1.Reporting quality and influencing factors of patient-reported outcomes in randomized controlled trials of lung cancer: Based on the CONSORT-PRO extension
Guiying ZHANG ; Yueyuan YOU ; Xiaoqin ZHOU ; Jing LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(03):322-331
Objective To evaluate the reporting quality and influencing factors of patient-reported outcome (PRO) data in randomized controlled trials (RCTs) of lung cancer. Methods RCTs of lung cancer with PRO as either primary or secondary endpoints were searched from PubMed, EMbase, Medline, CNKI, Wanfang Data, and VIP databases between January 1, 2010 and April 20, 2024. Reporting quality of included RCTs were assessed based on the CONSORT-PRO extension. Descriptive statistics and bivariate regression analysis were used to describe the reporting quality and analyze the factors influencing the reporting quality. Results A total of 740 articles were retrieved. After screening, 53 eligible RCTs of lung cancer with 22 780 patients were included. The patients were mainly with non-small cell lung cancer (84.91%), with the median sample size of the included studies was 364.0 (160.5, 599.5) patients. The primary PRO tool used was the EORTC QLQ-C30 (60.38%). There were 52 (98.11%) studies whose PRO measured the domain of "symptom management of cough, dyspnea, fatigue, pain, etc.", and 45 (84.91%) studies measured "health-related quality of life". Multicenter studies accounted for 84.91%, and randomized non-blind trials accounted for 62.26%. PRO was used as the primary endpoint in 33.96% of the studies and as secondary endpoints in 66.04%. The reliability and validity of the PRO tools were explicitly mentioned in 11.32% and 7.55% of the studies, respectively. The average completeness of reporting according to the CONSORT-PRO guidelines was 60.00%, ranging from 25.00% to 93.00%. The main factors affecting the completeness of CONSORT-PRO reporting included sample size and publication year. For every increment in sample size, the completeness of reporting increased by 27.5% (SE=0.00, t=2.040, P=0.046). Additionally, studies published after 2018 had a 67.2% higher completeness of reporting compared to those published in or before 2018 (SE=17.8, t=–3.273, P=0.006). Conclusion The study reveals that the overall reporting quality of PRO in lung cancer RCTs is poor. Particularly, the reporting of PRO measures reliability and validity, PRO assumptions, applicability, and handling of missing data need further improvement. Future research should emphasize comprehensive adherence to the CONSORT-PRO guidelines.
2.Research progress on advance care planning for elderly patients with chronic diseases
Yongpeng SUN ; Song LI ; Kangli SHI ; Guiying FENG
Chinese Medical Ethics 2025;38(3):281-288
With the continuous intensification of aging, chronic diseases among the elderly have become a widely concerned public health issue. In the terminal stage, they often lose the ability to express their medical care wishes autonomously, leading to a disconnect between medical decision-making and the actual needs of the patients and increasing their physical and psychological suffering. With the rapid aging process in China, the incidence of chronic diseases in the elderly is continuously rising, which has become a serious public health problem. Studies have shown that advance care planning (ACP) has achieved remarkable results in maintaining the dignity of life for terminal chronic disease patients, improving patients’ quality of life, as well as alleviating the physical, mental, and economic burdens on their families. Therefore, the implementation of ACP is crucial for elderly patients with chronic diseases. This paper reviewed the concept of ACP, as well as application effects, challenges and limitations, and corresponding recommendations and countermeasures of ACP in elderly patients with chronic diseases, with a view to providing a solid theoretical and practical basis for the application of ACP in elderly population with chronic diseases in China.
3.Zingiberis Rhizoma Alleviates Inflammatory Bowel Disease Through Regulating TLR4/MAPK Signaling Pathway in Ly6Chi Monocytes/Macrophages
Yalan LI ; Chonghao ZHANG ; Huachen LIU ; Jialong SU ; Na LI ; Mengyu ZHOU ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):66-75
ObjectiveTo investigate the potential mechanisms of Zingiberis Rhizoma in treating inflammatory bowel disease (IBD) by integrating network pharmacology with in vitro and in vivo experiments. MethodsTraditional Chinese Medicine Systems Pharmacology Database And Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) Database were used to obtain the active component targets of Zingiberis Rhizoma. GeneCards was used to obtain the IBD targets. DAVID was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on core targets. Cytoscape 3.10.2 was used to establish the "active component-disease target-signaling pathway" interaction network. Mice were randomly assigned to control, model, and Zingiberis Rhizoma (400 mg·kg-1) groups. An IBD model was induced via dextran sulfate sodium (DSS). The colonic tissue was collected post-treatment to assess histology, expression of Ly6C+ monocytes/macrophages, and mRNA levels of Toll-like receptor 4 (TLR4), and inflammatory cytokines. The effect of Zingiberis Rhizoma aqueous extract on RAW264.7 cell viability was evaluated. Furthermore, the effects of the extract at 100, 10, and 1 mg·L-1 on LPS-induced differentiation of RAW264.7 cells into Ly6Chi monocytes/macrophages, mRNA levels of TLR4 and inflammatory cytokines, and protein levels of factors in the TLR4/mitogen-activated protein kinase (MAPK) signaling pathway. ResultsA total of 241 targets were identified for Zingiberis Rhizoma and 6 787 for IBD, with 122 shared targets among Zingiberis Rhizoma, ulcerative colitis (UC), and Crohn's disease (CD). The enrichment analyses yielded 297 GO terms and 88 KEGG pathways. Associations were noted between Zingiberis Rhizoma's active component targets and IBD targets. In vivo experiments: Compared with the control group, the model group showed decreased body weight and disease activity index (DAI)(P<0.01), shortened colon length, damaged mucosal epithelium with inflammatory cell infiltration, raised pathological scores (P<0.05), increased Ly6Chi and Ly6Clo monocytes/macrophages (P<0.05), and up-regulated mRNA levels of TLR4, TNF-α, IL-1β, and IL-6 (P<0.05) and protein levels of TLR4, phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), and phosphorylated p38 MAPK (p-p38 MAPK) (P<0.05). Zingiberis Rhizoma intervention reversed these changes and reduced Ly6Chi monocytes/macrophages (P<0.01). In vitro experiments: compared with the control, LPS increased the proportion and number of Ly6Chi monocytes/macrophages and mRNA levels of TLR4, TNF-α, IL-1β, and IL-6 (P<0.01) and enhanced the expression of TLR4, p-ERK1/2, and p-p38 MAPK (P<0.05). Zingiberis Rhizoma reduced Ly6Chi monocytes/macrophages (P<0.05), down-regulated the mRNA levels of inflammatory cytokines (P<0.05), and suppressed the TLR4/MAPK pathway (P<0.05). ConclusionZingiberis Rhizoma alleviates IBD by suppressing the TLR4/ERK/p38 MAPK signaling pathway and reducing inflammatory cytokine levels in Ly6Chi monocytes/macrophages.
4.Mume Fructus Restores Intestinal Mucosal Epithelial Barrier Through MEK/ERK Signaling Pathway in Mouse Model of Inflammatory Bowel Disease
Huachen LIU ; Chonghao ZHANG ; Yalan LI ; Jie LIU ; Jialong SU ; Na LI ; Shaoshuai LIU ; Qing WANG ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):76-85
ObjectiveTo clarify the repair effect of Mume Fructus on the intestinal mucosal epithelial barrier in the mouse model of inflammatory bowel disease (IBD) and explore the repair mechanism. MethodsThirty-six male C57BL/6 mice were randomly assigned into six groups: normal, model, low-, medium-, and high-dose (200, 400, and 800 mg·kg-1) Mume Fructus, and sulfasalazine (300 mg·kg-1). Except the normal group, the rest groups had free access to 2% dextran sulfate sodium (DSS) solution for seven days to establish the IBD model, followed by a seven-day drug intervention. The body weight change and disease activity index (DAI) were recorded. After the last administration, spleen and colon tissue samples were collected to analyze the differences in colon length and spleen index. Hematoxylin-eosin staining was used to observe the morphology of the colon tissue. The level of diamine oxidase (DAO) in the serum was measured by the DAO assay kit. Immunohistochemistry was employed to determine the expression of tight junction proteins such as Claudin-1, Occludin, and zonula occludens-1 (ZO-1) in the colon tissue. Real-time PCR was performed to measure the mRNA levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the colon tissue. Finally, Western blot was employed to determine the protein levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase (ERK), phosphorylated (p)-MEK, and phosphorylated ERK in the colon tissue. ResultsCompared with the normal group, the model group exhibited decreases in body weight and colon length (P<0.01), increases in DAI, spleen index, and serum DAO level (P<0.01), damaged colonic epithelium and goblet cells, and obvious infiltration of inflammatory cells. In addition, the model group exhibited higher positive expression of Claudin-1, Occludin, and ZO-1 (P<0.01), higher mRNA levels of TNF-α and IL-1β (P<0.01), and higher protein levels of p-MEK and p-ERK (P<0.05, P<0.01) than the normal group. However, sulfasalazine and three doses of Mume Fructus markedly decreased the body weight and DAI (P<0.05), recovered the colon length and spleen index, alleviated colon tissue damage, lowered the level of DAO in the serum (P<0.01), and down-regulated the mRNA levels of TNF-α and IL-1β (P<0.01) and the protein levels of p-MEK and p-ERK (P<0.05). Sulfasalazine and low- and medium-dose Mume Fructus increased the positive expression of Occludin, Claudin-1, and ZO-1 (P<0.05, P<0.01). Furthermore, high-dose Mume Fructus elevated the protein expression of Occludin (P<0.05). ConclusionMume Fructus can restore the expression of intestinal epithelial tight junction proteins by inhibiting the phosphorylation of proteins in the MEK/ERK signaling pathway and down-regulating the levels of TNF-α and IL-1β, thus repairing the intestinal mucosal barrier in the mouse model of IBD.
5.Regulatory Effect of Modified Wumeiwan on Th17/Treg Balance and Intestinal Microbiota in Ulcerative Colitis with Dampness-heat Obstruction Syndrome in Human Flora-associated Model
Chonghao ZHANG ; Peiguang MA ; Huachen LIU ; Jialong SU ; Jie LIU ; Yalan LI ; Guichuan XU ; Na LI ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):86-93
ObjectiveTo investigate the modulating effect of modified Wumeiwan (MWMW) on the ulcerative colitis (UC)-associated intestinal helper T cell 17 (Th17)/regulatory T cell (Treg) balance and intestinal flora by using a human flora-associated model of UC patients with dampness-heat obstruction syndrome, thus providing a new idea for the UC-related research and therapeutic strategies. MethodsThe 24 male C57BL/6J mice were randomized into normal control, model, and MWMW groups (n=8). Model and MWMW groups were first treated with an antibiotic cocktail (vancomycin, 0.1 g·kg-1; neomycin sulfate, 0.2 g·kg-1; ampicillin, 0.2 g·kg-1; metronidazole, 0.2 g·kg-1) for 21 days. At the end of antibiotic treatment, the gavage of fecal microbiota suspension from UC patients with dampness-heat obstruction syndrome was started at a dose of 0.2 mL·d-1 for 19 consecutive days, by which a human flora-associated model of UC was obtained. The MWMW group was administrated daily with MWMW liquid (12.5 g·kg-1), while the normal control and model groups were administrated by gavage with an equal amount of sterile water for 7 consecutive days. The symptoms of dampness-heat obstruction were observed. The colon length and spleen index were measured and calculated, and the proportions of Th17 and Treg cells were detected by flow assay. The intestinal flora was analyzed by 16S rRNA high-throughput sequencing. ResultsCompared with the normal control group, the model group showed shortened colon (P<0.05) and increased spleen index (P<0.01). Compared with the model group, the MWMW group showed prolonged colon (P<0.01) and decreased spleen index (P<0.05). After the intervention of MWMW, the Th17 proportion and Th17/Treg ratio in the colon decreased (P<0.01), and the proportion of Treg cells increased (P<0.05). The number of species and alpha and beta diversity of intestinal flora in mice were regulated by MWMW (P<0.05). In terms of intestinal flora composition, MWMW increased the relative abundance of several phyla (Firmicutes, Proteobacteria, Fusobacteriota, Actinobacteriota, and Gemmatimonadota), the genus Bacteroides, and two species (Bacteroides thetaiotaomicron and B. fragilis) in model mice. Moreover, Spearman's correlation analysis showed that the relative abundance of B. thetaiotaomicron and B. fragilis were negatively correlated with the Th17 level (P<0.05). In addition, the above changes in intestinal flora caused the changes in microbial genes involved in 14 pathways, such as glycolysis, amino acid degradation, inorganic nutrient metabolism, biosynthesis of pyrimidine deoxyribonucleotides, antibiotic resistance, and degradation of polysaccharides. ConclusionsThe human flora-associated model successfully simulated the changes (marked by a decrease in the abundance of Bacteroides) of intestinal flora in UC patients with dampness-heat obstruction syndrome. MWMW can enrich the abundance of beneficial bacteria such as B. thetaiotaomicron and B. fragilis and promote the synergistic intestinal immune modulation with the metabolic functions centered on glycolysis, amino acid metabolism, and nucleotide synthesis through bacterial polysaccharide utilization sites to reduce the Th17/Treg ratio, thereby exerting a protective effect on UC.
6.Evolution of Medication Patterns in Traditional Chinese Medicine for Treating Inflammatory Bowel Disease
Chen WANG ; Xiaoyu CAO ; Yalan LI ; Shaoshuai LIU ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):94-102
ObjectiveTo explore the evolution of medication patterns and syndrome-herb associations of traditional Chinese medicine (TCM) in treating inflammatory bowel disease (IBD), providing a theoretical foundation for precise syndrome differentiation and treatment in clinical practice. MethodsMedical case literature on TCM treatment of IBD from 1960 to 2024 was retrieved to establish a database. Frequency statistics, cluster analysis, change point detection, and association rule mining were employed to comprehensively analyze the syndrome distribution, therapeutic methods, medication patterns, and their temporal variations. ResultsA total of 685 medical cases were included. Common syndromes were dampness-heat (66.42%) and spleen deficiency (56.20%). Primary therapeutic methods included heat clearing (63.65%), spleen invigorating (47.45%), and dampness draining (36.79%). High-frequency herbs included Coptidis Rhizoma (354), Paeoniae Radix Alba (303), Aucklandiae Radix (292), Codonopsis Radix (253), and Glycyrrhizae Radix et Rhizoma (244). Initial prescription clustering revealed three core therapeutic method combinations: heat clearing and detoxifying (represented by Baitouweng Tang), spleen invigorating and Qi reinforcing (represented by Shenling Baizhusan), and cold-heat regulation (represented by Wumeiwan combined with Shaoyao tang). Temporal analysis identified 2008 as a key transition point in TCM treatment of IBD, with significantly increased usage frequency of heat-clearing and dampness-drying herbs such as Fraxini Cortex, Phellodendri Chinensis Cortex, Sophorae Flavescentis Radix, and Scutellariae Radix as well as hemostatic herbs such as carbonized Sanguisorbae Radix, Bletillae Rhizoma, Agrimoniae Herba, and Notoginseng Radix et Rhizoma. Follow-up efficacy analysis showed median improvement rates of 64.0% at the first follow-up, 76.0% at the second follow-up, and 78.7% at the third follow-up. Syndrome-drug association analysis revealed specific herb pairs with significant therapeutic advantages, including Notoginseng Radix et Rhizoma + Coicis Semen, Sanguisorbae Radix + Coptidis Rhizoma, and Codonopsis Radix + Aconii Lateralis Radix Praeparaia. ConclusionTCM medication patterns for treating IBD demonstrate distinct temporal evolution characteristics, with significantly increased usage frequency of herbs such as Fraxini Cortex, Notoginseng Radix et Rhizoma, and Agrimoniae Herba. Significant therapeutic method-herb associations and syndrome-herb association patterns exist, with the formation of specific herb pairs, providing evidence-based support for precise syndrome differentiation and treatment of IBD.
7.Analysis of abnormal individual dose monitoring results in 206 medical institutions in a selected region in 2024
Hua TUO ; Wenyan LI ; Lantao LIU ; Guiying ZHANG ; Zeqin GUO ; Heyan WU
Chinese Journal of Radiological Health 2025;34(4):471-476
Objective To analyze the abnormal individual dose monitoring results in 206 medical institutions in a selected region in 2024, and to propose improvement measures. Methods Individuals with monitoring results exceeding the investigation level were subjected to high-dose investigation, and the results were statistically analyzed. Results In 2024, the individual dose monitoring of 206 medical institutions in a selected region showed 1.04% abnormal results. The proportions of abnormal results from primary, secondary, and tertiary medical institutions were 12.22%, 3.33%, and 84.45%, respectively. In analysis of the causes of abnormal results, 52.53% of the cases were due to personal dosimeters left in the radiation workplace, and 20.20% were due to the confusion in wearing personal dosimeters inside and outside the lead apron. In analysis of the occupational distribution of the radiation workers with abnormal monitoring results, interventional radiology and diagnostic radiology accounted for 73.34% and 24.44%, respectively. Statistical analysis of the dose range showed that doses in the ranges of 1.25-2.0 mSv and 2.0-5.0 mSv accounted for 42.22% and 33.33%, respectively. In the report of abnormal monitoring results, the proportions of reporting notional dose and reporting measured results accounted for 88.89% and 11.11%, respectively. Among institutions with consecutive abnormal results, primary, secondary, and tertiary medical institutions accounted for 15.39%, 7.69%, and 76.92%, respectively. Conclusion The level of the hospital, occupational type, the perceived importance of the hospital to the management of radiation protection, and the perceived importance and compliance of the radiation workers with the individual dose monitoring are potential causes of abnormal results. It is recommended that employers should enhance radiation protection training for their radiation workers to ensure proper wearing and storage of dosimeters, and progressively improve the standardization and effectiveness of individual dose monitoring practice.
8.Targeting the JAK2-STAT3-UCHL3-ENO1 axis suppresses glycolysis and enhances the sensitivity to 5-FU chemotherapy in TP53-mutant colorectal cancer.
Haisong XIN ; Zitong ZHAO ; Shichao GUO ; Ruoxi TIAN ; Liying MA ; Yang YANG ; Lianmei ZHAO ; Guanglin WANG ; Baokun LI ; Xuhua HU ; Yongmei SONG ; Guiying WANG
Acta Pharmaceutica Sinica B 2025;15(5):2529-2544
Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.
9.Microbiome, metabolome, and transcriptome analyses in esophageal squamous cell carcinoma: insights into immune modulation by F. nucleatum.
Xue ZHANG ; Jing HAN ; Yudong WANG ; Li FENG ; Zhisong FAN ; Yu SU ; Wenya SONG ; Lan WANG ; Long WANG ; Hui JIN ; Jiayin LIU ; Dan LI ; Guiying LI ; Yan LIU ; Jing ZUO ; Zhiyu NI
Protein & Cell 2025;16(6):491-496
10.Peripheral blood cell count composite score as a prognostic factor in patients with colorectal cancer
Peiyuan GUO ; Xuhua HU ; Baokun LI ; Ti LU ; Jiaming LIU ; Chaoyu WANG ; Wenbo NIU ; Guiying WANG ; Bin YU
Chinese Journal of Gastrointestinal Surgery 2024;27(9):953-965
Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

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