The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

Objective:To investigate the effectiveness and safety of domestic upper gastrointestinal endoscopic ultrasound (EUS).Methods:A total of 160 patients undergoing EUS at Shengjing Hospital of China Medical University (Center1) and Shenzhen People's Hospital (Center 2) from March to July 2021 were randomly selected by stratified blocked randomization, and were treated with SonoScape EG-UG5T (the test group) or Fujifilm EG-580UT (the control group). The primary outcome was the ultrasound image quality excellence rate, and the comparison was verified by non-inferiority. The secondary outcomes were the endoscopic image quality excellence rate, the operational performance excellence rate, and the system stability evaluation. The safety evaluation was based on the occurrence of intraoperative and postoperative adverse events in the subjects.Results:In the intention-to-treat analysis set (ITT), the excellence rate of ultrasound image quality in the test group and the control group was 100.0% (78/78) and 100.0% (77/77), respectively. The rate difference between the two groups was 0.0% (95% CI: -4.7%-4.8%). In the per protocol analysis set (PPS), the excellence rate of ultrasound image quality in the test group and the control group was 100.0% (78/78) and 100.0% (75/75), respectively. The rate difference between the two groups was 0.0% (95% CI: -4.7%-4.9%). The lower limit of the confidence interval of ultrasound image quality excellence rate of both data sets was greater than the non-inferiority threshold value of -8%, which inferred that the non-inferiority hypothesis of the test machine non-inferior to the control machine was valid. The endoscopic image quality excellence rate and the operational performance excellence rate of the test group and the control group was 100.0% in both the ITT and PPS analyses, and there was no statistically significant difference between the two groups ( P=1.000). The system instability event rate was 0.0% (0/78) in the test group and 3.9% (3/77) in the control group ( P=0.120). No adverse event occurred in either group. Conclusion:The domestic upper gastrointestinal endoscopic ultrasound is standard-compliant for clinical application under normal conditions in terms of effectiveness, safety, and stability.

Objective:To establish a method for obtaining planning target volume (PTV) and planning risk volume (PRV) margins caused by rotation in the use of adapt-to-position (ATP) modality of magnetic resonance linear accelerator (MRL) for patients with intracranial tumors.Methods:Clinical data of 6 patients with intracranial tumors (150 fractions in total) who received MRI-guided online ATP radiotherapy in Peking Union Medical College Hospital from November 2023 to January 2024 were retrospectively analyzed. The pre-planned CT structure was copied onto each segmented MR image and then the structures were traced back to the CT image according to the three-dimensional registration relationship. The anisotropic distance of the structure based on the original CT structure was calculated to obtain the variation range of the target and the organs at risk. The maximum anisotropic value was taken as the result of the PTV and the relationship between the results and intracranial location of different patients was analyzed. Group comparison was performed by Chi-square test. Two group comparison was conducted by post-hoc Wilcoxon signed-rank test. Results:After the rotation deviation was included, the range of target changes in the six directions of left and right (L/R), anterior and posterior (A/P) and superior and inferior (S/I) of the 6 patients were: (1.24± 0.86) mm/(1.91± 1.07) mm, (2.02± 1.26) mm/(1.66± 1.07) mm, (1.84± 1.84) mm /(2.94±1.93) mm, respectively. The results in the SI direction were significantly different, and the values in the I direction in 2 patients exceeded 4 mm, the margins suitable for all patients were 3.01 mm/2.4 mm(A/P), 1.9 mm/2.93 mm(L/R) and 3.14 mm/4.62 mm(S/I) in different directions, respectively. The L/R direction of the lens and the S/I direction of the optic nerve were significantly changed, and the A/P direction of the brain stem was (3.99± 4.64) mm. Larger values might be required when the target was in the posterior brain (left-down area, right-down area).Conclusions:The rotation deviation, organ movement and intracranial location affect the PTV and the organs at risk PRV in the MRI-guided ATP modality in intracranial tumors patients. The margin generation method based on image fusion can help to quantify the margin value reasonably.

Objective:To investigate the effects of TYRO protein tyrosine-binding protein(TYROBP)on neuroinflammation and autophagy via the PI3K/AKT signaling pathway in a transgenic APP/ PS1 mouse model of AD. Methods:C57BL/6J, TYROBP-/- and APP/ PS1 transgenic male mice aged 15-month-old were randomly divided into 3 group: the C57BL/6J group, the TYROBP-/- group and the APP/ PS1 group, with 19 in each group.The eight-arm maze test and novel object recognition test were conducted to assess the learning and memory ability of mice.The activation of microglia and NLRP3 inflammasomes were assessed by immunofluorescence.The mRNA levels of TNF-α, IL-6 and IL-1β were measured by real-time PCR, and the protein expression levels of NLRP3, cleaved caspase-1, SQSTM1, LC3B, TYROBP, p-PI3K, PI3K, p-AKT and AKT were assayed by Western blot. Results:Compared with the C57BL/6J group, the learning and memory abilities were significantly decreased(all P<0.05), activated microglia and NLRP3 inflammasomes were increased(all P<0.05), the mRNA and protein expression levels of TNF-α, IL-6, and IL-1β were increased(all P<0.05)and the protein expression levels of LC3B-Ⅱ, SQSTM1, TYROBP, p-PI3K, p-AKT were increased(all P<0.05)in the APP/ PS1 group.Compared with C57BL/6J group, the protein expression levels of TNF-α, IL-6, IL-1β, LC3B Ⅱ, SQSTM1, p-PI3K and p-AKT were decreased(all P<0.05). Conclusions:TYROBP promotes the inflammatory response and inhibits autophagy possibly by activating the PI3K/AKT signaling pathway, thus participating in the occurrence and development of AD.

Objective:To explore the correlation between serum microRNA(miR)-124 and miR-181c expression and the treatment outcome of Solitaire stent thrombectomy in patients with acute cerebral infarction and its influencing factors.Methods:Eighty-one patients with acute cerebral infarction performed Solitaire stent thrombectomyfrom June 2018 to October 2020 in the Affiliated Hospital of Jining Medical College were selected. The predictive value of miR-124, miR-181c expression in patients with acute cerebral infarction were analyzed.Results:In 81 patients, 21 patients with poor outcome(poor outcome group) and 60 patients with favorable outcome (favorable outcome group). The ratio of age ≥ 60 years in poor outcome group was higher than that in the favorable outcome group: 76.19% (16/21) vs. 46.67% (28/60), there was statistical difference ( χ2 = 5.46, P<0.05). The levels of miR-124, miR-181c before surgery and postoperative 1-day, 7-day in the favorable outcome group were higher than those in poor outcome group: 2.81 ± 0.82 vs. 2.24 ± 0.74, 3.01 ± 1.52 vs. 2.07 ± 1.04, 3.25 ± 1.67 vs. 1.86 ± 0.92; and the levels of miR-181c before surgery and postoperative 1-day, 7-day in the favorable outcome group were lower than those in the poor outcome group: 1.43 ± 0.59 vs. 1.79 ± 0.65, 1.35 ± 0.62 vs. 1.94 ± 0.79, 1.24 ± 0.60 vs. 2.16 ± 1.08, there were statistical differences ( P<0.05). The results of Logistic multivariate analysis showed that the age, the levels of miR-124, miR-181c before operation and postoperative 1-day, 7-day were influencing factors for the treatment outcome of Solitaire stent thrombectomy. The receiver operating characteristic (ROC) curve analysis showed that the area under the curve of miR-124, miR-181c on the postoperative 7-day were 0.806, 0.861, and were higher than those before operation and the postoperative 1-day, the diagnostic sensitivity were 71.43%, 76.19%, the specificity were 88.33%, 85.00%. Conclusions:The expression of miR-124 and miR-181c in the serum of acute cerebral infarction is related to the outcome of Solitaire stent thrombectomy, especially the expression level on the postoperative 7-day has better application value. It can be used to predict the outcome of surgery.

Objective To explore the clinical efficacy of marginal liver from elderly donors in liver transplantation. Methods According to the inclusion and exclusion criteria, the clinical data of 127 donors and recipients were retrospectively analyzed. According to the age of donors, 127 donors were divided into the elderly group (n=27) and control group (n=100). The recovery of liver function, the occurrence of postoperative complications and survival rate of the recipients after transplantation were statistically analyzed between two groups. Results The incidence of primary nonfunction (PNF) and initial poor graft function (IPGF) did not significantly differ between the elderly and control groups (both P > 0.05). Within postoperative 2 weeks, the average levels of alanine aminotransferase (ALT) and serum total bilirubin (TB) of liver transplant recipients in the elderly group was not significantly different from those in the control group (both P > 0.05). There was no significant difference in the incidence of postoperative complications in the postoperative elderly group compared with the control group (all P > 0.05). The 1-and 3-year survival rates of the recipients in the elderly group were 84% and 78% respectively, which did not significantly differ from 89% and 79% in the control group (both P > 0.05). Conclusions Strict and sufficient quality evaluation and functional maintenance should be done for elderly donor livers. It can achieve good transplantation results by intraoperative fine operation, reducing bleeding and trauma, shortening the time of cold ischemia and operation, strengthening postoperative monitoring and implementing enhanced recovery after surgery.

Enterohepatic circulation plays an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Bile acid is the basic substance of enterohepatic circulation and plays an important role in lipid metabolism, intestinal flora regulation, and host immunity. This article summarizes the research advances in bile acid which acts as a signal molecule to activate bile acid receptors in the liver and intestine, such as farnesoid X receptor, G protein-coupled receptor 5, pregnane X receptor, and vitamin D receptor, and is thus involved in the pathogenesis of NAFLD. It is expected to develop effective drugs for the treatment of NALFD based on the above targets, but there is still a need for further exploration.

OBJECTIVE: To summarize the clinical characteristics of testicular torsion and explore the relationship between its incidence and temperature, the value of supplementary examinations, and the factors causing misdiagnosis and testicular lesions. METHODS: We retrospectively analyzed the clinical data of the patients with testicular torsion diagnosed in 9 hospitals in Hunan Province from May 1, 2009 to November 1, 2018. The temperature at onset and WBC value after onset were analyzed. The misdiagnosis rate and testicular lesion rate in the first-visit hospitals were compared between the large general hospitals and local hospitals. The factors that affected the diagnosis and treatment of testicular torsion were analyzed. RESULTS: A total of 274 cases were included in this study, and misdiagnoses occurred in 151 cases (61.9%). The initial diagnosis was made in large general hospitals in 59 cases; misdiagnosis occurred in 30.5% of the cases and the rate of testicular lesions was 57.6%. Of the 215 cases first diagnosed in local hospitals, only 82 cases were diagnosed correctly, and the misdiagnosis rate was as high as 61.9%; the rate of testicular lesion was 85.6% in these cases. There were significant differences in the misdiagnosis rate and testicular lesion rate between the two groups ( < 0.05). CONCLUSIONS The first-visit misdiagnosis rate of testicular torsion is much lower and the probability of testicle preservation is significantly higher in large general hospitals than in the local hospitals, suggesting the importance of health education for testicular torsion, enhancing the awareness of this condition and training of the surgeons in primary hospitals.
Diagnostic Errors ; Humans ; Incidence ; Male ; Retrospective Studies ; Spermatic Cord Torsion ; Testis

Objective: To optimize the construction of combined hypoxia NASH rat model on the basis of preliminary work, and to explore the role of neovascularization in the process of hepatic fibrosis. Methods: 32 rats were divided randomly to four groups that were null control group(A group ), hypoxia group(B group), high fat diet group(C group ) and high fat diet plus hypoxia group (D group ),treated with null , Intraperitoneal injection of NaNO₂, high fat diet and high fat diet plus Intraperitoneal injection of NaNO₂ respectively. Every group was observed for 16 weeks, B and D group was treated with Intraperitoneal injection of NaNO₂ 20 mg/kg.d at the laster 8 weeks. Liver histology NASH activity score(NAS) and Fibro score(FibroS), biochemical index were detected in this combined hypoxia NASH rat model(D group), meanwhile the changes of HIF1α, inflammatory factor and neovascularization were measured by ELISA, realtime PCR and immunohistochemistry. Results: Liver tissue NAS > 4 was seen in C and D group. D group showed NASH characteristics, including significantly steatosis at liver acinar 3 area(mostly a microvesicular type fat droplets mixed with macrovesicular type), hepatocyte balloon degeneration, obvious lobular inflammation, while fibrosis score increased significantly, including visible hepatic sinusoid fibrosis, fibrosis around portal vein, and bridging fibrosis in a considerable portion of the rats. Compared with C group, biochemical indicators of aspartate aminotransferase (AST), HIF1α, neovascularization-related VEGFA, VEGFR2 mRNA level increased obviously and the expression of immunohistochemistry VEGFR2, CD34 enhanced markedly in D group(p < 0.05). Conclusion A combined hypoxia NASH rat model can be established throught feeding 16 weeks’ high-fat diet then intraperitoneal injection of NaNO₂ 20 mg / kg.d at the laster 8 weeks, meanwhile chronic hypoxia can accelerate this combined hypoxia NASH model liver fibrosis process. In this process neovascularization promoted the formation of hepatic fibrosis in this model.

Objective To observe the relationship between Toll-like receptor 4 (TLR4) and the sensitivity of PANC1 cells to gemcitabine (GEM),and to analyze the potential mechanism.Methods PANC1 cells were divided into GEM group,lipopolysaccharide (LPS) + GEM group and TLR4-siRNA + GEM group.GEM group was treated by GEM alone.LPS + GEM group was pretreated with 1 mg/L LPS for 4 h and then treated by GEM.TLR4-siRNA + GEM group was transfected with 100 pmol/mL TLR4-siRNA for 4 h and then treated by GEM.The untreated cells were used as the control group.MTT method was used to detect the cell proliferation.Morphological changes and apoptosis rate of the cells were examined by Hoechst33258 staining and flow cytometry,respectively.The protein expression of TLR4,phosphorylated AKT (p-AKT) and activated Caspase-3 were detected by Western blot.Results The median inhibition concentration (ICs0) of GEM in the GEM group,LPS + GEM group and TLR4-siRNA + GEM group was (8.9 ± 0.32),(14.21 ±0.95),(3.96 ± 0.27) mg/L,respectively.The IC50 in LPS + GEM group was significantly higher than that in GEM group (P ＜ 0.01),and the IC50 of GEM in TLR4-siRNA + GEM group was significantly lower than that in GEM group (P ＜0.01).Compared with that in GEM group,the cells with typical apoptotic morphological changes were decreased in LPS + GEM group,which was increased in TLR4-siRNA + GEM group.The apoptotic rate in control group,GEM group,LPS + GEM group,TLR4-siRNA + GEM group was (2.1 ± 0.3) ％,(15.1 ± 2.3) ％,(9.8 ± 1.5) ％,(22.9 ± 3.1) ％,respectively.Compared with that in GEM group,the cells apoptotic rate was significantly reduced in LPS + GEM group (P ＜0.01),which was significantly increased in TLR4-siRNA + GEM group (P ＜0.01).TLR4 protein level in the 4 groups was 0.83 ±0.08,0.81 ±0.07,0.85 ±0.07 and 0.16 ±0.03;p-AKT protein level 0.61 ±0.05,0.36 ±0.03,0.73 ± 0.07 and 0.21 ± 0.02;activated Caspase-3 protein level was 0.66 ± 0.05,0.73 ± 0.07,0.45 ± 0.04 and 0.91 ± 0.07,respectively.The expression of TLR4 and p-AKT in TLR4-siRNA + GEM group was significantly lower than that in GEM group (P ＜0.01),while the expression of activated Caspase-3 protein was increased significantly (P ＜ 0.05).Compared with the GEM group,the expression of p-AKT protein in LPS + GEM group was significantly increased (P＜0.01),and the expression of activated Caspase-3 protein was significantly decreased (P＜0.01).Conclusions TLR4 can inhibit the sensitivity of pancreatic cancer PNAC1 cells to GEM,and the mechanism is related to the activation of PI3K/AKT pathway and downregulation of activated Caspase-3.