1.Expression and clinical significance of Hsp90α in colon adenocarcinoma
Yang ZHANG ; Xiaoting WU ; Fang WANG ; Xingchen DAI ; Yuhuan ZHANG ; Yujing GAO
Chinese Journal of Clinical and Experimental Pathology 2024;40(8):845-852
Purpose To investigate the expression and po-tential clinical value of heat shock protein 90α(Hsp90α)in co-lon adenocarcinoma.Methods The expression level of Hsp90αin colon adenocarcinoma and its relationship with clinicopatho-logical features,prognosis and immune cell infiltration were ana-lyzed by bioinformatics and immunohistochemistry.The prolifer-ation ability of colon cancer cells before and after Hsp90AA1 knockout was detected by CCK-8 cell proliferation assay and plate cloning assay.Results The bioinformatics tools showed that Hsp90AA1 was abnormally higher in colon cancer tissues than adjacent tissues,and the higher the expression level,the worse the prognosis of patients.The expression of Hsp90AA1 was positively correlated with the infiltration levels of CD4+T cells(Th2),CD8+T cells,myeloid inhibitory cells,Tregs cells,neutrophils,macrophages,M1 macrophages and M2 macropha-ges.Immunohistochemical results showed that the expression of Hsp90α in colon cancer tissues was significantly higher than in its adjacent tissues.The expression of Hsp90α was related to age(P<0.05),not related to gender,tumor size,location,clini-cal classification,differentiation degree,tumor node metastasis,lympho-vascular invasion,perineural invasion(P>0.05).The high expression of Hsp90α was an independent risk factor for the prognosis of colon cancer patients.The results of cell experi-ments showed that Hsp90AA1 knockout inhibited the growth and proliferation of colon cancer cells.Conclusion Hsp90α is highly expressed in colon adenocarcinoma,which may be a po-tential molecular marker for poor prognosis of colon adenocarci-noma.
2.Rapid health technology assessment of linaclotide in the treatment of constipated irritable bowel syndrome
Yujing LENG ; Hufeng FANG ; Hao YANG ; Dan SU
China Pharmacy 2023;34(18):2263-2268
OBJECTIVE To comprehensively evaluate the effectiveness, safety and economics of linaclotide in the treatment of constipated irritable bowel syndrome (IBS-C), and to provide the evidence-based basis for clinical application. METHODS Rapid health technology assessment method was adopted; PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang data, VIP database, SinoMed, and related HTA websites were searched. Systematic review/meta-analysis, HTA reports and pharmacoeconomic research about linaclotide were collected. After literature screening, data extraction and quality evaluation, descriptive analysis was used to classify and summarize the research results. RESULTS A total of 11 literature were included, involving 7 systematic reviews/meta-analyses and 4 pharmacoeconomic research. In terms of effectiveness, compared with placebo, linaclotide could achieve FDA specified endpoint and European Medicines Agency-recommended endpoint faster, significantly improved patients’ complete spontaneous bowel movements (CSBM), abdominal pain, constipation and quality of life, and relieved patients’ global symptoms; compared with the indirect evidence of lubiprostone, plecanatide and tenapanor, the efficacy of linaclotide at the FDA specified endpoint, CSBM, abdominal pain relief, and global relief response were the best. In terms of safety, the incidence of overall adverse drug reactions, diarrhea and flatulence caused by linaclotide were significantly higher than placebo,but patients can tolerate them. In terms of economics, compared with traditional therapeutic drugs, linaclotide showed an economic advantage. CONCLUSIONS Linaclotide has advantages in efficacy, safety and economics in the treatment of IBS-C. It is an effective strategy for the treatment of IBS-C.
3.Introduction to revision of Technical Specification for Occupational Health Surveillance
Chen YU ; Dehong LI ; Daoyuan SUN ; Zubing WANG ; Chaoqiang JIANG ; Xunmiao ZHANG ; Yongjian YAN ; Weiming YUAN ; Yiqun XUAN ; Xin QIAO ; Yujing XIA ; Qiuhong ZHU ; Qiang HOU ; Hong WANG ; Yiwen JIANG ; Xuetao ZHANG ; Fang QI ; Xiangpei LÜ ; Huanqiang WANG
China Occupational Medicine 2023;50(2):209-216
To revise GBZ 188 Technical Specification for Occupational Health Surveillance based on national laws, regulations, standards, specifications and legal documents of occupational disease, and combination with the actual situation in China. The main modifications are as follows: the occupational health surveillance for workers exposed to toluene (xylene may implement by reference), bromopropane, methyl iodide, ethylene oxide, chloroacetic acid, indium and its compounds, coal tar, coal tarasphalt, asphalt, β-naphthylamine, dust of metal and its compounds(tin, iron, antimony, barium and its compounds), hard metal dust, erionite dust, low temperature, laser, tick-borne encephalitis virus, Borrelia burgdorferi, and human immunodeficiency virus, for scraper or grind operators, and underground workers using squatting or kneeling position, crawling position, side-lying position, or shoulder position for a long period of time are included. The emergency health screening for workers exposed to arsenic, fluorine and its inorganic compounds, and acrylamide are included. The occupational medical examination (OME) for workers exposed to amino and nitro compounds of benzene, phosgene, monomethylamine, organic fluorine and dimethyl sulfate has been adjusted and made mandatory, with corresponding assessments required upon leaving the job. The special occupational health surveillance for workers exposed to mycobacterium tuberculosis and hepatitis virus is removed. The OME conclusion of reexamination is removed, and standardize recheck/additional inspection requirements. The optional items in OME performed before, during and after leaving post are removed, but the optional items in emergency medical examination are retained. Additional OME items are added. The Guideline for OME Summary Reports is added as informative appendix, and so on. The revised GBZ 188 Technical Specification for Occupational Health Surveillance is more scientific and practical.
4.Role of HIS score in predicting the prognosis of anti-melanoma differentiation associated gene 5 antibody-positive dermatomyositis patients with interstitial lung disease
Jiajia WANG ; Lei WANG ; Lingxiao XU ; Chengyin LYU ; Yujing ZHU ; Fang WANG ; Miaojia ZHANG ; Wenfeng TAN
Chinese Journal of Rheumatology 2022;26(4):224-230
Objective:To investigate the role of HIS (hyperinflammatory syndrome) score in predicting the prognosis of anti-melanoma differentiation associated gene 5(MDA5) antibody-positive dermatomyositis (DM) patients with interstitial lung disease (ILD).Methods:A total of 43 patients with anti-MDA5 antibody-positive dermatomyositis and 228 connective tissue disease (CTD) patients with ILD hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2018 to April 2021 were enrolled into this study. All patients were complicated with ILD and their HIS score were assessed. Non-parametric Mann-Whitney U test, Chi-squared test, Fisher exact probability and receiver operating characteristic (ROC) curve were used for data analysis. Results:The HIS score of 43 patients with anti-MDA5 antibody-positive dermat-omyositis were collected. Among 228 CTD-ILD patients in the control groups, the primary disease consisted of 33(14.5%) anti-synthetase antibody syndrome (ASS), 44(19.3%) rheumatoid arthritis (RA), 65(28.5%) Sj?gren's syndromes (SS), 43 (18.9%) systemic sclerosis (SSc) and 43 (18.9%) systemic lupus erythematosus(SLE). The HIS score of anti-MDA5-positive DM-ILD patients [2(1, 3)] was higher than those in ASS patients [1(0, 2), Z=-2.06, P<0.05] and significantly higher than those in RA-ILD [1(0, 2), Z=-2.87, P<0.01], SS-ILD [0(0,1), Z=-5.78, P<0.01], SSC-ILD [1(0, 1), Z=-3.84, P<0.01] and SLE-ILD [1(0, 2), Z=-3.81, P<0.01]. Comparing HIS score of anti-MDA5-positive DM-ILD patients, the 3-months mortality rate in the low, medium and high groups was 0(0/15), 38.1%(8/21) and 85.7%(6/7). The area under ROC curve (95% CI) was 0.857[(0.747, 0.967), P<0.001] for HIS score in predicting 3-months mortality probability of anti-MDA5-positive DM-ILD. Conclusion:HIS score of anti-MDA5-positive DM-ILD is higher than that in CTD-ILD patients and the baseline level is related to the 3-months mortality rate.
5.Local recurrence pattern of pT 1-2N 1 breast cancer after modified radical mastectomy—a pooled-analysis of 5442 patients from 12 centers
Xinyuan GUO ; Yujing ZHANG ; Na ZHANG ; Yu TANG ; Xuran ZHAO ; Hao JING ; Hui FANG ; Ge WEN ; Jing CHENG ; Mei SHI ; Qishuai GUO ; Hongfen WU ; Xiaohu WANG ; Changying MA ; Yexiong LI ; Hongmei WANG ; Min LIU ; Shulian WANG
Chinese Journal of Radiation Oncology 2022;31(3):248-252
Objective:To analyze locoregional recurrence (LRR) pattern of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, with and without adjuvant radiotherapy (RT). Methods:A total of 5442 eligible patients with breast cancer from 12 Chinese centers were included. The LRR sites and the effect of RT at different sites on recurrence in patients with and without RT were analyzed. The Kaplan-Meier method was used to calculate the cumulative LRR rate, and the difference was compared by the log-rank test.Results:With a median follow-up time of 63.8 months for the entire cohort, 395 patients developed LRR. The chest wall and supraclavicular fossa were the most common LRR sites, regardless of RT or molecular subtypes. The 5-year chest wall recurrence rates for patients with and without chest wall irradiation were 2.5% and 3.8%( P=0.003); the 5-year supraclavicular lymph nodal recurrence rates for patients with and without supraclavicular fossa irradiation were 1.3% and 4.1%( P<0.001); the 5-year axillary recurrence-free rates for patients with and without axillary irradiation were 0.8% and 1.5%( HR=0.31, 95% CI: 0.04-2.23, P=0.219); and the 5-year internal mammary nodal recurrence-free rates for patients with and without internal mammary nodal irradiation were 0.8% and 1.5%( HR=0.45, 95% CI: 0.11-1.90, P=0.268). Conclusions:The chest wall and supraclavicular fossa are the most common LRR sites of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, which is not affected by adjuvant RT or molecular subtypes. The chest wall and supraclavicular fossa irradiation significantly reduce the risk of recurrence in the corresponding area. However, axillary and internal mammary nodal irradiation has no impact on the risk of recurrence in the corresponding area.
6.The predicting value of pretreatment neutrophil count and lymphocyte-to-monocyte ratio in peripheral blood for the pathological tumor responses in patients with locally advanced gastric adenocarcinoma after preoperative therapy
Nai LI ; Yujing ZHANG ; Yi FANG ; Li ZHANG ; Shaomin HUANG ; Zhiwei ZHOU
Chinese Journal of Radiation Oncology 2021;30(4):363-367
Objective:To analyze the predicting values of hematological indicators for the pathological response in patients with gastric adenocarcinoma after preoperative neoadjuvant therapy and radical surgery.Methods:The absolute count of neutrophils (NE), lymphocytes (LY) and monocytes (MO) of 102 patients with locally advanced gastric adenocarcinoma in a multi-center randomized phase Ⅲ clinical trial (NCT01815853) from June 2013 to Feburary 2019 were retrospectively analyzed. Patients were divided into the chemotherapy alone group (ChT, 3 cycles of XELOX regimen) and the chemoradiation group (CRT, 1 cycle of induced XELOX regimen and 4500 cGy/25f radiotherapy plus concurrent extenuated 2 cycles of XELOX regimen), 51 cases in each group. The pathological response indicators of tumors after radical surgery included tumor regression grade, pathological complete regression, pathological T stage (ypT), N stage (ypN) and TNM stage (ypTNM).Results:Univariate regression analysis and ROC curves demonstrated a significant association between the absolute neutrophil count (NE) and ypT, lymphocyte-to-monocyte ratio (LMR) and ypN 0, and LMR and ypTNM reduction in the entire cohort of patients. Multivariate regression analysis showed that higher NE (>4.10×10 9/L) was significantly associated with higher probability of ypT reduction ( OR=3.308, P=0.007). Higher LMR (>3.46) was significantly associated with higher ypN 0 probability ( OR=4.276, P=0.005) and better ypTNM reduction ( OR=2.805, P=0.019). In subgroup analysis, higher NE (>4.10) was significantly correlated with higher probability of ypT reduction ( OR=3.750, P=0.030) in the CRT group, and higher LMR (>3.46) was significantly associated with higher ypN 0 probability ( OR=8.500, P=0.050) and the probability of ypTNM stage reduction ( OR=4.000, P=0.026) in the ChT group. Conclusions:Pretreatment NE and LMR in the peripheral blood serve as independent predictors for tumor pathological responses after preoperative treatment, and immune condition is correlated with tumor regression after radical surgery in patients with locally advanced gastric cancer.
7.The relationship between Lauren classification and pathological response after preoperative chemoradiotherapy for locally advanced gastric cancer
Yi FANG ; Yujing ZHANG ; Nai LI ; Yihong LING ; Zhiwei ZHOU
Chinese Journal of Radiation Oncology 2020;29(5):349-353
Objective:To investigate the correlation between Lauren classification and pathological response after preoperative chemoradiotherapy in patients with locally advanced gastric cancer.Methods:From 2013 to 2019, 98 patients with definite Lauren classification who were enrolled in Sun Yat-sen University Cancer Center 5010 Phase Ⅲ clinical trials. Among them, 46 patients received preoperative chemoradiotherapy (CRT), and the remaining 52 cases received preoperative chemotherapy (ChT) and radical surgery. After preoperative therapy, the correlation between pathological response including the tumor regression grade (NCCN-TRG 0-3) and the lymph node stage (ypN 0-3) and Lauren classification was analyzed. A favorable pathological response (FPR) was defined as TRG 0-2 and ypN 0. Results:In the CRT group, patients with intestinal type (IT) tumors had a higher rate of ypN 0( OR=6.8, 95% CI: 1.8-25.0, P=0.004) and FPR ( OR=8.0, 95% CI: 2.2-29.9, P=0.002) than their counterparts with diffuse or mixed type tumors. However, Lauren classification was not significantly correlated with pathological response in the ChT group ( P>0.05). For patients with IT tumors, those receiving CRT had a higher likelihood of achieving a TRG 0-2 response ( P=0.033), an ypN 0 nodal regression ( P<0.001), and a FPR ( P<0.001) than their counterparts receiving ChT, whereas pathological response was not significantly associated with preoperative therapeutic method in patients with diffuse or mixed tumors ( P>0.05). Conclusion:Lauren classification may be a reliable predictor of the clinical efficacy of preoperative chemoradiotherapy for locally advanced gastric cancer, which can be utilized to select and optimize preoperative treatment.
8.Efficacy and prognosis of radiotherapy for patients with postoperative pelvic recurrence in uterine cervical cancer
Jiajia JIANG ; Hong LIU ; Yujing WANG ; Zhaohui FANG ; Qianying ZHANG ; Kiuxiu LI
Chinese Journal of Radiological Medicine and Protection 2019;39(3):208-212
Objective To analyze the result and adverse reactions of radiation therapy in patients with pelvic recurrence following cervical cancer postoperative.Methods A retrospective analysis of 147 patients with pelvic recurrence after surgical treatment of cervical cancer in the Fourth Hospital of Hebei Medical University from August 2004 to December 2016 was performed.All patients received radiotherapy with or without chemotherapy.According to different clinical factors and pathological factors,Logistic regression analysis was used to analyze the factors influencing radiotherapy outcomes in patients with pelvic recurrence after cervical cancer surgery.The Kaplan-Meier method was used to analyze the survival rate,and the corresponding survival curve was drawn.The survival rate and prognosis related factors were compared by using the log-rank test.The COX proportional hazards regression model was used for multivariate analysis of statistically relevant factors in univariate analysis.After treatment,toxicities were analyzed using chi-square test.Results The median follow-up time was 33.2 months.95% of the patients completed radiation therapy with a dose of ≥ 67 Gy (median radiotherapy dose),and 91 patients (61.9%) had complete remission (CR).The 5-year local control (LC),progression-free survival (PFS),distant metastasis-free survival (DMFS),and overall survival (OS) were 63.6%,56.0%,73.9%,and 55.0%,respectively.Univariate logistic regression analysis showed that FIGO staging (stage 0-ⅠB and ⅡA-ⅡB),pelvic sidewall involvement,and recurrent tumor volume were associated with complete remission (P<0.05).Multivariate statistical analysis found that FIGO staging and pelvic sidewall invasion were independent factors influencing the efficacy and survival of patients with pelvic recurrence after cervical cancer surgery (P<0.05).Patients with pelvic wall invasion after cervical cancer surgery had a higher incidence of ≥ grade 2 proctitis than those without pelvic walls involved,which were 26.9% and 16.7%,respectively.Conclusions This study shows that after the surgical treatment of cervical cancer patients with pelvic recurrence can be tolerated by toxicities after radiation therapy.In addition,the incidence of toxicities in patients with pelvic wall invasion was significantly higher than those without pelvic wall invasion.Preoperative staging and the pelvic wall involvement are independent influencing factors influencing the effect of radiotherapy and long-term prognosis in patients with pelvic recurrence after cervical cancer surgery.
9.Prognostic value of anemia in patients with extranodal nasal-type NK/T cell lymphoma:A multi-center study from CLROG
Hui FANG ; Suyu ZHU ; Liming XU ; Peiguo WANG ; Tao WU ; Liting QIAN ; Fuquan ZHANG ; Xiaorong HOU ; Shunan QI ; Yong YANG ; Jing JIN ; Yujing ZHANG ; Yuan ZHU ; Jianzhong CAO ; Shengmin LAN ; Junxin WU ; Yexiong LI
Chinese Journal of Radiation Oncology 2018;27(2):155-160
Objective To evaluate the prognostic value of anemia in patients diagnosed with extranodal nasal-type natural killer (NK)/T cell lymphoma (NKTCL).Methods Clinical data of 1 225 NKTCL patients receiving the first course of treatment from 10 medical institutions in China were retrospectively analyzed.According to the diagnostic criteria in China,anemia was defined as the hemoglobin (Hb) level< 120 g/L for the male and< 110 g/L for the female from the sea-level area.The severity of anemia was classified into the extremely severe anemia (Hb ≤ 30 g/L),severe anemia (31-60 g/L),moderate anemia (61-90 g/L) and mild anemia (>90 g/L).Results Among 1 225 patients,199(16.2%) were complicated with anemia,who had more adverse prognostic factors compared with their counterparts without anemia.Among NKTCL patients with anemia,the proportion of patients with stage Ⅱ-ⅣV,a median age> anemia,Eastern Cooperative Oncology Group (ECOG) score of 2-4 and NK/T-cell lymphoma prognostic index (NKTCLPI) ≥ 2 was relatively high.Patients with anemia obtained worse clinical prognosis than those without anemia.The 5-year overall survival (OS) and progression-free survival (PFS) in NKTCL patients with anemia were calculated as 49.4% and 35.4%,significantly lower compared with 63.3% and 56.0% in their counterparts without anemia (both P<0.01).Single factor analysis demonstrated that anemia,age,ECOG score,group B symptom,lactate dehydrogenase,primary tumor site,primary tumor invasion and staging were the prognostic factors of OS and PFS.Multivariate analysis revealed that anemia was still the independent prognostic factor.Conclusions Anemia is not common in patients with NKTCL and these patients obtain poor clinical prognosis.Anemia is an independent prognostic factor for patients with NKTCL.
10.Expression of voltage-gated sodium channel Nav1.5 in non-metastatic colon cancer and its associations with estrogen receptor(ER)-βexpression and clinical outcomes
Peng JIANHONG ; Ou QINGJIAN ; Wu XIAOJUN ; Zhang RONGXIN ; Zhao QIAN ; Jiang WU ; Lu ZHENHAI ; Wan DESEN ; Pan ZHIZHONG ; Fang YUJING
Chinese Journal of Cancer 2017;36(12):694-703
Background: Voltage-gated sodium channel 1.5 (Nav1.5) potentially promotes the migratory and invasive behaviors of colon cancer cells. Hitherto, the prognostic significance of Nav1.5 expression remains undetermined. The present study aimed to explore the associations of Nav1.5 expression with clinical outcomes and estrogen receptor-β (ER-β) expression in non-metastatic colon cancer patients receiving radical resection. Methods: A total of 269 consecutive patients with pathologically confirmed stages Ⅰ–Ⅲ colon cancer who under-went radical resection were selected. Nav1.5 and ER-β expression was detected by using immunohistochemistry (IHC) on tissue microarray constructed from paraffin-embedded specimens. IHC score was determined according to the percentage and intensity of positively stained cells. Statistical analysis was performed with the X-tile method, k coef-ficient, Chi square test or Fisher's exact test, logistic regression, log-rank test, and Cox proportional hazards models. Results: We found that Nav1.5 was commonly expressed in tumor tissues with higher mean IHC score as compared with matched tumor-adjacent normal tissues (5.1 ± 3.5 vs. 3.5 ± 2.7, P < 0.001). The high expression of Nav1.5 in colon cancer tissues was associated with high preoperative carcinoembryonic antigen level [odds ratio (OR) = 2.980;95% confidential interval (CI) 1.163–7.632; P = 0.023] and high ER-β expression (OR = 2.808; 95% CI 1.243–6.343;P = 0.013). Log-rank test results showed that high Nav1.5 expression contributed to a low 5-year disease-free survival (DFS) rate in colon cancer patients (77.2% vs. 92.1%, P = 0.048), especially in patients with high ER-β expression tumor (76.2% vs. 91.3%, P = 0.032). Analysis with Cox proportional hazards model demonstrated that high Nav1.5 expression [hazard ratio (HR) = 2.738; 95% CI 1.100–6.819; P = 0.030] and lymph node metastasis (HR = 2.633; 95% CI 1.632–4.248; P < 0.001) were prognostic factors for unfavorable DFS in colon cancer patients. Conclusions: High expression of Nav1.5 was associated with high expression of ER-β and indicated unfavorable oncologic prognosis in patients with non-metastatic colon cancer.

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