1.Prognostic Significance of KMT2D Gene Mutation and Its Co-mutated Genes in Patients with Diffuse Large B-Cell Lymphoma
Mutibaier·MIJITI ; Xiaolong QI ; Renaguli·ABULAITI ; Wenxin TIAN ; Sha LIU ; Weiyuan MA ; Zengsheng WANG ; Li AN ; Min MAO ; Muhebaier·ABUDUER ; Yan LI
Cancer Research on Prevention and Treatment 2025;52(2):127-132
Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2DmutBTG2mut had poorer OS than those with KMT2Dwt BTG2mut (P=0.07) and KMT2Dwt BTG2wt (P=0.05). On the contrary, patients with KMT2Dmut CD79Bmut had better OS than those with KMT2Dmut CD79Bwt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2DmutBTG2mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.
3.SRSF7 promotes pulmonary fibrosis through regulating PKM alternative splicing in lung fibroblasts.
Tongzhu JIN ; Huiying GAO ; Yuquan WANG ; Zhiwei NING ; Danyang BING ; Yan WANG ; Yi CHEN ; Xiaomu TIAN ; Qiudi LIU ; Zhihui NIU ; Jiayu GUO ; Jian SUN ; Ruoxuan YANG ; Qianqian WANG ; Shifen LI ; Tianyu LI ; Yuhong ZHOU ; Wenxin HE ; Yanjie LU ; Yunyan GU ; Haihai LIANG
Acta Pharmaceutica Sinica B 2025;15(6):3041-3058
Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.
4.An anti-complement homogeneous polysaccharide from Houttuynia cordata ameliorates acute pneumonia with H1N1 and MRSA coinfection through rectifying Treg/Th17 imbalance in the gut-lung axis and NLRP3 inflammasome activation.
Xinxing LI ; Wenxin DING ; Yan LU ; Haiyan ZHU ; Weilian BAO ; Yang LIU ; Jiaren LYU ; Lishuang ZHOU ; Hong LI ; Jiyang LI ; Daofeng CHEN
Acta Pharmaceutica Sinica B 2025;15(6):3073-3091
The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD50) and methicillin-resistant Staphylococcus aureus (MRSA, 107 CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.
5.Chinese version of evidence-based practice-knowledge, attitude, application, anticipated future use (EBP-KAPF) scale and its reliability and validity
Wenxin YAN ; Jiaojiao LIAO ; Qirui SHAO ; Lin ZENG ; Yiming ZHAO ; Jue LIU ; Liyuan TAO
Chinese Journal of Preventive Medicine 2024;58(4):481-488
Objective:To translate Evidence-based Practice-knowledge, attitude, application, anticipated future use (EBP-KAPF) scale into Chinese, and evaluate its reliability and validity.Methods:The Chinese version of the EBP-KAPF scale was determined through translation, adaptation, recall, review and pre-investigation. From July to August 2022, 250 clinicians from 28 provinces (autonomous regions and municipalities directly under the Central Government) were selected by using the convenience sampling method. A self-made questionnaire was used to investigate the EBP-KAPF scale in Chinese to investigate the EBM ability of clinicians, including the basic information of the respondents, the learning and use of Evidence-based medicine courses and related software. The item analysis, validity and reliability evaluation of the Chinese version of the EBP-KAPF scale were performed.Results:The Chinese version of the EBP-KAPF scale included 26 items in four dimensions: knowledge mastery, attitude, personal application and future use. A total of 265 questionnaires were sent out (including self-made questionnaires and the Chinese version of the EBP-KAPF scale), and 250 effective questionnaires were obtained, with a total effective rate of 94.3%. The total score of the Chinese version of the EBP-KAPF scale was (102.85±17.48) points, and the scores of knowledge mastery, attitude, personal application and future use sub-scales were (27.22±4.47), (13.56±7.70), (20.07±6.78), and (42.00±9.00) points, respectively. Except for item 16, all items were correlated with the total score of the scale, and the correlation coefficient ranged from 0.456 to 0.828. After item 16 was deleted, the determination values of the remaining 25 items ranged from 4.287 to 18.262 ( P<0.001). After item was removed one by one, the Cronbach′s α coefficient of the scale ranged from 0.870 to 0.888. After item 16 was removed, the Chinese version of the 25-item EBP-KAPF scale had good content validity, structural validity and discriminant validity. The content validity index (I-CVI) at the item level ranged from 0.875 to 1.000, and the content validity index at the overall agreement scale level was 0.615. The average S-CVI values were 0.952, and the probability of correction ( K*) values were 0.87 to 1.00. The results of confirmatory factor analysis showed that the structure fit was good [comparative fit index (CFI)=0.962, Tucker-Lewis index (TLI)=0.957, root mean square error of approximation (RMSEA)=0.060, χ2/ df=1.889]. Discriminant validity analysis showed that there were statistically significant differences in the EBP-KAPF scores among clinicians of different ages, evidence-based medicine course learning and related software use ( P<0.05). After item 16 was removed, the Cronbach′s α coefficient of the Chinese version of the EBP-KAPF scale was 0.893, and the Guttman half coefficients of each dimension were 0.915, 0.901, 0.812 and 0.906, respectively. The correlation coefficients were 0.902-0.982, 0.507-0.953, 0.517-0.744 and 0.632-0.986, respectively. Conclusion:The Chinese version of the EBP-KAPF scale is simple, easy to understand, unambiguous, and has good validity and reliability.
6.Application of nutrition management based on Patient-Generated Subjective Global Assessment in patients with pancreatic cancer undergoing chemotherapy
Wenxin ZHANG ; Pin ZHANG ; Jiayu HUANG ; Yan JIN ; Yang YANG ; Rumei DING
Chinese Journal of Practical Nursing 2024;40(13):976-983
Objective:To explore the effects of nutrition management based on Patient-Generated Subjective Global Assessment (PG-SGA) on nutritional idicators,quality of life and other indicators in patients with pancreatic cancer undergoing chemotherapy, to provide guidance for the implementation of the intervention plan for pancreatic cancer patients undergoing chemotherapy.Methods:This was a randomized controlled study. From January 2021 to December 2022, 96 patients with pancreatic cancer who received chemotherapy in Shanghai Changzheng Hospital and Affiliated Cancer Hospital of Fudan University were selected using convenience sampling method and divided into the observation group and the control group according to the random number table, with 48 cases in each group. The control group was given routine nursing intervention, and the observation group was given PG-SGA-based nutrition management intervention. Patients in both groups continued the intervention until discharge. Nutritional indexes, quality of life, the score of cancer-related fatigue, sleep quality and mental state before and after intervention, intervention compliance and satisfaction after intervention, and complications during intervention of both groups were compared.Results:There were 48 patients in each group ultimately. In the control group, there were 28 males, 20 females, aged (63.33 ± 4.31) years old; in the observation group, there were 27 males, 21 females, aged (63.15 ± 4.25) years old. After intervention, the PG-SGA score, serum triacylglycerol level, and scores of Revised Piper ′s Fatigue Scale and Arsens Insomnia Scale, Self-rating Anxiety Scale and Self-rating Depression Scale in the observation group were (3.87 ± 1.16) points, (1.35 ± 0.52) mmol/L, (3.79 ± 0.67) points, and (5.31 ± 2.05), (44.55 ± 5.14), (45.15 ± 5.08) points respectively, lower than the control group ′s (5.77 ± 1.58) points, (2.04 ± 0.35) mmol/L, (4.82 ± 0.88) points, and (7.29 ± 2.14), (51.74 ± 5.18), (52.26 ± 5.11) points, the differences were statistically significant ( t values were 4.63-7.63, all P<0.05); the serum levels of retinol binding protein and transferrin were (18.13 ± 2.41) mg/L and (61.25 ± 5.34) ng/L, respectively, higher than the control group ′s (15.29 ± 2.33) mg/L and (48.31 ± 5.28) ng/L, with statistical significance ( t=5.87, 11.94, both P<0.05). The symptom domain score in the observation group after intervention was (56.17 ± 5.25) points, lower than (66.22 ± 5.57) points in the control group, while the cognitive, social, emotional, role, and physical scores were (76.35 ± 5.71 ), (77.55 ± 6.51 ), (75.87 ± 6.45), (77.38 ± 6.61), (75.75 ± 6.37) points, higher than (66.29 ± 5.39), (65.74 ± 6.34 ), (64.22 ± 6.18), (66.56 ± 6.26), (65.74 ± 6.11) points in the control group ( t values were 7.86 to 9.10, all P<0.05). Conclusions:Nutritional management based on PG-SGA could reduce the degree of cancer-induced fatigue, relieve negative emotions, improve the overall nutritional status, improve intervention compliance, reduce the occurrence of complications; improve sleep quality, quality of life, and patient ′s satisfaction.
7.Chinese version of evidence-based practice-knowledge, attitude, application, anticipated future use (EBP-KAPF) scale and its reliability and validity
Wenxin YAN ; Jiaojiao LIAO ; Qirui SHAO ; Lin ZENG ; Yiming ZHAO ; Jue LIU ; Liyuan TAO
Chinese Journal of Preventive Medicine 2024;58(4):481-488
Objective:To translate Evidence-based Practice-knowledge, attitude, application, anticipated future use (EBP-KAPF) scale into Chinese, and evaluate its reliability and validity.Methods:The Chinese version of the EBP-KAPF scale was determined through translation, adaptation, recall, review and pre-investigation. From July to August 2022, 250 clinicians from 28 provinces (autonomous regions and municipalities directly under the Central Government) were selected by using the convenience sampling method. A self-made questionnaire was used to investigate the EBP-KAPF scale in Chinese to investigate the EBM ability of clinicians, including the basic information of the respondents, the learning and use of Evidence-based medicine courses and related software. The item analysis, validity and reliability evaluation of the Chinese version of the EBP-KAPF scale were performed.Results:The Chinese version of the EBP-KAPF scale included 26 items in four dimensions: knowledge mastery, attitude, personal application and future use. A total of 265 questionnaires were sent out (including self-made questionnaires and the Chinese version of the EBP-KAPF scale), and 250 effective questionnaires were obtained, with a total effective rate of 94.3%. The total score of the Chinese version of the EBP-KAPF scale was (102.85±17.48) points, and the scores of knowledge mastery, attitude, personal application and future use sub-scales were (27.22±4.47), (13.56±7.70), (20.07±6.78), and (42.00±9.00) points, respectively. Except for item 16, all items were correlated with the total score of the scale, and the correlation coefficient ranged from 0.456 to 0.828. After item 16 was deleted, the determination values of the remaining 25 items ranged from 4.287 to 18.262 ( P<0.001). After item was removed one by one, the Cronbach′s α coefficient of the scale ranged from 0.870 to 0.888. After item 16 was removed, the Chinese version of the 25-item EBP-KAPF scale had good content validity, structural validity and discriminant validity. The content validity index (I-CVI) at the item level ranged from 0.875 to 1.000, and the content validity index at the overall agreement scale level was 0.615. The average S-CVI values were 0.952, and the probability of correction ( K*) values were 0.87 to 1.00. The results of confirmatory factor analysis showed that the structure fit was good [comparative fit index (CFI)=0.962, Tucker-Lewis index (TLI)=0.957, root mean square error of approximation (RMSEA)=0.060, χ2/ df=1.889]. Discriminant validity analysis showed that there were statistically significant differences in the EBP-KAPF scores among clinicians of different ages, evidence-based medicine course learning and related software use ( P<0.05). After item 16 was removed, the Cronbach′s α coefficient of the Chinese version of the EBP-KAPF scale was 0.893, and the Guttman half coefficients of each dimension were 0.915, 0.901, 0.812 and 0.906, respectively. The correlation coefficients were 0.902-0.982, 0.507-0.953, 0.517-0.744 and 0.632-0.986, respectively. Conclusion:The Chinese version of the EBP-KAPF scale is simple, easy to understand, unambiguous, and has good validity and reliability.
8.Analysis of the causes for abnormal dissolution of lansoprazole enteric-coated tablets by multiple techniques and different dimensions
Wenxin LIU ; Yan LI ; Yaozuo YUAN ; Huanhuan JIA ; Minhui CHEN ; Jinlin ZHANG
Journal of China Pharmaceutical University 2024;55(2):224-229
Abstract: This study aims to find out the causes for the dissolution of unqualified samples found during evaluation sampling of lansoprazole enteric-coated preparations by the laser infrared imaging system and orbitrap high resolution mass spectrometry, with suggestions for improvement. Lansoprazole enteric-coated preparations were tested by current standard, the dissolution of a batch of samples was below the limit and other items were in line with the standard. Considering that this product is unstable to acid and alkali, the following exploratory experiments were designed from different dimensions, based on the conclusion of the unannounced inspection of the company, to explore the reasons for the unqualified batch, including the influence of high-temperature and high-humidity storage environment on the key quality properties of the sample, the influence of 2-hour acid resistance test on dissolution result, the imaging of the core and the measure of coating layer thickness, the optimization of chromatographic conditions of related substances, and the analysis of the source of impurities. It was found that improper storage in circulation and poor coating process caused the low dissolution of this batch: the high-temperature and high-humidity storage environment possible in the circulation process led to the decreasing efficacy of disintegrating agent in the samples and thus the difficulty to release the active pharmaceutical ingredient fully; the coating solution could not be uniformly sprayed on the core, resulting in thin isolation layer and different thickness, which then affected the protection of the main drug against acid degradation. The above two reasons together resulted in unqualified dissolution of this batch. The overall quality of lansoprazole enteric-soluble preparation is good, but the formulation and process in some companies need to be optimized; and the temperature and humidity in the circulation process need to be controlled in strict accordance with the regulations.
9.Psychological experience of patients with breast cancer during rehabilitation: a Meta synthesis of qualitative studies
Hong CHEN ; Xuecheng JIANG ; Fa XIAO ; Wenxin XIE ; Yuanyuan LUO ; Min LI ; Lyuting YAN ; Zhihui YANG
Chinese Journal of Modern Nursing 2024;30(13):1730-1737
Objective:To systematically integrate qualitative studies on psychological experience of breast cancer patients in rehabilitation period, so as to provide basis for improving psychological care and rehabilitation efficacy.Methods:Qualitative research on psychological experience of breast cancer patients during rehabilitation was electronically retrieved in databases, including PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang data, and China Biology Medical disc. The search period was from database establishment to September 2023. The quality evaluation of the literature was conducted using the 2020 version of the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center. The results were integrated using the aggregative Meta integration method.Results:A total of 18 articles were included. Sixty-six research topics were extracted and categorized into 10 new categories, forming three integrated results, namely, psychological adjustment of patients with negative emotions and rehabilitation needs in the process of coping, family and social factors affecting patient rehabilitation experience, and patients perceiving that the healthcare system was not yet perfect.Conclusions:Medical and nursing staff should pay attention to the psychological problems of breast cancer patients in the rehabilitation period, understand their rehabilitation needs, provide targeted counseling and services, pay attention to the family and social support factors of breast cancer patients, help them improve their quality of life, and actively promote rehabilitation.
10.Survival analysis of liver cancer in Shanghai:a population-based study from 2002 to 2013
Linmeng ZHANG ; Chunxiao WU ; Hui WANG ; Kai GU ; Liang SHI ; Cun WANG ; Wenxin QIN ; Yan SHI
Tumor 2023;43(4):347-353
Objective:To investigate the survival rates of patients with liver cancer in Shanghai from 2002 to 2013. Methods:Data on new cases and deaths of liver cancer patients withfollow-up information from 2002 to 2013 were obtained from the Population-Based Cancer Registry and Vital Statistics System of the Shanghai Municipal Center for Disease Control and Prevention.Incidence and survival rates were stratified by year of diagnosis,gender,district,age-group and stage at diagnosis for analysis.Statistical indicators,such as case numbers,proportions,median age and mean age were calculated.The 1-to 5-year observed survival rates were calculated based on the life table method.The probabilities of surviving from 0 to 99 years old were estimated with the Elandt-Johnson model,and then cumulative expected survival rates were calculated using the Ederer Ⅱ method.Finally,the 1-to 5-year relative survival rates were calculated. Results:A total of 49 455 new cases of liver cancer were diagnosed from 2002 to 2013 in Shanghai,including 35 115 males and 14 340 females.The ratio of males to females was 2.45:1.The proportions of stage Ⅰ,stage Ⅳ and stage unknown were 3.32%,13.93%and 69.13%,respectively.The median survival time of patients with liver cancer diagnosed from 2002 to 2013 was 0.77 years,the 5-year observed survival rate was 13.23%,and the 5-year relative survival rate was 14.47%.According to the 5-year observed survival rate and 5-year relative survival rate of the cases,both survival indicators were higher in urban areas than in suburban areas,higher in males than in females,higher in cases under 45 years of age than in those over 75 years of age,higher in cases diagnosed from 2011 to 2013 than those diagnosed from 2002 to 2004.Additionally,the survival rate of cases decreased with increasing stage at diagnosis. Conclusion:With the continuous improvement of the diagnosis and treatment of liver cancer in Shanghai,the survival rate of patients with liver cancer has shown a significant upward trend over time.However,compared with various malignant tumors such as gastric cancer and breast cancer,the improvement effect of liver cancer survival rate is still not significant.Additionally,a high proportion of cases with unknown clinical stage at the time of diagnosis and a low survival rate of stage Ⅳ cases were observed.This study provides a basis for the prevention and research of liver cancer.

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