Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

Objective To investigate the-75 G/A single-nucleotide polymorphism in the promoter region of apolipoprotein A1 gene(apoA1)and its association with gestational diabetes mellitus(GDM)in pregnant women and to provide references for the exploration in the molecular genetic basis of GDM.Methods A total of 626 GDM patients and 1022 normal pregnant women,ie,the controls,were included in the study.The genotyping of apoA1-75 G/A polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP)analysis.Total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),and glucose(Glu)were measured by enzymatic methods.Plasma insulin(INS)was measured by chemiluminescence immunoassay.The protein levels of apoA1 and apoB were measured by the turbidimetric immunoassay.Results Allele frequencies of G and A were 0.718 and 0.282 in the GDM group and 0.713 and 0.287 in the control group,respectively.Distribution of the genotype frequencies was found to be in Hardy-Weinberg equilibrium in both the GDM and control groups.There was no significant difference in the frequencies of alleles G and A and the genotypes of apoA1-75 G/A polymorphism between the GDM and the control group(P>0.05).In the GDM group,the carriers with the genotype AA were associated with significantly higher levels of TC,HDL-C,and apoA1 than those with genotypes GG and GA did(all P<0.05).After the GDM patients were divided into obese and non-obese subgroups,the genotype-related apoA1 variation was observed only in obese patients,while the genotype-related TC and HDL-C variations were evident in non-obese patients(P<0.05).In the control group,carriers of genotypes AA and GA had higher systolic blood pressure(SBP)and HDL-C than the carriers of genotype GG did(all P<0.05).Carriers of genotypes AA had significantly lower Glu levels than carriers of genotypes GG and GA did(P<0.05).The control subjects were further divided into subgroups according to their body mass index(BMI).Analysis of the subgroups showed that AA carriers were associated with higher SBP levels in the obese control women only,while lower Glu levels were evident in both obese and non-obese control women.Conclusion These results suggest that-75 G/A polymorphism in the apoA1 gene is not associated with GDM.However,the genetic variation is closed associated with the plasma apoA1,HDL-C,and TC levels in GDM patients and plasma HDL-C,Glu,and SBP levels in the control subjects.The apoA1 variant-associated lipids and SBP variation is BMI dependent in both groups.

Objective To retrospectively investigate the clinical features of localized primary small bowel stromal tumors (SBSTs) and the impacting factors for prognosis.Methods The clinical and pathological data of 89 consecutive SBSTs patients,with pathologically confirmed,who underwent complete resection in Ruijin hospital between January 2003 and September 2007 were collected and analyzed.All patients were followed up for assessment of tumor recurrence and metastasis.The impacts of clinical and pathologic factors on rate of disease free survival (DFS) of the patients was evaluated.Results In total of 89 follow-up patients,15 patients were diagnosed with tumor recurrence and 9 of them died.The tumor size,mitotic index and pathological risk stratification were statistically related with DFS (P=0.000,P=0.006,P=0.000,respectively) by using Kaplan-Meier univaritate analysis.Tumor size and mitotic index were proved to be independent prognostic factors for tumor recurrence by multivariate analysis COX regression model.Conclusions Tumor size and mitotic index are related with tumor recurrence,and can be regarded as independent predictive factors of tumor recurrence.

Objective To analyze the radiolngical findings of mediastinal ganglioneuroma and to improve its diagnostic accuracy. Methods Imaging data of 8 cases of pathologically proven mediastinal ganglioueuroma were restrospectively analyzed. Results These tumors could occur in the anterior mediastinum, middle mediastinum or posterior mediastinum, with a preference for the posterior mediastinum (6/8). No specific clinical symptoms and signs were observed. Well-defined enlargrment of mediastinum with homogeneous density was shown on plain X-Ray. CT scanning was performed in 7 cases, including non-contrast scan alone (n = 3 ), both non-coutrast and contrast-enhanced scans ( n = 4). Round or oval shaped, well circumscribed, homogeneous or slightly heterogeneous, hypadense masses were demonstrated on non-contrast scan. Spotty calification could be found in a few cases. Homogeneous or slightly heterogeneous enhancement was seen following the intravenous injection of contrast material. Large tumors showed a tendency of wedging into the space between adjacent organs and structures, and encasing the nearby large vessels. MR without contrast was performed in 1 case. T1 WI showed isointensity to adjacent muscle, T2WI showed homogeneous hyperintensity. Multi-planar reconstruction provided more information concerning the relationship of the mass lesions with neighboring structures. Conclusion Mediastinal ganglioneuromas have some specific characterstics on imaging studies, which could assist in pre-operative diagnosis and surgical planning.