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.
2.Fufang Kangjiaolv Capsules Treat Anxiety in Rat Model of Chronic Restraint Stress via Microbiota-gut-brain Axis
Wenxin FAN ; Tingyue JIANG ; Yu WANG ; Ge ZHANG ; Yifan LU ; Mengmeng LIU ; Jiayuan LI ; Renzhi MA ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):95-107
ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress (CRS) and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank, model, positive drug (diazepam, 1 mg·kg-1), and low-, medium-, and high-dose (0.75, 1.5, 3 g·kg-1, respectively) Fufang Kangjiaolv capsules groups. After 14 days of administration, the elevated plus maze test, open field test, light and dark box test, and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats, and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of zonula occludens-1 (ZO-1) and occludin in the colon of rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the colon, serum, and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1, occludin, nuclear factor-κB p65 (NF-κB p65) in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor (BDNF) in the hippocampal tissue. ResultsCompared with the blank group, the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze, the time and frequency of rats entering the central area of the open field, the time of entering the open box, the times of passing through the light and dark box, and the number of unburied beads (P<0.05, P<0.01). Compared with the model group, Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees, and the high-dose group had the best effect, with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze (P<0.05), the number of rats entering the central area in the open field (P<0.05), the time of entering the open box, the times of passing through the light and dark boxes, and the number of unburied beads (P<0.01). Moreover, the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes, Deferribacterota, Romboutsia, and Phascolarctobacterium, while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota, Bacteroides, norank f norank o Clostridia UCG-014, and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group, the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon (P<0.01), elevated levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated protein level of NF-κB p65 in the colon and hippocampus (P<0.01), and down-regulated protein level of BDNF in the hippocampus (P<0.05). Compared with the model group, high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon (P<0.01), lowered the levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated the protein levels of ZO-1 (P<0.01) and occludin (P<0.05) in the colon, down-regulated the protein level of NF-κB p65 in the colon and hippocampus (P<0.05), and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance, up-regulating the expression of tight junction proteins in the colon, repairing intestinal mucosal mechanical barrier, and down-regulating NF-κB/BDNF signaling pathway, thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis, providing a new idea for further research.
3.Jieduan Niwan Formula regulates AMPK to alleviate mitochondrial damage in HepG2 cells
Ruimin MA ; Hanjing WANG ; Wenxin ZHANG ; Chongyang MA ; Qiuyun ZHANG ; Yuqiong DU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):193-204
Objective:
To investigate the regulatory effect of Jieduan Niwan Formula (JDNWF) drug-containing serum on AMPK-mediated mitochondrial quality control in D-GalN-induced HepG2 cells.
Methods:
Twenty male Wistar rats were randomly divided into blank control and JDNWF-containing serum groups, 10 rats per group. The JDNWF-containing serum group was gavaged with JDNWF (21.7 g/kg), whereas the blank control group was gavaged with saline. Blood was collected to prepare JDNWF-containing and blank control serum. Cell viability, mitochondrial damage indicators, and MQC pathway protein expression levels were evaluated to determine the optimal volume fraction of JDNWF. HepG2 cells were divided into control, D-GalN, DMSO, AMPK inhibitor, JDNWF drug-containing serum, and JDNWF drug-containing serum plus AMPK inhibitor groups, and corresponding drug interventions were administered to each group. Cells were collected after the interventions, and the CCK-8 assay was used to measure cell viability, the 2′-7′-dichlorodihydrofluorescein diacetate fluorescent probe was used to detect reactive oxygen species (ROS) levels, JC-1 was used to detect mitochondrial membrane potential, thiobarbituric acid was used to measure malondialdehyde (MDA) levels, WST-8 was used to measure superoxide dismutase (SOD) activity, and western blotting was used to detect the expression levels of mitochondrial quality control-related proteins, including p-AMPK, AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1.
Results:
5% JDNWF drug-containing serum most significantly restored cell viability, mitochondrial damage markers, and MQC pathway protein expression in the model group. Therefore, it was chosen for intervention in subsequent experiments. Compared to the control group, the cell viability of the D-GalN, DMSO, and AMPK inhibitor groups was significantly reduced (P<0.01). In contrast, the heterogeneity of mitochondrial membrane potential, ROS, and MDA levels was significantly increased (P<0.01), and SOD activity was significantly decreased (P<0.01). The p-AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1 protein expression levels were significantly decreased (P<0.01). After JDNWF drug-containing serum intervention, compared to the DMSO group, cell viability significantly increased (P<0.01), mitochondrial membrane potential heterogeneity, ROS, and MDA levels significantly decreased (P<0.01), SOD activity significantly increased (P<0.01), and p-AMPK, PGC-1α, NRF1, TFAM, and MFN2 protein expression levels significantly increased (P<0.01), whereas DRP1 protein expression significantly decreased (P<0.01). Compared to the JDNWF drug-containing serum group, the cell viability in the JDNWF plus AMPK inhibitor group significantly decreased (P<0.01), mitochondrial membrane potential heterogeneity and ROS levels significantly increased (P<0.01), MDA levels significantly increased (P<0.05), SOD activity significantly decreased (P<0.05), p-AMPK, PGC-1α, NRF1, and TFAM protein expression levels significantly decreased (P<0.01), MFN2 protein expression significantly decreased (P<0.05), and DRP1 protein expression significantly increased (P<0.01).
Conclusion
JDNWF drug-containing serum may restore mitochondrial function and improve D-GalN-induced HepG2 cell injury by regulating AMPK-mediated mitochondrial quality control.
4.Clinical Application of Green Prescription of Traditional Chinese Medicine:Problems and Solution Strategies
Yike SONG ; Zhijun BU ; Wenxin MA ; Kai LIU ; Yuyi WANG ; Yuan SUN ; Yang SHEN ; Hongkui LIU ; Jianping LIU ; Zhaolan LIU
Journal of Traditional Chinese Medicine 2025;66(11):1094-1098
Green prescription is a written prescription aimed at improving health by promoting physical activity and improving diet, with advantages such as high cost-effectiveness, strong feasibility, and minimal harm to patients. The theory of traditional Chinese medicine (TCM) green prescription integrates the health philosophy of "following rule of yin and yang, and adjusting ways to cultivating health", the exercise philosophy of balancing yin-yang and the five elements, and the dietary philosophy of moderation and balance, which embody core TCM concepts such as treating disease before its onset and harmony between humans and nature. It has also developed traditional exercise practices like Tai Chi, Baduanjin, Wuqinxi, Yi-Gin-Ching, and Qigong, as well as dietary adjustments like medicated diet and herbal wines. However, it is believed that the TCM green prescription currently suffers from insufficient evidence-based research, low patient awareness and acceptance, and weak basic research. Based on this, it is proposed that large-sample clinical trials should be conducted in the future to improve the quality of evidence-based medicine, basic research can be carried out with the help of artificial intelligence and other methods in research design, the hospital information system (HIS) can be used for control at the implementation level, and publicity and patient education can be strengthened through the new media, so as to promote the development and application of the TCM green prescriptions in the field of global health treatment.
5.Application of Quality Evaluation of Blind Method in Clinical Trials of Traditional Chinese Medicine
Zeyang SHI ; Yuan SUN ; Wenxin MA ; Yuyi WANG ; Zhijun BU ; Xuehui WANG ; Youyou ZHENG ; Jianping LIU ; Zhaolan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):75-80
The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years, randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine (TCM), but the quality of the implementation of blind methods is uneven, and the evaluation criteria have not yet been formed. In this paper, the data collection methods, calculation principles, advantages, and disadvantages of two quantitative quality evaluation methods of blind methods, namely James Blinding Index (JBI) and Bang Blinding Index (BBI), were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time, a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally, the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.
6.Textual Analysis of Classical Prescription Yangweitang Based on Ancient Literature
Lyuyuan LIANG ; Jialei CAO ; Yiping WANG ; Mengmeng GENG ; Lujun ZHU ; Wenxin WEI ; Bingqi WEI ; Wenli SHI ; Bingxiang MA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):147-157
The classical prescription Yangweitang, derived from Zhengzhi Zhunsheng, is specialized in treating syndromes of chill and fever due to exogenous pathogens, inner-cooling, and malaria, and it has been included in the Catalogue of Ancient Classical Formulas (the First Batch) published by the National Administration of Traditional Chinese Medicine (TCM) in 2018. Through bibliographical research, the relevant ancient books and modern documents were systematically sorted out, and it was found that there were many prescriptions related to the Yangweitang from Zhengzhi Zhunsheng. They were interwoven with Yangweitang from Zhengzhi Zhunsheng and widely used in clinical practice. In order to clarify their history and evolution, this paper combed the historical origin of Yangweitang and its related prescriptions and conducted textual analysis on key information such as semantic composition, herb origin, processing method, and efficacy. A total of 896 pieces of data on Yangweitang from Zhengzhi Zhunsheng were collected. 26 pieces of effective data were included after the screening, involving 17 ancient TCM books. Then, a total of 28 pieces of data on prescriptions related to the Yangweitang from Zhengzhi Zhunsheng were included, involving 23 ancient TCM books for reference. The textual analysis showed that Yangweitang originated from the Renshen Yangweitang recorded in Taiping Huimin Heji Jufang in the Song dynasty. Based on the original formula, medical experts from later generations have modified it into many different versions. A comparative analysis showed that Yangweitang from different generations had similar compositions, and the herb origin and processing method were basically clear. The recommended prescriptions are as follows: 37.3 g of Pinelliae Rhizoma Praeparatum Cum Alumine, Magnoliae Officinalis Cortex(fried with ginger juice), and frying with rice water Atractlodis Rhizoma, 27.98 g of Citri Exocarpium Rubrum, 18.65 g of Pogostemon cablin leaf, Tsaoko Fructus, Poria, and Ginseng Radix et Rhizoma, and 9.33 g of Glycyrrhizae Radix et Rhizoma. They could be ground into a coarse powder, with 14.92 g for every dose, and they could be orally taken after being decocted with 450 mL of water, 7 g of fresh ginger, and 2 g of Mume Fructus to 270 mL in warm conditions. Yangweitang from Zhengzhi Zhunsheng has the effect of warming the middle and releasing the external, and it can treat many syndromes including spleen and stomach disharmony caused by chill and fever due to exogenous pathogens and inner-cooling, as well as all kinds of malaria. Modern clinical applications mainly focus on chronic atrophic gastritis and other digestive system diseases.
7.Effect of Huatan Sanjie Formula (化痰散结方) on Thyroid Angiogenesis and VEGFA/VEGFR2 Signaling Pathway in Graves' Disease Model Mice
Wenxin MA ; Xiaoyun ZHU ; Chengna WANG ; Jing XU ; Ximing LIU ; Yang TANG
Journal of Traditional Chinese Medicine 2024;65(19):2025-2031
ObjectiveTo investigate the possible mechanism of Huatan Sanjie Formula (化痰散结方, HSF) in treating Graves' disease (GD) from the perspective of thyroid angiogenesis. MethodsThirty-six BALB/c female mice were randomly divided into a normal control group (n=9) and a modeling group (n=27). Mice in the modeling group were injected with 2.0×109 PFU/ml of Ad-TSHR289 adenovirus into the tibialis anterior muscle to build GD model. Nine weeks after immunization, the successfully modeled mice were randomly divided into model group, methimazole (MMI) group and HSF group, with 9 mice in each group. The MMI group was given 5.2 mg/(kg·d) of methimazole tablets by gavage, while the HSF group was given HSF at a relative crude drug dosage of 7.02 g/(kg·d) by gavage. The normal control group and the model group were given 0.1 ml/10 g of pure water by gavage. All groups were administered intragastrically once a day for a total of 4 weeks. The levels of thyroxine (T4) and thyrotropin receptor autoantibodies (TRAb) in serum were detected by radioimmunoassay, while the pathological changes of the thyroid gland were assessed by HE staining. The vascular morphology of thyroid tissue was observed by CD34 immunohistochemical staining, and the microvessel density (MVD) was counted. The protein expression of vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor 2 (VEGFR2) in thyroid was detected by Western-blot. ResultsCompared to those in the normal control group, the thyroid volume of the mice in the model group significantly increased with excessive congestion, and the pathology showed significant thyroid follicular hyperplasia, columnar and proliferated epithelial cells, and enlarged follicle size; serum T4 and TRAb significantly increased, as well as the count of thyroid MVD, and the protein expressions of thyroid VEGFA and VEGFR2 (P<0.01). Compared to those in the model group, the thyroid glands of the mice in the MMI group and the HSF group were significantly reduced, and the congestion was improved; pathology showed that thyroid follicular hyperplasia and epithelial cell proliferation were reduced, with smooth edges of the follicles and the significantly reduced inward protrusion; serum T4 and TRAb significantly decreased, as well as the thyroid MVD, thyroid VEGFA and VEGFR2 protein expressions (P<0.05 or P<0.01). There was no significant difference in all indicators between the MMI group and the HSF group (P>0.05). ConclusionHSF may inhibit thyroid angiogenesis by down-regulating thyroid VEGFA/VEGFR2 signaling pathway, thereby improving goitre and hyperfunction in GD mice.
8.A Comparative Study on the Drugs in the Centralized Procurement List and the National Essential Medicine List of China
Xiaomei DENG ; Jin ZHANG ; Zhetao ZHANG ; Huiting LI ; Xiao LIU ; Yini MA ; Wenxin WU ; Tianlu SHI
Herald of Medicine 2024;43(7):1177-1180,后插1
Objective To compare and explore the differences between the eight batches of drugs in the centralized procurement list and the 2018 edition of the national essential medicine list,and to provide reference for updating and improving the national essential medicine list and the national centralized procurement list of drugs.Methods The category,generic name variety,specification,and other information of drugs included in the centralized drug procurement were collected and compared with the 2018 edition of the national essential medicine list,and the reasons for differences were analyzed.Results A proportion of 39%of centralized procurement drugs were listed in national essential medicines.Forty pharmacological classifications were not involved in the drugs of centralized procurement.Only anticoagulant and thrombolytic drugs with dual attributes accounted for a smaller variety proportion than the specification proportion.Conclusion There are some differences between the centralized procurement list and the 2018 edition of the national essential medicine list,which have some rationality,but also some problems to be solved.
9.Evaluation of perioperative safety of lung surgery for patients with COVID-19
Wenxin TIAN ; Yaoguang SUN ; Qingjun WU ; Chao MA ; Peng JIAO ; Hanbo YU ; Chuan HUANG ; Donghang LI ; Yi TIAN ; Hongfeng TONG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(12):1753-1758
Objective To evaluate the perioperative safety of lung surgery for patients with corona virus disease 2019 (COVID-19). Methods We retrospectively analyzed the clinical data of the patients recovered from COVID-19 infection and received lung surgery from December 2022 to February 2023 in the Department of Thoracic Surgery at Beijing Hospital. Patients who received lung surgery and without COVID-19 at the same time were selected as a control group. Perioperative data between the two groups were compared. Results A total of 103 patients were included with 44 males and 49 females at an average age of (62.2±12.1) years. All surgeries were performed by uniportal video-assisted thoracoscopic surgery (VATS). Among patients who recovered from COVID-19, 53 (51.5%) received lobectomy, 30 (29.1%) received segmentectomy, and 20 (19.4%) received wedge resection. The interval between diagnosis of infection and lung surgery was ≤1 month in 32 (31.1%) patients, and >1 month in 71 (68.9%) patients. The results of virus nucleic acid test for all patients before surgery were negative. A total of 13 (12.6%) patients had positive IgM, and 100 (97.1%) patients had positive IgG. A total of 20 patients experienced perioperative complications (13 patients with pulmonary air leakage, 3 patients with chylothorax, 2 patients with atrial fibrillation, and 2 patients with severe pulmonary complications). There was one perioperative death. Comparing the patients who recovered from COVID-19 with those without COVID-19, we found no statistical difference in perioperative outcomes including surgical duration, postoperative drainage, duration of thoracic tube, and duration of postoperative stay (P>0.05). There was no significant difference in perioperative complications between the two groups (P>0.05). Multivariable logistical regression analysis demonstrated that positive IgM before surgery (OR=7.319, 95%CI 1.669 to 32.103, P=0.008), and longer duration of surgery (OR=1.016, 95%CI 1.003 to 1.028, P=0.013) were independent risk factors of perioperative complications for patients who recovered from COVID-19. Conclusion It is safe for patients recover from COVID-19 to receive lung surgery when symptoms disappear and the nucleic acid test turn negative. However, positive COVID-19 IgM is an independent risk factor for perioperative complications. We suggest that lung surgery could be performed when the nucleic acid test and COVID-19 IgM are both negative for patients recover from COVID-19 infection.
10.Target Trial Emulation and Feasibility in Traditional Chinese Medicine Researches
Yuyi WANG ; Wenxin MA ; Xuehui WANG ; Zhijun BU ; Jianping LIU ; Zhaolan LIU
Journal of Traditional Chinese Medicine 2023;64(19):1969-1974
Target trial emulation, using observational data to emulate a target trial, applies the study design principles of randomized controlled trials to observational studies that aim to estimate the effect of an intervention. The advantage of target trial emulation is that observational data is used to emulate a target trial when it is not appropriate to conduct randomized controlled trials. Target trial emulation can control bias caused by the design of observational studies, and improve the effectiveness of causal inference from observational data. This paper introduced the methodological framework and key points in terms of eligibility criteria, treatment strategies, assignment procedures, grace period, outcomes, follow-up period, effect contrasts, and statistical plan for implementing target trial emulation. This article elucidated the feasibility and necessity of applying target trail emulation in the realm of traditional Chinese medicine researches, and highlighted the challenges encountered in its implementation, such as the need for specialized personnel, data collection and integration, and the control of confounding factors.


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