1.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
2.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
3.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
4.Progress of research on the preventive and therapeutic agents against radiation-induced injuries
Junfeng XUE ; Shu SUN ; Yunyun JIANG ; Weili QI ; Wei HU
Chinese Journal of Radiological Health 2024;33(1):106-110
Radiation-induced injury, a body dysfunction caused by irradiation, is associated with the dose, duration, and speed of radiation and is predominantly derived from radiation therapy for patients with malignant tumors. The current clinical treatment mainly includes amelioration of injury, alleviation of symptoms, and improvements in function restoration of the affected sites because of lack of targeted agents specific to radiation-induced injuries. Research and development of preventive and therapeutic agents against radiation-induced injuries are of great significance to reduce the body damages caused by radiotherapy and improve the quality of life of cancer survivors. This review summarizes the radiation-induced injury and its mechanisms, radioprotectants, and therapeutic agents for radiation, and proposes future development directions, so as to provide a reference for alleviation of radiation-induced injury and improvement in prognosis.
5.Xuandi Ziyin Mixture (玄地滋阴合剂) for Central Precocious Puberty in Girls with Syndrome of Yin Deficiency and Fire Exuberance: A Prospective Cohort Study
Wenqin WANG ; Yating LIN ; Lin YUAN ; Jingwei HE ; Xinghui HAN ; Yonghong WANG ; Jian YU ; Weili YAN ; Wen SUN
Journal of Traditional Chinese Medicine 2024;65(16):1673-1680
ObjectiveTo observe the clinical effectiveness and safety of Xuandi Ziyin Mixture (玄地滋阴合剂) for central precocious puberty (CPP) in girls with syndrome of yin deficiency and fire exuberance, and to analyse the effect of body mass index (BMI) on the effectiveness. MethodsA total of 236 girls with CPP of yin deficiency and fire exuberance syndrome were included, and all of them were given Xuandi Ziyin Mixture, 30 ml each time, twice a day, for a total treatment period of 6 months. Before and after treatment, children's weight, height and bone age were measured, BMI and BMI Z-score (BMI Z) and the difference between bone age and actual age were calculated; ultrasound was used to detect uterine and ovarian sizes, and to calculate uterine volume (Vuterus), bilateral ovarian volume (Vleft ovary, Vright ovary), and bilateral maximal follicle diameters (rleft follicle and rright follicle); and serum sex hormones were measured, including follicle-stimulating hormone (FSH), luteinising hormone (LH), prolactin (PRL), estradiol (E2), and testosterone (T), and were scored for traditional Chinese medicine (TCM) syndrome. Multiple linear regression was used to analyse the influence factors of the difference between bone age and actual age, and changes in uterine volume. The children were divided into the normal weight group and the overweight/obesity group according to baseline BMI, and the bone age, the difference between bone age and actual age, Vuterus and BMI Z scores before and after treatment were compared between the two groups. ResultsFinally, 199 children entered the statistical analysis. Compared with pre-treatment, the bone age, BMI and BMI Z scores of the children increased after treatment, and the difference between bone age and actual age, TCM syndrome scores, Vuterus, Vleft ovary, Vright ovary, rleft follicle and rright follicle decreased; and the levels of serum FSH, LH, E2, and T significantly decreased (P<0.05 or P<0.01). The difference between bone age and actual age was negatively correlated with LH and Vuterus (P<0.05), and changes in uterine volume were positively correlated with LH (P<0.01). Comparing between the groups before and after treatment, the bone age, difference between bone age and actual age, and BMI Z scores of children in the normal weight group (100 cases) were significantly smaller than those in the overweight/obesity group (99 cases) (P<0.01). Compared with pre-treatment, the bone age of the children in both groups increased, but the difference between bone age and actual age and Vuterus were significantly smaller (P<0.01). Further comparison of Δ bone age and actual age difference and ΔVuterus (Δ = post-treatment value
6.Prognosis and its influencing factors in patients with non-gastric gastrointestinal stromal tumors at low risk of recurrence: a retrospective multicenter study in China
Linxi YANG ; Weili YANG ; Xin WU ; Peng ZHANG ; Bo ZHANG ; Junjun MA ; Xinhua ZHANG ; Haoran QIAN ; Ye ZHOU ; Tao CHEN ; Hao XU ; Guoli GU ; Zhidong GAO ; Gang ZHAI ; Xiaofeng SUN ; Changqing JING ; Haibo QIU ; Xiaodong GAO ; Hui CAO ; Ming WANG
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1123-1132
Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.
7.Analysis of the prognostic value of NLR in the treatment of PD-1 inhibitors in patients with HER2-negative advanced gastric cancer
Yalin DOU ; Weili CHENG ; Mingqi SUN ; Shuanghong WU ; Tingting YANG ; Dapeng LI
China Pharmacist 2024;27(6):1063-1071
Objective To explore the prognostic value of serum neutrophils/lymphocytes(NLR)for first-line treatment of patients with advanced gastric cancer using programmed cell death receptor 1(PD-1)inhibitors.Methods A total of 168 patients with advanced gastric cancer who were treated with immunotherapy combined with chemotherapy in the Fourth Hospital of Qinhuangdao from January 2018 to January 2021 were selected as study subjects,and the follow-up period was terminated at January 2023.The patients'data were collected,hematological and tumor markers before the combined treatment were analyzed,and the optimal cut-off value of NLR was calculated using X-tile software.The effect of NLR expression on the survival rate of patients with advanced gastric cancer was analysed by the Kaplan-Meier survival curve.Receiver operating curve(ROC)was used to analyze the predictive value of NLR in patients with advanced gastric cancer.The related factors affecting the disease progression of patients with advanced gastric cancer were screened combined with Cox proportional risk model.Results Among 168 patients,the optimal cut-off value of serum NLR before treatment was 2.41.Patients were divided into high NLR group(NLR>2.41,n=93)and low NLR group(NLR<2.41,n=75).NLR was related to tumor differentiation,distant metastasis,composite positive scores of PD-L1,carcinoembryonic antigen and cancer antigen 125(P<0.05);the effective rate in the low NLR group was significantly higher than that in the high NLR group(P<0.05);the median progression free survival(PFS)and the overall survival(OS)of patients in the low NLR group were both longer than those in the high NLR group(PFS:P=0.006;OS:P=0.023);ROC analysis showed that the area under the curve of NLR for the prognosis of advanced gastric cancer patients was 0.740,sensitivity was 81.50%,and specificity was 69.70%;in multivariate analysis,except initial NLR value,tumor differentiation degree and distant metastasis were also independent predictors of poor prognosis in patients with advanced gastric cancer(P<0.05).Conclusion Among patients with advanced gastric cancer who received first-line immunotherapy combined with chemotherapy,pretreatment NLR is correlated with efficacy and PFS/OS,and has high value in predicting the prognosis of immunotherapy for advanced gastric cancer.
8.Visualization of research progress on hand, foot and mouth disease and meteorological factors: analysis based on Citesapce and VOSviewer software
Huaiming CAO ; Yanqing YANG ; Weili PAN ; Lingling SUN
Journal of Public Health and Preventive Medicine 2024;35(6):27-30
Objective To understand the research hotspot and development trend of meteorological factors in the field of hand, foot and mouth disease at home and abroad, and to provide references for domestic scholars to explore the frontier of this field. Methods Relevant literature published from the retrievable date to August 31, 2022 was searched in CNKI, Wanfang, VIP, China Biomedical Literature Database, Web of Science Core Collection and PubMed database. CiteSpace and VOSviewer software were used to retrieve related research literature on hand, foot and mouth disease and meteorological factors, and visualization analysis was conducted from the aspects of publication volume, relevant authors, keywords and journal analysis. Results A total of 610 literatures were included in this study, including 339 foreign documents and 271 Chinese documents. The number of published literatures in this field showed an increasing trend year by year. In foreign literature, there were 147 core authors, and 209 keywords appeared more than 3 times. In Chinese literature, there were 57 core authors, and 66 keywords appeared more than 3 times. In recent years, time series analysis and Bayesian spatiotemporal models had been widely used to explore the relationship between hand, foot and mouth disease and meteorological factors. Science of the Total Environment (28 articles) and Disease Surveillance (12 articles) accounted for the largest number of publications in foreign and Chinese journals, respectively. Compared with Chinese journals, foreign journals formed a stable group of journals. Conclusion In general, the research content in this field is rich, and the research trend has shifted from epidemiological research to the application of new methods in this field to explore the impact of meteorological factors on the incidence of hand, foot and mouth disease.
9.Effect of angiotensin converting enzyme inhibitors or angiotensin Ⅱ receptor blockers combined with glucocorticoid in the treatment of IgA nephropathy
Xiaoli SUN ; Weili XIN ; Yongbing GUO
Journal of Xinxiang Medical College 2024;41(6):581-584
Objective To investigate the clinical efficacy of angiotensin converting enzyme inhibitors(ACEI)or angiotensin Ⅱ receptor blockers(ARB)combined with glucocorticoid in treating IgA nephropathy patients.Methods A total of 125 IgA nephropathy patients admitted to Anyang District Hospital from October 2019 to October 2022 were selected as the research subjects.The patients were randomly divided into the control group(n=62)and the observation group(n=63).Patients in the control group were given ACEI or ARB treatment,while patients in the observation group were given ACEI or ARB combined with fluticasone propionate inhalation aerosol.All patients were treated continuously for 3 months.The treatment effect was compared between the two groups.The 24-hour urinary protein quantitation,serum creatinine(Scr),glomerular filtration rate(GFR),white blood cell(WBC)count,hemoglobin(HGB)level,and platelet(PLT)count of patients in the two groups were measured before and after treatment.The occurrence of adverse reactions during treatment in the two groups was recorded.Results The overall effective rates of patients in the control group and the observation group were 54.84%(34/62)and 84.13%(53/63),respectively;the overall effective rate of patients in the observation group was significantly higher than that in the control group(x2=12.669,P<0.05).Before treatment,there was no significant difference in 24-hour urinary protein quantitation,Scr and GFR between the two groups(P>0.05).There was no significant difference in 24-hour urinary protein quantitation of patients before and after treatment in the control group(P>0.05),and the 24-hour urinary protein quantitation of patients after treatment in the observation group was significantly lower than that before treatment(P<0.05).After treatment,Scr in the two groups was significantly lower than that before treatment,and GFR was significantly higher than that before treatment(P<0.05).After treatment,24-hour urinary protein quantitation in the observation group was significantly lower than that in the control group(P<0.05);and there was no significant difference in Scr and GFR between the two groups(P>0.05).There was no significant difference in WBC,HGB and PLT of patients before and after treatment in the two groups(P>0.05).No adverse reactions,such as abnormal glucose tolerance,steroid diabetes and elevated blood pressure,occurred in the two groups during treatment.Conclusion Fluticasone propionate inhalation aerosol combined with ACEI or ARB can re-duce the 24-hour urinary protein quantitation and improve the renal function of IgA nephropathy patients,without the risk of causing blood system damage.It is a safe approach with significant efficacy.
10.Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients: A 12-week randomized placebo-controlled phase III trial with long-term extension
Chen YU ; Songmei GENG ; Bin YANG ; Yunhua DENG ; Fuqiu LI ; Xiaojing KANG ; Mingye BI ; Furen ZHANG ; Yi ZHAO ; Weili PAN ; Zhongwei TIAN ; Jinhua XU ; Zhenghua ZHANG ; Nan YU ; Xinsuo DUAN ; Shuping GUO ; Qing SUN ; Weiquan LI ; Juan TAO ; Zhijun LIU ; Yuanyuan YIN ; Gang WANG
Chinese Medical Journal 2024;137(10):1190-1198
Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.


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