1.Recent advances and remaining challenges in lung cancer therapy
Tasha BARR ; Shoubao MA ; Zhixin LI ; Jianhua YU
Chinese Medical Journal 2024;137(5):533-546
Lung cancer remains the most common cause of cancer death. Given the continued research into new drugs and combination therapies, outcomes in lung cancer have been improved, and clinical benefits have been expanded to a broader patient population. However, the overall cure and survival rates for lung cancer patients remain low, especially in metastatic cases. Among the available lung cancer treatment options, such as surgery, radiation therapy, chemotherapy, targeted therapies, and alternative therapies, immunotherapy has shown to be the most promising. The exponential progress in immuno-oncology research and recent advancements made in the field of immunotherapy will further increase the survival and quality of life for lung cancer patients. Substantial progress has been made in targeted therapies using tyrosine kinase inhibitors and monoclonal antibody immune checkpoint inhibitors with many US Food And Drug Administration (FDA)-approved drugs targeting the programmed cell death ligand-1 protein (e.g., durvalumab, atezolizumab), the programmed cell death-1 receptor (e.g., nivolumab, pembrolizumab), and cytotoxic T-lymphocyte-associated antigen 4 (e.g., tremelimumab, ipilimumab). Cytokines, cancer vaccines, adoptive T cell therapies, and Natural killer cell mono- and combinational therapies are rapidly being studied, yet to date, there are currently none that are FDA-approved for the treatment of lung cancer. In this review, we discuss the current lung cancer therapies with an emphasis on immunotherapy, including the challenges for future research and clinical applications.
2.The nursing care of a patient with large skin ulcers caused by EBV positive T/NK-cell lymphoproliferative diseases based on TIME Clinical-Decision-Support-Tool
Zhixin WANG ; Cong LI ; Junjie ZHANG ; Yongping MA ; Wenhua ZHOU
Chinese Journal of Practical Nursing 2024;40(31):2461-2466
To summarize the nursing experience of a patient with large skin ulcers caused by EBV positive T/NK-cell lymphoproliferative diseases based on TIME Clinical-Decision-Support-Tool. The main points of nursing care were as follows: early identification of the cause of ulceration and active treatment of the underlying disease; accurate and continuous assessment of patients and their wounds; multidisciplinary consultation to ensure the integrity and comprehensiveness of diagnosis and treatment; active identification of obstacle factors and risk control; providing different dressing change programs according to different wound healing stages; evaluation of treatment effects at any time; timely pain management; improving the nutritional status of patients; providing health education and psychological nursing care. After 367 days of wound dressing, the patient′s wound was fully healed, and EBV-DNA was not detected in genetic examination after hematopoietic stem cell transplantation.
3.ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification.
Wenle YE ; Jinghan WANG ; Jiansong HUANG ; Xiao HE ; Zhixin MA ; Xia LI ; Xin HUANG ; Fenglin LI ; Shujuan HUANG ; Jiajia PAN ; Jingrui JIN ; Qing LING ; Yungui WANG ; Yongping YU ; Jie SUN ; Jie JIN
Frontiers of Medicine 2023;17(4):685-698
Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.
Humans
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Antineoplastic Agents/therapeutic use*
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Apoptosis
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beta Catenin/metabolism*
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Biomarkers, Tumor/metabolism*
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Cell Line, Tumor
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Coenzyme A Ligases/metabolism*
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Leukemia, Myeloid, Acute/metabolism*
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Lipoylation
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Prognosis
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Wnt Signaling Pathway
4.Efficacy and adverse effects of first-line immunotherapy combined with chemotherapy in real world elderly patients with small cell lung cancer
Zhixin BIE ; Yuxia WANG ; Bin AI ; Xiaoyan CHEN ; Juanjuan LIU ; Junling MA ; Jiangyong YU
Chinese Journal of Geriatrics 2023;42(12):1418-1424
Objective:To investigate the efficacy and adverse effects of first-line immunotherapy combined with chemotherapy in elderly patients with small cell lung cancer(SCLC)in population of real world.Methods:A total of 148 elderly SCLC patients(age ≥65 years old)underwent pathological diagnosis were retrospectively analyzed from January 2013 to June 2023.103 patients received chemotherapy(chemotherapy group), and 45 patients received immunotherapy combined with chemotherapy(combination group). Patients were divided into senior group(≥75 years old)and younger group(<75 years old)by age.To compare the efficacy of different regimens in first-line treatment, the expression of programmed death-ligand 1(PD-L1)and tumor mutational burden(TMB)were evaluated.Response evaluation criteria in solid tumors(RECIST)version 1.1 was used to evaluate the efficacy, and common terminology criteria for adverse events(CTCAE)version 4.03 was used to evaluate immune-related adverse.Kaplan-meier and Log-rank test were performed.Cox regression was used in prognostic analysis.Results:The overall response rate(ORR)of the first-line combination group in elderly SCLC patients was 79.1%(34/43), which was higher than that of the chemotherapy group 63.2%(60/95), but the difference did not reach statistical significance( χ2=3.451, P=0.063). ORR was significantly higher in the combination group than in the chemotherapy group for patients in the ≥75-year-old group, 87.5%(7/8) vs.48.6%(17/35), respectively( χ2=4.001, P=0.045). The difference in median progression-free survival time(mPFS)in the combination group compared with the chemotherapy group was not statistically significant in the overall patients(5.43 months vs.6.07 months, P=0.660). The combination group prolonged patients' median overall survival time(mOS)compared with the chemotherapy group, but the difference did not reach statistical significance(13.63 months vs.11.97 months, P=0.205). In patients ≥75 years old, mPFS was lower in the combination group than in the chemotherapy group(2.97 months vs.6.47 months), but mOS was prolonged compared with that in the chemotherapy group(13.50 months vs.11.40 months), and none of the differences reached statistical significance(both P>0.05). The differences in mPFS and mOS between the combination group and the chemotherapy group were not statistically significant in patients <75 years old(both P>0.05). In elderly patients with severe comorbidities, mPFS and mOS were lower in the combination group than in the chemotherapy group(5.40 months vs.7.30 months and 10.70 months vs.12.27 months, both P>0.05). In patients without severe comorbidities, the difference in mPFS between the combination group and the chemotherapy group was not statistically significant( P>0.05), but the mOS was significantly longer in the combination group(20.57 months vs.11.57 months, P=0.054). Elderly SCLC patients had a positive PD-L1 tumor cell positive proportion score(TPS)rate(≥1%)of 23.5%(4/17)and a high TMB(≥9 mut/Mb)expression rate of 69.0%(11/16). The overall incidence of immune-related adverse reactions was 71.0%(32/45), grade 3 or higher 33.3%(15/45), and the most common grade 3 adverse reactions were rash, immune-related pneumonia and malaise. Conclusions:First-line immune-combination chemotherapy improves ORR and mOS over chemotherapy in elderly SCLC patients; mOS benefit of immune-combination chemotherapy is more pronounced in patients ≥75 years of age without severe comorbidities, low PD-L1 positivity and high TMB expression are present in elderly SCLC patients, and immune-related adverse effects are generally manageable in elderly patients.
5.Advances and challenges in clinical research on hepatic hydrothorax
Bo MA ; Tianling SHANG ; Jianjie HUANG ; Zhixin TU ; Yan WANG ; Yujin HAN ; Xiaoyu WEN ; Qinglong JIN
Journal of Clinical Hepatology 2022;38(2):452-456
Hepatic hydrothorax (HH) is a challenging complication of liver cirrhosis associated with portal hypertension, and its pathogenesis and therapeutic measures remain unknown. This article summarizes and reviews the advances and challenges in the research on the pathogenesis, clinical manifestations, diagnosis, and treatment of HH and proposes a multidisciplinary treatment strategy, including reducing the production of ascites, preventing effusion from entering the thoracic cavity, removing pleural effusion, occluding the pleural cavity, and performing liver transplantation, so as to provide a reference for more clinicians.
6.LncRNA DACH1 protects against pulmonary fibrosis by binding to SRSF1 to suppress CTNNB1 accumulation.
Jian SUN ; Tongzhu JIN ; Zhihui NIU ; Jiayu GUO ; Yingying GUO ; Ruoxuan YANG ; Qianqian WANG ; Huiying GAO ; Yuhan ZHANG ; Tianyu LI ; Wenxin HE ; Zhixin LI ; Wenchao MA ; Wei SU ; Liangliang LI ; Xingxing FAN ; Hongli SHAN ; Haihai LIANG
Acta Pharmaceutica Sinica B 2022;12(9):3602-3617
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.
7.Hepatitis C combined with diffuse large B-cell lymphoma: A case report
Zhixin TU ; Jianjie HUANG ; Yan WANG ; Bo MA ; Yujin HAN ; Liang GUO ; Xiaoyu WEN ; Qinglong JIN
Journal of Clinical Hepatology 2022;38(10):2334-2336
8.The application of hierarchical teaching based on the "competency-based" concept in the standardized training of respiratory nursing interns
Dongwei MA ; Zhixin XU ; Gengli CUI
Chinese Journal of Medical Education Research 2022;21(10):1409-1412
Objective:To explore the role of hierarchical teaching based on the "competency-based" concept in the standardized training of respiratory nursing interns.Methods:A total of 70 nursing interns who came to the Department of Respiratory Medicine in Beijing Jishuitan Hospital for standardized training from September 2019 to August 2020 were selected as the study subjects. They were randomly divided into the study group and the control group by coin tossing method, 35 in each group. The study group used hierarchical teaching based on the "competency-based" concept, while the control group adopted conventional hierarchical teaching. The nursing ability and teaching quality of the two groups of nurses were compared. SPSS 23.0 was used for t-test and Chi-square test. Results:The theoretical knowledge scores of the nurses in the two groups after the standardized training [(95.29±3.13), (86.29±5.13)] were higher than those before the training [(78.22±4.48), (77.29±5.13)]. The scores of theoretical knowledges, operation skills, medical record reporting, and the comprehensive quality scores of the study group after the standardized training were higher than those of the control group, and the differences were statistically significant ( P<0.05). The satisfaction of teaching quality in study group was higher than that in control group, and the difference was statistically significant ( P<0.05). Conclusion:The hierarchical teaching based on the "competency-based" concept can significantly improve the teaching quality in the standardized training and the comprehensive quality of respiratory nursing interns, which is worthy of application.
9.Correlation between systemic immune-inflammation index and prognosis in patients with hepatic alveolar echinococcosis
Xiaobin CHEN ; Jiaqi YUAN ; Zhixin WANG ; Haining FAN ; Zhaojun XU ; Xuepeng MEI ; Haijiu WANG ; Jiamin MA ; Ying ZHOU ; Lizhao HOU
Journal of Clinical Hepatology 2021;37(2):375-379
ObjectiveTo investigate the correlation between systemic immune-inflammation index (SII) and prognosis in patients with hepatic alveolar echinococcosis. MethodsA retrospective analysis was performed for the clinical data of 242 patients who were admitted to Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, from January 2015 to December 2018 and underwent surgery for hepatic alveolar echinococcosis, and SII was calculated. The chi-square test was used for comparison of categorical data between two groups, and a Spearman correlation analysis was performed. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of SII; the Kaplan-Meier method was used to plot survival curves and analyze overall survival time in the two groups, and the log-rank test was used for comparison of survival rates between the two groups; univariate and multivariate Cox regression analyses were used to identify the influencing factors for the prognosis of patients with hepatic alveolar echinococcosis. ResultsThe Spearman correlation analysis showed that SII was positively correlated with the postoperative fatality rate of patients with hepatic alveolar echinococcosis (r=0.267, P<0.001). The ROC curve showed that the optimal cut-off value of SII before surgery was 758.92, and based on this, 242 patients with hepatic alveolar echinococcosis were divided into low SII (SII ≤758.92) group with 126 patients and high SII (SII >758.92) group with 116 patients. The low SII group had 1-, 3-, and 5-year survival rates of 98.20%, 88.47%, and 6610%, respectively, and the high SII group had 1-, 3-, and 5-year survival rates of 90.80%, 53.05%, and 27.40%, respectively. The low SII group had a cumulative survival rate of >50% and a mean survival time of 55.584 months (95% confidence interval[CI]: 53550-57.617), while the high SII group had a cumulative survival rate of <50%, a mean survival time of 39.384 months (95% CI: 35.070-43.698), and a median survival time of 43 months (95% CI: 34.694-51.306). The low SII group had a significantly better survival rate than the high SII group, and there was a significant difference in overall survival rate between the two groups (χ2=46.979, P<005). The univariate analysis showed that SII >758.92 (hazard ratio [HR]=5.907, 95% CI: 3.386-10.306, P=0.001) was an influencing factor for the overall survival time of patients with hepatic alveolar echinococcosis, and the multivariate Cox regression analysis showed that preoperative peripheral blood SII (HR=3.507, 95% CI: 1.911-6.435, P=0.001) was an independent risk factor for the overall survival rate of patients with hepatic alveolar echinococcosis. ConclusionPreoperative SII level is clearly correlated with the prognosis of patients with hepatic alveolar echinococcosis and can thus be used as a clinical indicator to evaluate the prognosis of patients. The higher the peripheral blood SII before surgery, the worse the prognosis of patients.
10.Role of IFNLR1 gene in PRRSV infection of PAM cells
Ming QIN ; Wei CHEN ; Zhixin LI ; Lixue WANG ; Lixia MA ; Jinhong GENG ; Yu ZHANG ; Jing ZHAO ; Yongqing ZENG
Journal of Veterinary Science 2021;22(3):e39-
Background:
Interferon lambda receptor 1 (IFNLR1) is a type II cytokine receptor that clings to interleukins IL-28A, IL29B, and IL-29 referred to as type III IFNs (IFN-λs). IFN-λs act through the JAK-STAT signaling pathway to exert antiviral effects related to preventing and curing an infection. Although the immune function of IFN-λs in virus invasion has been described, the molecular mechanism of IFNLR1 in that process is unclear.
Objectives:
The purpose of this study was to elucidate the role of IFNLR1 in the pathogenesis and treatment of porcine reproductive and respiratory syndrome virus (PRRSV).
Methods:
The effects of IFNLR1 on the proliferation of porcine alveolar macrophages (PAMs) during PRRSV infection were investigated using interference and overexpression methods.
Results:
In this study, the expressions of the IFNLR1 gene in the liver, large intestine, small intestine, kidney, and lung tissues of Dapulian pigs were significantly higher than those in Landrace pigs. It was determined that porcine IFNLR1 overexpression suppresses PRRSV replication. The qRT-PCR results revealed that overexpression of IFNLR1 upregulated antiviral and IFN-stimulated genes. IFNLR1 overexpression inhibits the proliferation of PAMs and upregulation of p-STAT1. By contrast, knockdown of IFNLR1 expression promotes PAMs proliferation. The G0/G1 phase proportion in IFNLR1-overexpressing cells increased, and the opposite change was observed in IFNLR1-underexpressing cells. After inhibition of the JAK/STAT signaling pathway, the G2/M phase proportion in the IFNLR1-overexpressing cells showed a significant increasing trend. In conclusion, overexpression of IFNLR1 induces activation of the JAK/STAT pathway, thereby inhibiting the proliferation of PAMs infected with PRRSV.
Conclusion
Expression of the IFNLR1 gene has an important regulatory role in PRRSVinfected PAMs, indicating it has potential as a molecular target in developing a new strategy for the treatment of PRRSV.

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