1.Pathogenesis Evolution and Stage-based Treatment of Gout: An Exploration Based on Theory of ''Endogenous Dampness Leading to Bi Syndrome''
Yingjie ZHANG ; Fan YANG ; Ruifang YANG ; Zhuoming ZHENG ; Siwei PENG ; Yan XIAO ; Peng CHEN ; Youxin SU ; Jiemei GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):74-83
Gout is a crystal-associated arthropathy caused by the deposition of monosodium urate crystals and is closely related to purine metabolic disorders and impaired uric acid excretion. It is clinically characterized by hyperuricemia, recurrent joint swelling and pain, and tophus formation. The disease course is divided into three stages: The hyperuricemia stage, acute attack stage, and chronic gouty arthritis stage. Modern medicine has reached a consensus on its pathology, but traditional Chinese medicine (TCM) lacks a systematic stage-specific understanding of gout pathogenesis and its underlying mechanisms, making it difficult to guide precise syndrome differentiation and treatment. By integrating classical TCM theory, clinical practice, and modern medical understanding, and drawing upon descriptions of Bi syndrome caused by endogenous dampness and turbidity in classical texts such as Huangdi Neijing·Ling Shu and Synopsis of the Golden Chamber, our team proposes the pathogenic concept of gout as ''endogenous dampness leading to Bi syndrome'' and the core pathogenesis of ''spleen deficiency with internal retention of dampness-turbidity''. We systematically elucidate the evolution of pathogenesis across different stages and corresponding therapeutic strategies. This study posits that metabolic byproducts such as urate fall under the category of ''endogenous pathogenic dampness-turbidity''. When genetic or dietary factors lead to metabolic abnormalities, it manifests as ''spleen deficiency with impaired transport and transformation'', resulting in ''internal retention of pathogenic dampness-turbidity''. When damp-turbidity stagnates in the blood vessels, serum uric acid levels rise. When it stagnates in the viscera and limbs, monosodium urate crystals deposit in the joints. Triggered by precipitating factors, this leads to gout attacks—the core pathological process of ''endogenous dampness leading to Bi syndrome''. Based on this theory, the stage-specific pathogenic characteristics of gout are proposed: The hyperuricemia stage is characterized by ''spleen deficiency with impaired transport and transformation, internal retention of pathogenic dampness-turbidity'', the acute attack stage is primarily marked by ''dampness-turbidity and static heat obstructing the limbs and joints'', while the chronic stage is defined by ''spleen deficiency with internal retention of pathogenic dampness-turbidity, intermingled with phlegm-stasis binding''. The treatment principle centers on ''strengthening the spleen and draining dampness'' throughout all stages. During the hyperuricemia stage, treatment focuses on ''strengthening the spleen, draining dampness, and eliminating turbidity''. In the acute attack stage, the treatment should "strengthen the spleen, drain dampness, clear heat, eliminate turbidity, alleviate swelling, and relieve pain''. In the chronic stage, the treatments emphasizes to ''strengthen the spleen, drain dampness, transform turbidity, clear heat, resolve phlegm, and activate blood circulation''. This approach has yielded favorable therapeutic outcomes in clinical practice. This theoretical system clarifies the nature of gout as ''spleen deficiency being the root, dampness-turbidity being the secondary manifestation'' and systematically analyzes its pathogenesis evolution process and characteristics. The constructed stage-based treatment protocol has been validated through clinical and basic research, providing systematic theoretical guidance and a practical framework for the precise TCM management of gout, thereby promoting the modernization of TCM pathogenesis theory related to gout.
2.The application of ANXA2 gene knockout mouse models in lung cancer metastasis
Weijie SONG ; Fan ZHANG ; Zhaosong WANG ; Jianfei TIAN ; Ruifang NIU
Chinese Journal of Oncology 2025;47(3):254-261
Objective:ANXA2 plays a crucial role in cancer metastasis, but its mechanism is not yet fully understood. Therefore, it is necessary to establish an ANXA2 gene knockout mouse model to provide an effective tool for subsequent studies on ANXA2-related mechanisms.Methods:A gene knockout mouse model was constructed using CRISPR/Cas9 technology. The model was validated through tissue DNA extraction followed by polymerase chain reaction (PCR), sequencing, and western blot to confirm ANXA2 genotype and protein expression. The successfully constructed models were divided into a model group and a wild-type (WT) group for the creation of a mouse tail vein injection Lewis lung carcinoma (LLC) metastasis model. Metastatic foci formation was monitored using in vivo imaging technology, and the survival rates of the two groups were compared. Results:An sgRNA sequence targeting the first exon of ANXA2 was designed, and 16 founder mice were obtained through microinjection. Through consanguineous hybridization, 30 homozygous offspring were ultimately acquired. After establishing the strains of the mouse model, mice were divided into the ANXA2 knockout group and the WT group, with 8 mice in each group. An LLC lung metastasis model was established in both groups. Compared with the WT group, the number of metastatic foci was significantly increased in the ANXA2 knockout group (7 vs. 1), and the fluorescence intensity was stronger in the WT group than in the knockout group ( P=0.002). Using the GEPIA2 database to analyze ANXA2 gene expression in tumor tissues and normal tissues of lung cancer patients, it was found that ANXA2 expression levels were significantly higher in lung cancer tumor tissues compared to normal tissues ( P<0.05). The database included data from 478 lung cancer patients, and patients were stratified into high-expression and low-expression groups based on ANXA2 levels. Compared to the low-expression group, patients in the high-expression group exhibited significantly shorter disease-free survival and overall survival ( P<0.05, respectively). The survival time of mice in the ANXA2 knockout group (median survival time, 43 days) was significantly longer compared to the WT group (median survival time, 26 days; P=0.017). Additionally, ANXA2 expression is significantly associated with the prognosis of lung cancer patients ( P=6.4e-14). Conclusions:ANXA2 is closely associated with cancer metastasis and holds potential as a new target for metastasis treatment. Further in-depth research will greatly facilitate the transition of ANXA2 from basic research to clinical application.
3.Advances in conversion therapy for unresectable hepatocellular carcinoma
Ke YU ; Jiajia JIA ; Ying SHA ; Yufan TANG ; Baiquan ZHOU ; Bingbing WEN ; Luyao LI ; Jixiang LIU ; Ruifang FAN
Chinese Journal of Hepatobiliary Surgery 2025;31(9):706-711
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Surgical resection remains the preferred treatment modality, offering the potential for cure. However, over half of HCC patients present as intermediate to advanced stages at diagnosis, with multiple factors precluding surgical resection. Conversion therapy represents an important treatment strategy by enabling tumor downstaging, offering future resectability for patients with intermediate-to-advanced HCC who are initially unresectable. This article reviews the relevant concepts and research progress in conversion therapy for HCC.
4.Analysis of efficacy and safety of sintilimab combined with SOX regimen in adjuvant treatment of stage Ⅲ gastric cancer
Zhou BAIQUAN ; Liu LIN ; Tang YUFAN ; Wen BINGBING ; Sha YING ; Jia JIAJIA ; Yu KE ; Xu SHUMEI ; Fan RUIFANG
Chinese Journal of Clinical Oncology 2025;52(17):870-876
Objective:To investigate the efficacy and safety of sintilimab combined with the SOX regimen for adjuvant treatment of stage Ⅲgastric cancer after D2 radical resection and to provide a reference for individualized clinical treatment.Methods:The clinical data of 245 pa-tients with stage III gastric cancer who underwent D2 radical resection at the 940th Hospital of the Joint Support Force of the People's Liber-ation Army from June 2019 to May 2022 were retrospectively analyzed.The 180 patients who received only the SOX regimen were desig-nated the control group,and the 65 patients who received sintilimab combined with the SOX regimen were designated the experimental group.The 3-year disease-free survival(DFS)rate,overall survival(OS)rate,and adverse reactions among the two groups and different sub-groups(HER-2 positive,dMMR,CPS≥5)were compared.Results:The 3-year DFS(81.5%vs.59.4%)and OS(84.6%vs.70.6%)rates in the experimental group were significantly higher than those in the control group(both P<0.05).Group analysis showed that in patients with CPS≥5,the 3-year DFS(91.5%vs.67.0%)and OS(95.7%vs.71.6%)rates within the experimental group were significantly better than those in the control group(both P<0.05).Intra-group analysis within the experimental group showed that the 3-year DFS rate(91.5%vs.55.6%)and OS rate(95.7%vs.55.6%)of patients with CPS≥5 were significantly better than those of patients with CPS<5(both P<0.05).The overall and grade≥3 incidences of liver and kidney function damage,thyroid dysfunction,colitis,pneumonia,and rash in the experimental group were higher than those in the control group(all P<0.05),while the differences in other adverse reactions,including leukopenia were not statistic-ally significant(all P>0.05).Conclusions:Sintilimab combined with the SOX regimen can significantly improve 3-year DFS and OS rates in pa-tients with stage Ⅲ gastric cancer after surgery,especially in the CPS≥5 subgroup,with significant benefits and controllable safety.
5.Advances of neoadjuvant and conversion therapy with PD-1 inhibitors in gastric cancer
Yufan TANG ; Baiquan ZHOU ; Simeng DAI ; Bingbing WEN ; Jixiang LIU ; Luyao LI ; Ruifang FAN
Chinese Journal of Gastrointestinal Surgery 2025;28(2):217-224
Gastric cancer (GC) is one of the most common malignant tumors of the digestive system in China. With the progress of immunotherapy research, programmed death receptor-1 (PD-1) inhibitor-based combinatory therapy offers new ideas for the treatment of advanced gastric cancer. In recent years, with the increasing status of immunotherapy in the treatment of advanced gastric cancer, a growing number of domestic and international clinical studies shown that immunotherapy could achieve better efficacy in the neoadjuvant therapy and conversion therapy for patients with advanced gastric cancer. This paper reviews the current research progress on the application of PD-1 inhibitors in the neoadjuvant therapy and conversion therapy of gastric cancer.
6.Research advances of immune checkpoint inhibitors for neoadjuvant therapy in locally advanced gastric cancer
Ying SHA ; Ke YU ; Jiajia JIA ; Yufan TANG ; Bingbing WEN ; Baiquan ZHOU ; Shumei XU ; Ruifang FAN
Chinese Journal of Digestive Surgery 2025;24(9):1214-1220
Gastric cancer is one of the most common malignant tumors in the digestive system, characterized by high incidence and mortality rates. In recent years, with the rapid develop-ment of molecular immunology, the application of immune checkpoint inhibitors (ICIs) in neoadju-vant therapy has significantly improved pathological response rates and survival outcomes for patients with resectable locally advanced gastric cancer. The authors systematically review current research progress on combination strategies involving immune checkpoint inhibitors in neoadjuvant therapy for locally advanced gastric cancer, aiming to provide an evidence for optimizing individua-lized therapeutic regimens.
7.Analysis of efficacy and safety of sintilimab combined with SOX regimen in adjuvant treatment of stage Ⅲ gastric cancer
Zhou BAIQUAN ; Liu LIN ; Tang YUFAN ; Wen BINGBING ; Sha YING ; Jia JIAJIA ; Yu KE ; Xu SHUMEI ; Fan RUIFANG
Chinese Journal of Clinical Oncology 2025;52(17):870-876
Objective:To investigate the efficacy and safety of sintilimab combined with the SOX regimen for adjuvant treatment of stage Ⅲgastric cancer after D2 radical resection and to provide a reference for individualized clinical treatment.Methods:The clinical data of 245 pa-tients with stage III gastric cancer who underwent D2 radical resection at the 940th Hospital of the Joint Support Force of the People's Liber-ation Army from June 2019 to May 2022 were retrospectively analyzed.The 180 patients who received only the SOX regimen were desig-nated the control group,and the 65 patients who received sintilimab combined with the SOX regimen were designated the experimental group.The 3-year disease-free survival(DFS)rate,overall survival(OS)rate,and adverse reactions among the two groups and different sub-groups(HER-2 positive,dMMR,CPS≥5)were compared.Results:The 3-year DFS(81.5%vs.59.4%)and OS(84.6%vs.70.6%)rates in the experimental group were significantly higher than those in the control group(both P<0.05).Group analysis showed that in patients with CPS≥5,the 3-year DFS(91.5%vs.67.0%)and OS(95.7%vs.71.6%)rates within the experimental group were significantly better than those in the control group(both P<0.05).Intra-group analysis within the experimental group showed that the 3-year DFS rate(91.5%vs.55.6%)and OS rate(95.7%vs.55.6%)of patients with CPS≥5 were significantly better than those of patients with CPS<5(both P<0.05).The overall and grade≥3 incidences of liver and kidney function damage,thyroid dysfunction,colitis,pneumonia,and rash in the experimental group were higher than those in the control group(all P<0.05),while the differences in other adverse reactions,including leukopenia were not statistic-ally significant(all P>0.05).Conclusions:Sintilimab combined with the SOX regimen can significantly improve 3-year DFS and OS rates in pa-tients with stage Ⅲ gastric cancer after surgery,especially in the CPS≥5 subgroup,with significant benefits and controllable safety.
8.Effect of Zi Zhu Ointment combined with herbal fumigation on treatment of patients with diabetic foot infection
Xiaoyan GUO ; Xinan ZHAO ; Meijin LI ; Chenyao FAN ; Dongfang CHEN ; Ruifang CUI ; Feng ZHANG
Chinese Journal of Nosocomiology 2025;35(9):1337-1341
OBJECTIVE To explore the effect of Zi Zhu Ointment combined with herbal fumigation on wound heal-ing,oxidative stress and microribonucleic acid(miR)-200b of the patients with diabetic foot infection.METHODS A total of 102 patients with diabetic foot infection who were treated in Heping Hospital Affiliated to Changzhi Medical College from Sep.2020 to Sep.2023 were enrolled in the study and were divided into the control group with 48 cases and the study group with 54 cases according to the treatment program.The control group was trea-ted with conventional therapy and herbal fumigation,the study group was given additional Zi Zhu Ointment on ba-sis of the treatment of the control group,and both groups were persistently treated for 1 month.The clinical cura-tive effect,wound healing status,hemodynamics indexes of dorsal foot,pain score,oxidative stress indexes and miR-200b expression levels were observed and compared between the two groups of patients.RESULTS The effec-tive rate of clinical treatment of the study group was higher than that of the control group after the treatment(Z=2.138,P=0.033).The wound area of the study group was(0.42±0.05)cm2 after the treatment,smaller than that of the control group;the cover area of neoplastic granulation tissue of the study group was(16.87±3.21)cm2,larger than that of the control group;the coverage fraction of the neoplastic granulation tissue of the study group was(55.23±6.17)%,greater than that of the control group;there were significant differences between the two groups(P<0.05).The blood vessel diameter of dorsal foot of the study group was greater than that of the control group after the treatment,the blood flow velocity of the study group was greater than that of the control group,and the visual analogue scale(VAS)score of the study group was lower than that of the control group(P<0.05).There were no significant differences in the expression levels of advanced oxidative protein product(AOPP),superoxide dismutase(SOD),malondialdehyde(MDA)and miR-200b between the two groups of pa-tients before the treatment;the expression levels of AOPP,MDA and miR-200b of the study group were lower than those of the control group after the treatment,while the SOD level of the study group was higher than that of the control group(P<0.05).CONCLUSIONS Zi Zhu Ointment combined with herbal fumigation can remarkably improve the clinical curative effect on the patients with diabetic foot infection,promote the wound healing,im-prove the arterial hemodynamics of dorsal foot,and relieve the pain.The mechanism may be associated with the improvement of oxidative stress response and downregulated expression level of miR-200b.
9.Advances of neoadjuvant and conversion therapy with PD-1 inhibitors in gastric cancer
Yufan TANG ; Baiquan ZHOU ; Simeng DAI ; Bingbing WEN ; Jixiang LIU ; Luyao LI ; Ruifang FAN
Chinese Journal of Gastrointestinal Surgery 2025;28(2):217-224
Gastric cancer (GC) is one of the most common malignant tumors of the digestive system in China. With the progress of immunotherapy research, programmed death receptor-1 (PD-1) inhibitor-based combinatory therapy offers new ideas for the treatment of advanced gastric cancer. In recent years, with the increasing status of immunotherapy in the treatment of advanced gastric cancer, a growing number of domestic and international clinical studies shown that immunotherapy could achieve better efficacy in the neoadjuvant therapy and conversion therapy for patients with advanced gastric cancer. This paper reviews the current research progress on the application of PD-1 inhibitors in the neoadjuvant therapy and conversion therapy of gastric cancer.
10.Effect of Zi Zhu Ointment combined with herbal fumigation on treatment of patients with diabetic foot infection
Xiaoyan GUO ; Xinan ZHAO ; Meijin LI ; Chenyao FAN ; Dongfang CHEN ; Ruifang CUI ; Feng ZHANG
Chinese Journal of Nosocomiology 2025;35(9):1337-1341
OBJECTIVE To explore the effect of Zi Zhu Ointment combined with herbal fumigation on wound heal-ing,oxidative stress and microribonucleic acid(miR)-200b of the patients with diabetic foot infection.METHODS A total of 102 patients with diabetic foot infection who were treated in Heping Hospital Affiliated to Changzhi Medical College from Sep.2020 to Sep.2023 were enrolled in the study and were divided into the control group with 48 cases and the study group with 54 cases according to the treatment program.The control group was trea-ted with conventional therapy and herbal fumigation,the study group was given additional Zi Zhu Ointment on ba-sis of the treatment of the control group,and both groups were persistently treated for 1 month.The clinical cura-tive effect,wound healing status,hemodynamics indexes of dorsal foot,pain score,oxidative stress indexes and miR-200b expression levels were observed and compared between the two groups of patients.RESULTS The effec-tive rate of clinical treatment of the study group was higher than that of the control group after the treatment(Z=2.138,P=0.033).The wound area of the study group was(0.42±0.05)cm2 after the treatment,smaller than that of the control group;the cover area of neoplastic granulation tissue of the study group was(16.87±3.21)cm2,larger than that of the control group;the coverage fraction of the neoplastic granulation tissue of the study group was(55.23±6.17)%,greater than that of the control group;there were significant differences between the two groups(P<0.05).The blood vessel diameter of dorsal foot of the study group was greater than that of the control group after the treatment,the blood flow velocity of the study group was greater than that of the control group,and the visual analogue scale(VAS)score of the study group was lower than that of the control group(P<0.05).There were no significant differences in the expression levels of advanced oxidative protein product(AOPP),superoxide dismutase(SOD),malondialdehyde(MDA)and miR-200b between the two groups of pa-tients before the treatment;the expression levels of AOPP,MDA and miR-200b of the study group were lower than those of the control group after the treatment,while the SOD level of the study group was higher than that of the control group(P<0.05).CONCLUSIONS Zi Zhu Ointment combined with herbal fumigation can remarkably improve the clinical curative effect on the patients with diabetic foot infection,promote the wound healing,im-prove the arterial hemodynamics of dorsal foot,and relieve the pain.The mechanism may be associated with the improvement of oxidative stress response and downregulated expression level of miR-200b.

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