1.Long-term efficacy analysis of salvage re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy
Guangbin GAO ; Chen ZHENG ; Qihui LI ; Qing LIU ; Wenpeng JIAO ; Yajing WU ; Yunjie CHENG ; Chang ZHAI ; Yueping LIU ; Jun WANG
Chinese Journal of Radiation Oncology 2024;33(8):711-718
Objective:To analyze clinical features, short-term efficacy and side effects of salvage re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy, to investigate the prognostic factors of re-irradiation with precise radiotherapy techniques.Methods:A retrospective analysis was performed on patients with locally recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy treated in the Fourth Hospital of Hebei Medical University from January 2008 to December 2016. The patients underwent re-irradiation therapy (re-RT) or re-irradiation therapy concurrent chemotherapy (re-CCRT). The main observation index was after-recurrence survival (ARS), which was calculated by Kaplan-Meier method for survival analysis. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox regression model.Results:A total of 109 patients were included, with a median age of 66 years (43-89 years), and a median follow-up time of 120.8 months (79.0-176.5 months). The objective response rates (ORR) and dysphagia improvement rates (DIR) in all patients were 64.2% and 63.0%, respectively. The median ARS and 1-, 3-, 5-, 8-year survival rates in all patients were 7.8 months and 32.1%, 9.2%, 7.3% and 2.3%, respectively. The median ARS and 1-, 3-, 5-years survival rates were 10.8 months and 45.9%, 13.5%, 10.8% for patients with time to recurrence (TTR) ≥24 months, significantly longer than those of 5.7 months and 25.0%, 6.9%, 5.6% for patients with TTR<24 months ( χ2=7.99, P=0.005). The median ARS in groups with re-irradiation dose of ≤50 Gy,>50-54 Gy, and>54 Gy groups were 5.7, 10.0 and 8.1 months, respectively ( χ2=6.94, P=0.031). The 1-, 3- and 5-year survival rates were 30.4%, 5.1%, and 3.8% for re-RT versus 36.7%, 20.0%, and 16.7% for re-CCRT ( χ2=2.12, P=0.145). Multivariate analysis showed that TTR ( HR=0.607, 95% CI=0.372-0.991, P=0.046) and lesion length ( HR=0.603, 95% CI=0.371-0.982, P=0.042) were the independent factors for ARS. There was no significant difference in ≥2 grade pneumonitis and 2-3 grade radiation esophagitis between the re-RT and re-CCRT groups ( χ2=0.25, P=0.619; χ2=0.51, P=0.808). The morbidity of ≥2 grade myelosuppression in the re-RT group was significantly lower than that in the re-CCRT group (3.7% vs. 36.7%, χ2=18.15, P<0.001). Conclusions:Precise re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy can alleviate dysphagia, but ARS remains poor. Re-irradiation dose range from>50-54 Gy may be suitable for locally relapse patients as salvage treatment. Patients with TTR≥24 months and lesion length ≤5 cm obtain favorable prognosis.
2.Study on efficacy and safety of oral mucosal exfoliated cells used in rapid detection of MTHFR C677T gene mutation in patients with hypertension
Jiangli YU ; Bizhen GAO ; Shuyi DANG ; Junfeng WANG ; Yunjie WEI ; Gangyan ZHOU ; Xiao DONG
Chongqing Medicine 2024;53(14):2125-2129
Objective To study the accuracy and safety of oral mucosal exfoliated cell specimens used in the bedside rapid detection of MTHFR C677T genotype by using the fluorescent probe method.Methods The outpatients and inpatients with hypertension visited and admitted in the department of cardiovascular medicine of this hospital from January 2019 to September 2020 were selected.The plasma homocysteine (Hcy) level in all patients was detected in the laboratory,a total of 482 hypertensive patients with Hcy≥10 μmol/L were se-lected,and the oral mucosal cells and whole blood sample were collected in all patients,and the genotypes of the above specimens were detected by the oral mucosal exfoliative cell fluorescent probe method and whole blood sample contrast reagents.If the two test results were inconsistent,the "gold standard" Sanger sequen-cing method was used to detect the whole blood sample for the final determination of MTHFR C677T geno-type.The coincidence rate was compared between the two detection methods,and the probability of adverse e-vents during the samples collection was observed and recorded.The accuracy and safety of fluorescence probe method for detecting MTHFR C677T genotype in the patients with oral mucosa exfoliation was evaluated.Re-sults The oral mucosal exfoliated cell samples and whole blood samples from 482 hypertensive patients were successfully collected,and no obvious adverse reactions occurred during the sampling process.The incidence rate of total mutation of MTHFR C677T gene detected by the fluorescence probe method and contrast reagent all were 73.23% (353/482),the coincidence rate of homozygous wild type (CC type) in MTHFR C677T gene detected by the two methods was 100.00% (95%CI:97.11-100.00),which of heterozygous mutant type (CT type) was 99.14% (95%CI:96.91-99.76),which of homozygous mutant type (TT type) was 99.17%(95%CI:95.47-99.85),the total coincident rate of MTHFR C677T genotype was 99.38% (95%CI:98.19-99.79)and the detection results consistency Kappa value was 0.9902.Conclusion The detection of MTHFR C677T gene mutation in oral mucosal exfoliated cells by fluorescent probe method is simple with less invasion,moreover which is rapid,safe and accurate.
3.Effect of Xielitang on TLR4/NF-κB/HIF-1α Signaling Pathway in Mice with Ulcerative Colitis
Xiaotian WANG ; Yue WANG ; Yaning BIAO ; Jingmiao GAO ; Li LI ; Yangzi LU-AI ; Yunjie YIN ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(8):142-149
ObjectiveTo explore the protective effect of Xielitang on ulcerative colitis (UC) mice induced by dextran sodium sulfate (DSS) and its possible mechanism. MethodSixty C57BL/6 mice were randomly divided into normal group, model group, sulfasalazine group and and low-, medium-, and high-dose Xielitang groups. Free drinking DSS solution to build the chronic UC model mice. Except for normal group, other groups were given 1.5% DSS for 3 cycles of drinking (days 1-7, days 22-28 and days 43-49) and distilled water for the rest of the time (days 8-21, days 29-42 and days 50-63). After the first cycle, corresponding drugs were given for 42 days. The changes of general condition, body weight and disease activity index (DAI) score of mice were daily recorded during the experiment. At the end of the treatment, serum and colon tissue samples were collected, colon length was measured, intestinal weight index and colonic mucosal injury (CMDI) score were calculated. The pathological status of colon tissue was observed by hematoxylin-eosin (HE) staining. The levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and tumour necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The gene and protein expressions of Toll like receptor 4 (TLR4), nuclear transcription factor-κB (NF-κB) and hypoxia inducible factor-1α (HIF-1α) in colon tissue was detected by Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultCompared with the normal group, the body weight, colon length and IL-10 content in the model group were significantly decreased (P<0.01), DAI score, intestinal weight index, CMDI score, IL-6 and TNF-α contents, and mRNA and protein expression levels of TLR4, NF-κB and HIF-1α in the model group were significantly increased (P<0.01). Moreover, the structure of colonic mucosa was destroyed and inflammatory cells infiltrated in the model group. Compared with model group, body weight, colon length and IL-10 content in each dose group of Xielitang were significantly increased (P<0.05, P<0.01), DAI score, intestinal weight index and CMDI score, IL-6 and TNF-α contents, mRNA and protein expression levels of TLR4, NF-κB and HIF-1α were notably decreased (P<0.05, P<0.01). The pathological injury of colon was obviously alleviated. ConclusionXielitang can significantly improve the inflammatory response of UC mice induced by DSS, and its mechanism may be related to the regulation of TLR4/NF-κB/HIF-1α signaling pathway.
4.Correlation analysis of learning initiative and on-line teaching effectiveness in medical students—with Physiology teaching as an example
Yuanlong SONG ; Yisheng LÜ ; Huamin LIANG ; Minjie ZHU ; Yunjie ZHENG ; Linlin GAO
Chinese Journal of Medical Education Research 2023;22(3):439-442
Objective:To evaluate the effects of learning initiative on teaching effectiveness.Methods:The research subjects were the 2nd year medical students of Tongji Medical College of Huazhong University of Science and Technology. The learning initiative factor was calculated from the data of the attendance registration of the on-line learning of Physiology, and the performance of the on-line test was used as an evaluation indicator of teaching effectiveness. SPSS software was used to perform correlation analysis between the learning initiative factor and teaching effectiveness. Results:We found that learning initiative could significantly affect the teaching effectiveness, with differences among different specialties. There was a positive correlation between learning initiative and teaching effectiveness in clinical and pediatric medicine, while no correlation was observed in preventive medicine and medical imaging.Conclusion:In conclusion, learning initiative can affect teaching effectiveness, and the intensity of this effect shows difference among different specialties.
5.Glutamate-releasing BEST1 channel is a new target for neuroprotection against ischemic stroke with wide time window.
Shuai XIONG ; Hui XIAO ; Meng SUN ; Yunjie LIU ; Ling GAO ; Ke XU ; Haiying LIANG ; Nan JIANG ; Yuhui LIN ; Lei CHANG ; Haiyin WU ; Dongya ZHU ; Chunxia LUO
Acta Pharmaceutica Sinica B 2023;13(7):3008-3026
Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.
6.Clinical characteristics and prognosis of severe coronal virus disease 2019 pneumonia combined with coronary artery disease in the elderly
Ruijin XU ; Ge LIU ; Yuying SU ; Juan CHEN ; Yunjie GE ; Junjie GAO ; Liu LIU
Chinese Journal of Geriatrics 2022;41(8):961-964
Objective:To investigate the clinical manifestations and prognosis of severe coronal virus disease 2019(COVID-19)pneumonia combined with coronary artery disease(CAD)in the elderly.Methods:A total of 351 old patients(≥60 years)with severe COVID-19 pneumonia combined with CAD admitted to Tongji Hospital of Wuhan from February 2020 to March 2020 were enrolled in this retrospective study.The patients were divided into CAD group(n=52)and non-CAD group(n=299). The clinical data, the changes of blood tests and cardiovascular complications were observed.Results:Compared with non-CAD group, CAD group showed a longer time of stay in hospital[(12.3±2.6)d and(9.3±2.1)d, t=3.24, P=0.002], and higher incidence of cardiovascular complications, such as myocardial infarction(7.7% and 0.0%, χ2=21.6, P<0.001), heart failure(15.4% and 0.3%, χ2=34.7, P<0.001), arrhythmia(50.0% and 12.4%, χ2=24.45, P<0.001)and all-cause mortality(15.4% and 4.3%, χ2=7.94, P=0.005). The serum levels of interleukin-2 receptor, interleukin 6, CK-MB, cTnI, NT-proBNP, D-dimer and fibrinogen were higher in CAD group than in non-CAD group.The oxygenation index was significantly lower and the blood lactic acid level was higher in CAD group than in non-CAD group. Conclusions:The aged patients with severe COVID-19 pneumonia combined with CAD show obvious inflammatory reaction, high incidence of cardiovascular complications and high mortality.
7.A novel PGAM5 inhibitor LFHP-1c protects blood-brain barrier integrity in ischemic stroke.
Chenglong GAO ; Yazhou XU ; Zhuangzhuang LIANG ; Yunjie WANG ; Qinghong SHANG ; Shengbin ZHANG ; Cunfang WANG ; Mingmin NI ; Dalei WU ; Zhangjian HUANG ; Tao PANG
Acta Pharmaceutica Sinica B 2021;11(7):1867-1884
Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate
8.Clinical application of 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus
Yunjie GAO ; Huijing WANG ; Fanghao CAI ; Yanhong MA ; Lan LAN ; Pingping REN ; Yaomin WANG ; Xiaoqi SHEN ; Jianghua CHEN ; Fei HAN
Chinese Journal of Nephrology 2021;37(10):789-794
Objective:To analyze the weight score and clinical application of 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) systemic lupus erythematosus (SLE) classification criteria in lupus nephritis patients.Methods:Lupus nephritis patients with renal biopsy results who were admitted in the First Affiliated Hospital of Zhejiang University College of Medicine between January 2014 and December 2018 were enrolled retrospectively. According to whether these patients were treated with glucocorticoids and/or immunosuppressants at the time of renal biopsy, they were divided into untreated group and post-treatment group. The weight scores were compared between the two groups, and the relationship between each weight score and remission after treatment was analyzed. Taking no remission as the end event, Cox regression analysis was used to analyze the influence of each weighted integral on the end event.Results:A total of 153 patients were enrolled, including 131 (85.6%) females. These were 70 (45.8%) patients in the untreated group and 83 (54.2%) patients in the post-treatment group. The patients in the untreated group had higher scores of fever (>38.3℃), blood system involvement, low complement and positive specific antibodies than those in post-treated group (all P<0.05). In a median follow-up of 34 (6-50) months, 99 patients (64.7%) achieved complete remission, 38 patients (24.8%) achieved partial remission and 16 patients (10.5%) had no remission. With no remission as the endpoint event, univariate Cox regression analysis showed that proliferative lupus nephritis (renal score of 10 points vs 8 points) and neuropsychiatric involvement were the risk factors (both P<0.05), while multivariate Cox regression analysis showed that neuropsychiatric involvement ( HR=4.758, 95% CI 1.324-17.101, P=0.017) was an independent risk factor. Conclusion:The weight scores of 2019 EULAR/ACR SLE classification diagnostic criteria have certain predictive value for remission of patients with lupus nephritis.
9.Diagnosis and treatment of 40 cases of gastritis cystica profunda
Shuai GONG ; Shiying YANG ; Hanbing XUE ; Yunjia ZHAO ; Yao ZHANG ; Yunjie GAO ; Haiying CHEN ; Hui DING ; Xiaobo LI ; Zhizheng GE
Chinese Journal of Digestive Endoscopy 2019;36(7):483-486
Objective To investigate the clinical,endoscopic and pathological features of gastritis cystica profunda (GCP).Methods A total of 40 patients with GCP confirmed by pathology who received endoscopic or surgical treatment at Renji Hospital,School of Medicine,Shanghai Jiaotong University from May 2013 to May 2018,were included in the retrospective analysis.The clinical data such as population composition,clinical manifestations,endoscopic findings and pathological results were summarized and analyzed.Results Among the 40 patients were predominantly males (75.0%,30/40),and the mean age of onset was 61.2 years.The most common sites were cardia (32.5%,13/40) and gastric antrum (30.0%,12/40).The clinical symptoms of the patients were atypical and it was difficult to diagnose GCP with routine endoscopy examination.The endoscopic findings were mostly type 0-Ⅱ (50.0%,20/40).GCP with neoplastic lesions accounted for 55% (22/40).Unconditional logistic regression analysis showed that male (P =0.013,OR =31.093,95% CI:2.079-464.976) and Helicobacter pylori infection (P =0.041,OR =10.225,95% CI:1.096-95.411) were risk factors for GCP with neoplastic lesions.Conclusion GCP commonly occurs in middle-aged and elderly men,and varies in different manifestations under white light endoscopy.GCP is not a benign lesion,but can also coexist with neoplastic lesions,which are mostly differentiated intramucosal cancer.

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