1.Recurrence mechanisms and treatment strategies for IDH wild-type glioblastoma
Tao WANRU ; Lv LEI ; Wang ZIJUN ; Bao LEILEI
Chinese Journal of Clinical Oncology 2025;52(6):309-313
Isocitrate dehydrogenase(IDH)wild-type glioma is a type of highly invasive brain tumor with poor prognosis and a high recur-rence rate.The recurrence process is driven by multiple complex and interwoven factors.Although the current standard treatment regi-mens can temporarily alleviate patients'symptoms,they still face significant challenges in effectively preventing tumor recurrence.The re-currence mechanism of this tumor is intricate and covers multiple aspects such as genomic instability,maintenance of stem cell characterist-ics and mesenchymal transformation,as well as dynamic changes in the tumor microenvironment.This article aims to comprehensively sum-marize the recurrence mechanism of glioblastoma and deeply explore potential countermeasures targeting these mechanisms,hoping to open up new perspectives and approaches for the treatment of recurrent tumors.
2.Recurrence mechanisms and treatment strategies for IDH wild-type glioblastoma
Tao WANRU ; Lv LEI ; Wang ZIJUN ; Bao LEILEI
Chinese Journal of Clinical Oncology 2025;52(6):309-313
Isocitrate dehydrogenase(IDH)wild-type glioma is a type of highly invasive brain tumor with poor prognosis and a high recur-rence rate.The recurrence process is driven by multiple complex and interwoven factors.Although the current standard treatment regi-mens can temporarily alleviate patients'symptoms,they still face significant challenges in effectively preventing tumor recurrence.The re-currence mechanism of this tumor is intricate and covers multiple aspects such as genomic instability,maintenance of stem cell characterist-ics and mesenchymal transformation,as well as dynamic changes in the tumor microenvironment.This article aims to comprehensively sum-marize the recurrence mechanism of glioblastoma and deeply explore potential countermeasures targeting these mechanisms,hoping to open up new perspectives and approaches for the treatment of recurrent tumors.
3.Research progress on the mechanisms of isocitrate dehydrogenase mutations in tumor development
Wang ZIJUN ; Tao WANRU ; Bao LEILEI
Chinese Journal of Clinical Oncology 2024;51(23):1227-1231
Isocitrate dehydrogenase(IDH)mutation occurs frequently in glioma,cholangiocarcinoma,acute myeloid leukemia,chondro sar-coma and other tumors,and it's a potential target for cancer treatment.The novel cancer metabolite 2-hydroxyglutaric acid(2-HG)pro-duced after mutation has become an important marker for cancer treatment and prognosis evaluation.IDH mutation accurately down-regu-lates various biological processes such as glucose metabolism,lipid metabolism and amino acid metabolism in tumors.In addition,IDH mutation also affects the balance of immune microenvironment and epigenetic regulation,and its mechanism of action in the occurrence and development of cancer needs to be further explored and studied.This article reviews the mechanism of action and potential therapeut-ic strategies of IDH mutation in the development of tumors,aiming to provide novel therapeutic options for patients with IDH mutation.
4.Clinical characteristics and prognostic factors of 145 patients with drug-induced liver injury
Hongli DU ; Xu LI ; Xuechun SHAN ; Yunying HU ; Leilei BAO ; Hui WANG
Academic Journal of Naval Medical University 2024;45(10):1259-1265
Objective To explore the clinical characteristics of patients with drug-induced liver injury(DILI),so as to provide references for its diagnosis and treatment.Methods The clinical data of inpatients diagnosed as DILI in The Third Affiliated Hospital of Naval Medical University(Second Military Medical University),from Jan.2017 to Dec.2021 were retrospectively analyzed,including basic information,underlying diseases,drug use history,clinical manifestations,laboratory indexes,severity and prognosis of DILI.Results Among 145 patients with DILI,112 cases(77.24%)were hepatocellular type,25 cases(17.24%)were cholestatic type,and 8 cases(5.52%)were mixed type.The types of drugs causing DILI mainly included traditional Chinese medicine,proprietary Chinese medicine and anti-infective drugs,and the proportions were 48.72%(76/156),16.03%(25/156),and 10.26%(16/156),respectively.The common clinical manifestations of DILI patients were jaundice(76.55%),poor appetite(52.41%),and fatigue(49.66%).The levels of alanine transaminase(ALT),aspartate transaminase,alkaline phosphatase(ALP),total bilirubin(TBil),γ-glutamyl transferase and albumin(ALB),as well as the length of hospital stay and severity distribution were significantly different among different types of liver injury(all P<0.05).The levels of ALT and ALB in the good prognosis group were significantly higher than those in the poor prognosis group,while the levels of TBil and international normalized ratio in the good prognosis group were significantly lower than those in the poor prognosis group(all P<0.05).Multivariate analysis showed that INR was an independent predictor of the prognosis of DILI(P<0.05).Conclusion Serum biochemistry indicators can help to identify the clinical classification and prognosis of DILI.Traditional Chinese medicine,proprietary Chinese medicine and other drugs can cause DILI.Medical staff should pay attention to it and strengthen public health education.
5.Mechanism and strategies of hypoxia-inducible factor-mediated resistance to tyrosine kinase inhibitors in hepato-cellular carcinoma
Xiaoying GE ; Dan ZHENG ; Xue JIANG ; Leilei BAO ; Jun BIAN
China Pharmacy 2024;35(10):1280-1284
The use of tyrosine kinase inhibitors (TKI) has been an important advance in the systemic treatment of hepatocellular carcinoma, but their sustained anti-angiogenic therapy leads to increased tumor hypoxia, accelerates the development of a hypoxic microenvironment and promotes the expressions of hypoxia-inducible factors (HIF), thereby inducing drug resistance of tumor patients to TKI. This paper summarizes the mechanism of action of HIF mediating TKI resistance in hepatocellular carcinoma in aspects of metabolic reprogramming, abnormal expressions of cancer and cancer-associated genes, and ferroptosis, and sorts resistance response strategies to provide reference for clinical solutions to TKI resistance issues. As results show, HIF/ glycolysis axis inhibitors (isoflavonoid genistein, simvastatin, etc.) can improve TKI resistance based on metabolic reprogramming mechanism; oncogene-targeted inhibitors combined with TKI (the combination of capsaicin and sorafenib) can improve TKI resistance based on abnormal expression of cancer and cancer-related genes; fatty acid synthase inhibitor (orlistat) can improve TKI resistance based on ferroptosis mechanism.
6.Effects of different suture-occluded models of cerebral ischemia on brain regions and behaviors in mice
Deliang LIU ; Hui LIU ; Jing REN ; Xingting YANG ; Yiyang HUANG ; Leilei BAO
Journal of Navy Medicine 2024;45(6):599-605
Objective To explore the differences of brain regions and behaviors in cerebral ischemia mouse models caused by 3 suture-occluded models.Methods A total of 120 ICR mice were randomly divided into 4 groups:sham operation group,method A group(common carotid artery to internal carotid artery 8 mm),method B group(external carotid artery to internal carotid artery 10 mm),and method C group(common carotid artery to internal carotid artery 10 mm),with 30 mice in each group.After 1.5 h of cerebral ischemia and 24 of reperfusion,mice were stained with 2,3,5-triphenyltetrazolium chloride(TTC)to observe the site of cerebral ischemia and to calculate the area of ischemia.The neuromotor function of the mice was evaluated by the Longa score.The strength of the forelimb was measured by the grip test.The stamina of the mice was evaluated by the swimming test.The permeability of the blood-brain barrier was determined by the Evans blue staining.The cerebral edema was evaluated by the calculation of brain water content.Pathological changes of brain tissues were observed by hematoxylin-eosin(H-E)staining.Results TTC staining showed different sites and areas of cerebral infarcts caused by the 3 methods in mice.No significant difference was found in the infarct area between groups A and B(P>0.05),but the infarct area of method C was significantly different from that of groups A and B(all P<0.05).No infarct was detected in the sham operation group.The results of behavioral experiments of A,B,and C groups were significantly different from those of the sham operation group(all P<0.05).No significant difference was found in the Longa score between B and C groups(P>0.05),but the Longa score in A group was significantly different from that in B and C groups(both P<0.05).There was significant difference in the result of forelimb grip strength experiment between method A and C groups(P<0.05).No significant difference was found in the swimming time between B and C groups(P>0.05),but the swimming time in A group was significantly different from that in B and C groups(both P<0.05).The results of Evans blue staining,brain water content testing,and H-E staining revealed that cerebral ischemia caused by method C resulted in more severe brain damage in mice compared with methods A and B.Conclusion The 3 suture-occluded models can cause ischemia in different brain regions of cerebral ischemia mouse models,and ischemia in the cortex is more likely to cause motor dysfunction.
7.Research progress on the mechanisms of isocitrate dehydrogenase mutations in tumor development
Wang ZIJUN ; Tao WANRU ; Bao LEILEI
Chinese Journal of Clinical Oncology 2024;51(23):1227-1231
Isocitrate dehydrogenase(IDH)mutation occurs frequently in glioma,cholangiocarcinoma,acute myeloid leukemia,chondro sar-coma and other tumors,and it's a potential target for cancer treatment.The novel cancer metabolite 2-hydroxyglutaric acid(2-HG)pro-duced after mutation has become an important marker for cancer treatment and prognosis evaluation.IDH mutation accurately down-regu-lates various biological processes such as glucose metabolism,lipid metabolism and amino acid metabolism in tumors.In addition,IDH mutation also affects the balance of immune microenvironment and epigenetic regulation,and its mechanism of action in the occurrence and development of cancer needs to be further explored and studied.This article reviews the mechanism of action and potential therapeut-ic strategies of IDH mutation in the development of tumors,aiming to provide novel therapeutic options for patients with IDH mutation.
8.Method establishment of components identification and content determination of index components in Gantaishu capsules
Xiaoli WANG ; Ping ZHU ; Yanni ZHOU ; Leilei BAO
China Pharmacy 2023;34(18):2198-2203
OBJECTIVE To establish methods to identify the chemical components of Gantaishu capsule, and determine the contents of 6 index components including glycyrrhizic acid. METHODS The chemical components of Gantaishu capsule were determined by HPLC-TOF/MS; the contents of 6 index components including glycyrrhizic acid were determined by UPLC-MS/MS. RESULTS A total of 41 chemical components were identified in Gantaishu capsules. The linear ranges of glycyrrhizic acid, mangiferin, luteolin, costunolide, oleanolic acid and berberine were 200-10 000 ng/mL(r were all greater than 0.999). The limits of quantification were 200, 20, 10, 1, 10, 0.5 ng/mL, and the limits of detection were 100, 10, 5, 0.5, 5, 0.25 ng/mL, respectively; RSDs of precision, stability (24 h) and reproducibility tests were all less than 5.0% (n=6 or n=3); the recoveries were 99.05%-101.08% (RSD were all less than 2.0%, n=6). The contents of them were 2.42-2.66, 0.85-1.16, 0.35-0.46, 6.18- 6.46, 0.99-1.29, 5.22-5.56 mg/g. CONCLUSIONS The established methods for identification and content determination are rapid and simple, and can be used for the identification of chemical components and the content determination of index components in Gantaishu capsule.
9.Research progress on therapeutic DC vaccine against melanoma
Xinyue ZHANG ; Zongguang TAI ; Quangang ZHU ; Zhongjian CHEN ; Leilei BAO
Journal of Pharmaceutical Practice 2023;41(11):643-647
Melanoma is the most aggressive skin malignant tumor, which is prone to early metastasis and relapse after treatment. Therapeutic tumor vaccines are new immunotherapies, which have the advantages of low toxicity and inhibiting tumor metastasis. Melanoma has a high mutation load and a large number of specific antigens. Currently, various types of tumor vaccines have been developed for melanoma, especially those based on dendritic cells (DC). Although the efficacy of therapeutic DC vaccines in melanoma has been confirmed by a number of studies, these vaccines still have problems such as insufficient immune effect and poor efficacy when used alone, and there is still a large room for improvement. In this paper, the current research status of therapeutic DC vaccines for melanoma was reviewed, and the research key points and optimization strategy of therapeutic DC tumor were prospected.
10.Risk factors of linezolid-related thrombocytopenia in patients in the department of hepatobiliary surgery
Xuechun SHAN ; Xu LI ; Hongli DU ; Leilei BAO ; Hui WANG
Journal of Pharmaceutical Practice 2023;41(11):694-699
Objective To provide the evidence for clinical medication safety by the investigation of the risk factors of linezolid-related thrombocytopenia in cancer patients in the department of hepatobiliary surgery. Methods Patients who received linezolid for anti-infective treatment from January 2017 to December 2021 were selected. The patients were divided into thrombocytopenia group and non-thrombocytopenia group according to whether thrombocytopenia occurred or not after administration of linezolid. The general data and laboratory indicators of the two groups were compared, and the risk factors of linezolid-related thrombocytopenia were screened by multivariate logistic regression analysis. Results A total of 104 patients were included in the study, including 84 patients who underwent surgery and 20 patients who did not. The incidence of linezolid-related thrombocytopenia was 24.0%. There were significant differences in gender, age, duration of linezolid use, platelet count, white blood cell count, alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin, creatinine, estimated glomerular filtration rate between the two groups (P<0.05); logistic regression analysis suggested that age ≥60 years (OR=7.093; P=0.017), duration of linezolid use ≥12 days (OR=4.399; P=0.035), baseline platelet count ≤200×109/L (OR=8.470; P=0.004), baseline AST≥50 U/L (OR=15.465; P<0.001), and baseline white blood cell count ≥11×109/L (OR=11.436; P=0.001) were the risk factors for linezolid-related thrombocytopenia in cancer patients. Conclusion During the treatment of linezolid in cancer patients, attention should be paid to the adverse reactions of thrombocytopenia in the patients, especially those with old age, long-term treatment, low baseline platelets, poor baseline liver function, and high baseline white blood cell counts.

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