In recent years,the incidence and mortality of malignant tumors have been increasing year by year,becoming a se-rious challenge to global public health.Unlike traditional treatment methods,tumor immunotherapy activates the body's own immune system to against tumors,and has significant advantage such as minimal side effects,long-lasting efficacy,and strong targeting.Howev-er,immunotherapy also has issues such as frequent adverse reactions and high treatment costs.In order to enhance the efficacy of im-munotherapy,some phytochemicals are used in the field of immunotherapy as modulators.These phytochemicals not only increase the sensitivity of tumor cells to immune cells,but also reduce the expression of immune checkpoint proteins.Therefore,this article provides a review of phytochemicals that play an important role in tumor immunotherapy and their related mechanisms of action.

Objective:To investigate the dose characteristics of the Zeiss INTRABEAM system in air and water, providing dose reference for electronic brachytherapy.Methods:A Monte Carlo program was used to establish a three-dimensional model of a miniature X-ray source vacuum drift tube and a 4 cm spherical applicator. The process of electron beam bombardment on a gold target to generate X-rays was simulated, and parameters such as photon fluence spectrum, percentage depth dose, and half-value layer were calculated. Additionally, the radial dose uniformity in water was measured.Results:The average energy of X-rays at 3 cm in air was 20.8 keV, with a half-value layer of 0.08 mm Al. Under the influence of the applicator, the spectrum becomes hardened, with axial and radial average energies of 28.7 and 29.0 keV, respectively. In water, the percentage depth dose (PDD) curve follows an inverse cubic decay with depth, indicating strong dose concentration and rapid fall-off in near-field irradiation. The radial dose uniformity in water exceeded 99.5%.Conclusions:The INTRABEAM device emits low-energy X-rays characterized by shallow penetration depth, and concentrated dose delivery. Its highly uniform dose distribution ensures comprehensive coverage of the target area, making it particularly suitable for treating superficial tumors and for intraoperative radiotherapy at close range.

In recent years,the incidence and mortality of malignant tumors have been increasing year by year,becoming a se-rious challenge to global public health.Unlike traditional treatment methods,tumor immunotherapy activates the body's own immune system to against tumors,and has significant advantage such as minimal side effects,long-lasting efficacy,and strong targeting.Howev-er,immunotherapy also has issues such as frequent adverse reactions and high treatment costs.In order to enhance the efficacy of im-munotherapy,some phytochemicals are used in the field of immunotherapy as modulators.These phytochemicals not only increase the sensitivity of tumor cells to immune cells,but also reduce the expression of immune checkpoint proteins.Therefore,this article provides a review of phytochemicals that play an important role in tumor immunotherapy and their related mechanisms of action.

Objective:To investigate the dose characteristics of the Zeiss INTRABEAM system in air and water, providing dose reference for electronic brachytherapy.Methods:A Monte Carlo program was used to establish a three-dimensional model of a miniature X-ray source vacuum drift tube and a 4 cm spherical applicator. The process of electron beam bombardment on a gold target to generate X-rays was simulated, and parameters such as photon fluence spectrum, percentage depth dose, and half-value layer were calculated. Additionally, the radial dose uniformity in water was measured.Results:The average energy of X-rays at 3 cm in air was 20.8 keV, with a half-value layer of 0.08 mm Al. Under the influence of the applicator, the spectrum becomes hardened, with axial and radial average energies of 28.7 and 29.0 keV, respectively. In water, the percentage depth dose (PDD) curve follows an inverse cubic decay with depth, indicating strong dose concentration and rapid fall-off in near-field irradiation. The radial dose uniformity in water exceeded 99.5%.Conclusions:The INTRABEAM device emits low-energy X-rays characterized by shallow penetration depth, and concentrated dose delivery. Its highly uniform dose distribution ensures comprehensive coverage of the target area, making it particularly suitable for treating superficial tumors and for intraoperative radiotherapy at close range.

OBJECTIVE To study the inhibitory effect mechanism of rhynchophylline solid lipid nanoparticles （Rhy-SLN） on the proliferation of airway smooth muscle cells （ASMCs） in asthmatic model mice. METHODS Asthma model was prepared by ovalbumin+calmogastrin sensitization. The primary isolation and culture of ASMCs were performed， and morphological observation and identification were also conducted [when α -smooth muscle actin （α -SMA） appeared red and Desmin appeared green in ASMCs， indicating successful cultivation of ASMCs]. The cells were divided into blank group （ASMCs of normal mice）， model group （ASMCs of asthma model mice）， Rhy-SLN group （ASMCs of asthma model mice）， recombinant suppressors of cytokine signaling 1 （SOCS1） overexpression group （ASMCs of asthma model mice transfected with SOCS1 vector）， SOCS1-RNAi group （ASMCs of asthma model mice transfected with SOCS1-RNAi vector） and SB203580 group [p38 mitogen-activated protein kinase （p38 MAPK） inhibitor， ASMCs of asthma model mice]. The cells of each group were added into the corresponding culture medium containing drug （10 μmol/L） or not containing drug for 24 hours. MTT method was used to detect the proliferation of ASMCs in asthmatic mice； Western blot assay was used to detect the protein expressions of α-SMA， interleukin-1β （IL-1β）， SOCS1， p38 MAPK and phosphorylated p38 MAPK （p-p38 MAPK） in ASMCs. RESULTS The primary ASMCs of mice varied in shape and size， presenting irregular， spindle and triangular shapes；α-SMA appeared red and Desmin appeared green， indicating successful cultivation of ASMCs. Compared with model group， ASMCs absorbance values and protein expressions of α -SMA， p38 MAPK， and p-p38 MAPK were reduced significantly in Rhy- SLN group， SOCS1 overexpression group and SB203580 E-mail：wangmeng106@163.com group， while protein expression of SOCS1 （except for group） was increased significantly （P＜0.05）； protein expressions of IL-1β was reduced significantly in ASMCs （P＜ 0.05）. ASMCs absorbance values and protein expressions of α-SMA， SOCS1， p38 MAPK and p-p38 MAPK were increased significantly in SOCS1-RNAi group （P＜0.05）. CONCLUSIONS Rhy-SLN can inhibit the proliferation of ASMCs， the mechanism of which may be associated with overexpression of SOCS1 and inhibiting the protein expressions of IL-1β and p38 MAPK.

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6^-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

Objective:To propose automatic measurement of global and local tessellation density on color fundus images based on a deep convolutional neural network (DCNN) method.Methods:An applied study. An artificial intelligence (AI) database was constructed, which contained 1 005 color fundus images captured from 1 024 eyes of 514 myopic patients in the Northern Hospital of Qingdao Eye Hospital from May to July, 2021. The images were preprocessed by using RGB color channel re-calibration method (CCR algorithm), CLAHE algorithm based on Lab color space, Retinex algorithm for multiple iterative illumination estimation, and multi-scale Retinex algorithm. The effects on the segmentation of tessellation by adopting the abovemetioned image enhancement methods and utilizing the Dice, Edge Overlap Rate and clDice loss were compared and observed. The tessellation segmentation model for extracting the tessellated region in the full fundus image as well as the tissue detection model for locating the optic disc and macular fovea were built up. Then, the fundus tessellation density (FTD), macular tessellation density (MTD) and peripapillary tessellation density (PTD) were calculated automatically.Results:When applying CCR algorithm for image preprocessing and the training losses combination strategy, the Dice coefficient, accuracy, sensitivity, specificity and Jordan index for fundus tessellation segmentation were 0.723 4, 94.25%, 74.03%, 96.00% and 70.03%, respectively. Compared with the manual annotations, the mean absolute errors and root mean square errors of FTD, MTD, PTD automatically measured by the model were 0.014 3, 0.020 7, 0.026 7 and 0.017 8, 0.032 3, 0.036 5, respectively.Conclusion:The DCNN-based segmentation and detection method can automatically measure the tessellation density in the global and local regions of the fundus of myopia patients, which can more accurately assist clinical monitoring and evaluation of the impact of fundus tessellation changes on the development of myopia.

OBJECTIVE：To establish the metho d for the content determination of 8 nucleosides in wild and cultivated Pinellia ternate，and to conduct the difference analysis. METHODS ：The contents of uracil ，uridine，inosine，xanthine，adenine， guanosine，β-thymidine and adenosine in 20 batches of P. ternate （wild product YS 1-YS8，cultivated product ZP 1-ZP12）were determined by HPLC method. Based on the contents of the above 8 nucleosides，cluster analysis ，principal component analysis （PCA），partial least squares analysis （OPLS-DA）were used to comprehensively evaluate the wild and cultivated P. ternata . RESULTS：The contents of uracil ，uridine，inosine，xanthine，adenine，guanosine，β-thymidine and adenosine in 20 batches of P. ternate were 0.02-0.24，0.01-0.24，0.06-0.37，0.02-0.14，0.04-0.22，0.14-0.42，0.01-0.09，0-0.32 mg/g，respectively. Cluster analysis，PCA and OPLS-DA showed that 8 batches of wild P. ternate （YS1-YS8）were clustered into one category ，and 12 batches of cultivated P. ternate （ZP1-ZP12）were clustered into one category. Main characteristic markers of wild P. ternate were guanosine，uridine，adenosine and adenine ，while the main characteristic markers of cultivated P. ternate were urinine ，xanthine， inosine，and β-thymidine. CONCLUSIONS：The method for the content determination of 8 nucleosides in P. ternate is established. Nucleosides as quality markers can effectively distinguish wild and cultivated P. ternata ，and the quality of the wild P. ternate was better than that of cultivated P. ternate .

Primary ureteral plasmacytoid carcinomas is a rare tumor with high grade and poor diagnosis. Pathological and immunohistochemical staining play an extremely key role in diagnosis since there is no specific clinical and radiological evidence. The surgical removement is the first line treatment. Herein, we report a case of ureteral plasmacytoid carcinoma that was well controlled with multimodal therapy.

Objective: To evaluate the risk factors of postoperative upgrade to pT₃a of cT₁ renal cell carcinoma, and to establish a nomogram prediction model to improve the ability of predicting locally advanced renal cell carcinoma and provide a reference for clinical surgical decision-making. Methods: Clinical data of 1 376 patients with cT₁ (diameter ≤ 7 cm) renal tumor hospitalized for surgery from January 2010 to December 2016 were retrospectively analyzed. There were 979 males and 397 females, with the mean age of (57.65±10.92) years. The mean body mass index (BMI) was (25.47±3.27) kg/m² and the average tumor size was (4.02±1.52) cm. There were 711 tumors on the left and 665 on the right. There were 363 cases with clinical symptoms, 567 patients with smoking history , 732 cases with history of chronic disease. There were 289 cases with tumor necrosis, 636 cases with tumor protrusion, 822 cases with irregular tumor , and 738 cases with renal sinus compression. Partial nephrectomy and radical nephrectomy were performed in 396 cases and 980 cases respectively. Mann-whitney U test and chi-square test were used for univariate analysis, logistic regression analysis was used for multivariate analysis to analyze the predictors of upgrading, R software was used to construct the nomogram predictive model, C-index was used to evaluate the model discrimination, and calibration curve method was used to evaluate the consistency of the model. Results: Postoperative pathology of total 1 376 cases showed that there were 1 195 cases of clear cell carcinoma of kidney, 48 cases of papillary cell carcinoma, 57 cases of chromophobe cell carcinoma, and 76 cases of other types. Among the 1 376 patients with cT₁ renal tumor, 75 patients were upgraded to pT_3a, accounting for 5.5% of all patients. Univariate analysis showed that the patients who upgraded to pT_3a were older [(63.08±10.17) years old and (57.34±10.88) years old], and the tumor length and diameter were larger [(5.24±1.35) cm and (3.95±1.51) cm]. Patients with clinical symptoms [46.7% (35/75) vs. 25.2%(328/1 301)], patients with CT indication of tumor necrosis [40.0%(30/25 975) vs. 19.9% (259/1 301)], patients with irregular tumor contour [73.3%(55/76 775) vs. 59.0%(767/1 301)], and patients with radical nephrectomy were higher [(92.1% (70/91 075) vs. 70%(910/1 301)]. All the differences were statistically significant (P<0.01). Multivariate analysis showed that the independent predictors of upgrading were age (OR=1.046, P<0.001), larger tumor (OR=1.504, P<0.001), clinically symptom (OR=2.153, P=0.004), irregular tumor profile (OR=2.466, P=0.002), and tumor necrosis on CT (OR=2.588, P<0.001). The C-index was 0.808, the calibration curve of forecasting curve with the standard curve fit was good, and the prediction of renal cancer are better in predict consistency. Conclusions Based on the five preoperative predictors, including age, tumor size, clinical presence or absence of symptoms, tumor profile, and whether or not the tumor necrosis indicated by CT, this study developed a nomogram of cT₁ renal cancer upgrade to pT_3a. This nomogram has a good statistical significance, and this model can provide prognosis consultation for patients and provide reference for doctors to make decisions before treatment.