1.Screening of key genes co-regulating immune and mitochondrial energy metabolism and analysis of immune infiltration in glioma based on the Cancer Genome Atlas database
Dan HUA ; Qiang GE ; Liushuan CHANG ; Yifan HE ; Yongheng SHI
Cancer Research and Clinic 2024;36(7):496-502
Objective:To screen key genes that co-regulate immune and mitochondrial energy metabolism through bioinformatics methods and to investigate the relationship between the key genes and immune infiltration.Methods:A total of 671 glioma samples (the tumor group) and 5 non-tumor brain tissue samples (the control group) were collected from the Cancer Genome Atlas (TCGA) database on November 13, 2023. Through a comprehensive search of the GeneCards database and immune-related genes (IRG) and mitochondrial energy metabolism-related genes (MEMRG) in previous published literatures, 76 IRG and MEMRG (IR & MEMRG) were obtained by taking the intersection of IRG and MEMRG after merging and deduplicating. The limma package in R software was used to screen the differentially expressed genes (DEG) between the tumor group and the control group. Then, immune-related & mitochondrial energy metabolism-related differentially expressed genes (IR&MEMRDEG) were obtained by intersecting with IR & MEMRG. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the IR&MEMRDEG through the clusterProfiler package in R software. The STRINGv12.0 online database (https://cn.string-db.org/) was employed to construct a protein interaction network based on IR&MEMRDEG and to identify the top 5 key core genes. Single-sample gene-set enrichment analysis (ssGSEA) was used to determine the relative abundance of immune cell infiltration in all samples, and the immune cell infiltration matrices for both the tumor and the control groups were acquired. The expression differences in infiltration abundance of the immune cells in the tumor group and the control group were analyzing by using the ggplot2 package in R software. The heat map was drawn by utilizing the R software pheatmap package to show self-correlation of immune cells. The correlation between the top 5 key genes in the protein interaction network and immune cells was calculated by using the Spearman algorithm and the R software ggplot2 package.Results:A total of 3 623 DEGs were identified from the TCGA database in both groups, including 1 711 up-regulated genes and 1 912 down-regulated genes. After taking the intersection of DEG and IR&MEMRG, 11 IR&MEMRDEG were obtained including EIF4EBP1, TP53, IDH1, PRCKZ, CD200, GPI, PGM2, PKLR, AK2, ATP4A, and ALDH3B1. GO enrichment analysis results showed that 11 IR&MEMRDEG were mainly enriched in ADP metabolic process, ATP metabolic process, purine nucleoside diphosphate metabolic process, purine ribonucleoside diphosphate metabolic process, and ribonucleoside diphosphate metabolic process at the biological level; in the fibronectin-1 rich granule, secretory granule lumen, cytoplasmic vesiclelumen, vesiclelumen, and nuclear matrix at the cellular component level; in magnesium ion binding, potassium ion binding, and alkali metal ion binding at the molecular functional level. The KEGG enrichment analysis results showed that 11 IR&MEMRDEGs were mainly enriched in glycolysis/gluconeogenesis, carbon metabolism, insulin signaling pathway, pentose phosphate pathway, starch and sucrose metabolism signaling pathways. The protein interaction network analysis from the STRING database revealed that 5 highest scoring core proteins were identified, namely EIF4EBP1, TP53, IDH1, PRKCZ, and AK2.The immune infiltration abundances of 28 immune cells were calculated by using the ssGSEA algorithm. The infiltration abundance of 15 immune cells in the tumor group was higher than that in the control group, and the differences were statistically significant (all P < 0.05). The findings from the immune infiltration analysis indicated a positive correlation among 15 types of immune cells, in which there was a strongest correlation between effector memory CD8 + T cell and myeloid derived suppressor cells. EIF4EBP1, TP53, IDH1, and AK2 exhibited a positive correlation with a large number of immune cells (all P < 0.05), whereas PRKCZ demonstrated a negative correlation with more immune cells (all P < 0.05). Conclusions:PRKCZ, AK2, and EIF4EBP1 have the potential to be the new targets of immunotherapy for gliomas.
2.Prognosis of epilepsy after operation for low-grade insular glioma
Panjie SHI ; Yongheng WANG ; Yingjie HAN ; Jianhua ZHAO ; Zhiguang HAN ; Ying HAN
Journal of Clinical Surgery 2023;31(11):1023-1026
Objective To explore the influencing factors and prognosis of epilepsy after operation for insular low-grade gliomas.Methods The clinical data of 120 patients with insular low-grade gliomas with pre-operative seizure symptoms in the Chinese glioma Genome Atlas Project(CGGA)database from July 2008 to June 2014 were retrospectively analyzed.The seizure control and survival prediction information of the patients were followed up one year after operation.The risk factors affecting post-operative seizures were analyzed by Logistic multiple factor regression analysis,Kapla-Meier curve was used to analyze the effect of postoperative epilepsy control factors on progression free survival(PFS)and overall survival(OS).Results Before operation,36 cases(30.0%)had simple focal seizures,53 cases(44.2%)had focal seizures with different degrees of cognitive impairment,and 31 cases(25.8%)had generalized seizures.During the follow-up after one year of surgical treatment,72 patients(60%)had a complete improvement in epilepsy symptoms(Engel grade Ⅰ),33 patients(27.5%)had a significant improvement(Engel grade Ⅱ),11 patients(9.2%)had a significant improvement(Engel grade Ⅲ),and 4 patients(3.3%)had no improvement or deterioration(Engel grade Ⅳ).Larger tumor resection degree,no putamen involved,IDH1 mutation are favorable factors for postoperative control of epilepsy.Improvement of seizures was a favorable prognostic factor for PFS and OS.Conclusion Epilepsy is the most common symptom of insular gliomas.The improvement of postoperative epilepsy symptoms is related to the degree of tumor resection,involvement of putamen and IDH1 mutation status.Complete improvement of epilepsy symptoms can prolong the progression free survival time and overall survival time of patients.
3.Impact of Yuyetang on Cognitive Impairment of Rats with Type 2 Diabetes Mellitus Based on Regulation of Ghrelin Level
Ruihua ZHANG ; Yong SHI ; Shanshan CAO ; Xinyi WANG ; Chaojun HAN ; Yongheng SHI ; Chuan WANG ; Bin WANG ; Jiping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(16):35-41
ObjectiveTo observe the regulatory effect of Yuyetang on Ghrelin level in rats with type 2 diabetes mellitus (T2DM)-induced cognitive impairment (DCI) and explore the pathway in the prevention and treatment of DCI. MethodThe T2DM model was induced in rats by intraperitoneal injection of streptozotocin (STZ) combined with the high-fat and high-sugar diet (STZ). The model rats were divided into model group, metformin group (200 mg·kg-1), and low-,medium-, and high-dose Yuyetang groups(4.575,9.15, 18.3 g·kg-1)according to the blood glucose, with 10 rats in each group. A normal group was also set up. The rats were administered with corresponding drugs by gavage for 30 days, and the body weight and blood glucose of the rats in each group were observed and recorded. After drug intervention, the learning and memory abilities of rats were tested by the Morris water maze. After the test, the whole brains of rats were sampled for hematoxylin-eosin (HE) staining to observe the pathological changes in the hippocampal CA1 region, and the expression of Ghrelin in gastric tissues and hippocampal CA1 region was detected by immunohistochemistry. ResultCompared with the normal group , the model group showed increased blood glucose(P<0.01),reduced body weight(P<0.01),prolonged escape latency(P<0.05,P<0.01), shortened retention time and movement distance in the target area,decreased number of platform crossings(P<0.01), abnormal morphology and structure of cells with disordered arrangement and reduced number in the hippocampal CA1 region, and decreased expression of Ghrelin in the serum,hippocampal CA1 region, and gastric tissues(P<0.05, P<0.01). Compared with the model group, the medium- and high-dose Yuyetang groups showed increased body weight, while all Yuyetang groups showed reduced blood glucose(P<0.01), shortened escape latency (P<0.05), prolonged retention time and movement distance in the target area,increased platform crossings (P<0.05, P<0.01), improved morphology and structure of cells, increased number of normal cell in the hippocampal CA1 region, and elevated Ghrelin levels in the serum, gastric tissues, and hippocampal CA1 region(P<0.05, P<0.01). ConclusionYuyetang can effectively improve the cognitive ability of DCI rats, and its mechanism may be related to the regulation of Ghrelin levels in the serum, hippocampal CA1 region, and gastric tissues.
4.Targeted therapy for small cell carcinoma of prostate: a case report
Chenfei CHI ; Jiazhou LIU ; Liancheng FAN ; Yongheng SHI ; Zhixiang XIN ; Jiahua PAN ; Jianjun SHA ; Yinjie ZHU ; Wei XUE ; Baijun DONG
Chinese Journal of Urology 2022;43(4):299-300
A patient aged 68 years old presented urinary frequency, urgency, and gross hematuria for 1 month, with initial PSA of 72.72 ng/ml and alkaline phosphatase (ALP)of 114 U/L. Prostate biopsy pathology showed small cell neuroendocrine carcinoma of prostate. The patient was immediately administered 6 cycle of chemotherapy including etoposide and cisplatin combined with medical castration. The CDK4 gene was detected 1.99 times amplification by peripheral blood free DNA (cfDNA)gene analysis. The chemotherapy was followed by parbosini therapy. The number and density of bone metastases continued to decrease significantly by bone scan at 3 and 6 months after treatment, with a continuous decline of ALP and PSA. After 1 year of follow-up, pelvic MRI and bone systemic imaging indicated stable lesions, with PSA of 0.05 ng/ml and ALP of 59 U/L.
5.Pedicled bridge transplantation for soft tissue defects at the contrallateral leg with medial leg skin flap and medial hemi-soleus muscle flap
Gonglin ZHANG ; Fugui SHI ; Jun HU ; Tiejun GONG ; Yongheng WANG ; Laixu ZHAO ; Junlin YANG ; Jianhua ZHOU ; Qinyi XUE
Chinese Journal of Orthopaedic Trauma 2020;22(2):162-165
Objective:To evaluate the pedicled bridge transplantation with medial leg skin flap and medial hemi-soleus muscle flap for the treatment of soft tissue defects at the contrallateral leg.Methods:Between January of 2012 and January of 2016, 8 patients with soft tissue defects at the leg were treated at Department of Orthopedic Surgery, Hand and Foot Surgery Hospital of Lanzhou. They were 5 men and 3 women, aged from 19 to 50 years (mean, 35 years). All of them were treated by bridge transplantation with medial leg skin flap and medial hemi-soleus muscle flap pedicled with posterior tibial artery. The size of the defects ranged from 10 cm×9 cm to 13 cm×8 cm. The immediate coverage of the muscle flaps and vessel pedicle was repaired by a meshed split-thickness skin graft. The donor site was closed directly. The therapeutic efficacy was assessed at the final follow-up according to the criteria by Iowa for tibial fractures.Results:All the skin flaps and muscle flaps survived without any vascular crisis. One case developed necrosis of small skin graft at the distal muscle flap which spontaneously healed after dressing change for 2 weeks. Their follow-up ranged from 2.5 to 4.5 years (mean, 3.8 years). A good contour was confirmed at the recipient area. By the Iowa criteria at the final follow-up, 3 cases were excellent, 4 good and one fair.Conclusion:Pedicled bridge transplantation with medial leg skin flap and medial hemi-soleus muscle flap is a good treatment for soft tissue defects at the contrallateral leg which has only one major blood vessel, reducing damage to the donor site.
6.Patterns of failure and clinical outcomes of radiotherapy for cervical esophageal carcinoma
Dan ZHAO ; Baomin ZHENG ; Shaowen XIAO ; Xiaolong XU ; Yong CAI ; Yongheng LI ; Xianggao ZHU ; Rong YU ; Huiming YU ; Anhui SHI ; Weihu WANG ; Yan SUN
Chinese Journal of Radiological Medicine and Protection 2019;39(1):44-50
Objective To review the failure patterns and clinical outcomes for patients with cervical esophageal carcinoma (CEC) undergoing definitive radiotherapy (RT).Methods Medical records,clinical characteristics and outcomes of patients with CEC treated by definitive RT from August 2008 to May 2017 were retrospectively reviewed and analyzed.Results A total of 97 patients with squamous cell CEC were enrolled in this study with a median age of 59 years old (range 18-78 years old).There were 34 patients with limited cervical esophagus,and 63 patients with diseases beyond cervical region,respectively.There were 69,7,and 6 patients with Bronchi invasion,thyroid lobes involvement and aortic involvement,respectively.There were 11,80 and 6 patients with stage Ⅱ,Ⅲ and Ⅳ (non-regional lymph node metastases),respectively.The median dose to the gross tumor volume (GTV) was 66 Gy,in which 46 patients received above 66 Gy and 51 patients received less than 66 Gy,respectively.The median progression free survival (PFS) and overall survival (OS) were 16.03 and 23.30 months,respectively,with a median follow-up of 14.90 months.The 1,2,3-year PFS and OS were 56.86%,30.35%,26.34%,and 72.54%,47.94%,40.81%,respectively.Sixty-one patients had treatment failure at their last follow-up,in which 40,27,and 18 patients developed local failure,regional failure,and distant metastasis,respectively.Univariate analysis revealed that thyroid lobes involvement resulted in lower PFS (x2 =5.773,P<0.05) and OS (x2 =13.461,P<0.05),and bronchi involvement (x2 =4.283,P<0.05) was associated with lower OS.Multivariate analysis indicated that aortic involvement and thyroid lobes involvement were associated with lower PFS (x2 =6.796,4.548,P<0.05) and OS (x2 =13.421,10.581,P<0.05),and GTV dose above 66 Gy was associated with higher OS (x2=5.296,P<0.05).Conclusions Local-regional recurrence was the main failure pattern for patients with CEC after definitive RT.Aortic,thyroid lobes,and/or bronchi involvement were associated with poor prognosis,and GTV dose ≥66 Gy tended to improve OS.Prospective studies with larger population were needed to further confirm this study.
7.Clinicopathological observation of 5 cases of primary liver adenosquamous carcinoma
Manmei LONG ; Wei HE ; Qiao HE ; Yongheng SHI ; Qiang LIU
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(2):267-269
Primary liver adenosquamous carcinoma is a rare kind of liver malignant tumor with very poor prognosis. Clinical data of 5 cases were analyzed retrospectively, four male and one female, whose average age was 60.2 years (50-67 years) old. Adenosquamous carcinoma contains both adenocarcinoma and squamous carcinoma histologically, and squamous carcinoma cells are dominant (>80%). Four cases underwent surgical resection and one received liver transplantation. The postoperative follow-up period ranged from 6 to 35 months and the mean survival time of these cases was about 15 months. Three patients died during the follow-up period. The survival rates 1 and 2 years after operation were 60% and 20%, respectively.
8.HPLC Fingerprint of the Ingredients in Simiao Junyi Ointment
Qun HE ; Siyuan PENG ; Guangyu CHEN ; Shi WANG ; Yongheng HE ; Zuowei XIAO
China Pharmacist 2017;20(1):38-42
Objective:To establish an analytical method for HPLC fingerprint chromatography of Simiao Junyi ointment to provide basis for the quality control standard. Methods:The separation conditions were established to obtain the HPLC fingerprint chromatog-raphy of the main ingredients in Simiao Junyi ointment. The conditions were as follows:the chromatographic column was Ultimate C18-ODS(250 mm ×4.6 mm,5 μm), the mobile phase was acetonitrile-0.1% phosphate solution, the flow rate was 1.0 ml·min-1, the detection wavelength was 280 nm, and the column temperature was 35℃. The common peaks in the chromatography were analyzed for their belongings. Results:Gradient elution was performed under the above optimal separation conditions, the constituents in Simiao Ju-nyi ointment were separated from each other perfectly, and the optimal fingerprint chromatography was obtained. Though the methodolo-gy examination, the indicators such as precision, stability and repeatability of the method were all promising, and the fingerprint chro-matography could be seen clearly and was easy to be analyzed. The relationships between Simiao Junyi ointment and the common peaks of four medicinal materials in the fingerprint chromatography were preliminary determined, which provided important basis for the quali-ty control of Simiao Junyi ointment. Conclusion:The HPLC fingerprint chromatography of Simiao Junyi ointment can be used as an a-nalysis method for the quality control of Simiao Junyi ointment, which provides reference for the quality control standard for the finished product.
9.Influence of Gamma-rays Radiation Sterilization on the Content and Fingerprint Chromatography of Effec-tive Constituents in Simiao Junyi Ointment
Qun HE ; Guangyu CHEN ; Shi WANG ; Siyuan PENG ; Yongheng HE ; Kun LUO
China Pharmacist 2017;20(3):405-408
Objective:To explore the degradation effect of gamma-rays radiation sterilization on the effective constituents in Simiao Junyi ointment and study the changes of fingerprint chromatography before and after the sterilization to provide basis for the feasibility of gamma-rays radiation sterilization for Simiao Junyi ointment. Methods:The contents of tetrahydropalmatine and PNS ( Panax Notogin-seng saponins) in Simiao Junyi ointment were determined by HPLC, and the fingerprint chromatography was established. The content changes of tetrahydropalmatine and PNS in Simiao Junyi ointment before and after the gamma-rays radiation sterilization were compared among the same batch and various batches, and the relative retention time and relative peak area in the fingerprint chromatography were also compared. Results:The content of tetrahydropalmatine had no change basically before and after the gamma-rays radiation steriliza-tion(P >0. 05), and there was no change in the total content of PNS (P >0. 05). Comparing the HPLC fingerprint chromatography at 280 nm, the relative retention time had statistically significant change after the gamma-rays radiation sterilization ((P <0.05), while the relative peak area had no statistically significant change(P >0. 05). The number of characteristic peaks reduced by one, namely the C8 characteristic peak disappeared in the pasteurized chromatography, and the areas of C6, C9 and C14 peak decreased significantly, while that of C12 increased. Conclusion:Gamma-rays radiation sterilization have no notable effect on the content of tet-rahydropalmatine and PNS in Simiao Junyi ointment, it can be used for the sterilization of Simiao Junyi ointment.
10.Clinicopathologic features of 9 cases of adult rhabdomyosarcoma
Yongheng SHI ; Manmei LONG ; Qiang LIU ; Xiaoyu CHEN
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(7):1015-1019
Objective·To investigate the clinicopathologic characteristics and prognosis of adult rhabdomyosarcoma (RMS).Methods·The clinical and pathological data,immunohistochemical test results of 9 RMS were analyzed retrospectively.Results·The information of 6 males and 3 females were collected in this research,whose average age was (46.89+20.09) years old.The tumors had a wide range distribution.The subtypes of histology included 6 cases of embryonal RMS,1 case of alveolar RMS,1 case of spindle cell RMS and 1 case of pleomorphic RMS.Immunohistochemically study showed that 6 cases were myogenin positive,4 cases were MyoDl positive and 8 cases were desmin positive.During the follow-up period of the 7 cases,only 2 patients survived free of tumors,2 patients presented with tumor recurrence and metastasis after the operations,and 3 patients died of tumor.Conclusion·In this study,embryonaI RMS is the most common type,and immunohistochemistry test is helpful to diagnosis of RMS.

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