Objective:To explore the teaching resources innovation and the teaching quality improvement for international students in clinical medicine based on the bilingual test question database of digitalized systematic anatomy.Methods:The test question database was set up and applied to Batch 2018 international students of clinical medicine (experiment group). The results of the usual test, final theory, and experimental examination of Batch 2017 international students (control group) were compared to verify the application value of the test question database. Questionnaires were used to get feedback from international students, and the feasibility of developing the test question database and the driving effect of teaching reform were further evaluated. SPSS 20.0 was used for data analysis, and the examination achievements of the two groups were compared with independent-samples t test and the measurement data were expressed by (mean ± standard deviation). Results:There was no significant difference between the two groups in the usual test results ( P>0.05), and in the experimental group, the results of final theory and experimental examination were significantly higher than those in the control group ( P<0.05). According to the questionnaire, more than 89.55%(155) of the international students highly appraised the test question database in terms of learning resources, quality of questions, examination mode and experience evaluation, while only 52.02%(90) of them recognized the bilingual form of the test questions. Conclusion:The bilingual test question database of digital systematic anatomy has effectively expanded the teaching resources and promoted the teaching reform of international students.

Objective:To explore the roles and mechanisms of metformin in the improvement of cognitive dysfunction induced by chronic cerebral hypoperfusion in rats.Methods:Total 82 SD male rats (SPF grade) aged 3-4 months were randomly divided into four groups: sham operation control group (Con group, n=15), sham operation with metformin treatment group (Met group, n=20), 2-vessel occlusion group (2VO group, n=22), and 2-vessel occlusion with metformin administration group (2VO+ Met group, n=25). The chronic cerebral hypoperfusion model was established by bilateral common carotid artery ligation, and the carotid arteries of rats in Con group and Met group were only separated without ligation.After 2VO operation, rats in 2VO+ Met group and Met group were given metformin solution in drinking water at a dose of 100 mg/kg per day for 4 weeks.After 4-week continuous intervention with metformin, Morris water maze was performed to test the spatial cognitive function of the rats, in vivo electrophysiological technology was used to detect the long-term potential of the rats, and enzyme-linked immunosorbent assay(ELISA) was used to detect the concentrations of inflammatory factor tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6) in the hippocampus.The density of dendritic spines of hippocampal neurons was observed by Golgi staining, and the synaptic structure of hippocampal neurons, especially the vesicle density, was observed by transmission electron microscopy.SPSS 16.0 software was used for statistical analysis.Repetitive measurement ANOVA was used for the escape latency data of 7 days repeated learning training in water maze.One-way ANOVA was used for the comparison of other data among multiple groups, and Dunnett's t test was used for further pairwise comparison. Results:Morris water maze results showed that during 7 days of learning training, the time and group interaction for escape latency was not significant in the 4 groups of rats ( F=0.93, P>0.05), but the time main effect ( F=25.90, P<0.05) and group main effect ( F=13.20, P<0.05) were significant.Morris water maze test showed that from the 3rd to 7th day, the escape latencies in 2VO group were significantly longer than those in Con group and 2VO+ Met group(all P<0.05). The short-term memory of rats was detected after 1 day of rest.The results showed that the escape latency in 2VO group was significantly longer than that in Con group and 2VO + Met group( P<0.01). The retention time and crossing times in the platform area of 2VO rats were less than those in Con group and 2VO + Met group ( P<0.01). Electrophysiological results showed that the relative field excitatory postsynaptic potential slope of 2VO group (1.29±0.09) was significantly lower than that in Con group (2.07±0.09) and 2VO + Met group (1.69±0.08)( P<0.01). ELISA results showed that TNF-α level in hippocampal tissue of 2VO group was significantly higher than that in Con group and 2VO+ Met group; IL-1β and IL-6 levels in hippocampal tissue of 2VO group were significantly higher than those in Con group and 2VO + Met group.Density of dendritic spines in hippocampal neurons of 2VO group was significantly lower than that in Con group and 2VO+ Met group.The density and proportion of immature dendritic spines in hippocampal neurons of 2VO group were significantly higher than those in Con group and 2VO + Met group.Synaptic vesicle density of neurons in CA1 area of hippocampus in 2VO group ((230.29±19.44) vescicles/μm 2) was significantly lower than that in the Con group ((414.52±13.17) vescicles/μm 2) and 2VO+ Met group ((313.19±12.42) vescicles/μm 2). Conclusion:Metformin can reduce neuroinflammation of hippocampus with chronic cerebral hypoperfusion and improve synaptic plasticity and cognitive dysfunction.It may have potential application value in the treatment of vascular cognitive dysfunction.

Objective:To explore the protective effects and mechanisms of L-carnitine (LCAR) on cognitive dysfunction in chronic cerebral hypoperfusion rats.Methods:Totally 90 SD male rats (SPF class) aged 3-4 months were divided into four groups according to random number talbe: sham operated control group (SHAM group, n=15), sham operated with L-carnitine treatment group (LCAR group, n=25), 2-vessel occlusion group (2VO group, n=25), and 2-vessel occlusion with L-carnitine treatment group (2VO+ LCAR group, n=25). The chronic cerebral hypoperfusion model was established by bilateral common carotid artery ligation, and the carotid arteries from SHAM group and LCAR group were only separated without ligation.L-carnitine was administered intraperitoneally (300 mg·kg -1·d -1) for 30 days after surgery in the LCAR and 2VO+ LCAR groups.After 30 days of L-carnitine intervention, Morris water maze was performed to test the spatial cognitive function of the rats, the ATP level of hippocampal tissue was detected by chemiluminescence, the mitochondrial structure and synaptic structure of hippocampal neurons were observed by transmission electron microscopy, the degree of mitochondrial damage was scored, the vesicle density was counted and measured, the level of N-methyl-D-aspartate receptor subunit 2A or 2B(NR2A/B) and postsynaptic density 95(PSD95) in hippocampal tissue were detected by Western blot.The expression and distribution levels of transcription factor cAMP response element-binding protein(CREB) in brain tissues were observed by immunofluorescence.SPSS 16.0 software was used for statistical analysis.The escape latency data of repeated learning training in Morris water maze was conducted by repetitive measurement ANOVA, while other data were adopted by one-way ANOVA, and Dunnett's t test was used for further pairwise comparison. Results:(1)Morris water maze results showed that the time and group interaction of escape latency was not significant among the 4 groups of rats ( F=1.4, P>0.05), but the time main effect and group main effect were significant( F=21.6, 15.2, both P<0.05). Morris water maze results showed that platform position learning from 3rd to 7th day, the escape latencies in 2VO group were longer than those in SHAM group and 2VO+ LCAR group (all P<0.05). The results of short-term memory showed that the escape latency in 2VO group was longer than those in SHAM group and 2VO+ LCAR group (all P<0.05). Meanwhile, the retention time and crossing times in the platform area of 2VO group were less than those in SHAM group and 2VO+ LCAR group (all P<0.05). (2) The absolute and relative levels of ATP in hippocampus showed that the difference among the 4 groups were statistically significant ( F=14.6, 13.2, both P<0.05). ATP level of hippocampus in 2VO group was lower than those in SHAM group and 2VO+ LCAR group (both P<0.05). Electron microscopic observation of mitochondrial morphology showed that the Flameng score of mitochondrial damage in the hippocampus of rats in 2VO group (2.82±0.17) was higher than those in SHAM group (0.25±0.07) and 2VO+ LCAR group (1.76±0.09) (both P<0.05). (3) The density of synaptic vesicles in the hippocampus of rats in 2VO group ((289.09±22.41)/μm 2)was lower than those in SHAM group ((497.49±28.89)/μm 2)and 2VO+ LCAR group ((401.23±45.09)/μm 2) (both P<0.01). Western blot results showed that the relative levels of synaptic proteins NR2A/B, PSD95 and CREB in 2VO group were lower than those in SHAM group and 2VO+ LCAR group (all P<0.05). Immunofluorescence results showed that the relative level of CREB expression in hippocampal subregions and cortex in 2VO group was lower than those in SHAM group and 2VO+ LCAR group (both P<0.01). Conclusion:L-carnitine can improve spatial learning and memory dysfunction in rats with chronic cerebral hypoperfusion, which are related with promoting ATP production and protecting mitochondrial morphology, and promoting synaptic vesicle synthesis and synaptic protein expression.

OBJECTIVE: To explore the feasibility and accuracy of ultrasound volume navigation (UVN) combined with X-ray fluoroscopy-guided percutaneous pedicle screw implantation through a prospective randomized controlled study. METHODS: Patients with thoracic and lumbar vertebral fractures scheduled for percutaneous pedicle screw fixation between January 2022 and January 2023 were enrolled. Among them, 60 patients met the selection criteria and were included in the study. There were 28 males and 32 females, with an average age of 49.5 years (range, 29-60 years). The cause of injury included 20 cases of traffic accidents, 21 cases of falls, 17 cases of slips, and 2 cases of heavy object impact. The interval from injury to hospital admission ranged from 1 to 5 days (mean, 1.57 days). The fracture located at T ₁₂ in 15 cases, L ₁ in 20 cases, L ₂ in 19 cases, and L ₃ in 6 cases. The study used each patient as their own control, randomly guiding pedicle screw implantation using UVN combined with X-ray fluoroscopy on one side of the vertebral body and the adjacent segment (trial group), while the other side was implanted under X-ray fluoroscopy (control group). A total of 4 screws and 2 rods were implanted in each patient. The implantation time and fluoroscopy frequency during implantation of each screw, angle deviation and distance deviation between actual and preoperative planned trajectory by imaging examination, and the occurrence of zygapophysial joint invasion were recorded. RESULTS: In terms of screw implantation time, fluoroscopy frequency, angle deviation, distance deviation, and incidence of zygapophysial joint invasion, the trial group showed superior results compared to the control group, and the differences were significant ( P<0.05). CONCLUSION UVN combined with X-ray fluoroscopy-guided percutaneous pedicle screw implantation can yreduce screw implantation time, adjust dynamically, reduce operational difficulty, and reduce radiation damage.
Male ; Female ; Humans ; Middle Aged ; Pedicle Screws ; Prospective Studies ; X-Rays ; Surgery, Computer-Assisted/methods* ; Spinal Fusion/methods* ; Fluoroscopy/methods* ; Lumbar Vertebrae/injuries*

OBJECTIVE: To compare the effectiveness of O-arm navigation and ultrasound volume navigation (UVN) in guiding screw placement during minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) surgery. METHODS: Sixty patients who underwent MIS-TLIF surgery for lumbar disc herniation between June 2022 and June 2023 and met the selection criteria were included in the study. They were randomly assigned to group A (screw placement guided by UVN during MIS-TLIF) or group B (screw placement guided by O-arm navigation during MIS-TLIF), with 30 cases in each group. There was no significant difference in baseline data, including gender, age, body mass index, and surgical segment, between the two groups ( P>0.05). Intraoperative data, including average single screw placement time, total radiation dose, and average single screw effective radiation dose, were recorded and calculated. Postoperatively, X-ray film and CT scans were performed at 10 days to evaluate screw placement accuracy and assess facet joint violation. Pearson correlation and Spearman correlation analyses were used to observe the relationship between the studied parameters (average single screw placement time and screw placement accuracy grading) and BMI. RESULTS: The average single screw placement time in group B was significantly shorter than that in group A, and the total radiation dose of single segment and multi-segment and the average single screw effective radiation dose in group B were significantly higher than those in group A ( P<0.05). There was no significant difference in the total radiation dose between single segment and multiple segments in group B ( P>0.05), while the total radiation dose of multiple segments was significantly higher than that of single segment in group A ( P<0.05). No significant difference was found in the accuracy of screw implantation between the two groups ( P>0.05). In both groups, the grade 1 and grade 2 screws broke through the outer wall of the pedicle, and no screw broke through the inner wall of the pedicle. There was no significant difference in the rate of facet joint violation between the two groups ( P>0.05). In group A, both the average single screw placement time and screw placement accuracy grading were positively correlated with BMI ( r=0.677, P<0.001; r=0.222, P=0.012), while in group B, neither of them was correlated with BMI ( r=0.224, P=0.233; r=0.034, P=0.697). CONCLUSION UVN-guided screw placement in MIS-TLIF surgery demonstrates comparable efficiency, visualization, and accuracy to O-arm navigation, while significantly reducing radiation exposure. However, it may be influenced by factors such as obesity, which poses certain limitations.
Humans ; Imaging, Three-Dimensional ; Lumbar Vertebrae/surgery* ; Minimally Invasive Surgical Procedures ; Pedicle Screws ; Retrospective Studies ; Spinal Fusion ; Surgery, Computer-Assisted ; Tomography, X-Ray Computed ; Treatment Outcome

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

【Objective】 To explore the factors influencing the survival and prognosis of patients with bladder urothelial carcinoma (BUC) after surgical treatment, and to establish an artificial intelligence algorithm to predict the effects of different surgical regimens. 【Methods】 BUC patients treated with surgery during Jan.2007 and Jan.2019 in The Second Hospital of Dalian Medical University and Nanfang Hospital of Southern Medical University were enrolled. The complete clinical and follow-up data were collected. Deep neural network (DNN) was used to establish an artificial intelligence algorithm model. A prediction model of survival and prognosis was established, and the influencing factors of survival were explored and ranked by the artificial intelligence algorithm. 【Results】 A total of 832 patients were involved, including 438 (52.64%) treated in The Second Hospital of Dalian Medical University, and 394 (47.36%) treated in Nanfang Hospital of Southern Medical University. Of all cases, 579 (69.6%) were non-muscle invasive bladder cancer, and 253 (30.4%) were muscle invasive bladder cancer. Transurethral resection of bladder tumor was conducted in 539 (64.8%) cases, partial cystectomy in 66 (7.9%) cases, and total cystectomy in 227 (27.3%) cases. The data of patients treated in Second Hospital of Dalian Medical University were used for DNN modeling, and the data of patients treated in Nanfang Hospital of Southern Medical University were used for external verification after modeling. Finally, it was concluded that the factors affecting survival and prognosis were T stage, pathological grade, hypertension or cardiovascular and cerebrovascular disease, hemoglobin, blood calcium, smoking, albumin, lymphocytes, age, ratio of albumin/globulin, operation method, N stage, and creatinine clearance rate in descending order. The model could be used for preoperative prediction. 【Conclusion】 Through DNN modeling and external verification, the influencing factors of postoperative survival can be predicted for patients with bladder cancer, and the surgical effects can also be predicted before operation. The model can provide artificial intelligence algorithm support for the selection of surgical methods and postoperative follow-up plans.

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.
Consensus ; Humans ; Oral Ulcer/therapy*

Objective:To investigate the short-term clinical efficacy of laparo-gastroscopic esophagectomy (LGE).Methods:The retrospective and descriptive study was conducted. The clini-copathological data of 11 patients with esophageal cancer who underwent LGE in the Zhongshan Hospital of Fudan University from June 2020 to October 2021 were collected. There were 8 males and 3 females, aged (68±4)years. Sorted by operation time, the sentinel lymph nodes navigation (SLN) was performed since the sixth patient in the cohort, and abdominal surgery and neck surgery were performed simultaneously to complete LGE. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect death of patients during postoperative 30 days. Patients were followed up during postoperative 30 days. Measurement data with normal distribution were represented as Mean± SD, and count data were described as absolute numbers. Results:(1) Surgical situations. Of the 11 patients, 5 cases received SLN with satisfactory visualization, 6 cases did not receive SLN, 1 case terminated the operation as sentinel lymph nodes biopsy showing positive results and the rest of 10 cases completed LGE successfully without conversion to thoracotomy. The operation time and tumor diameter of the 10 patients completing LGE was (204±27)minutes and (2.5±1.0)cm, respec-tively. (2) Postoperative situations. Of the 10 patients completing LGE, 2 cases had pulmonary complications after surgery and recovered well with symptomatic treatment, and none of patient had anastomotic leakage or other serious complication. Results of postoperative histopathological examination showed squamous cell carcinoma in the 10 patients completing LGE. Nine patients were classified as T1b?3N0M0 stage and 1 patient was classified as T1bN1M0 stage. Ten patients completing LGE had R 0 resection and the number of lymph nodes dissected was 14±4. There were 3 cases with nerve bundle invasion, 2 cases with vascular invasion and 5 cases without nerve bundle and vascular invasion. The postoperative treatment time at intensive care unit and duration of hospital stay of the 10 patients completing LGE were (4.0±2.4)days and (7.2±1.5)days. (3) Follow-up. The 10 patients completing LGE were followed up and none of them died during the postoperative 30 days. Conclusions:LGE is safe and feasible. Combined with SLN can guarantee the oncology effect of surgery.

Objective:To explore the role and mechanism of kidney brain protein (KIBRA) down-regulation in cognitive dysfunction caused by chronic cerebral hypoperfusion.Methods:Ninety male SPF grade Sprague Dawley (SD) rats were divided into four groups according to random number table: sham operation group ( n=15), chronic hypoperfusion group (2VO group, n=25), chronic hypoperfusion stereotaxic injection of AAV-KIBRA group (2VO+ AAV-KIBRA group, n=25), chronic hypoperfusion stereotaxic injection of AAV-Vector group (2VO+ AAV-vector group, n=25). Chronic cerebral hypoperfusion model was established by bilateral ligation of common carotid artery, and stereotactic injection of 2 μL AAV-KIBRA or AAV-vector was performed for 30 days.Morris water maze, in vitro electrophysiology, p21-activated kinase 3(PAK3) activity detection, Western blot, immunoprecipitation and Golgi staining were used to detect spatial learning and memory ability, long-term potentiation(LTP), KIBRA level expression, PAK3 activity changes and the distribution of dendritic spines.SPSS 16.0 statistical software was used for statistical data.One-way ANOVA was used to compare the differences between groups.LSD test was used to compare the significance of data differences between the two groups.Welch test was used for uneven variance. Results:After 1 month of chronic cerebral hypoperfusion, the level of KIBRA in the hippocampus of rats was detected by homogenate and Western blot, and it was found that the level of KIBRA in 2VO group was lower than that of sham group(73.49±4.12)% ( P<0.01). AAV-KIBRA injection in hippocampal CA1 region significantly up-regulated the level of KIBRA to (91.91±7.01)% over 2VO group ( P<0.01). Morris water maze test showed that the latency of the 2VO group(3rd-7th day trail data: (48.18±2.82)s, (43.45±2.27)s, (32.27±2.22)s, (26.55±2.37)s, (17.18±2.67)s) were significantly longer than those of the sham group((41.67±2.74)s, (32.58±2.57)s, (22.50±2.94)s, (16.91±2.39)s, (8.75±1.52)s) (all P<0.05), and the latencies of the 2VO+ AAV-KIBRA group 3rd-7th day trail data: (43.83±2.95)s, (35.25±2.15)s, (26.58±2.03)s, (19.92±2.17)s, (17.75±1.35)s) was significantly shorter than that of the 2VO group ((all P<0.01). The Morris water maze test with the platform removed showed that the latency of rats in the 2VO group to reach the platform region was significantly longer than that of the sham group, while the latency of rats in the 2VO+ AAV-KIBRA group to reach the platform region was significantly shorter than that in the 2VO group ( P<0.01). At the same time, the retention time and the crossing times in the platform region of 2VO group were less than those of the sham group ( P<0.01), but the retention time and the crossing times in the platform region of 2VO+ AAV-KIBRA group were significantly higher than those in the 2VO group ( P<0.01). The electrophysiological records of the brain slices showed that the relative excitatory postsynaptic field potential of 2VO group (1.43±7.43) was significantly lower than that of sham group (2.21±6.54) after high frequency stimulation, while the relative excitatory postsynaptic field potential of 2VO+ AAV-KIBRA group (1.90±8.15) was higher than that of 2VO group ( P<0.01). Immunoprecipitation in rat hippocampus revealed that PAK3 could be detected by Western blot assay when KIBRA was precipitated.The results showed that the relative enzyme activity of PAK3 in 2VO hippocampal tissue (0.64±0.04) was significantly lower than that in sham group (1.02±0.07), while the relative enzyme activity of PAK3 in 2VO+ AAV-KIBRA group (0.86±0.03) was significantly higher than that in 2VO group.Golgi staining showed that the density of dendritic spines in 2VO hippocampal neurons((6.85±0.43)/10 μm) was significantly lower than that in sham group((11.83±0.58)/10 μm), while the density of dendritic spines in 2VO+ AAV-KIBRA group((10.22±0.39)/10 μm) was significantly higher than that in 2VO group. Conclusion:The down-regulated of KIBRA after chronic cerebral hypoperfusion plays a key role in cognitive dysfunction and is also involved in the decrease of synaptic functional plasticity.The downregulation of KIBRA is involved in the structural plasticity of dendrites through the regulation of PAK3 activity.Therefore, KIBRA may be an important target for the prevention and treatment of cognitive function of chronic cerebral hypoperfusion.