1.The relationship between MTHFR gene polymorphisms, plasma homocysteine levels and diabetic retinopathy in type 2 diabetes mellitus.
Jiazhong SUN ; Yancheng XU ; Yilian ZHU ; Hongyun LU ; Haohua DENG ; Youyun FAN ; Suxin SUN ; Ying ZHANG
Chinese Medical Journal 2003;116(1):145-147
OBJECTIVETo evaluate the role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and plasma homocysteine levels in patients with type 2 diabetes mellitus and diabetic retinopathy (DR).
METHODSTotal of 208 patients with type 2 diabetes mellitus and 57 controls were recruited into the study. MTHFR genetic C677T polymorphisms were determined by PCR-RFLP. Plasma total homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection.
RESULTSThe frequencies of MTHFR TT homogeneous type, CT heterogeneous type and allele T (28.18%, 41.82%, 49.09%) were significantly higher in the type 2 diabetes mellitus with diabetic retinopathy group than those without retinopathy (18.37%, 29.59%, 33.16%) and those of controls (17.54%, 28.07%, 31.58%). The presence of the T allele appeared to have a strong association with the development of diabetic retinopathy. The odds ratio was 1.94 with a 95% confidence interval of 1.31 - 2.88. Moreover, plasma homocysteine levels were remarkably higher in patients with TT or CT genotype than in patients with the CC genotype.
CONCLUSIONMTHFR gene C677T mutation associated with a predisposition to increased plasma homocysteine levels may be considered as a genetic risk factor for diabetic microangiopathy (such as DR) in Chinese patients with type 2 diabetes mellitus.
Aged ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Retinopathy ; etiology ; Female ; Genotype ; Homocysteine ; blood ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; Middle Aged ; Mutation ; Oxidoreductases Acting on CH-NH Group Donors ; genetics ; Polymorphism, Genetic
2.The relationship of methylenetetrahydrofolate reductase gene polymorphism and plasma homocysteine levels in type 2 diabetes mellitus patients with diabetic retinopathy.
Jiazhong SUN ; Yancheng XU ; Yilian ZHU ; Hongyun LU ; Haohua DENG ; Youjun FAN ; Suxin SUN ; Ying ZHANG
Chinese Journal of Medical Genetics 2003;20(2):131-134
OBJECTIVETo evaluate the role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and plasma homocysteine levels in Chinese patients with type 2 diabetes mellitus and diabetic retinopathy (DR).
METHODSMTHFR genetic C677T polymorphisms were determined by PCR-restriction fragment length polymorphism. Total plasma homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection.
RESULTSThe frequencies of MTHFR T homogenetic type and CT heterogenetic type and allele T (28.18%, 41.82%, 49.09%) in type 2 diabetic patients with diabetic retinopathy were significantly higher than those in diabetic patients without retinopathy (18.37%,29.59%,33.16%) or the normal controls (17.54%, 28.07%, 31.58%). Howerver, there were no significant differences in the frequency of MTHFR genotype and allele between the type 2 diabetic patients without retinopathy and the normal controls. The presence of T allele appeared to have a strong association with the development of diabetic retinopathy. The odds ratio was 1.94 and the 95% confidence interval was 1.31-2.88. Moreover, the plasma homocysteine levels in patients with TT or CT genotype were markedly higher than those in patients with CC genotype.
CONCLUSIONMTHFR gene C677T mutation associated with a predisposition to increase of plasma homocysteine may represent a genetic risk factor for diabetic retinopathy in Chinese type 2 diabetes mellitus.
Adult ; Alleles ; DNA ; genetics ; metabolism ; Deoxyribonucleases, Type II Site-Specific ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; complications ; genetics ; Diabetic Retinopathy ; blood ; etiology ; genetics ; Female ; Gene Frequency ; Genotype ; Homocysteine ; blood ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; Middle Aged ; Oxidoreductases Acting on CH-NH Group Donors ; genetics ; Point Mutation ; Polymorphism, Genetic
3.USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer.
Dexin YANG ; Yuqin FENG ; Haohua LU ; Kelie CHEN ; Jinming XU ; Peiwei LI ; Tianru WANG ; Dajing XIA ; Yihua WU
Journal of Zhejiang University. Science. B 2023;24(2):143-156
This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‒1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‒2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95% CI, 0.48‒1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‒1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‒0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‒0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‒8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‒6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
Humans
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Carcinoma, Non-Small-Cell Lung/genetics*
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ErbB Receptors/genetics*
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Extracellular Matrix Proteins/genetics*
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Immune Checkpoint Inhibitors/therapeutic use*
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Lung Neoplasms/genetics*
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Mutation
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Protein Kinase Inhibitors/therapeutic use*
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Proto-Oncogene Proteins p21(ras)/genetics*
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Treatment Outcome
4.Impact of antitumor regimens on the outcomes of cancer patients with COVID-19: a pooled analysis.
Haohua LU ; Yu SHI ; Kelie CHEN ; Zhi CHEN ; Haihong ZHU ; Yuequn NIU ; Dajing XIA ; Yihua WU
Journal of Zhejiang University. Science. B 2021;22(10):876-884
Since the outbreak of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) discovered in December 2019, the disease has emerged as a global pandemic (Shi et al., 2020; World Health Organization, 2020). Several studies have shown a higher incidence of COVID-19, as well as related poor outcomes in patients with malignancies as compared with those without them (Liang et al., 2020; Tian et al., 2020). The impact of cancer on COVID-19 may be attri‑buted to the use of antitumor treatments that may disturb the host response to SARS-CoV-2 infection (Wang et al., 2020), while the current studies on this topic have drawn controversial conclusions. Some implied that anticancer treatments might elevate the risk of death (García-Suárez et al., 2020; Liu et al., 2020). On the contrary, others pointed out that this association is not significant (Brar et al., 2020; Lee et al., 2020a). Although previous systematic reviews have investigated this important issue (Wang and Huang, 2020), the heterogeneity of findings is obvious and the general conclusion has remained unclear. Considering this ambiguity, it is difficult for clinicians to make therapeutic decisions when facing patients with both cancer and COVID-19; therefore, a high-quality and accurate evaluation of the impact of anticancer treatments on COVID-19 patients is necessary. Accordingly, we conducted a pooled analysis with the original data of each patient for the first time to provide a comprehensive perspective into the association between anticancer regimens and the outcomes of cancer patients with COVID-19.
Adult
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Aged
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Aged, 80 and over
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COVID-19/complications*
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Female
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Humans
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Male
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Middle Aged
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Neoplasms/therapy*
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SARS-CoV-2
5.Application of magnetic surgery technique in thoracic surgery
ZHANG Yong ; YAN Xiaopeng ; SHI Aihua ; WANG Haohua ; MA Feng ; LIU Shiqi ; LU Yi ; FU Junke
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(03):336-342
The earliest research of magnetic surgery was the application of magnetic anastomotic device to anastomose the blood vessels. Now, it has been widely used for anastomosis of blood vessels, gastrointestinal tract and biliary tract. The concept of "magnetic surgery" was named firstly by LU Yi in 2010 and magnetic surgery was classified into magnetic anchoring technique, magnetic navigation technique, magnetic compression technique, magnetic tracing technique, and magnetic suspension technique. The applications of magnetic surgery in the field of thoracic surgery mainly include magnetic compression technique, magnetic anchoring technique and magnetic navigation technique. This paper summarizes the application of magnetic surgery in thoracic surgery and prospects its future development in the field of thoracic surgery.
6.Localization of small pulmonary nodules with magnetic beads: An animal experiment
Lu LV ; Aihua SHI ; Xiaopeng YAN ; Zhixuan ZHANG ; Guxiang ZHOU ; Junke FU ; Feng MA ; Haohua WANG ; Yi LV ; Yong ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(11):1360-1364
Objective To investigate the feasibility of using magnetic beads to locate small pulmonary nodules. Methods Twelve rabbits were randomly divided into two groups, 6 in each group. One group underwent thoracotomy after anesthesia and the other group underwent percutaneous puncture under the guidance of X-ray. One and two cylindrical tracer magnets (magnetic beads) with a diameter of 1 mm and a height of 3 mm were injected adjacent to the imaginary pulmonary nodules in left lung in each group. The magnetic beads beside the imaginary nodules were attracted by a pursuit magnet with a diameter of 9 mm and a height of 19 mm. The effectiveness of localization by magnetic beads were determined by attraction between tracer and pursuit magnets. Results All processes were uneven in 12 rabbits. There was micro hemorrhage and no hematoma in the lung tissue at the injection site of the magnetic beads. When tracked with the pursuit magnets, there was one bead divorce in cases that one bead was injected, but no migration or divorce of the magnetic beads in cases that two magnetic beads were simultaneously injected to localize the small pulmonary nodules. Conclusion The feasibility of using magnetic beads to locate small pulmonary nodules has been preliminarily verified.