Objective:To develop and validate a nomogram model for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) based on preoperative enhanced computed tomography imaging features and clinical data.Methods:The clinical data of 210 patients with HCC undergoing surgery in the Second Affiliated Hospital of Anhui Medical University from May 2018 to May 2022 were retrospectively analyzed, including 172 males and 38 females, aged (59±10) years old. Patients were randomly divided into the training group ( n=147) and validation group ( n=63) by systematic sampling at a ratio of 7∶3. Preoperative enhanced computed tomography imaging features and clinical data of the patients were collected. Logistic regression was conducted to analyze the risk factors for HCC with MVI, and a nomogram model containing the risk factors was established and validated. The diagnostic efficacy of predicting MVI status in patients with HCC was assessed by receiver operating characteristic (ROC) curve, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) of the subjects in the training and validation groups. Results:The results of multifactorial analysis showed that alpha fetoprotein ≥400 μg/ml, intra-tumor necrosis, tumor length diameter ≥3 cm, unclear tumor border, and subfoci around the tumor were independent risk factors predicting MVI in HCC. A nomogram model was established based on the above factors, in which the area under the curve (AUC) of ROC were 0.866 (95% CI: 0.807-0.924) and 0.834 (95% CI: 0.729-0.939) in the training and validation groups, respectively. The DCA results showed that the predictive model thresholds when the net return is >0 ranging from 7% to 93% and 12% to 87% in the training and validation groups, respectively. The CIC results showed that the group of patients with predictive MVI by the nomogram model are highly matched with the group of patients with confirmed MVI. Conclusion:The nomogram model based on the imaging features and clinical data could predict the MVI in HCC patients prior to surgery.

Tumors in which the microenvironment is characterized by lack of immune cell infiltration are referred as "cold tumors" and typically exhibit low responsiveness to immune therapy. Targeting the factors contributing to "cold tumors" formation and converting them into "hot tumors" is a novel strategy for improving the efficacy of immunotherapy. Adenosine, a hydrolysis product of ATP, accumulates with a significantly higher concentration in the tumor microenvironments compared with normal tissue and exerts inhibitory effects on tumor-specific adaptive immunity. Tumor cells, dendritic cells, macrophages, and T cells express abundant adenosine receptors on their surfaces. The binding of adenosine to these receptors initiates downstream signaling pathways that suppress tumor antigen presentation and immune cell activation, consequently dampening adaptive immune responses against tumors. Adenosine down-regulates the expression of major histocompatibility complex Ⅱ and co-stimulatory factors on dendritic cells and macrophages, thereby inhibiting antigen presentation to T cells. Adenosine also inhibits ligand-receptor binding and transmembrane signaling on T cells, concomitantly suppressing the secretion of anti-tumor cytokines and impairing T cell activation. Furthermore, adenosine hinders effector T cell trafficking to tumor sites and infiltration by inhibiting chemokine secretion and KCa3.1 channels. Additionally, adenosine promotes the secretion of immunosuppressive cytokines, increases immune checkpoint protein expression, and enhances the activity of immunosuppressive cells, collectively curbing cytotoxic T cell-mediated tumor cell killing. Given the immunosuppressive role of adenosine in adaptive antitumor immunity, several inhibitors targeting adenosine generation or adenosine receptor blockade are currently in preclinical or clinical development with the aim of enhancing the effectiveness of immunotherapies. This review provides an overview of the inhibitory effects of adenosine on adaptive antitumor immunity, elucidate the molecular mechanisms involved, and summarizes the latest advances in application of adenosine inhibition strategies for antitumor immunotherapy.
Humans ; Adenosine/pharmacology* ; T-Lymphocytes ; Adaptive Immunity ; Cytokines ; Neoplasms/therapy* ; Tumor Microenvironment

Objective:To evaluate the dosimetric characteristics of Zap-X system and CyberKnife (CK) G4 system of stereotactic radiosurgery (SRS) for single brain metastasis.Methods:Twelve patients with single brain metastasis had been treated with CK were selected retrospectively. The prescribed dose of planning target volume (PTV) was 18-24 Gy for 1-3 fractions. The PTV was ranged from 0.44 to 11.52 cm 3. The 12 patients were re-planned in the Zap-X planning system using the same prescription dose and organs at risk constraints, and the prescription dose of PTV was normalized to 70% for both Zap-X and CK. The planning parameters and dosimetric parameters of PTV and organs at risk were compared and evaluated between two plans. All data were read at MIM Maestro. A paired Wilcoxon' signed-rank test was adopted for statistical analysis. A P value of less than 0.05 was considered as statistical significance. Results:For the target coverage, CK was significantly higher than Zap-X (99.14±0.57% vs. 97.55±1.34%, P<0.01), but Zap-X showed a higher conformity index (0.81±0.05 vs. 0.77±0.07, P<0.05), a lower Paddick gradient index (2.98±0.24 vs. 3.15±0.38), and a higher gradient score index (GSI) than CK. The total monitor unit (MU) of Zap-X was significantly lower than that of CK (11 627.63 ±5 039.53 vs. 23 522.16 ±4 542.12, P<0.01) and the treatment time was shorter than that of CK [(25.08 ±6.52) vs. (38.08 ±4.74) min, P<0.01]. Zap-X had lower dose volumes than CK for the dose of brain ( P<0.05). Zap-X had a lower D mean and D max of brainstem (both P<0.05), but a higher value of eyes and lens. For optic nerves and optic chiasm, there were no significant differences between two groups. In addition, for the protection of skin (V 22.5 Gy), Zap-X seemed better than CK [(4.15±4.48) vs. (4.37±4.50) cm 3, P<0.05]. Conclusions:For SRS treating single brain metastasis, Zap-X could provide a high quality plan equivalent to or even better than CK, especially reducing the treatment time. With continuous improvement and upgrading of Zap-X system, it may become a new SRS platform for the treatment of brain metastasis.

Objective:To compare the dosimetric characteristics of beams between Zap-X and G4 CyberKnife and provide reference for clinical application of Zap-X.Methods:PTW three-dimensional water tank and dosimetry diode ionization chamber were used to measure the two orthogonal off-axis ratio and field size at isocenter of 7 different collimators (5 mm, 7.5 mm, 10 mm, 12.5 mm, 15 mm, 20 mm and 25 mm) of Zap-X and CyberKnife at the water depth of maximum dose, 50 mm, 100 mm, and 200 mm. The penumbra, flatness, symmetry and field size under each parameter condition were analyzed by using PTW supporting software PTW MEPHYSTO (version 5.1). Data analysis and graph were performed using Origin 2021 software.Results:With the same collimator, the dose plateau area of Zap-X was wider than that of G4 CyberKnife, and the dose fall-off at the field edge of Zap-X system was faster. With the increase of the collimator, the penumbra of Zap-X and CyberKnife tended to become larger, and the flatness tended to become smaller, the penumbra and flatness of Zap-X were significantly smaller than those of CyberKnife. Both of them had excellent symmetry (<1%), and the symmetry results of CyberKnife (<0.39%) were better than that of Zap-X (0.99%). The accuracy of Zap-X collimator size at isocenter was better than that of CyberKnife.Conclusion:Compared with G4 CyberKnife, Zap-X system has smaller penumbra, better flatness and higher accuracy of collimator size, which is suitable for stereotactic radiosurgery.

Objective To study the therapeutic effect of anti-CD80 bivalent antibody on mouse lu-pus nephritis and to explore the possible molecular mechanism. Methods A mouse model of lupus nephritis was established through intraperitoneal injection of 0. 5 ml of pristine in female C57BL/6J mice. Appearance of urinary protein and significantly increased levels of peripheral antinuclear antibody ( ANA) and anti-doub-le-stranded DNA ( anti-dsDNA) antibody in the fourth month after injection indicated that the mouse model was established successfully. Then the mice were divided into two groups including anti-CD80 bivalent anti-body intervention group (injected with 200μg of anti-CD80 bivalent antibody at day 1, 3, 5, 8 and 15, fol-lowed by three times of injection with an interval of one month) and model group ( injected with the same protein using the same strategy). A normal control group was set up accordingly. Albustix test paper was used to monitor the dynamic changes in mouse urinary protein. Flow cytometry was used to analyze the acti-vation of immune-related cells in spleen. Levels of autoantibodies ( ANA and anti-dsDNA) and levels of IFN-γ and IL-4 in serum were detected by indirect immunofluorescence assay. Renal tissue samples were an-alyzed with hematoxylin and eosin ( HE) staining and immunocomplex ( IC) assay. Results Urinary pro-tein level of the anti-CD80 bivalent antibody intervention group was significantly lower than that of the model group (P<0. 05). Activated macrophages, dendritic cells, neutrophils and B cells in spleen tissues of the anti-CD80 bivalent antibody intervention group were significantly less than those of the model group ( P<0. 05), and the numbers of CD4+ and CD154+ T cells were significantly less than those of the model group (P<0. 05). Positive rates and titers of ANA and dsDNA in serum samples of the intervention group were lower than those of the model group (P<0. 05). Levels of IFN-γand IL-4 in serum samples of the interven-tion group were decreased as compared with those of the model group (P<0. 05). HE staining and immuno-fluorescence assay showed that glomerular inflammatory injury and necrosis were alleviated and kidney im-mune complex deposition was reduced after anti-CD80 bivalent antibody intervention. Conclusion Anti-CD80 bivalent antibody specifically binds to the CD80 molecule on antigen presenting cell surface, blocks the CD80/CD28 co-stimulatory signaling pathway and down-regulates the body′s immune response, which al-leviates and reverses the lupus-like nephritis-induced pathological damages in mice.

Objective To discuss and evaluate the dosimetric characteristics of different plans implementing stereotactic radiotherapy(SRT)for intracranial tumors using Fixed and Iris collimators of CyberKnife VSI.Methods Twenty patients with intracranial tumors were selected and divided into group A with a small target volume(≤30 cm3)and group B with a large target volume(≥30 cm3). There were 10 patients in each group,and the prescribed dose to the target was 21 Gy in 3 fractions. For each patient, two treatment plans were designed using Fixed and Iris collimators. By analyzing the dosimetric parameters such as conformity index(CI),homogeneity index(HI), gradient index(GI), gradient score index(GSI), and organs at risk (OAR),the quality and efficiency of the plans were evaluated in order to discuss the beam characteristics for two sets of collimators. The difference was analyzed with the paired t-test. Results The mean time of Iris plan for delivering was significantly less than that of Fixed plan(group A:P=0.001;group B:P=0.000). In group B,the peripheral dose(20% and 10% of the prescribed dose)volumes of Fixed plan were significantly less than those of Iris plan(P=0.001 and 0.009). For OAR,D minof the visual pathway and D meanor D minof the eyeball in group B were significantly different between Fixed and Iris plans(all P<0.05), while in group A, only D minof the optic chiasm was significantly different between the two plans(P=0.043). For the other parameters of targets,there were no significant differences between Fixed and Iris plans in both groups(all P>0.05). Conclusions Apart from less treatment time in the Iris plan, there are no significant dosimetric differences between the two collimator plans of CyberKnife VSI in treating small intracranial tumor. For the large and complex tumor,although Iris plan meets the requirement for OAR dose constraints,its low-dose volumes are larger than those of Fixed plan. Further studies of the dosimetric characteristics in CyberKnife should be done.

Objective To synthesize 2-(5-[18 F] fluoro-pentyl)-2-methyl-malonic acid (18 F-ML-10) and to investigate the biodistribution in mice and the primary clinical application.Methods 18F-ML-10 was synthesized by domestic synthesis module MF-2V-IT-1.Quality control of the probe was performed after automated synthesis.The biological characteristics of 18F-ML-10 were assessed by biodistribution assay on male Kunming mice and microPET imaging on a male SD rat.Six patients with brain metastasis (4males,2 females,and age 21-68 years) were enrolled in this study.18F-ML-10 PET images were acquired before and at 48 h after radiotherapy.SUVmean and SUVmax of ROI were calculated.GTV changes were measured by MRI before and 3 months after radiotherapy.Response of brain metastasis to radiotherapy was assessed by PET imaging with 18F-ML-10.Two-sample t test was used.Results The non-corrected radiochemical yield of 18F-ML-10 was (26.5±7.3)％ with acceptable quality.The radiochemical purity exceeded 99％.18F-ML-10 was excreted through the kidneys,and the radiouptake in the blood was declined rapidly.The radiotracer accumulation was low in most of other organs.The testis showed a significant uptake.The SUVmean and SUVmax after radiotherapy (5.54±2.72 and 7.29±3.09) were significantly higher than the baseline values(3.81±1.13 and 4.97±1.05;t=2.670,2.663,both P＜0.05).The GTV after radiotherapy was significantly lower than the baseline value:(13.14±9.39) cm3 vs (23.34± 18.13) cm3;t =3.002,P＜0.05.Conclusions 18F-ML-10 could be synthesized reliably and repeatedly by domestic synthesis module.It has satisfactory properties in vivo and is probably suitable for early assessment of the response to radiotherapy in patients with brain metastasis.

OBJECTIVETo explore the mechanism and strategies of prevention and treatment of vision deterioration after transsphenoidal surgery for removal of pituitary adenoma.

METHODSFrom January 1980 to February 2001, 1 412 patients were operated on by transsphenoidal surgery to remove pituitary adenoma. Fourteen patients experienced vision deterioration after operation. Clinical data from the 14 patients with vision deterioration were analyzed retrospectively.

RESULTSIn this group, the incidence of vision deterioration was 0.99%. Over packing of the adenoma bed was seen in 5 patients, apoplexy of residual tumor in 3, high intracranial pressure in 2, vascular spasm in 2, injury of the optic nerve in the cannel in 1 and unknown reason in 1.

CONCLUSIONSVision deterioration is a severe complication after transsphenoidal surgery. Early diagnosis and treatment can greatly improve the vision.

Adenoma ; surgery ; Adult ; Aged ; Female ; Humans ; Ischemia ; complications ; Male ; Middle Aged ; Optic Nerve ; blood supply ; Optic Nerve Injuries ; etiology ; prevention & control ; Pituitary Neoplasms ; surgery ; Postoperative Complications ; etiology ; prevention & control ; Retrospective Studies ; Sphenoid Sinus ; Vision Disorders ; etiology ; prevention & control

s Objective To observe the changes in the expression of ?-amyloid precursor protein (?-APP) in selected brain areas in early stage of diffuse axonal injury (DAI) in rats. Methods DAI was induced in SD rats by a self-made rotating injury device. 16 rats in injury group were sacrificed by decapitation at 3 hours and 6 hours post-trauma, while the other 8 rats in sham injury group were put to death after 24 hours. The samples of the rat brain were stained with ?-APP for immunohistochemistry in order to detect the early stage pathological changes in subcortex white matter, hippocampus, corpus callosum and brain stem at different time points. Results The ?-APP expression was positive at 3 hours and was particularly strong at 6 hours after injury. The results of semi-quantitative analysis showed a significant differentiation of 3 hours and 6 hours in the immuno-positive expression of brain stem, corpus callosum and hippocampus. Histological results demonstrated that DAI occurred in all rats of injury group. Conclusion ?-APP is a kind of sensitive and useful immunochemical marker for early DAI diagnosis, and it indicates axonal lesion or breakage.

Objective To determine whether cyclosporin A(CsA) could exert neuroprotective effects after diffuse axonal injury (DAI) in the rat. Methods Twenty four SD rats were randomly assigned into three groups: non injur group ( n =8); control brain injury group ( n =8), in which normal saline was given; and experimental group ( n =8), the injured rats were treated with CsA. The beam balance test device and Morris water maze were used to test for balance and cognitive performance. Results Control brain injury animals displayed severe defects in balance and cognitive performande after diffuse axonal injury. Compared with control brain injury animals, rats treated with CsA displayed better motor performance in beam balance tests and improved learning ability in the Morris water maze. Conclusions It is demonstrated that CsA exhibits substantial neuroprotective activity in a rat model of DAI. These findings support that CsA is a useful therapeutic agent in the treatment of DAI.