Objective To establish an orthotopic transplantation tumor model of pancreatic cancer derived from transgenic LSL-KrasG12D/+ LSL-Trp53R172H/+ Pdx1-Cre(KPC)mice.To provide a stable and reliable drug preclinical research animal model to study the developmental mechanism and treatment strategies of pancreatic cancer.Methods Tumor tissue derived from KPC transgenic mice with spontaneous pancreatic cancer was transplanted into the C57BL/6J mouse pancreas.Ultrasound was used to monitor tumor growth.HE and immunofluorescence staining was used to evaluate the pathological characteristics of this model.Results The tumor derived from KPC mice grew steadily on the pancreas of C57BL/6J mice.Tumor cell proliferation index Ki67,matrix fibrosis marker αSMA,and immune cell markers CD45 and CD206 were all stably expressed in the tumor.The model stably retained the pathological features of primary pancreatic cancer.Widespread tumor metastases,which were similar to those observed in patients with pancreatic cancer,developed in this model.Conclusions An orthotopic transplantation model derived from a transgenic mouse with spontaneous pancreatic cancer was established successfully.The model simulates the stromal environment and immune cell infiltration of pancreatic cancer and retains strong stability and uniformity with the original tumor.It can be used as an effective drug preclinical research model to study pancreatic cancer progression and treatment strategies.

Objective To analyze the expression of CREM in gastric cancer(GC)and its correlation with prognosis of the patients.Methods TCGA and GEO databases were used to analyze the expression levels of CREM mRNA in GC and adjacent tissues.Immunohistochemistry was used to examine the expression of CREM protein in 43 pairs of GC and adjacent tissues,and the correlation of CREM expression with clinicopathological features of the patients was analyzed.Kaplan-Meier survival analysis was used to explore the relationship between CREM expression and survival of GC patients.LinkedOmics database was used to annotate the GO function and KEGG pathway enrichment of CREM-related genes.Results Database analysis showed that CREM was highly expressed in GC tissues(P<0.05)and positively correlated with poor prognosis in GC patients(P=0.01).Immunohistochemistry results showed significantly higher CREM expression in GC tissues than in paired adjacent tissues(P<0.0001),and its expression level was correlated with T-stage and N-stage of the tumor(P<0.05).The overall survival of GC patients with high expression of CREM was shorter(RR=4.02,P=0.0046).Gene enrichment analysis showed that high CREM expression promotes occurrence and progression of GC very likely through the cell adhesion signaling pathway.Conclusion CREM is highly expressed in GC,and its high expression is associated with a poor prognosis of GC patients,suggesting the potential of CREM to serve as a prognostic indicator for GC.

Mucinous adenocarcinoma of the renal pelvis is rare in clinical practice. This article reported a case of primary renal pelvis mucinous adenocarcinoma mixed with signet ring cell carcinoma. The patient was admitted to hospital due to right low back pain, and was diagnosed with right kidney stones accompanied by hydrops and infection, right kidney abscess, and nonfunctional right kidney after complete examination. Right renal puncture drainage was performed twice, followed by laparoscopic robot assisted right neprectomy. The postoperative pathological diagnosis was right renal pelvis primary mucinous adenocarcinoma (mixed with signet-ring cell carcinoma). Eleven months after the operation, regular "sodium folinate + oxaliplatin + 5-fluorouracil" chemotherapy was performed for 12 courses, and imaging showed no signs of recurrence or metastasis.

Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines.In this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients.We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla.Through conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were validated.By integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm.The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant difference.Finally,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and vanylglycol.Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.

Objective To analyze the expression of CREM in gastric cancer(GC)and its correlation with prognosis of the patients.Methods TCGA and GEO databases were used to analyze the expression levels of CREM mRNA in GC and adjacent tissues.Immunohistochemistry was used to examine the expression of CREM protein in 43 pairs of GC and adjacent tissues,and the correlation of CREM expression with clinicopathological features of the patients was analyzed.Kaplan-Meier survival analysis was used to explore the relationship between CREM expression and survival of GC patients.LinkedOmics database was used to annotate the GO function and KEGG pathway enrichment of CREM-related genes.Results Database analysis showed that CREM was highly expressed in GC tissues(P<0.05)and positively correlated with poor prognosis in GC patients(P=0.01).Immunohistochemistry results showed significantly higher CREM expression in GC tissues than in paired adjacent tissues(P<0.0001),and its expression level was correlated with T-stage and N-stage of the tumor(P<0.05).The overall survival of GC patients with high expression of CREM was shorter(RR=4.02,P=0.0046).Gene enrichment analysis showed that high CREM expression promotes occurrence and progression of GC very likely through the cell adhesion signaling pathway.Conclusion CREM is highly expressed in GC,and its high expression is associated with a poor prognosis of GC patients,suggesting the potential of CREM to serve as a prognostic indicator for GC.

Objective:To explore the effect of multidisciplinary management combined with 60-second high-risk diabetic foot screening in diabetic foot.Methods:From January to December 2022, 138 patients with diabetic foot were selected from Xinxiang Central Hospital by convenience sampling. The patients were randomly divided into a control group and an observation group, with 69 cases in each group. Control group implemented routine follow-up management of diabetic foot, and observation group carried out multidisciplinary management combined with 60-second high-risk diabetic foot screening on the basis of control group, and the intervention lasted for six months. The progress of Wagner grading of diabetic foot and foot self-care were compared between the two groups.Results:After intervention, the number of Wagner grading progression patients in observation group and control group was four cases (5.80%) and 10 cases (14.49%), respectively. The number of progression patients in observation group was less than that in control group, and the difference was statistically significant (χ 2=4.161, P=0.041). The total score and dimension scores of diabetic foot self-management in the two groups after the intervention were higher than those before the intervention, but only the scores of observation group before and after the intervention were statistically significant ( P<0.05). After intervention, the total score and dimension scores of diabetic foot self-management in observation group were higher than those in control group, with a statistically significant difference ( P<0.05) . Conclusions:Multidisciplinary management combined with 60-second high-risk diabetic foot screening can effectively delay the progress of diabetic foot and improve patients' foot self-care.

Purpose To explore the ability of proton density fat fraction(PDFF)and decay constant T2* values in MRI to reflect skeletal muscle aging.Materials and Methods 3T MRI data of skeletal muscle in the middle thigh of 211 healthy adults from the Third Affiliated Hospital of Southern Medical University from August to December 2023 were prospectively collected.Gender,age,height,weight and body mass index(BMI)were recorded.PDFF value and T2* value of thigh skeletal muscle were measured at post-processing workstation,and statistical differences among different age,gender and BMI groups were analyzed.The correlation between PDFF value and T2* value of thigh skeletal muscle and age and BMI was analyzed.Results There were statistically significant differences in PDFF values of thigh skeletal muscle among different age groups(H=18.476-85.619,all P<0.01).There were significantly differences in T2*values of the left and right quadriceps muscles,hamstrings and adductors among different age groups(H=13.342-47.566,all P<0.05).There were statistically significant differences in the PDFF values of right quadriceps,left and right hamstring,adductor and sartor muscles between male and female groups(Z=-4.929--1.626,all P<0.05),while there were statistically significant differences in T2* values of left sartor muscle(Z=-2.971,P=0.003).There was no statistical significance in PDFF value of skeletal muscle of thigh in different BMI groups(P>0.05),but there were statistically significant differences in T2* value of left and right quadriceps muscle,hamstring muscle and adductor muscle(H=9.542-24.495,all P<0.05).There was a moderate positive correlation between age and PDFF value of thigh skeletal muscle(r=0.635,P<0.01),but a slight negative correlation with T2* value of left and right quadriceps,hamstring and sarcoleus(r=-0.451--0.189,all P<0.01).There was a slight positive correlation between BMI and T2* values of thigh skeletal muscle(r=0.317,P<0.01).There was a moderate negative correlation between the PDFF value and T2* value of all thigh skeletal muscles(r=-0.749--0.624,P<0.01).The PDFF and T2* values of the front and back thigh muscles(quadriceps,hamstring)were most significantly correlated with age and BMI.Conclusion PDFF based on MRI can reflect the age-related changes in the microenvironment of thigh skeletal muscle,and is a potential imaging biological marker for accurate and non-invasive quantitative evaluation of thigh skeletal muscle aging.

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4⁺ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8⁺ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.

Objective:To investigate the imaging characteristics and diagnosis of thalamic dementia caused by medial tentorial dural arteriovenous fistula (TDAVF).Methods:The clinical and imaging data of 4 patients with medial TDAVF diagnosed at Nanjing Brain Hospital from August 2022 to September 2023 were retrospectively collected, summarized and analyzed.Results:Four patients were all males, with an average age of 67 years. The duration of cognitive impairment varies from 13 days to 2 months, with an average of about 1 month. The average score on the Mini-Mental State Examination (MMSE) was 13, while the average score on the Montreal Cognitive Assessment (MoCA) was 15. One patient was unable to complete these tests. MRI showed bilateral thalamic swelling, with scattered microbleeding lesions on diffusion-weighted imaging and susceptibility-weighted imaging ( n=3). Enhanced scans showed patchy or clumpy enhancement of the bilateral thalamus. Magnetic resonance angiography showed abnormal blood vessels along the straight sinus area ( n=4), while magnetic resonance venography showed no straight sinus development ( n=4). Magnetic resonance spectroscopy showed neuronal swelling and damage ( n=3), with no increase in choline peak. Arterial spin labeling perfusion imaging showed decreased perfusion in the lesions. Digital subtraction angiography confirmed TDAVF with straight sinus thrombosis. Two patients underwent embolization, with significant improvement in postoperative memory impairment. One patient underwent surgical clipping, while the other was transferred to other hospital for treatment. Conclusions:Patients with medial TDAVF often present with thalamic dementia. Imaging examinations show typical bilateral thalamic swelling with microbleeds, and early visualization of vascular shadows, without development of straight sinus. These features would be beneficial for the early diagnosis of TDAVF.

With the progress of population aging, cerebral small vessel disease is increasingly becoming a common and frequent disease threatening human health, which is a common reason leaing to cognitive function decline.The changes of white matter, especially white matter hyperintensities, are the most common and typical imaging marker of small cerebral vascular disease.In recent years, a number of studies has found that white matter hyperintensities are associated with cognitive decline.These studies mainly focused on the relationship between white matter hyperintensities and cognitive frailty, and the correlation between the size, location and dynamic evolution of white matter hyperintensities and cognitive impairment of small cerebral vascular disease.Functional magnetic resonance imaging studies also revealed that patients with cognitive impairment of cerebral small vessel disease had abnormal white matter changes and structural network connectivity.Structural network can be used for quantitative analysis because of its good stability.Diffusion tensor imaging and quantitative measurement of multi-dimensional structural network were used qualitatively.It was found that the structural network integrity was damaged, the network connection efficiency was reduced, and the connection was interrupted within the white matter hyperintensity.Big data and artificial intelligence research can make early prediction of white matter hyperintensity and structural networks in patients with cerebral small vessel disease with cognitive impairment.These studies provide a reliable basis for the discovery of abnormal microstructure and network changes in the early stage of white matter hyperintensities in cerebral small vessel disease with cognitive impairment.The paper reviews the research progress of white matter hyperintensity and brain structural network in patients with cognitive impairment of cerebral small vessel disease in recent years, and in order to improve the early diagnosis of the disease and promote the early prevention and treatment.