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

Sepsis associated encephalopathy (SAE) is one of the common encephalopathy in critically ill patients. It is a brain dysfunction caused by inflammatory reaction caused by non central nervous system infection. The pathogenesis of SAE is complex and unclear, and there is a lack of effective criteria for the diagnosis of SAE. SAE patients are often in critical condition with high mortality. At present, there is no specific method to treat SAE. The research on SAE treatment has a long way to go. This paper introduces the possible pathogenesis, diagnostic methods and treatment of SAE.

Objective:To determine mutations in the PTPN11 gene in a family with LEOPARD syndrome.Methods:Clinical evaluation was carried out in a large pedigree with confirmed LEOPARD syndrome diagnosed in Hwa Mei Hospital, University of Chinese Academy of Sciences. Peripheral blood samples were obtained from 4 patients and 2 unaffected healthy members in the family, as well as 100 unrelated healthy controls. DNA was extracted from the blood samples, and PCR was performed to amplify all exons of the PTPN11 genes, followed by Sanger sequencing.Results:There were 14 members in 3 generations of the family, 6 of whom were affected (3 males and 3 females) , demonstrating an autosomal dominant inheritance pattern. Skin lesions were mainly distributed on the face, trunk and limbs, accompanied by special facial features and cardiovascular system abnormalities. A missense mutation c.1632G>T (p.R558L) in the PTPN11 gene was identified in the 4 patients, which resulted in the substitution of arginine by leucine at amino acid position 558. This mutation had not yet been reported previously. No mutation was detected in the PTPN11 gene in the 2 unaffected family members or 100 healthy controls.Conclusion:The missense mutation c.1632G>T in exon 13 of the PTPN11 gene may be the molecular basis for LEOPARD syndrome in this family.

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*

Primary liver cancer (PLC) is an aggressive tumor and prone to metastasize and recur. According to pathological features, PLC are mainly categorized into hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed hepatocellular cholangiocarcinoma, and fibrolamelic hepatocellular carcinoma, etc. At present, surgical resection, radiotherapy and chemotherapy are still the main treatments for PLC, but the specificities are poor and the clinical effects are limited with a 5-year overall survival rate of 18%. Liver cancer stem cells (LCSCs) are a specific cell subset existing in liver cancer tissues. They harbor the capabilities of self-renewal and strong tumorigenicity, driving tumor initiation, metastasis, drug resistance and recurrence of PLC. Therefore, the identification of molecular markers and the illustration of mechanisms for stemness maintenance of LCSCs can not only reveal the molecular mechanisms of PLC tumorigenesis, but also lay a theoretical foundation for the molecular classification, prognosis evaluation and targeted therapy of PLC. The latest research showed that the combination of 5-fluorouracil and CD13 inhibitors could inhibit the proliferation of CD13+ LCSCs, thereby reducing overall tumor burden. Taken together, LCSCs could be the promising therapeutic targets of PLC in the future. This review summarizes the latest progress in molecular markers, mechanisms for stemness maintenance and targeted therapies of LCSCs.
Carcinoma, Hepatocellular/genetics* ; Humans ; Liver Neoplasms/genetics* ; Neoplastic Stem Cells ; Prognosis

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

OBJECTIVE：To establish pre -column derivatization-HPLC fingerprint of Polyporus polysaccharide ，and to determine the contents of main monosaccharide components ，so as to provide reference for quality evaluation of Polyporus umbellatus. METHODS ：Polyporus polysaccharide was extracted with boiling water and precipitated by ethanol and deproteinized by Sevage from 11 batches of P. umbellatus from different producing areas. The samples were firstly hydrolyzed with trifluoro-acetic acid （TFA）and then derivatized by 1-phenyl-3-methyl-5-pyrazolone（PMP）. HPLC analysis was then conducted. The determination was carried out on HypersiL BDS C 18 column with mobile phase composed of 0.1 mol/L phosphate buffer （pH 6.84）-acetonitrile（84∶16，V/V）by gradient elution at the flow rate of 1.0 mL/min. The detection wavelength was set at 254 nm， and column temperature was 30 ℃. The sample size was 20 µL. The similarity of 11 batches of Polyporus polysaccharide was evaluated by using TCM Chromatographic Fingerprint Similarity Evaluation System （2012A edition ），and the contents of main monosassharide components were detected. The peak was identified by comparing with the reference substance ，and cluster analysis was performed by using SPSS 23.0 software. RESULTS ：In HPLC fingerprints of the 11 batches of samples ，3 common peaks were identified ，namely mannose ，glucose and galactose. The similarity of all samples was above 0.94. Cluster analysis classified 11 batches of samples into three categories. S 1-S6，and S 8 were grouped into category 1；S7，S10 and S 11 were grouped into category 2；S9 was individually grouped into one category. Results of content determination showed that the contents of mannose ranged from 1.571 to 8.771 mg/g；those of glucose ranged from 26.072 to 132.194 mg/g，and those of galactose ranged from 3.420 to 36.593 mg/g. CONCLUSIONS ：Established pre-column derivatization HPLC fingerprints can provide reference for quality evaluation of P. umbellatus . The monosaccharide composition of different batches of Polyporus polysaccharide is the same ；there is no significant correlation between fingerprint characteristic peak and the origin of herbs ；there is significant difference in the content of monosaccharide of P. umbellatus .