1.Effect of CCNA2 on Prognosis of Colon Cancer by Regulating Immune Microenvironment of Tumor Cells
Peng YANG ; Ziyi QIU ; Lingling WANG ; Yuan HU ; Zhengzhen CHEN ; Meizhen ZHONG ; Feiyue YU ; Rongyuan QIU
Cancer Research on Prevention and Treatment 2025;52(4):305-312
Objective To investigate the relationship between cyclin A2 (CCNA2) and the prognosis of colon cancer, and its possible mechanism from the perspective of immune infiltration. Methods We downloaded the transcriptome data of colon cancer patients from The Cancer Genome Atlas database. Clinicopathological feature analysis and survival analysis were performed based on the expression levels of CCNA2. A total of 75 specimens of colon cancer and normal tissues were collected, and the expression level of CCNA2 was analyzed using immunohistochemical methods. Multivariate analysis was conducted to explore its relationship with clinicopathological features. Gene Set Enrichment Analysis (GSEA) was used to assess the potential molecular functions of CCNA2 in colon cancer. CIBERSORT algorithm was applied to calculate the correlation between CCNA2 and immune-cell infiltration in colon cancer. Results Database and immunohistochemical analyses indicated that CCNA2 was expressed at a significantly higher level in colon cancer tissues than normal tissues (P<0.001). The overall survival, disease-specific survival, and progression-free interval were all longer in the group with high CCNA2 expression than the group with low expression (all P<0.05). In tumor tissues, the expression level of CCNA2 decreased with increased pathological and TNM stages (P<0.05). The expression level of CCNA2 in normal tissues was consistently lower than that in colon cancer tissues across all clinical stages (all P<0.001). GSEA suggested that Wnt/β-catenin, KRAS, and other signaling pathways were enriched when CCNA2 was lowly expressed. CIBERSORT analysis revealed an increase in the infiltration of immune cells such as regulatory T cells and macrophages M0 when CCNA2 expression was low. Conclusion CCNA2 is highly expressed in colon cancer and closely associated with grade of pathology and TNM stage. It may recruit regulatory T cells through the KRAS and Wnt/β-catenin pathways, thereby reducing immune-cell infiltration and promoting colon cancer progression, leading to poor prognosis.
2.Management of Cutaneous Immune-Related Adverse Events of Malignant Tumors Induced by Immune Checkpoint Inhibitors Based on Theory of "Fire and Original Qi are Restricted"
Shiliang SHAO ; Lijing JIAO ; Yichao WANG ; Decai WANG ; Qishan HUA ; Yabin GONG ; Ling XU
Journal of Traditional Chinese Medicine 2025;66(16):1656-1661
Guided by the theory of "fire and original qi are restricted", it is believed that original qi depletion is the root of the cutaneous immune-related adverse events (cirAEs) related to immune checkpoint inhibitors (ICIs), and the yin fire exuberance is the branch. Among them, original qi depletion is the internal foundation of the disease, while the drug toxicity of ICIs harming original qi is the initiating factor, and exuberant yin fire is the key pathogenesis. In clinical practice, the general treatment principle advocates banking up original qi to consolidate the root and draining fire to raise yang. Buzhong Yiqi Decoction (补中益气汤) can be used to activate transportation of middle jiao (焦) and promote ascent and dispersion of clear yang, thereby restoring the balance of qi and fire, and medicinals such as Huangqin (Radix Scutellariae), Huanglian (Rhizoma Coptidis) and Huangbai (Cortex Phellodendri Chinensis) can be supplementetd to clear and drain yin fire. At the same time, considering the accompanying symptoms such as dampness-stasis and fluids depletion, the methods of removing dampness and dispelling stasis, supplementing blood and nourishing yin should be added flexibly. This approach can provide a new perspective and treatment strategy for reducing ICIs-related cirAEs in malignant tumors.
3.Treatment Strategies for Postoperative Complications of Lung Cancer from Protecting Healthy Qi and Treating Qi
Jiajun SONG ; Yichao WANG ; Xueqi TIAN ; Yi LIU ; Lijing JIAO ; Ling XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):94-105
Pulmonary complications, the most common postoperative complications of lung cancer, not only affect the quality of life of the patients after surgery but also increase the prognostic risks of postoperative recurrence and metastasis, threatening the life safety. At present, a multidisciplinary model of diagnosis and rehabilitation with integrated traditional Chinese medicine (TCM) and Western medicine has been initially formed under the guidance of the concept of rapid rehabilitation post operation for lung cancer. However, the treatment that only aims at shortening hospital stay and reducing the incidence of postoperative complications does not pay enough attention to the postoperative functional rehabilitation of the lung and the impact of follow-up adjuvant therapy, which affects the completeness of rehabilitation. This paper classifies the typical postoperative symptoms and manifestations of lung cancer into five groups: Lung system, emotion, digestive tract, pain, and nerve. On this basis, this paper summarizes the three core pathogeneses of postoperative complications of lung cancer as failure of Qi to ascend and descend leading to insecurity of defensive exterior, vessel block leading to Qi stagnation and fluid retention, and lung Qi deficiency leading to spleen and kidney deficiency. Accordingly, this paper proposes the treatment principle of protecting healthy Qi and treating Qi with the core of descending-tonifying-ascending-dispersing Qi and puts forward three treatment methods. The first is replenishing Qi and consolidating exterior, and expelling phlegm and regulating lung. The second is replenishing Qi and promoting blood flow to resolve stasis and relieving pain. The third is replenishing Qi and tonifying lung, and invigorating spleen and tonifying kidney. Furthermore, this paper elaborates on the pathogenesis and treatment principles of four common postoperative complications: Lung infection, pleural effusion, atelectasis, and bronchopleural fistula. On the basis of Western medical treatment, the TCM treatment characteristics of treating symptoms in the acute phase and eradicating the root cause in the chronic phase should be played. While dispelling the pathogen, measures should be taken to protect the healthy Qi, including tonifying lung Qi, regulating spleen Qi, and replenishing kidney Qi. This study summarizes the pathogenesis and treatment strategy of common postoperative complications of lung cancer according to the principle of protecting healthy Qi and treating Qi, aiming to provide guidance for the future treatment of postoperative complications of lung cancer.
4.Mechanism of Mahuang Fuzi Gancao Tang and Its Pungent Single Herbs in Treating Primary Podocytopathies via TRPC5-RAC1 Feedforward Loop Based on Sweat Pore Theory
Meng JIA ; Yi WANG ; Shisheng HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):205-214
ObjectiveTo investigate the molecular mechanisms of Mahuang Fuzi Gancao Tang and its pungent single herbs, Ephedrae Herba and Aconiti Lateralis Radix Praeparaia, in repairing podocyte injury based on the sweat pore theory, with a focus on the podocyte cytoskeletal transient receptor potential canonical 5 (TRPC5)-Ras-related C3 botulinum toxin substrate 1 (RAC1) feedforward loop. MethodsAn animal model with puromycin aminonucleoside (PAN)-induced overexpression of TRPC5 was established. Interventions included Mahuang Fuzi Gancao Tang, Ephedrae Herba alone, and Aconiti Lateralis Radix Praeparaia alone. Biochemical parameters , histopathological changes, and podocyte ultrastructure were analyzed. Western blotting was performed to determine the expression of cytoskeletal protein synaptopodin and mechanism-related proteins TRPC5, RAC1-GTP, and RAC1 in the kidney. Primary podocytes were isolated and cultured for three-dimensional imaging of foot processes, cytoskeletal fluorescence analysis, and TRPC5-RAC1 co-staining via immunofluorescence. ResultsCompared with the model group, Mahuang Fuzi Gancao Tang, Ephedrae Herba alone, and Aconiti Lateralis Radix Praeparaia alone increased serum albumin (ALB), decreased UPCR, reduced podocyte foot process fusion rate, upregulated synaptopodin expression, and downregulated TRPC5, RAC1-GTP, and RAC1 expression (P<0.05). Moreover, the interventions increased the phalloidin fluorescence area/field area ratio (P<0.01) and mean fluorescence intensity (P<0.05), while decreasing the proportion of TRPC5-RAC1 co-stained double-positive cells/total cells per field (P<0.01) in primary podocytes. ConclusionMahuang Fuzi Gancao Tang and its pungent single herbs, Ephedrae Herba and Aconiti Lateralis Radix Praeparaia, ameliorated podocyte injury in the model with PAN-induced TRPC5 overexpression by reducing proteinuria and suppressing the TRPC5-RAC1 feedforward loop-mediated podocyte cytoskeletal damage.
5.Mechanism of Mahuang Fuzi Gancao Tang and Its Pungent Single Herbs in Treating Primary Podocytopathies via TRPC5-RAC1 Feedforward Loop Based on Sweat Pore Theory
Meng JIA ; Yi WANG ; Shisheng HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):205-214
ObjectiveTo investigate the molecular mechanisms of Mahuang Fuzi Gancao Tang and its pungent single herbs, Ephedrae Herba and Aconiti Lateralis Radix Praeparaia, in repairing podocyte injury based on the sweat pore theory, with a focus on the podocyte cytoskeletal transient receptor potential canonical 5 (TRPC5)-Ras-related C3 botulinum toxin substrate 1 (RAC1) feedforward loop. MethodsAn animal model with puromycin aminonucleoside (PAN)-induced overexpression of TRPC5 was established. Interventions included Mahuang Fuzi Gancao Tang, Ephedrae Herba alone, and Aconiti Lateralis Radix Praeparaia alone. Biochemical parameters , histopathological changes, and podocyte ultrastructure were analyzed. Western blotting was performed to determine the expression of cytoskeletal protein synaptopodin and mechanism-related proteins TRPC5, RAC1-GTP, and RAC1 in the kidney. Primary podocytes were isolated and cultured for three-dimensional imaging of foot processes, cytoskeletal fluorescence analysis, and TRPC5-RAC1 co-staining via immunofluorescence. ResultsCompared with the model group, Mahuang Fuzi Gancao Tang, Ephedrae Herba alone, and Aconiti Lateralis Radix Praeparaia alone increased serum albumin (ALB), decreased UPCR, reduced podocyte foot process fusion rate, upregulated synaptopodin expression, and downregulated TRPC5, RAC1-GTP, and RAC1 expression (P<0.05). Moreover, the interventions increased the phalloidin fluorescence area/field area ratio (P<0.01) and mean fluorescence intensity (P<0.05), while decreasing the proportion of TRPC5-RAC1 co-stained double-positive cells/total cells per field (P<0.01) in primary podocytes. ConclusionMahuang Fuzi Gancao Tang and its pungent single herbs, Ephedrae Herba and Aconiti Lateralis Radix Praeparaia, ameliorated podocyte injury in the model with PAN-induced TRPC5 overexpression by reducing proteinuria and suppressing the TRPC5-RAC1 feedforward loop-mediated podocyte cytoskeletal damage.
6.Transcriptomic Analysis of Wuzi Yanzongwan on Testicular Spermatogenic Function in Semi-castrated Male Mice
Dixin ZOU ; Yueyang ZHANG ; Xuedan MENG ; Wei LU ; Shuang LYU ; Fanjun ZENG ; Kun CHEN ; Chang LIU ; Zhongxiu ZHANG ; Yu DUAN ; Yihang DAI ; Zhaoyi WANG ; Zhimin WANG ; Ruichao LIN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):61-69
ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice, and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group, model group, testosterone propionate group(0.2 mg·kg-1·d-1, intramuscular injection) and Wuzi Yanzongwan group(1.56 g·kg-1·d-1, intragastric administration) according to body weight, with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function, while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention, hematoxylin-eosin(HE) staining was used to observe the histopathology of testis, enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of serum testosterone(T), luteinizing hormone(LH) and follicle stimulating hormone(FSH). The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group, the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened, and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) to verify the transcriptome data. Through the annotation analysis of Gene Ontology(GO) and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG), the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group, the testicular tissue of mice in the model group showed spermatogenic injury, contraction and vacuolization of the seminiferous tubules, reduction of spermatogenic cells at all levels, widening of the interstitial space, obstruction of spermatogonial cell development and other morphological abnormalities, and serum T significantly decreased, LH significantly increased(P<0.01), and FSH elevated but no statistically significant difference, the count and vitality of epididymal sperm significantly decreased(P<0.01). There were 882 differentially expressed mRNAs in the testicular tissues, of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group, the damage to testicular tissue in the Wuzi Yanzongwan group was reduced, the structure of the seminiferous tubules was intact, vacuolization was reduced, and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased, LH significantly decreased(P<0.01), and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased(P<0.01). Moreover, Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice, of which 32 were up-regulated and 127 were down-regulated, and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis, renewal, differentiation, metabolism, apoptosis and signal transduction of spermatogenic cells, and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function, endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice, and its mechanism may be related to the regulation of testicular transcriptional regulatory network, the synthesis of sex hormones in testicular interstitial cells, the function of spermatogenic stem cells, the whole cell cycle process of spermatogenesis, as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.
7.Dyadic coping experience of patients undergoing cancer surgery and their spouses:a qualitative study
Yueyang ZHANG ; Luyao SUN ; Dongsen LǙ ; Jing LI ; Angran WANG ; Qiong LI
Modern Clinical Nursing 2024;23(2):34-39
Objective To investigate the dyadic coping experience of patients undergoing cancer surgery and their spouses.Methods Sixteen cancer patients who were initially diagnosed with cancer and underwent cancer surgery in a general hospital in Henan province as well as and their spouses were selected as the study subjects by objective sampling method.All the patients and their spouses were included in the postoperative follow-up for dyadic coping experiences though a 3 months interview.The acquired data were summarised and analysed by Colaizzi's phenomenological method to identify relevant themes.Results A total of eight themes were identified,including three themes over the phase of confirmed diagnosis,strong stress response,coping with stress alone and consistent attitude towards seeking medical treatment;two themes over the perioperative phase,lack of coping ability and change in relationship;and three themes over the phase of home recovery,lack of disease information,poor communication skills and post-trauma growth of both patient and spouse.Conclusions The dyadic coping experience of patients who undergo cancer surgery and their spouses varies with the stages across the treatment.Therefore,medical staff should offer targeted nursing care according to the dyadic coping experience at different stages,hence to improve the physical and mental health of the cancer patients and their spouses.
8.Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.
Shuo ZHANG ; Hong-Jin LI ; Chun-Mei YANG ; Liu LIU ; Xiao-Ying SUN ; Jiao WANG ; Si-Ting CHEN ; Yi LU ; Man-Qi HU ; Ge YAN ; Ya-Qiong ZHOU ; Xiao MIAO ; Xin LI ; Bin LI
Chinese journal of integrative medicine 2024;30(3):222-229
OBJECTIVE:
To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.
METHODS:
Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.
RESULTS:
TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).
CONCLUSIONS
TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male
;
Animals
;
Mice
;
Tripterygium
;
Psoriasis/drug therapy*
;
Keratinocytes
;
Skin Diseases/metabolism*
;
Cytokines/metabolism*
;
Imiquimod/metabolism*
;
Dermatitis/pathology*
;
Disease Models, Animal
;
Mice, Inbred BALB C
;
Skin/metabolism*
9.Clinical Efficacy of Qushi Huayu Granules in Treating Non-alcoholic Fatty Liver Disease (NAFLD) with Dampness-heat Accumulation
Cong HE ; Huichao WANG ; Bingduo ZHOU ; Jing KONG ; Xiaosu WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):139-145
ObjectiveTo observe the clinical efficacy of Qushi Huayu granules in treating non-alcoholic fatty liver disease (NAFLD) with dampness-heat accumulation. MethodSixty NAFLD patients with the syndrome of dampness-heat accumulation treated in the outpatient and inpatient departments of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine from July 2018 to May 2020 were selected according to the diagnostic criteria and inclusion criteria of both traditional Chinese medicine (TCM) and Western medicine. The patients were assigned into a control group and an observation group by a random, controlled, double-blind, and double simulated method. The observation group was treated with Qushi Huayu granules combined with the mimetic agent of Dangfei Liganning capsules, and the control group was treated with Dangfei Liganning capsules combined with the mimetic agent of Qushi Huayu granules. The treatment course of both groups was 24 weeks. The TCM symptom scores, liver imaging parameters [controlled attenuation parameter (CAP) in Fibroscan and liver-to-spleen ratio in upper abdominal computerized tomography (CT)], serum levels of alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (γ-GT), and safety indicators of the two groups were measured. Result① The total response rate in terms of TCM symptoms in the observation group was 89.29% (25/28), which was higher than that (48.15%, 13/27) in the control group (Z=-3.582,P<0.01). The total score of the primary and secondary symptoms in both groups of patients declined after treatment (P<0.05), and the observation group outperformed the control group in decreasing the total score of the main and secondary symptoms as well as the scores of right rib swelling pain, abdominal fullness and distension or pain, sticky stool, and yellow urine (P<0.05). ② The response rate in terms of Fibroscan CAP of the liver in the observation group was 75.00% (21/28), which was higher than that (48.15%, 13/27) in the control group (Z=-1.968,P<0.05). ③ The response rate in terms of the serum enzyme levels in the observation group was 75.00% (21/28), which was higher than that (44.44%, 12/27) in the control group (Z=-2.018,P<0.05). The serum levels of ALT and γ-GT in the two groups declined after treatment (P<0.05, P<0.01) and were lower in the observation group than in the control group (P<0.05, P<0.01). ④ The response rate in terms of liver CT in the observation group was 67.86% (19/28), which was higher than that (30.77%,8/26) in the control group (Z=-2.507,P<0.05). ConclusionQushi Huayu granules were safe and effective in the clinical treatment of NAFLD patients with the syndrome of dampness-heat accumulation, which improved the evidence in TCM treatment of NAFLD and was worthy of in-depth clinical research and promotion. Qushi Huayu granules outperformed Dangfei Liganning capsules in terms of TCM symptoms, serum levels of ALT and γ-GT, and liver imaging parameters.
10.Exploration of the Disease Mechanism and Treatment of Colorectal Cancer Based on the "One Qi Circulation"
Zhiying WANG ; Ling XU ; Jialin YAO ; Jiajun SONG ; Yun LI ; Shujuan FU ; Yabin GONG ; Yi ZHONG
Journal of Traditional Chinese Medicine 2024;65(10):1068-1071
Based on the theory of "one qi circulation" founded by HUANG Yuanyu, the core disease mechanism of colorectal cancer is the innate spleen deficiency and stomach qi failing to bear downward, which leads to the turbidity assemble in large intestine, forming the carcinoma toxin, and ultimately transforms into colorectal cancer. The treatment should base on recovering the circulation of qi, Huangya Decoction (黄芽汤) as the basic formula, the circulation of qi ascending and descending as the base, adjusting ascending and descending together with Xiaqi Decoction (下气汤), and differentiating the syndrome on yin-yang excess-deficiency; for spleen-kidney yang deficiency syndrome, treated with Tianhun Decoction (天魂汤) to supplement liver, kidney and assist yang; for liver-kidney yin deficiency syndrome, treated wtih Dipo Decoction (地魄汤) to supplement lung, kidney, and assist yang. They jointly prompt one qi circulation to provide the thoughts for the treatment of colorectal cancer by traditional Chinese medicine.

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