Objective A rat model of cerebral small vessel disease(CSVD)was established by unilateral injection of a single dose of sodium laurate into the internal carotid artery.The effectiveness of the model was assessed by behavior scoring and analysis of serum-related indicators,cerebral infarction volume,cerebral microvascular density,hemodynamics,brain histopathology and the expression of blood-brain barrier(BBB)-related proteins.Methods SPF-grade male SD rats were divided randomly into a control group and a model group(n=6 per group).The model group received a single injection of 100 μL of sodium laurate(2 g/L)via the internal carotid artery,while the control group underwent the same surgical procedure but received an equal volume of saline.Neurobehavioral assessments were conducted using the Longa score and postural reflex test.Serum homocysteine(HCY)levels were measured by enzyme-linked immunosorbent assay.Cerebral infarction volume was detected by magnetic resonance imaging and changes in cerebral vascular density were observed by cerebrovascular imaging.The resistance index(RI)and perfusion index(PI)were measured by ultrasonography.Histopathological changes in brain tissue were evaluated by hematoxylin and eosin(HE)staining.Expression of the cerebral microvascular marker CD31 and tight junction proteins ZO-1 and Occludin in brain cortex tissue were detected by immunohistochemical staining.Results The Longa score,postural reflex score(P＜0.05),and cerebral infarction volume were significantly increased(P＜0.05)while the cerebral vascular density was decreased in the model group compared with the control group.Serum HCY levels,carotid RI,and PI values were all significantly increased in the model group(P＜0.05).HE staining revealed solidified neuronal nuclei and enlarged perivascular spaces in the brain cortex in the model group.Immunohistochemical staining revealed that CD31,ZO-1,and Occludin expression were significantly reduced in the brain cortex in the model group compared with the control group(P＜0.05).Conclusions A rat model of CSVD can be established rapidly and effectively by a single unilateral injection of high-concentration sodium laurate via the internal carotid artery.This model is characterized by neurobehavioral abnormalities,cerebral infarction,insufficient cerebral blood supply,reduced vascular density,and disruption of the BBB,suggesting that it may serve as an effective rat model for the study of CSVD.

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 A rat model of cerebral small vessel disease(CSVD)was established by unilateral injection of a single dose of sodium laurate into the internal carotid artery.The effectiveness of the model was assessed by behavior scoring and analysis of serum-related indicators,cerebral infarction volume,cerebral microvascular density,hemodynamics,brain histopathology and the expression of blood-brain barrier(BBB)-related proteins.Methods SPF-grade male SD rats were divided randomly into a control group and a model group(n=6 per group).The model group received a single injection of 100 μL of sodium laurate(2 g/L)via the internal carotid artery,while the control group underwent the same surgical procedure but received an equal volume of saline.Neurobehavioral assessments were conducted using the Longa score and postural reflex test.Serum homocysteine(HCY)levels were measured by enzyme-linked immunosorbent assay.Cerebral infarction volume was detected by magnetic resonance imaging and changes in cerebral vascular density were observed by cerebrovascular imaging.The resistance index(RI)and perfusion index(PI)were measured by ultrasonography.Histopathological changes in brain tissue were evaluated by hematoxylin and eosin(HE)staining.Expression of the cerebral microvascular marker CD31 and tight junction proteins ZO-1 and Occludin in brain cortex tissue were detected by immunohistochemical staining.Results The Longa score,postural reflex score(P＜0.05),and cerebral infarction volume were significantly increased(P＜0.05)while the cerebral vascular density was decreased in the model group compared with the control group.Serum HCY levels,carotid RI,and PI values were all significantly increased in the model group(P＜0.05).HE staining revealed solidified neuronal nuclei and enlarged perivascular spaces in the brain cortex in the model group.Immunohistochemical staining revealed that CD31,ZO-1,and Occludin expression were significantly reduced in the brain cortex in the model group compared with the control group(P＜0.05).Conclusions A rat model of CSVD can be established rapidly and effectively by a single unilateral injection of high-concentration sodium laurate via the internal carotid artery.This model is characterized by neurobehavioral abnormalities,cerebral infarction,insufficient cerebral blood supply,reduced vascular density,and disruption of the BBB,suggesting that it may serve as an effective rat model for the study of CSVD.

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: 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

Objective: To investigate the clinicopathological characteristics, treatment and prognosis of head and neck carcinosarcoma. Methods: The clinical data of 14 patients with head and neck carcinosarcoma treated in the First Affiliated Hospital of Zhengzhou University from January 2010 to May 2020 were retrospectively analyzed, including 11 males and 3 females, with age range from 30 to 72 years old. Clinicopathological characteristics, treatments and follow-up results of patients were evaluated. Kaplan-Meier method was used to estimate the cumulative survival rate. Results: Histopathological examination showed the co-existence of malignant epithelial and mesenchymal components in all cases. Immunohistochemical staining of 13 cases showed cytokeratin and epithelial membrane antigens were positively expressed in the epithelial areas, whereas vimentin was positive in the malignant mesenchymal tissue area. Among 14 cases, 5 cases were treated with surgery, 3 cases with surgery and radiotherapy, and 6 cases with surgery, radiotherapy and chemotherapy. The follow-up time was 2-81 months, with a median follow-up time of 22.5 months. Except for one patient who was lost to follow-up in 21 months after treatment, among the remaining 13 patients, 4 patients had recurrence, 8 patients died, and 5 patients had a tumor-free survival. The Kaplan-Meier analysis showed that the 1, 3, and 5-year cumulative survival rates of 14 patients with head and neck carcinosarcoma were 64.3%, 57.1%, and 42.9%, respectively. Conclusions: Carcinosarcoma of the head and neck is rare in clinic, histopathological and immunohistochemical examinations are important basis for diagnosis, and surgery is a preferred treatment. Carcinosarcoma of the head and neck has a poor prognosis, and patients should be followed up for a long time.
Adult ; Aged ; Carcinosarcoma/therapy* ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies

Genome editing is a genetic manipulation technique that can modify DNA sequences at the genome level, including insertion, knockout, replacement and point mutation of specific DNA fragments. The ultimate principle of genome editing technology relying on engineered nucleases is to generate double-stranded DNA breaks at specific locations in genome and then repair them through non-homologous end joining or homologous recombination. With the intensive study of these nucleases, genome editing technology develops rapidly. The most used nucleases include meganucleases, zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats associated Cas proteins. Based on introducing the development and principles of above mentioned genome editing technologies, we review the research progress of CRISPR/Cas9 system in the application fields of identification of gene function, establishment of disease model, gene therapy, immunotherapy and its prospect.
CRISPR-Cas Systems/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; Gene Editing ; Technology ; Transcription Activator-Like Effector Nucleases/metabolism*