Objective:To investigate the effect of age factor on glymphatic function in patients with Parkinson′s disease (PD) and its potential correlation with overall cognitive performance based on diffusion tensor imaging analysis along the perivascular space(DTI-ALPS) index.Methods:The study was cross-sectional. Clinical and imaging data of 77 PD patients (PD group) who attended the Provincial Hospital of Shandong First Medical University from October 2021 to June 2024 were retrospectively analyzed. In the same period, 30 healthy volunteers matched by age and gender were collected as the normal control (NC) group. All subjects underwent MRI scanning and DTI-ALPS index was calculated based on diffusion tensor imaging. Cognitive functions of 46 patients in the PD group were assessed using the mini-mental state examination (MMSE) and montreal cognitive assessment (MoCA) scores. Independent samples t-tests were used to compare the differences in DTI-ALPS index between the PD and NC groups. After adjusting for confounders, the relationship between DTI-ALPS and age was explored using partial correlation analyses, multiple linear regression models. A mediation model was further developed to explore the mediating effect of DTI-ALPS index between age and cognitive function scores. Results:The DTI-ALPS indices of PD and NC groups were 1.66±0.20 and 1.44±0.17, respectively, and the differences were statistically significant ( t=5.27, P<0.001). The age of patients in the PD group was negatively correlated with the DTI-ALPS index ( r=-0.54, P<0.001), and age (β=-0.467, P<0.001) was an independent influencer of DTI-ALPS index. The DTI-ALPS index was positively correlated with MMSE scores ( r=0.53, P<0.001) and positively correlated with MoCA scores ( r=0.56, P<0.001). The mediation model showed that the DTI-ALPS index fully mediated between age and MMSE scores and partially mediated between age and MoCA scores, with an effect share of 33.25%. Conclusion:Age is an independent risk factor for impaired glymphatic pathway in PD patients, and it may induce cognitive decline in PD patients by exacerbating glymphatic pathway impairment.

Objective:To explore brain MRI features of methylmalonic acidemia (MMA).Methods:This observational study retrospectively analyzed the clinical and imaging data of 123 patients with MMA diagnosed at Shandong Provincial Hospital Affiliated to Shandong First Medical University and Qilu Hospital of Shandong University from January 2010 to November 2022. The 123 patients were divided into 7 stages according to age of onset, neonatal period (0 to<1 month), infancy (1 month to<1 year), early childhood (1 to<4 years), preschool (4 to<7 years), school age (7 to<13 years), adolescent (13 to 17 years) and adult (>17 years). All patients underwent brain MRI scanning. The imaging performances were evaluated, including the number, location, morphology of the lesions.Results:Of the 123 patients, 40 were in the neonatal period, 29 in infancy, 13 in early childhood, 9 in preschool, 6 in school age, 13 in adolescence, and 13 in adulthood. The first symptoms of patients in the neonatal period were mainly digestive system abnormalities, such as difficulty in breastfeeding (37.5%, 15/40) and vomiting (25.0%, 10/40), with neurological symptoms gradually becoming the main manifestations from infancy. Seventy-three cases (59.3%) showed significant abnormalities on cranial MRI, including 17 cases with 33 foci in the neonatal period, 23 cases with 53 foci in infancy, 11 cases with 16 foci in early childhood, 2 cases with 2 foci in preschool, 3 cases with 7 foci in school age, 7 cases with 9 foci in adolescence, and 10 cases with 16 foci in adulthood. In neonatal period, the main manifestations were myelin dysplasia (18%,6/33), dilatation of the lateral ventricular system (18%,6/33), and pallidal bulb infarct foci (18%,6/33); in infancy, the main manifestations were hypoplasia or thinning of the corpus callosum (30%,16/53); in early childhood, the main manifestations were pallidal bulb infarct foci (38%,6/16); and the two MRI abnormalities in preschool were pallidum and thalamic infarct foci; in school age, the main manifestations were infarct foci in the chiasmatic nucleus (29%,2/7) and in the caudate nucleus (29%,2/7); in adolescence, the main manifestation was dilatation of the lateral ventricular system (33%,3/9); and in adulthood, the main manifestation was dilatation of the lateral ventricular system (19%,3/16).Conclusion:By staging the age of onset, it is found that the imaging manifestations of MMA patients show significant differences with age, suggesting that there is a dynamic nature of MMA damage to brain structures at different developmental stages.

Objective:To investigate the efficacy and safety of combined chemotherapy based on radical radiotherapy in elderly patients with cervical cancer, as well as the influence of the sequence of radiotherapy and chemotherapy on clinical prognosis.Methods:Clinical data of 112 elderly patients with cervical cancer aged 65-80 years who received radical radiotherapy in Department of Radiotherapy Oncology of the First Affiliated Hospital of Soochow University from January 2018 to July 2022 were retrospectively analyzed. The follow-up deadline was January 31, 2023. A total of 26 patients received radical radiotherapy alone (radiotherapy alone group), while 86 patients received radical radiotherapy combined with chemotherapy (chemoradiotherapy group), including sequential chemoradiotherapy group ( n=57) and concurrent chemoradiotherapy group ( n=29). The recent efficacy, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of adverse reactions in patients between the chemoradiotherapy group and radiotherapy alone group, sequential chemoradiotherapy group and concurrent chemoradiotherapy group, elderly patients aged ≥70 years old were analyzed by Chi-square test, Fisher exact probability method, one-way ANOVA, paired sample t-test and Kruskal-Wallis test. Results:There were no significant differences in recent efficacy, ORR and DCR between chemoradiotherapy group and radiotherapy alone group ( P=0.245, 0.715 and 0.551). The median PFS was 25 months vs. 19 months ( P=0.265), and the median OS was 53 months vs. 30 months ( P=0.040). Lymphocytopenia was the most common grade 3-4 adverse reactions between two groups, and there were statistically significant differences in hematological adverse reactions and gastrointestinal adverse reactions between two groups (both P<0.05). There were no significant differences in recent efficacy, ORR, DCR, median PFS and median OS between sequential chemoradiotherapy group and concurrent chemoradiotherapy group (all P>0.05). However, the gastrointestinal adverse reactions in the concurrent chemoradiotherapy group were significantly higher than those in the sequential chemoradiotherapy group ( P=0.024). The results of elderly patients aged ≥70 years old were basically consistent with those between the chemoradiotherapy group and radiotherapy alone group. Conclusions:Combined chemotherapy based on radical radiotherapy is an effective and relatively safe treatment for elderly patients even those aged ≥70 years old with cervical cancer. Sequential and concurrent chemoradiotherapy have similar therapeutic effects in elderly patients, but the incidence of gastrointestinal reactions is significantly reduced in the former.

Objective:To investigate the effect of age factor on glymphatic function in patients with Parkinson′s disease (PD) and its potential correlation with overall cognitive performance based on diffusion tensor imaging analysis along the perivascular space(DTI-ALPS) index.Methods:The study was cross-sectional. Clinical and imaging data of 77 PD patients (PD group) who attended the Provincial Hospital of Shandong First Medical University from October 2021 to June 2024 were retrospectively analyzed. In the same period, 30 healthy volunteers matched by age and gender were collected as the normal control (NC) group. All subjects underwent MRI scanning and DTI-ALPS index was calculated based on diffusion tensor imaging. Cognitive functions of 46 patients in the PD group were assessed using the mini-mental state examination (MMSE) and montreal cognitive assessment (MoCA) scores. Independent samples t-tests were used to compare the differences in DTI-ALPS index between the PD and NC groups. After adjusting for confounders, the relationship between DTI-ALPS and age was explored using partial correlation analyses, multiple linear regression models. A mediation model was further developed to explore the mediating effect of DTI-ALPS index between age and cognitive function scores. Results:The DTI-ALPS indices of PD and NC groups were 1.66±0.20 and 1.44±0.17, respectively, and the differences were statistically significant ( t=5.27, P<0.001). The age of patients in the PD group was negatively correlated with the DTI-ALPS index ( r=-0.54, P<0.001), and age (β=-0.467, P<0.001) was an independent influencer of DTI-ALPS index. The DTI-ALPS index was positively correlated with MMSE scores ( r=0.53, P<0.001) and positively correlated with MoCA scores ( r=0.56, P<0.001). The mediation model showed that the DTI-ALPS index fully mediated between age and MMSE scores and partially mediated between age and MoCA scores, with an effect share of 33.25%. Conclusion:Age is an independent risk factor for impaired glymphatic pathway in PD patients, and it may induce cognitive decline in PD patients by exacerbating glymphatic pathway impairment.

Objective:To explore brain MRI features of methylmalonic acidemia (MMA).Methods:This observational study retrospectively analyzed the clinical and imaging data of 123 patients with MMA diagnosed at Shandong Provincial Hospital Affiliated to Shandong First Medical University and Qilu Hospital of Shandong University from January 2010 to November 2022. The 123 patients were divided into 7 stages according to age of onset, neonatal period (0 to<1 month), infancy (1 month to<1 year), early childhood (1 to<4 years), preschool (4 to<7 years), school age (7 to<13 years), adolescent (13 to 17 years) and adult (>17 years). All patients underwent brain MRI scanning. The imaging performances were evaluated, including the number, location, morphology of the lesions.Results:Of the 123 patients, 40 were in the neonatal period, 29 in infancy, 13 in early childhood, 9 in preschool, 6 in school age, 13 in adolescence, and 13 in adulthood. The first symptoms of patients in the neonatal period were mainly digestive system abnormalities, such as difficulty in breastfeeding (37.5%, 15/40) and vomiting (25.0%, 10/40), with neurological symptoms gradually becoming the main manifestations from infancy. Seventy-three cases (59.3%) showed significant abnormalities on cranial MRI, including 17 cases with 33 foci in the neonatal period, 23 cases with 53 foci in infancy, 11 cases with 16 foci in early childhood, 2 cases with 2 foci in preschool, 3 cases with 7 foci in school age, 7 cases with 9 foci in adolescence, and 10 cases with 16 foci in adulthood. In neonatal period, the main manifestations were myelin dysplasia (18%,6/33), dilatation of the lateral ventricular system (18%,6/33), and pallidal bulb infarct foci (18%,6/33); in infancy, the main manifestations were hypoplasia or thinning of the corpus callosum (30%,16/53); in early childhood, the main manifestations were pallidal bulb infarct foci (38%,6/16); and the two MRI abnormalities in preschool were pallidum and thalamic infarct foci; in school age, the main manifestations were infarct foci in the chiasmatic nucleus (29%,2/7) and in the caudate nucleus (29%,2/7); in adolescence, the main manifestation was dilatation of the lateral ventricular system (33%,3/9); and in adulthood, the main manifestation was dilatation of the lateral ventricular system (19%,3/16).Conclusion:By staging the age of onset, it is found that the imaging manifestations of MMA patients show significant differences with age, suggesting that there is a dynamic nature of MMA damage to brain structures at different developmental stages.

Objective:To investigate the efficacy and safety of combined chemotherapy based on radical radiotherapy in elderly patients with cervical cancer, as well as the influence of the sequence of radiotherapy and chemotherapy on clinical prognosis.Methods:Clinical data of 112 elderly patients with cervical cancer aged 65-80 years who received radical radiotherapy in Department of Radiotherapy Oncology of the First Affiliated Hospital of Soochow University from January 2018 to July 2022 were retrospectively analyzed. The follow-up deadline was January 31, 2023. A total of 26 patients received radical radiotherapy alone (radiotherapy alone group), while 86 patients received radical radiotherapy combined with chemotherapy (chemoradiotherapy group), including sequential chemoradiotherapy group ( n=57) and concurrent chemoradiotherapy group ( n=29). The recent efficacy, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of adverse reactions in patients between the chemoradiotherapy group and radiotherapy alone group, sequential chemoradiotherapy group and concurrent chemoradiotherapy group, elderly patients aged ≥70 years old were analyzed by Chi-square test, Fisher exact probability method, one-way ANOVA, paired sample t-test and Kruskal-Wallis test. Results:There were no significant differences in recent efficacy, ORR and DCR between chemoradiotherapy group and radiotherapy alone group ( P=0.245, 0.715 and 0.551). The median PFS was 25 months vs. 19 months ( P=0.265), and the median OS was 53 months vs. 30 months ( P=0.040). Lymphocytopenia was the most common grade 3-4 adverse reactions between two groups, and there were statistically significant differences in hematological adverse reactions and gastrointestinal adverse reactions between two groups (both P<0.05). There were no significant differences in recent efficacy, ORR, DCR, median PFS and median OS between sequential chemoradiotherapy group and concurrent chemoradiotherapy group (all P>0.05). However, the gastrointestinal adverse reactions in the concurrent chemoradiotherapy group were significantly higher than those in the sequential chemoradiotherapy group ( P=0.024). The results of elderly patients aged ≥70 years old were basically consistent with those between the chemoradiotherapy group and radiotherapy alone group. Conclusions:Combined chemotherapy based on radical radiotherapy is an effective and relatively safe treatment for elderly patients even those aged ≥70 years old with cervical cancer. Sequential and concurrent chemoradiotherapy have similar therapeutic effects in elderly patients, but the incidence of gastrointestinal reactions is significantly reduced in the former.

Objective: Signaling lymphocytic activation molecule family members (SLAMFs) play a critical role in immune regulation of malignancies. This study aims to investigate the prognostic value and function of SLAMFs in ovarian cancer (OC). Methods: The expression analysis of SLAMFs was conducted based on The Cancer Genome Atlas Ovarian Cancer Collection (TCGA-OV) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was further performed on tissue arrays (n=98) to determine the expression of SLAMF7. Kaplan-Meier plotter and multivariate Cox regression model were used to evaluate the correlation of SLAMF7 expression with survival outcomes of patients. The molecular function of SLAMF7 in OC was further investigated using Gene Set Enrichment Analysis (GSEA). Results: SLAMF7 mRNA expression were significantly upregulated in OC tumor tissue compared to normal tissue. IHC revealed that SLAMF7 expression was located in the interstitial parts of tumor tissue, and higher SLAMF7 expression was associated with favorable survival outcomes. GSEA demonstrated that SLAMF7 is involved immune-related pathways. Further analysis showed that SLAMF7 had a strong correlation with the T cellspecific biomarker (CD3) but not with the B cell (CD19, CD22, and CD23) and natural killer cell-specific biomarkers (CD85C, CD336, and CD337). Furthermore, IHC analysis confirmed that SLAMF7 was expressed in tumor-infiltrating T cells, and the IHC score of SLAMF7 was positively correlated with CD3 (r=0.85, p<0.001). Conclusion SLAMF7 is expressed in the interstitial components of clinical OC tissue, and higher SLAMF7 expression indicated a favorable prognosis for patients with OC.Additionally, SLAMF7 is involved in T-cell immune infiltration in OC.

Objective: Signaling lymphocytic activation molecule family members (SLAMFs) play a critical role in immune regulation of malignancies. This study aims to investigate the prognostic value and function of SLAMFs in ovarian cancer (OC). Methods: The expression analysis of SLAMFs was conducted based on The Cancer Genome Atlas Ovarian Cancer Collection (TCGA-OV) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was further performed on tissue arrays (n=98) to determine the expression of SLAMF7. Kaplan-Meier plotter and multivariate Cox regression model were used to evaluate the correlation of SLAMF7 expression with survival outcomes of patients. The molecular function of SLAMF7 in OC was further investigated using Gene Set Enrichment Analysis (GSEA). Results: SLAMF7 mRNA expression were significantly upregulated in OC tumor tissue compared to normal tissue. IHC revealed that SLAMF7 expression was located in the interstitial parts of tumor tissue, and higher SLAMF7 expression was associated with favorable survival outcomes. GSEA demonstrated that SLAMF7 is involved immune-related pathways. Further analysis showed that SLAMF7 had a strong correlation with the T cellspecific biomarker (CD3) but not with the B cell (CD19, CD22, and CD23) and natural killer cell-specific biomarkers (CD85C, CD336, and CD337). Furthermore, IHC analysis confirmed that SLAMF7 was expressed in tumor-infiltrating T cells, and the IHC score of SLAMF7 was positively correlated with CD3 (r=0.85, p<0.001). Conclusion SLAMF7 is expressed in the interstitial components of clinical OC tissue, and higher SLAMF7 expression indicated a favorable prognosis for patients with OC.Additionally, SLAMF7 is involved in T-cell immune infiltration in OC.

Objective: Signaling lymphocytic activation molecule family members (SLAMFs) play a critical role in immune regulation of malignancies. This study aims to investigate the prognostic value and function of SLAMFs in ovarian cancer (OC). Methods: The expression analysis of SLAMFs was conducted based on The Cancer Genome Atlas Ovarian Cancer Collection (TCGA-OV) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was further performed on tissue arrays (n=98) to determine the expression of SLAMF7. Kaplan-Meier plotter and multivariate Cox regression model were used to evaluate the correlation of SLAMF7 expression with survival outcomes of patients. The molecular function of SLAMF7 in OC was further investigated using Gene Set Enrichment Analysis (GSEA). Results: SLAMF7 mRNA expression were significantly upregulated in OC tumor tissue compared to normal tissue. IHC revealed that SLAMF7 expression was located in the interstitial parts of tumor tissue, and higher SLAMF7 expression was associated with favorable survival outcomes. GSEA demonstrated that SLAMF7 is involved immune-related pathways. Further analysis showed that SLAMF7 had a strong correlation with the T cellspecific biomarker (CD3) but not with the B cell (CD19, CD22, and CD23) and natural killer cell-specific biomarkers (CD85C, CD336, and CD337). Furthermore, IHC analysis confirmed that SLAMF7 was expressed in tumor-infiltrating T cells, and the IHC score of SLAMF7 was positively correlated with CD3 (r=0.85, p<0.001). Conclusion SLAMF7 is expressed in the interstitial components of clinical OC tissue, and higher SLAMF7 expression indicated a favorable prognosis for patients with OC.Additionally, SLAMF7 is involved in T-cell immune infiltration in OC.

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment