1.The role of DNA methylation detection in the early diagnosis and prognosis of lung cancer
Xinwen ZHANG ; Shixuan PENG ; Qing YANG ; Jiating ZHOU ; Xuan ZHANG ; Zilan XIE ; Mengle LONG ; Qingyang WEN ; Yi HE ; Zhi LI ; Yongjun WU
Chinese Journal of Laboratory Medicine 2024;47(4):371-378
Lung cancer is the leading type of cancer death, and most patients with lung cancer are diagnosed at an advanced stage and have a very poor prognosis. Although low-dose computed tomography (LDCT) has entered the clinic as a screening tool for lung cancer, its false-positive rate is more than 90%. As one of the epigenetic modifications of research hotspots, DNA methylation plays a key role in a variety of diseases, including cancer.Hypermethylation of tumor suppressor genes and hypomethylation of proto-oncogenes are important events in tumorigenesis and development. Therefore, DNA methylation analysis can provide some useful information for the early screening, diagnosis, treatment and prognosis of lung cancer. Although invasive methods such as tissue biopsy remain the gold standard for tumor diagnosis and monitoring, they also have limitations such as inconvenience in sampling. In recent years, there has been a rapid development of liquid biopsy, which can detect primary or metastatic malignancies and reflect the heterogeneity of tumors. In addition, the blood sample can be collected in a minimally invasive or non-invasive format and is well tolerated in older and frail patients. This article explores some of the emerging technologies for DNA methylation analysis and provides an overview of the application of DNA methylation in the diagnosis and treatment of lung cancer.
2.Correlation study between advanced age and inferior prognosis in stage Ⅱ colorectal cancer patients
Ruoxin ZHANG ; Zilan YE ; Junyong WENG ; Xinxiang LI
China Oncology 2024;34(5):485-492
Background and purpose:With the aging population,the number of elderly patients with colorectal cancer(CRC)is increasing.To date,elderly patients with stage Ⅱ CRC often receive a weakened chemotherapy regimen or even no chemotherapy after radical surgery,and It is still unclear whether this will lead to adverse oncological outcomes.This study aimed to explore the prognostic impact of advanced age on stage Ⅱ CRC patients after removing bias through a multivariate COX regression approach.Methods:We retrospectively collected data of 3314 colorectal cancer patients with postoperative pathology of stage Ⅱ,no history of previous tumors,no secondary primary tumors within 5 years after surgery and no preoperative neoadjuvant therapy.This study was reviewed by the medical ethics committee of Fudan University Shanghai Cancer Center(ethics number:050432-4-2108*).The optimal threshold for calculating age relative to survival using survminer package of R software(version 3.0)(surv_cutpoint algorithm)was 73 years.We compared the clinical and pathological characteristics,overall survival(OS)and disease-free survival(DFS)between the older group(age>73 years)and the younger group(age≤73 years).The alignment diagram prediction model was drawn using the survival package and RMS package.Results:The elderly and non-elderly groups were evenly comparable in terms of gender,tumor location,differentiation,vascular invasion,perineural invasion and pT stage.Multivariate COX regression showed that advanced age was an independent prognostic risk factor for OS[hazard ratio(HR)=3.725(3.051-4.549),P<0.001]and DFS[HR=2.431(2.029-2.912),P<0.001].The nomogram(alignment diagram)prediction model constructed based on multivariate COX regression could effectively evaluate the prognosis of stage Ⅱ CRC patients and provide guidance for practical clinical work.Conclusion:In stage Ⅱ CRC patients,older age is associated with shorter OS and DFS.Adequate intensity of adjuvant chemotherapy may be necessary.Treatment decisions can be adjusted based on the predicted model scores of the patient's alignment diagram.
3.Exploring the guiding role of the number of adverse pathological features in risk stratification for recurrence of stage Ⅰ-Ⅲ colorectal cancer:a retrospective cohort study of 9875 cases
Junyong WENG ; Zilan YE ; Ruoxin ZHANG ; Qi LIU ; Xinxiang LI
China Oncology 2024;34(6):527-536
Background and purpose:According to current consensus,adverse high-risk pathological features are only associated with adjuvant therapy for stage Ⅱ colorectal cancer(CRC).As important prognostic factors,we further explored the possibility of identifying patients with potential recurrence and poor prognosis based on these incorporating high-risk pathological features.Methods:This is a cohort study.A retrospective analysis was conducted on clinical data of CRC patients who underwent surgical treatment at the Second Department of Colorectal Surgery,Fudan University Affiliated Shanghai Cancer Center from 2008 to 2018.This study was approved by the Ethics Committee of the Fudan University Shanghai Cancer Center(approval No.:050432-4-2108*),and the study complies with the Declaration of Helsinki.A total of 9875 patients were enrolled,including 5859 males and 4016 females,aged[M(IQR)]60(16)years(range:16 to 94).Median follow-up time was 1779.0 days[95%CI:1750.1-1807.9].We used the Kaplan-Meier method to plot survival curves for different groups.Cox multivariate analysis was used to identify independent risk factors for 5-year overall survival(OS),disease-free survival(DFS)and recurrence-free survival(RFS).Finally,a column chart model was constructed to evaluate and stratify patient prognosis.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this cohort study.Results:According to the number of incorporating high-risk pathological features,patients were divided into five groups:Hr_0 group(0 incorporating high-risk pathological feature),Hr_1 group(1 incorporating high-risk pathological feature),Hr_2 group(2 incorporating high-risk pathological features),Hr_3 group(3 incorporating high-risk pathological features),and Hr_4 group(4 or more incorporating high-risk pathological features).The Kaplan-Meier survival curve results indicated significant differences in OS,DFS and RFS among different groups(all P<0.001).Subgroup analysis was conducted on stage Ⅱ colorectal cancer,and the survival curves of OS,DFS and RFS in different Hr groups overlapped with each other.Compared to the overall population,the survival differences in different groups were significantly reduced,indicating that stage Ⅱ colon cancer patients with incorporating high-risk pathological features may benefit from adjuvant chemotherapy.The independent prognostic factors for RFS included age,pT stage,pN stage and Hr group.The survival curves of OS,DFS and RFS indicated that the prognosis of Hr_4 group was significantly worse than that of stage Ⅲc patients;5.2%and 14.1%of stage Ⅰ and Ⅱ patients had two or more incorporating high-risk pathological features(Hr group≥2),respectively.Finally,a column chart model was constructed by incorporating the independent prognostic risk factors for CRC mentioned above.The calibration curve showed a good consistency between the actual observations and the predictions made by the nomogram,and the decision curve analysis(DCA)indicated that the model constructed in this study had good efficacy in stratifying recurrence.Conclusion:The number of incorporating high-risk pathological features is an independent prognostic factor for RFS in patients with stage Ⅰ-ⅢCRC.Combining it as a multiclass variable with age,pT and pN stage has good prognostic stratification and recurrence stratification efficacy,which is expected to guide clinical treatment.
4.Clinical efficacy of AERD in the treatment of residual aortic dissection on Stanford type B aortic dissection patients after endovascular repair
Jinglong ZHANG ; Jia CHEN ; Chao LI ; Zilan SUN ; Zilin LI ; Jian ZUO
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(6):331-334
Objective:Evaluate the safety and efficacy of aortic endovascular remodeling device (AERD) in the treatment of residual aortic dissection on Stanford type B aortic dissection patients after endovascular repair.Methods:Adopting a prospective cohort study design, according to the inclusion and exclusion criteria, a total number of 60 patients with Stanford B-type aortic dissection after TEVAR surgery from January 2022 to December 2023 were included. Collecting CTA imaging data of patients before and after endovascular treatment with AERD and using computer 3D reconstruction fluid dynamics to evaluate distal aortic remodeling.Results:The incidence of major adverse events and mortality rate associated with aortic dissection within 30 days were 0 after endovascular treatment with AERD. In the short term, AERD was safe for the treatment of residual aortic dissection on Stanford type B aortic dissection patients after endovascular repair. Endovascular treatment with AERD significantly increased the volume of the true lumen of the aorta in the dissection segment, with an increase of 88.44%. At the same time, endovascular treatment with AERD significantly reduced the volume of the false lumen of the aorta in the dissection segment, with a decrease of 61.04%. Endovascular treatment with AERD has no significant effect on the longest true lumen diameter of distal aorta of stent and upper margin aorta of superior mesenteric artery. Comparing to the longest diameter of the true lumen of the aorta, the change in the shortest diameter of the true lumen of the aorta is more significant, with the shortest diameter of true lumen of distal aortic of the stent increasing by 32.29%, the shortest diameter of true lumen of the narrowest part of the aorta increasing by 204.15%, the shortest diameter of true lumen of the upper margin aorta of superior mesenteric artery increasing by 80.76%, the shortest diameter of true lumen of the lower edge aorta of the renal artery increasing by 115.26%, the shortest diameter of the opening of the left iliac artery increasing by 152.01%, and the shortest diameter of opening of the right iliac artery increasing by144.21%.Conclusion:AERD is safe and effective in the treatment of residual aortic dissection on Stanford type B aortic dissection patients after endovascular repair. Endovascular treatment with AERD promotes true lumen dilation and false lumen reduction in the early postoperative stage and promotes benign remodeling of the distal aorta after TEVAR surgery.
5.Influence and mechanism of intolerance of uncertainty on anxiety
Xiaomei ZHANG ; Leran WANG ; Zilan ZHANG ; Letian YANG ; Junyuan PENG ; Xichao WANG ; Hao WU
Sichuan Mental Health 2023;36(1):80-84
The purpose of this paper is to review the research on the influence and mechanism of intolerance of uncertainty (IU) on anxiety both at home and abroad in recent years. IU refers to the individual's disgust response due to the intolerance of perceived lack of prominent, critical or sufficient information, and it has individual tendency. IU plays an important role in the occurrence and development of anxiety, but the specific process and mechanism remain unclear. This paper reviews the influence of IU on anxiety, and clarifies its mechanism of action on the generation and development of anxiety from the perspectives of cognition, emotion and behavior, so as to provide references for preventing the development of general anxiety into anxiety disorders and developing new psychological intervention and treatment strategies.
6. Interactions and clinical significance of gut microbiota and levothyroxine
Jiating ZHOU ; Zilan XIE ; Zhi LI ; Jiating ZHOU ; Zilan XIE ; Zhi LI ; Jiating ZHOU ; Zilan XIE ; Zhi LI ; Jiating ZHOU ; Zilan XIE ; Zhi LI ; Xuan ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(11):1307-1314
Levothyroxine is a class of thyroid hormone medication mainly used in the clinical treatment of thyroid hormone replacement therapy and thyrotropin suppression therapy. In recent years, studies have found a close correlation between the human gut microbiota and the occurrence and development of thyroid diseases, as well as changes in thyroid hormone levels. Therefore, understanding the impact of levothyroxine on the gut microbiota, as well as the effects of the gut microbiota on the metabolism and absorption of levothyroxine, is of great significance for the treatment of thyroid diseases and the rational use of clinical medication. This article explores the interaction between the gut microbiota and levothyroxine and summarizes the current clinical findings of the gut microbiota in levothyroxine therapy.
7.Shoot rot of Zizania latifolia and the first record of its pathogen Pantoea ananatis in China.
Zilan XIAO ; Jianping DENG ; Xiaojun ZHOU ; Liyan ZHU ; Xiaochan HE ; Jingwu ZHENG ; Deping GUO ; Jingze ZHANG
Journal of Zhejiang University. Science. B 2022;23(4):328-338
The aquatic grass Zizania latifolia grows symbiotically with the fungus Ustilago esculenta producing swollen structures called Jiaobai, widely cultivated in China. A new disease of Z. latifolia was found in Zhejiang Province, China. Initial lesions appeared on the leaf sheaths or sometimes on the leaves near the leaf sheaths. The lesions extended along the axis of the leaf shoots and formed long brown to dark brown streaks from the leaf sheath to the leaf, causing sheath rot and death of entire leaves on young plants. The pathogen was isolated and identified as the bacterium Pantoea ananatis, based on 16S ribosomal RNA (rRNA) gene sequencing, multilocus sequence analysis (atpD (β-subunit of ATP synthase F1), gyrB (DNA gyrase subunit B), infB (translation initiation factor 2), and rpoB (β-subunit of RNA polymerase) genes), and pathogenicity tests. Ultrastructural observations using scanning electron microscopy revealed that the bacterial cells colonized the vascular tissues in leaf sheaths, forming biofilms on the inner surface of vessel walls, and extended between vessel elements via the perforated plates. To achieve efficient detection and diagnosis of P. ananatis, species-specific primer pairs were designed and validated by testing closely related and unrelated species and diseased tissues of Z. latifolia. This is the first report of bacterial sheath rot disease of Z. latifolia caused by P. ananatis in China.
Pantoea/genetics*
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Plant Diseases/microbiology*
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Poaceae/microbiology*
;
Virulence
8.Small molecules targeting the innate immune cGAS‒STING‒TBK1 signaling pathway.
Chunyong DING ; Zilan SONG ; Ancheng SHEN ; Tingting CHEN ; Ao ZHANG
Acta Pharmaceutica Sinica B 2020;10(12):2272-2298
Multiple cancer immunotherapies including chimeric antigen receptor T cell and immune checkpoint inhibitors (ICIs) have been successfully developed to treat various cancers by motivating the adaptive anti-tumor immunity. Particularly, the checkpoint blockade approach has achieved great clinic success as evidenced by several U.S. Food and Drug Administration (FDA)-approved anti-programmed death receptor 1/ligand 1 or anti-cytotoxic T lymphocyte associated protein 4 antibodies. However, the majority of cancers have low clinical response rates to these ICIs due to poor tumor immunogenicity. Indeed, the cyclic guanosine monophosphate-adenosine monophosphate synthase‒stimulator of interferon genes‒TANK-binding kinase 1 (cGAS‒STING‒TBK1) axis is now appreciated as the major signaling pathway in innate immune response across different species. Aberrant signaling of this pathway has been closely linked to multiple diseases, including auto-inflammation, virus infection and cancers. In this perspective, we provide an updated review on the latest progress on the development of small molecule modulators targeting the cGAS‒STING‒TBK1 signaling pathway and their preclinical and clinical use as a new immune stimulatory therapy. Meanwhile, highlights on the clinical candidates, limitations and challenges, as well as future directions in this field are also discussed. Further, small molecule inhibitors targeting this signaling axis and their potential therapeutic use for various indications are discussed as well.
9.Correlation analysis between thrombelastography and conventional coagulation indexes in breast cancer patients
Zilan LYU ; Binlin WANG ; Bianqin GUO ; Yang ZHANG ; Lixiang WU
International Journal of Laboratory Medicine 2019;40(2):218-221
Objective To analyze the correlation between thrombelastography (TEG) and conventional coagulation indexes in breast cancer patients, and to compare the differences between the two methods in the detection of coagulation function in breast cancer patients.Methods Retrospectively analyzed the clinical data of180patients with breast cancer who were performed TEG, coagulation and blood test in the same day in our hospital from November 2016to May 2017.Linear correlation and regression analysis were performed among the parameters.The differences of positive rates of TEG parameters and conventional coagulation indexes were compared.Results The R value of TEG parameters of breast cancer patients was positively correlated with K and APTT, and negatively correlated withα-Angle, MA, CI, DD, FDPs.K was positively correlated with APTT and TT, and negatively correlated withα-Angle, MA, FIB, DD, FDPs and PLT.α-Angle was positively correlated with MA, CI, FIB, DD, FDPs and PLT.MA was positively correlated with CI, FIB, DD, FDPs and PLT.CI was positively correlated with FIB, DD, FDPs and PLT.α-Angle, MA and CI were all negatively correlated with APTT and TT, the difference were statistically significant (P<0.05).A linear regression equation of TEG parameters and coagulation indexes was obtained.There was no significant difference between TEG detection positive rate and conventional coagulation test (P>0.05).Conclusion There are significant correlation between the TEG parameters and routine coagulation or platelet, and the results are consistent.
10.Correlation analysis between thrombelastogram and coagulation test and platelet count in patients with malignant tumor
Zilan LV ; Binlin WANG ; Yang ZHANG ; Bianqin GUO ; Bo LONG ; Xiaohua WANG ; Lixiang WU
International Journal of Laboratory Medicine 2018;39(4):443-446,449
Objective To analyze the correlation between thrombelastography(TEG)and coagulation, platelet count(PLT)in patients with malignant tumor.Methods Retrospectively analyzed the clinical data of 241 cases with tumor who were performed TEG,coagulation and blood test in the same day in Chongqing Cancer Institute from November 2016 to March 2017.Linear correlation and regression were carried out to an-alyze relationship among the parameters.The number of patients with positive blood clotting,PLT and TEG parameters were counted,and the χ2test was used to compare the difference between them.Using Mann-Whit-ney U test to compare the differences between multiple parameters of liver cancer,breast cancer,and pancreatic cancer.Results The R value of TEG parameters in patients with malignant tumor was positively correlated with APTT,negatively correlated with TT,DD and FDPs.K was positively correlated with APTT and TT, and negatively correlated with FIB and PLT.The relationship between α and FIB,PLT were positive,between APTT and TT were negative.MA was positively correlated with FIB and PLT,negatively correlated with TT, CI was positively correlated with FIB and PLT,and negatively correlated with APTT(P<0.05).The correla-tion between FIB,PLT and MA was the highest.And the linear regression equation of TEG parameters and coagulation indexes was obtained.The positive rate of TEG was lower than that of coagulation(P<0.05). Same certain differences of TEG and coagulation parameters were existed in liver cancer,breast cancer and pancreatic cancer patients.Conclusion TEG is significantly associated with PLT and conventional coagulation test,and the results of TEG and conventional coagulation test are consistent to a certain degree,but the overall agreement is generally not interchangeable.TEG might be play a complementary role with coagulation tests and platelet counts.And the TEG of different cancer types is not exactly the same as the coagulation parameters.

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