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 explore the clinical efficacy and safety of daratumumab-based combined regimens for relapsed/refractory multiple myeloma (RRMM).Methods:A retrospective case series study was conducted. The clinical data of 38 patients with RRMM in Jining NO.1 People's Hospital from Janunary 2020 to December 2022 were retrospectively analyzed. All patients were treated with daratumumab-based combined regimens. The Dd regimen (12 cases) was treated with daratumumab and dexamethasone, the DPD regimen (20 cases) was treated with pomalodomide based on the Dd regimen, the DVD regimen (6 cases) was treated with bortezomib based on the Dd regimen. The therapeutic efficacy and adverse reactions of all groups were analyzed. Kaplan-Meier method was used for survival analysis.Results:The median follow-up time was 9.5 months (1.0 months, 32.5 months) and the median treatmemt time was 6.2 months (3.2 months, 25.6 months). Among 38 patients, 7 cases (18.7%) achieved complete remission, 9 cases (23.6%) achieved very good partial remission, 10 cases (26.3%) achieved partial remission, 4 cases (10.5%) achieved minimal remission, 5 cases (13.1%) achieved stable disease, 3 cases (7.9%) had the progression of the disease. The overall response rate (ORR) was 78.9% (30/38). The ORR was 66.7%(8/12), 83.3%(5/6), 85.0%(17/20), respectively in the Dd group, DVD group and DPD group. There was no statistically significant difference in the ORR between the DVD group and DPD group ( χ2 = 0.01, P>0.05); there was no statistically significant difference in the ORR between the DVD group and Dd group ( χ2 = 0.55, P>0.05); there was no statistically significant difference in the ORR between the DPD group and Dd group ( χ2 = 1.47, P>0.05). The median progression-free survival (PFS) time was 12.5 months (95% CI: 8.5-24.2 months),the median overall survival (OS) time was not reached, and the 1-year OS rate was 89.4%. Among 38 patients, the main adverse reactions during treatment were infusion-related adverse reactions in 5 cases, grade 3 neutropenia in 7 cases, grade 3 thrombocytopenia in 9 cases, severe anemia in 12 cases; no one had drug discontinuation or drug reduction due to the intolerance of adverse reactions. Conclusions:Daratumumab-based combined regimens in the treatment of RRMM show a favorable efficacy and safety.

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 explore the clinical effect and safety of venetoclax combined with azacitidine for high-risk myelodysplastic syndromes (MDS).Methods:A retrospective case series study was conducted. The clinical data of 48 patients with high-risk MDS in Jining No.1 People's Hospital from January 2020 to May 2023 were collected, and all patients were divided into the control group (20 cases) and the test group (28 cases) according to medications. The control group was treated with azacitidine alone, and the test group was treated with venetoclax combined with azacitidine regimen. The total effective rate and adverse reactions of the 2 groups were compared after 3 courses of treatment.Results:Among 48 patients, 30 cases were male and 18 cases were females; the median onset age [ M ( Q1, Q3)] was 62 years (54 years, 75 years). There were no statistically significant differences in gender, age, white blood cell count, neutrophil count, hemoglobin, platelet count, bone marrow original cells proportion between the 2 groups (all P>0.05). After 3 courses of treatment, the total effective rate in the test group was 75% (22/28), and the rate in the control group was 45% (9/20), and there was a statistically significant difference between the two groups ( χ2 = 5.74, P<0.05). The incidence of grade 3 and the above adverse reactions in the control group and the test group was 25% (5/20), 54% (15/28), respectively, and the difference was statistically significant ( χ2 = 1.62, P>0.05). Conclusions:Venetoclax combined with azacitidine regimen for high-risk MDS can improve the clinical efficacy, and the adverse reactions can be tolerated.

Objective To investigate the advantages and efficacy of traction with titanium clips in endoscopic submucosal dissection(ESD)for large laterally spreading tumor(LST)in rectum and sigmoid colon.Methods 67 patients with large sigmoid or rectal LST underwent ESD from January 2018 to June 2022 were analyzed retrospectively,including 32 patients in Group A and 35 patients in Group B.Group A was treated with clip-line traction and group B was treated with traditional ESD.The size of lesion,the total operation time,the submucosal dissection time,submucosal dissection rate,submucosal injection number,en bloc resection rate,R0 resection rate,curative resection rate and complications of the two groups were compared.Results LST-G-M was the most common type and villous adenoma was the main pathology in both groups.There were no differences in en bloc resection rate,R0 resection rate and incidence of complications between the two groups.The average size of group A was(13.6±8.4)cm2,significantly larger than that in group B(9.3±4.7)cm2,the total operation time was(42.3±10.3)min in group A,significantly shorter than that in group B(47.9±10.1)min,submucosal dissection time was(30.7±8.2)min in group A,significantly shorter than that in group B(36.1±7.6)min,submucosal injection number was(2.7±1.1)times in group A,significantly less than that in group B(3.5±1.2)times,submucosal dissection rate was(0.4±0.2)cm2/min in group A,significantly faster than that in group B(0.2±0.1)cm2/min,the differences were statistically significant(P<0.05).Conclusion Compared with traditional ESD,clip-line traction can provide a better surgical field and more effective dissection for large LST in rectum and sigmoid colon.

Objective To assess the myocardial blood flow and reserve function by rest and stress 13 N-NH3 PET myocardial perfusion imaging ( MPI) , and evaluate the diagnostic value of PET and risk fac-tors of non-obstructive coronary microvascular disease ( CMVD) type 1. Methods A total of 56 patients (28 males, 28 females;age:(52.0±7.6) years) with clinical suspected CMVD type 1 from April 2017 to December 2018 were prospectively enrolled. The coronary CT angiography, coronary angiography and other clinical data were recorded. All patients underwent one-day rest and stress 13 N-NH3 PET MPI. Images were analyzed and the absolute myocardial blood flow ( MBF) and coronary flow reserve ( CFR) were obtained. Patients were divided into CMVD type 1 ( CMVD) group and non-CMVD group. The differences between 2 groups were analyzed by two-sample t test and logistic regression. Results Among 56 patients, 20 patients were diagnosed as CMVD type 1, and 36 patients were excluded as non-CMVD group. The proportion of smoking and diabetes in the CMVD group was significantly higher than that in the non-CMVD group (χ2 val-ues:9.433 and 4.114, both P<0.05). The stress MBF ((2.37±0.61) vs (3.83±1.25) ml·min-1·g-1;t=-4.807, P<0.001) and CFR (2.67±0.60 vs 3.81±0.96;t=-4.751, P<0.001) were lower in smokers than those in non-smokers, and the stress MBF was lower in diabetes patients than that in non-diabetes patients ((2.63±0.98) vs (3.62±1.28) ml·min-1·g-1;t=-2.758, P=0.008). Smoking might be the risk factor for lower stress MBF (odd ratio (OR)=0.310, 95％ CI:0.114-0.880) and lower CFR (OR=0.278, 95％ CI:0. 080-0.894), and diabetes might be the risk factor for lower stress MBF (OR=0.254, 95％ CI:0.073-0. 887) . Conclusions PET MPI can be used for the diagnosis of CMVD type 1. Smoking and diabetes are likely to be associated with the onset of CMVD type 1.