1 WT MDS patients. Furthermore, SF3B1 K700E patients were associated with a better OS compared with SF3B1 non-K700E MDS patients. SF3B1 mutation could not overcome the poor prognostic effect of excess blasts, which highlights the importance of the SF3B1 mutation subtype in risk assessment of MDS without excess blasts.
9.Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity.
Fuhua WU ; Shuang LUO ; Yongshun ZHANG ; Yangsen OU ; Hairui WANG ; Zhaofei GUO ; Chunting HE ; Shuting BAI ; Penghui HE ; Min JIANG ; Xiaoyan CHEN ; Guangsheng DU ; Xun SUN
Acta Pharmaceutica Sinica B 2023;13(5):2219-2233
Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.
10.The expression of miR⁃381⁃3p in acute myeloid leukemia and its effect on the proliferation and apoptosis of leukemia cells
Hongxia Zhang ; Kui Wang ; Guangsheng Wu
Acta Universitatis Medicinalis Anhui 2023;58(7):1164-1170
Objective :
To investigate the expression , clinical significance , progression , and prognosis of miR⁃381 ⁃3p in acute myeloid leukemia (AML) , as well as its impact on AML cell proliferation and apoptosis , in order to provide theoretical basis for the treatment of AML.
Methods :
Bioinformatics analysis was used to identify differentially expressed miRNAs , clinical data and blood samples of AML patients were collected , and the expression levels of miRNAs in the bone marrow fluid of the included patients were measured to further elucidate the relationship between miRNAs and AML. The included patients were followed up to calculate overall survival (OS) and disease⁃free survival (DFS) ; AML cells were cultured in vitro , miR⁃381 ⁃3p plasmids were constructed , miR⁃381 ⁃3p was overexpressed and miR⁃381 ⁃3p was knocked down in AML , and they were divided into five groups : control , miR⁃381 mimics , mimics NC , miR⁃381 inhibitor , inhibitor NC . The proliferation and apoptosis of AML cells were detected using CCK⁃8 and flow cytometry .
Results :
Differentially expressed miRNAs were identified using bioinforDifferentially expressed miRNAs were identified using bioinfor included . The expression level of miR⁃381 in AML patients was lower than that in the control group , and all FAB subtypes were lower than those in the normal group . The expression level of miR⁃381 was not related to the age , gender , peripheral blood leukocytes , lymphocytes , and FAB typing of AML patients , and the OS and DFS of miR⁃381 patients with high expression were significantly prolonged , with statistically significant differences . In vitro experiments had shown that knocking down miR⁃381 could inhibit apoptosis and promote proliferation of AML cells . Overexpression of miR⁃381 could promote apoptosis and inhibit proliferation of AML cells .
Conclusion
MiR⁃381 ⁃ 3p is low expressed in AML patients , and its overexpression can significantly prolong OS and DFS . miR⁃381 ⁃3p can promote apoptosis of AML cells , inhibit proliferation , and may become a targeted molecule for the treatment of AML.


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