1.Analysis of AZF gene microdeletions on Y chromosome in male infertility patients from Dongguan
International Journal of Laboratory Medicine 2015;(6):791-792,795
Objective The multiple polymerase chain reaction(PCR) technique was adopted to detect AZF microdeletion of Y chromosome in 120 patients with idiopathic oligozoospermia and azoospermia and contemporaneous 60 cases of normal semen rou‐tine examination in the outpatient department .At the same time the peripheral blood chromosome karyotype analysis was performed on these 120 patients .Methods Multiple PCR (Polymerase chain reaction) technique were used to analyze 15 locus of the azoosper‐mia factor (AZF) in the 120 patients with idiopathic azoospermia and oligozoospermia and 60 mormal cases .using the Karyotype a‐nalysis technique to analyze karyotype of the 120 male infertile patients ,at the same time .Results Among 120 cases of male infer‐tility ,no obvious abnormal karyotype was found .23 cases were detected AZFc deletions with the detection rate of 19 .2% ,no mi‐crodeletions at other loci were detected .Conclusion AZFc is the major candidate gene for AZF gene screening in male infertility pa‐tients from this area .The Y chromosome microdeletion is the important cause leading to male infertility .
2.Regulation and control of transcription factor Cup2 on Cu,2+ metabolism and oxidative stress in Candida albicans
Jinyu ZHANG ; Lihong WANG ; Yulin QIN ; Lulu ZHANG ; Yuanying JIANG ; Yongbing CAO
Journal of Pharmaceutical Practice 2017;35(3):224-228
Objective To detect the transcription factors of copper ion (Cu,2+) metabolism and oxidative stress by Candida albicans knocked down different transcription factors.Methods Spot assay, growth curve were used.Results The sensitivity to Cu,2+ in Cup2Δ/Δ was increasing and the growth of Cup2Δ/Δ was inhibited in 5 mmol /L Cu,2+ medium.The results showed that Cup2Δ/Δ also increased the sensitivity to H2O2, interestingly, Cu,2+and H2O2 played a synergistic antifungal effect.The tolerance of Cup2Δ/Δ and SN250 to H2O2 induced oxidative stress was increased after BCS chelating Cu,2+.In the fluconazole, miconazole and ketoconazole susceptibility experiments, Cup2Δ/Δ did not show susceptibility to azole drugs.Conclusion Knockout transcription factor Cup2, which could increase the sensitivity to Cu,2+ and H2O2in Candida albicans.Transcription factor Cup2 might be involved in the regulation and control of Candida albicansmetabolism on Cu,2+ and oxidative stress induced by H2O2, but not involved in the regulation and control of drug resistance to azole drugs.
3.Impact of adjuvant transcatheter arterial chemoembolization with anti-tumor drug for prevention early recurrence of hepatocellular carcinoma patients with microvascular invasion after radical hepatectomy
Peng LIU ; Yuwei XIE ; Luxun ZHANG ; Xiangyu XU ; Yixiu WANG ; Jinyu PEI ; Bin TAN ; Cong WANG ; Kui LIU ; Kun LI ; Jinzhong PANG ; Jingyu CAO
Chinese Journal of Hepatobiliary Surgery 2021;27(9):652-657
Objective:To study combined adjuvant transcatheter arterial chemoembolization (TACE) with anti-tumor drug treatment on early hepatocellular carcinoma (HCC) recurrence in patients with microvascular invasion (MVI) after partial hepatectomy with curative intent.Methods:The clinical and pathological data of 169 patients with HCC who underwent partial hepatectomy with curative intent from January 2015 to December 2018 at the Affiliated Hospital of Qingdao University were retrospectively analyzed. MVI was diagnosed by postoperative histopathology. There were 147 males and 22 females, with the median age 56 years(ranged 32-79 years). The patients were divided into surgery group ( n=62, patients who did not receive adjuvant therapy), TACE group ( n=42, patients who only received TACE) and combined group ( n=65, patients who received TACE with anti-tumor drug) according to the therapies after resection. Patients in each group were further divided into grade M1 (mild) and grade M2 (severe) subgroups according to the severity of MVI. All patients were followed-up for observing tumor recurrence. The relapse-free survival in the three groups were compared using the Kaplan-Meier method and the log-rank test was used to compare the tumor-free survival rates. Results:The tumor-free survival rates of 169 patients at 1 and 2 years after operation were 59.2% and 40.8%. The tumor-free survival rates at 1 and 2 years after operation were 45.2% and 25.8% in surgery group, 61.9% and 40.5% in TACE group, 70.8% and 52.3% in combined group respectively. The differences among the three groups were significant: TACE group was better than surgery group, and combined group was better than TACE group, combined group was better than surgery group (all P<0.05). In TACE group and combined group, tumor-free survival rates of M1patients better than M2 patients, and the difference was significant ( P<0.05). Among M1 patients and M2 patients, tumor-free survival rates of combined group patients were better than surgery group and TACE group, the difference was significant (all P<0.05). The cumulative tumor-free survival rate was not significantly affected by different antineoplastic agents. Conclusion:Adjuvant TACE reduced the early recurrence rate of HCC patients with MVI. Adjuvant TACE combined with anti-tumor drug further reduced early tumor recurrence.
4.Efficacy comparison of robot-assisted percutaneous screw implantation and free-hand open screw implantation by Wiltse approach in the treatment of thoracolumbar fracture
Shengyang DU ; Jun DAI ; Zhentao ZHOU ; Bingchen SHAN ; Xiaofeng LIU ; Peng ZHANG ; Yingzi ZHANG ; Fengxian JIANG ; Jinyu BAI ; Lei CAO ; Xiaozhong ZHOU
Chinese Journal of Trauma 2022;38(2):109-115
Objective:To compare the clinical efficacy of robot-assisted percutaneous screw implantation and free-hand open screw implantation by Wiltse approach in the treatment of thoracolumbar fracture.Methods:A retrospective cohort study was performed to analyze the clinical data of 71 patients with thoracolumbar fracture admitted to Second Affiliated Hospital of Soochow University from May 2018 to May 2020. There were 52 males and 19 females, with age range of 22-54 years[(41.0±7.8)years]. Of all, 33 patients were treated with robot-assisted percutaneous screw implantation (Group A) and 38 patients were treated with free-hand open screw implantation by Wiltse approach (Group B). Following parameters were measured, including frequency of radiation exposure, operation time, intraoperative blood loss, length of hospital stay, incidence of complications, rate of fracture healing at 3 months and 6 months postoperatively, visual analogue scale (VAS) and Oswestry dysfunction index (ODI) at 3 days, 3 months, 6 months postoperatively and at the last follow-up, anterior vertebral body height ratio and sagittal Cobb angle preoperatively, at 3 days postoperatively and at the last follow-up, and rate of screw implantation of grade A and B and rate of facet joint violation at 3 days postoperatively.Results:All patients were followed up for 10-24 months[(15.2±4.4)months]. Frequency of radiation exposure and operation time showed no statistical differences between the two groups (both P>0.05). Intraoperative blood loss was 100(100, 135)ml in Group A, less than 160(120, 200)ml in Group B ( P<0.01). Length of hospital stay was 8(7, 11) days in Group A, shorter than 12(10, 16)days in Group B ( P<0.01). There were no complications such as infection, spinal nerve injury or cerebrospinal fluid leakage in both group. There were no significant differences between the two groups in the rate of fracture healing at 3 and 6 months postoperatively (all P>0.05). VAS and ODI in Group A was 3(2, 4)points and 21(18, 23)points at 3 days postoperatively, lower than 4 (3, 5)points and 27(20, 32)points in Group B ( P<0.05 or 0.01), and the two groups showed no significant differences in VAS and ODI at other time points (all P>0.05). There were no significant difference in the anterior vertebral body height ratio or sagittal Cobb angle between the two groups at 3 days postoperatively and at the last follow-up (all P>0.05). Rate of screw implantation of grade A and B was 96.5% (191/198) in Group A, higher than 90.4% (206/228) in Group B ( P<0.05). Rate of facet joint violation was 4.0%(8/198) in Group A, lower than 11.8% (27/228) in Group B ( P<0.01). Conclusion:For thoracolumbar fracture, robot-assisted percutaneous screw implantation is superior to free-hand open screw implantation by Wiltse approach in terms of less bleeding, shorter hospitalization, earlier pain alleviation, higher accuracy of screw implantation and lower risk of facet joint violation.
5.Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor.
Qian LI ; Tao SUN ; Hua ZHANG ; Wei LIU ; Yu XIAO ; Hongqi SUN ; Wencheng YIN ; Yanhong YAO ; Yangchun GU ; Yan'e LIU ; Fumei YI ; Qiqi WANG ; Jinyu YU ; Baoshan CAO ; Li LIANG
Chinese Journal of Lung Cancer 2022;25(3):137-146
BACKGROUND:
The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear.
METHODS:
A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization.
RESULTS:
There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not.
CONCLUSIONS
In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use*
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Glucuronosyltransferase/genetics*
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Humans
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Lung Neoplasms/drug therapy*
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Mutation
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Polymorphism, Genetic
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Retrospective Studies
6.Tetrahedral DNA nanostructures synergize with MnO2 to enhance antitumor immunity via promoting STING activation and M1 polarization.
Siping LIANG ; Jiaying LI ; Zhengyu ZOU ; Miao MAO ; Siqi MING ; Fan LIN ; Ziyan ZHANG ; Can CAO ; Jinyu ZHOU ; Yuanqing ZHANG ; Jiaping LI ; Minhao WU
Acta Pharmaceutica Sinica B 2022;12(5):2494-2505
Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn2+ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn2+, we constructed a TDN-MnO2 complex and found that it displayed a much higher efficacy than TDN plus Mn2+ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO2. These findings provide new therapeutic opportunities for cancer therapy.