1.Jianpi Yiqi Prescription Inhibits Proliferation and Invasion of Hepatic Carcinoma Cells by Targeting PTPN1
Shanshan SUN ; Jing HONG ; Shufan SONG ; Zongxi SUN ; Chao WANG ; Shaoyuan ZHUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):80-88
ObjectiveTo investigate the key targets of Jianpi Yiqi prescription (JYP) in the treatment of hepatocellular carcinoma (HCC) based on network pharmacology and explore the effect of JYP on the invasion and proliferation of hepatocellular carcinoma cells via protein tyrosine phosphatase, non-receptor type 1 (PTPN1) by bioinformatics analysis and CRISPR/Cas9. MethodsThe potential targets of JYP in the treatment of HCC were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SwissTargetPrediction, GeneCards, NCBI, and CTD. Additionally, the active components of JYP that could interact with PTPN1 were screened out, and then molecular docking between the targets and active components was performed in Autodock 4.0. UALCAN, HPA, and LinkedOmics were used to analyze the expression of PTPN1 in the HCC tissue, and the relationship of PTPN1 expression with the overall survival (OS) of HCC patients was discussed. CRISPR/Cas9 was used to knock down the expression of PTPN1 in HepG2 and SK-hep-1 cells, and the knockdown effect was examined by sequencing, Real-time PCR, and Western blot. HepG2 cells were classified into blank control, low-, medium-, and high-dose JYP (5.25, 10.5, 21 g·kg-1), and PTPN1 knockout groups. Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of PTPN1 in HepG2 cells of each group. The effects of JYP and PTPN1 knockdown on the proliferation, invasion, and apoptosis of HepG2 cells were detected by Cell Counting Kit-8 (CCK-8), Transwell, and Annexin V-FITC/PI methods, respectively. ResultsJYP had the most active components targeting PTPN1, and 31 of the active components had the binding energy less than -5.0 kcal·mol-1 in molecular docking. The mRNA and protein levels of PTPN1 in the HCC tissue were higher than those in the normal tissue (P<0.01). Compared with that in the normal tissue, the mRNA level of PTPN1 in the HCC tissue was up-regulated at the pathological stages Ⅰ-Ⅲ and grades G1-G3 (P<0.01), and it was not significantly up-regulated at the stage Ⅳ or grade G4. The mRNA level of PTPN1 in the TP53-mutated HCC tissue was higher than that in the TP53-unmutated HCC tissue (P<0.01). The high mRNA level of PTPN1 was associated with the OS reduction (P<0.01). After treatment with the JYP-containing serum or knockdown of PTPN1, HepG2 cells demonstrated decreased proliferation and invasion and increased apoptosis (P<0.01). ConclusionPTPN1 may be one of the core targets of JYP in the treatment of HCC. It is highly expressed in the HCC tissue and cells, which is associated with the poor prognosis of patients. The expression level of PTPN1 is significantly up-regulated in the HCC tissue of the patients with TP53 mutation. However, TP53 mutation or deletion does not affect the expression of PTPN1 in HCC cells. JYP can significantly down-regulate the expression of PTPN1 to inhibit the proliferation and invasion and promote the apoptosis of HCC cells.
2.Effects of insulin-like growth factor-1 on the mechanism of myopia-related factors secreted by human scleral fibroblasts
Rongrong CHAO ; Zhixiang DING ; Jing FAN ; Liu ZHENG
International Eye Science 2025;25(2):198-205
AIM: To investigate the effects of insulin-like growth factor 1(IGF-1)on the secretion of transforming growth factor β2(TGF-β2), matrix metalloproteinase 2(MMP-2)and hypoxia-inducible factor 1α(HIF-1α)in human scleral fibroblasts(HSF)and their mechanism.METHODS: The cells were cultured with IGF-1 and PI3K/AKT pathway inhibitor LY294002, respectively. CCK-8 method was used to detect cell viability and determine the optimal concentration and time of drug action. Cell migration activity was observed by cell scratch method. To determine the effects of IGF-1 on HSF cells and the regulatory role of PI3K/AKT pathway, HSF cells were divided into control group(without drugs), IGF-1(80 μg/L)group, IGF-1+LY294002(80 μg/L+5 mmol/L)group, and LY294002(5 mmol/L)group, and were cultured for 24 h; the protein expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT were detected by Western blot; the fluorescence expression of TGF-β2, MMP-2 and HIF-1α was detected by cellular immunofluorescence.RESULTS: The results of CCK-8 showed that the cell viability of the 80 μg/L IGF-1 group cultured with different concentrations of IGF-1 was the highest(all P<0.05), and the cell viability of the 80 μg/L IGF-1 group at 24 h was the highest under different culture times. Therefore, the concentration of IGF-1 was selected as 80 μg/L for 24 h. The viability of cells cultured with different concentrations of LY294002 gradually decreased from 6 h(all P<0.05). According to the IC50 value, therefore, the concentration of LY294002 was selected as 5 mmol/L for 24 h. The cell scratch results showed that compared with the control group, the cell mobility of 40 μg/L and 80 μg/L IGF-1 groups was increased(all P<0.05). Compared with the control group, cell mobility in the 2.5 and 5 mmol/L LY294002 groups was decreased(all P<0.05). Western blot results showed that compared with the control group, the protein expressions of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1+LY294002 group were decreased(all P<0.05). The results of cell immunofluorescence showed that compared with the control group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1+LY294002 group were significantly decreased(all P<0.05).CONCLUSION: IGF-1 promoted the proliferation and migration of human HSF. IGF-1 may up-regulate the expression of TGF-β2, MMP-2 and HIF-1α in HSF through the PI3K/AKT signaling pathway, and participate in the occurrence and development of myopia.
3.Efficacy of phacoemulsification with corneoscleral limbus incision in the treatment of cataract
Jing KANG ; Zhuang MA ; Yuancheng MA
International Eye Science 2025;25(5):808-812
AIM: To observe the effect of phacoemulsification with corneoscleral limbus incision on cataract.METHODS: Prospective study. A total of 84 cases(84 eyes)of cataract patients admitted to our hospital from October 2021 to December 2022 were randomly grouped into two groups using the random number table method. The control group consisted of 42 cases(42 eyes)that underwent phacoemulsification with upper transparent corneal incision, while the study group consisted of 42 cases(42 eyes)that underwent phacoemulsification with corneoscleral limbus incision. The uncorrected visual acuity, astigmatism, ocular surface function, corneal sensitivity, and complications were compared between the two groups.RESULTS: There was a statistically significant difference in uncorrected visual acuity between the two groups of patients before and after surgery, as well as over time(both P<0.05). The uncorrected visual acuity of both groups showed a decreasing trend before and after surgery at 4 and 12 wk(both P<0.05). There were statistically significant differences in preoperative and postoperative astigmatism and corneal fluorescein staining(FLS)scores between the two groups of patients, as well as at different time points(both P<0.05). The astigmatism and FLS scores of the two groups of patients showed a trend of first increasing and then decreasing before and after surgery at 4 and 12 wk(both P<0.05). There was a statistically significant difference in breakup time of tear film(BUT)between the two groups of patients before and after surgery(both P<0.05); the BUT of both groups of patients showed a trend of first decreasing and then increasing before and after surgery at 4 and 12 wk(both P<0.05). There was a statistically significant difference in the Schirmer Ⅰ test(SⅠt), upper corneal sensitivity, and central corneal sensitivity between the two groups of patients before and after surgery, as well as at different times(all P<0.05). The SⅠt, upper corneal sensitivity, and central corneal sensitivity of the two groups of patients showed a trend of first decreasing and then increasing before and after surgery at 4 and 12 wk(all P<0.05). There was no significant difference in the total incidence of complications between the control group(12%, 5/42)and the study group(14%, 6/42; χ2=0.105, P=0.746).CONCLUSION: Compared to the phacoemulsification with upper transparent corneal incision, the phacoemulsification with corneoscleral limbus incision can reduce the adverse effects on uncorrected visual acuity, astigmatism, ocular surface function, and corneal sensitivity in patients with cataract, and does not increase the incidence of complications.
4.Epidemiological characteristics of mumps in Guangxi in 2012-2024
Jiagui CHEN ; Qiuyun DENG ; Rencong YANG ; Jing LIU ; Sha LI ; Ying HUANG ; Jianan WEI ; Jinfa DU
Journal of Public Health and Preventive Medicine 2025;36(6):21-24
Objective To analyze the epidemiological characteristics of mumps in Guangxi from 2012 to 2024, and to provide a scientific basis for formulating prevention and control strategies. Methods Descriptive epidemiological methods were used to analyze the incidence data of mumps in Guangxi from 2012 to 2024. Results A total of 159 873 mumps cases were reported from 2012 to 2024 in Guangxi, with an average annual reported incidence of 25.41/100 000, and no death. Mumps occurred every month, with the peak incidence mainly concentrated in April to July and October to January of the next year. There were 96,118 male cases (29.43 /100 000), and 63 755 female cases (21.07 /100 000). The male to female ratio was 1.40:1, and the difference between male and female was significant (χ2=4 321.276,P<0.05). The annual incidence of mumps showed a certain periodic change, with the incidence peak and trough alternating every 4 - 5 years. The majority of patients were under 15 years old, accounting for 85.32% of the total number of cases. The patients mainly included students, preschool children and scattered children. The highest average incidence was in Nanning City with 40 231 cases (42.08/100 000), and the lowest was in Qinzhou City with 3 466 cases (8.16/100 000). From 2012 to 2024, a total of 210 mumps outbreaks with 4 483 cases were reported in Guangxi. Conclusion The incidence of mumps in Guangxi from 2012 to 2024 shows a periodic change and obvious seasonality. People under 15 years old are the key group at risk of mumps. The prevention and control of the epidemic of mumps in schools and kindergartens should be strengthened. It is suggested to carry out long-term monitoring of mumps as well as immune effect research, and continue to maintain a high vaccination rate of 2 doses of mumps-containing vaccines.
5.Suppression of Hepatocellular Carcinoma through Apoptosis Induction by Total Alkaloids of Gelsemium elegans Benth.
Ming-Jing JIN ; Yan-Ping LI ; Huan-Si ZHOU ; Yu-Qian ZHAO ; Xiang-Pei ZHAO ; Mei YANG ; Mei-Jing QIN ; Chun-Hua LU
Chinese journal of integrative medicine 2025;31(9):792-801
OBJECTIVE:
To evaluate the anti-hepatocellular carcinoma (HCC) activity of total alkaloids from Gelsemium elegans Benth. (TAG) in vivo and in vitro and to elucidate their potential mechanisms of action through transcriptomic analysis.
METHODS:
TAG extraction was conducted, and the primary components were quantified using high-performance liquid chromatography (HPLC). The effects of TAG (100, 150, and 200 µg/mL) on various tumor cells, including SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116, were assessed. Effects of TAG on HCC proliferation and apoptosis were detected by colony formation assays and cell stainings. Caspase-3, Bcl-2, and Bax protein levels were detected by Western blotting. In vivo, a tumor xenograft model was developed using H22 cells. Totally 40 Kunming mice were randomly assigned to model, cyclophosphamide (20 mg/kg), TAG low-dose (TAG-L, 0.5 mg/kg), and TAG high-dose (TAG-H, 1 mg/kg) groups, with 10 mice in each group. Tumor volume, body weight, and tumor weight were recorded and compared during 14-day treatment. Immune organ index were calculated. Tissue changes were oberseved by hematoxylin and eosin staining and immunohistochemistry. Additionally, transcriptomic and metabolomic analyses, as well as quatitative real-time polymerase chain reaction (RT-qPCR), were performed to detect mRNA and metabolite expressions.
RESULTS:
HPLC successfully identified the components of TAG extraction. Live cell imaging and analysis, along with cell viability assays, demonstrated that TAG inhibited the proliferation of SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116 cells. Colony formation assays, Hoechst 33258 staining, Rhodamine 123 staining, and Western blotting revealed that TAG not only inhibited HCC proliferation but also promoted apoptosis (P<0.05). In vivo experiments showed that TAG inhibited the growth of solid tumors in HCC in mice (P<0.05). Transcriptomic analysis and RT-qPCR indicated that the inhibition of HCC by TAG was associated with the regulation of the key gene CXCL13.
CONCLUSION
TAG inhibits HCC both in vivo and in vitro, with its inhibitory effect linked to the regulation of the key gene CXCL13.
Animals
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Apoptosis/drug effects*
;
Liver Neoplasms/genetics*
;
Carcinoma, Hepatocellular/genetics*
;
Humans
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Alkaloids/therapeutic use*
;
Gelsemium/chemistry*
;
Cell Line, Tumor
;
Cell Proliferation/drug effects*
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Mice
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Xenograft Model Antitumor Assays
6.Beneficial Effects of Dendrobium officinale Extract on Insomnia Rats Induced by Strong Light and Noise via Regulating GABA and GABAA Receptors.
Heng-Pu ZHOU ; Jie SU ; Ke-Jian WEI ; Su-Xiang WU ; Jing-Jing YU ; Yi-Kang YU ; Zhuang-Wei NIU ; Xiao-Hu JIN ; Mei-Qiu YAN ; Su-Hong CHEN ; Gui-Yuan LYU
Chinese journal of integrative medicine 2025;31(6):490-498
OBJECTIVE:
To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia.
METHODS:
Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry.
RESULTS:
DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABAA receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01).
CONCLUSION
DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABAA receptors expressions and GA/GABA ratio.
Animals
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Dendrobium/chemistry*
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Rats, Sprague-Dawley
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Male
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Sleep Initiation and Maintenance Disorders/blood*
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Plant Extracts/therapeutic use*
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Receptors, GABA-A/metabolism*
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Noise/adverse effects*
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Light/adverse effects*
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gamma-Aminobutyric Acid/metabolism*
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Sleep/drug effects*
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Rats
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Receptors, GABA/metabolism*
7.Immunoregulatory mechanisms in the aging microenvironment: Targeting the senescence-associated secretory phenotype for cancer immunotherapy.
Haojun WANG ; Yang YU ; Runze LI ; Huiru ZHANG ; Zhe-Sheng CHEN ; Changgang SUN ; Jing ZHUANG
Acta Pharmaceutica Sinica B 2025;15(9):4476-4496
The aging microenvironment, as a key driver of tumorigenesis and progression, plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype (SASP). SASP consists of a variety of interleukins, chemokines, proteases, and growth factors. It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms, thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment. Furthermore, these secreted factors activate key signaling pathways such as NF-κB, cGAS-STING, and mTOR, which regulate the expression of immune-related molecules (such as PD-L1) and promote the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment. Furthermore, the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms, including approaches to inhibit SASP secretion or eliminate senescent cells. Although these strategies have shown promise in certain tumor models, the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies. This highlights the need for further research into adaptive stratification and personalized treatment approaches. Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.
8.Current situation of clinical trial registration in acupuncture anesthesia: A scoping review.
Yue LI ; You-Ning LIU ; Zhen GUO ; Mu-En GU ; Wen-Jia WANG ; Yi ZHU ; Xiao-Jun ZHUANG ; Li-Ming CHEN ; Jia ZHOU ; Jing LI
Journal of Integrative Medicine 2025;23(3):256-263
BACKGROUND:
Modern acupuncture anesthesia is a combination of Chinese and Western medicine that integrates the theories of acupuncture with anesthesia. However, some clinical studies of acupuncture anesthesia lack specific descriptions of randomization, allocation concealment, and blinding processes, with subsequent systematic reviews indicating a risk of bias.
OBJECTIVE:
Clinical trial registration is essential for the enhancement of the quality of clinical trials. This study aims to summarize the status of clinical trial registrations for acupuncture anesthesia listed on the World Health Organization International Clinical Trials Registry Platform (ICTRP).
SEARCH STRATEGY:
We searched the ICTRP for clinical trials related to acupuncture anesthesia registered between January 1, 2001 and May 31, 2023. Additionally, related publications were retrieved from PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. Registrations and publications were analyzed for consistency in trial design characteristics.
INCLUSION CRITERIA:
Clinical trials that utilized one of several acupuncture-related therapies in combination with pharmacological anesthesia during the perioperative period were eligible for this review.
DATA EXTRACTION AND ANALYSIS:
Data extracted from articles included type of surgical procedure, perioperative symptoms, study methodology, type of intervention, trial recruitment information, and publication information related to clinical enrollment.
RESULTS:
A total of 166 trials related to acupuncture anesthesia from 21 countries were included in the analysis. The commonly reported symptoms in the included studies were postoperative nausea and vomiting (19.9%) and postoperative pain (13.3%). The concordance between the publications and the trial protocols in the clinical registry records was poor, with only 31.7% of the studies being fully compatible. Inconsistency rates were high for sample size (39.0%, 16/41), blinding (36.6%, 15/41), and secondary outcome indicators (24.4%, 10/41).
CONCLUSION
The volume of acupuncture anesthesia clinical trials registered in international trial registries over the last 20 years is low, with insufficient disclosure of results. Postoperative nausea and vomiting as well as postoperative pain, are the most investigated for acupuncture intervention. Please cite this article as: Li Y, Liu YN, Guo Z, Gu ME, Wang WJ, Zhu Y, Zhuang XJ, Chen LM, Zhou J, Li J. Current situation of clinical trial registration in acupuncture anesthesia: A scoping review. J Integr Med. 2025; 23(3): 256-263.
Humans
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Acupuncture Analgesia
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Acupuncture Therapy
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Anesthesia
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Clinical Trials as Topic
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Registries
9.International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025).
Sheng-Sheng ZHANG ; Lu-Qing ZHAO ; Xiao-Hua HOU ; Zhao-Xiang BIAN ; Jian-Hua ZHENG ; Hai-He TIAN ; Guan-Hu YANG ; Won-Sook HONG ; Yu-Ying HE ; Li LIU ; Hong SHEN ; Yan-Ping LI ; Sheng XIE ; Jin SHU ; Bin-Fang ZENG ; Jun-Xiang LI ; Zhen LIU ; Zheng-Hua XIAO ; Jing-Dong XIAO ; Pei-Yong ZHENG ; Shao-Gang HUANG ; Sheng-Liang CHEN ; Gui-Jun FEI
Journal of Integrative Medicine 2025;23(5):502-518
Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy*
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Humans
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Medicine, Chinese Traditional/methods*
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Practice Guidelines as Topic
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Drugs, Chinese Herbal/therapeutic use*
10.Artesunate attenuating intestinal mucosal barrier injury in acute graft-versus-host disease mice
Jing KANG ; Xu CHENG ; Jin-Miao ZHENG ; Yu-Xue LI ; Li-Zhuang HAN ; Shu YANG
Acta Anatomica Sinica 2025;56(5):566-575
Objective To investigate the mechanism by which artesunate(ART)attenuates intestinal mucosal barrier damage in acute graft-versus-host disease(aGVHD)and the synergistic effect of ART in combination with dexamethasone(DXM)in the treatment of aGVHD mice.Methods The aGVHD mouse model was established by bone marrow haematopoietic stem cell transplantation.The mice were divided into 9 groups,including normal mice control(Ctrl),aGVHD mice(aGVHD),normal mice receiving ART[30 mg/(kg·d)],aGVHD mice receiving low-dose ART[10 mg/(kg·d)],aGVHD mice receiving medium-dose ART[30 mg/(kg·d)],aGVHD mice receiving high-dose ART[50 mg/(kg·d)],aGVHD mice receiving DXM[20 mg/(kg·d)],aGVHD mice receiving ART[30 mg/(kg·d)]and DXM[20 mg/(kg·d)],and aGVHD mice receiving ART[30 mg/(kg·d)]and halved DXM[10 mg/(kg·d)].Survival rate and clinical parameters were assessed.HE staining and Alcian blue-periodic acid-Schiff(AB-PAS)staining were used to observe the histopathological changes in the intestinal mucosa of the mice;Real-time PCR,Western blotting and immunohistochemistry were used to detect the structure of the intestinal mucosal barrier,the T cell differentiation related transcription factors and cytokines,and the key enzymes of energy metabolism.Flow cytometry was used to detect the T helper cell 17(Th17)and regulatory T cells(Treg).Results After 30 days of ART treatment,aGVHD mice showed significant relief of systemic symptoms and increase in survival rate.In aGVHD mice treated with ART,the intestinal mucosal barrier structure was restored,and the intestinal mucosal permeability was reduced.The activity of AMP-activated protein kinase(AMPK)/mTOR pathway was inhibited,and the energy metabolism pattern of T cells was dominated by fatty acid synthesis.The balance of Th17/Treg was restored due to the decrease of Th 17 and the increase of Treg.The effect of ART+DXM treatment on aGVHD mice was comparable to that of DXM treatment alone,and the survival rate of mice was higher.In particular,the recovery of the intestinal mucosal barrier function was most obvious in the mice treated with ART+half-dose DXM.Conclusion ART reduces the immune injury of allo-T cells to the intestinal mucosal barrier by recovering the Th17/Treg balance,thus maintaining the integrity of the intestinal mucosal barrier function.The synergistic effect of ART and DXM combination treatment in aGVHD mice can reduce the incidence of DXM side effects by decreasing the dosage of DXM.


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