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      Vol. 30 ， Issue 12 ， 2024

        Original Article

      • ZENG Hai-ping,CAO Li-xing,DIAO De-chang,WEN Ze-huai,OUYANG Wen-wei,OU Ai-hua,WAN Jin,PENG Zhi-jun,WANG Wei,CHEN Zhi-qiang
        Vol. 30, Issue 12, Pages: 1059-1067(2024) DOI: 10.1007/s11655-024-3813-6
        Abstract：Objective:To evaluate the efficacy and safety of Wuda Granule (WDG) on recovery of gastrointestinal function after laparoscopic bowel resection in the setting of enhanced recovery after surgery (ERAS)-based perioperative care.Methods:A total of 108 patients aged 18 years or older undergoing laparoscopic bowel resection with a surgical duration of 2 to 4.5 h were randomly assigned (1:1) to receive either WDG or placebo (10 g/bag) twice a day from postoperative days 1–3, combining with ERAS-based perioperative care. The primary outcome was time to first defecation. Secondary outcomes were time to first flatus, time to first tolerance of liquid or semi-liquid food, gastrointestinal-related symptoms and length of stay. Subgroup analysis of the primary outcome according to sex, age, tumor site, surgical time, histories of underlying disease or history of abdominal surgery was undertaken. Adverse events were observed and recorded.Results:A total of 107 patients [53 in the WDG group and 54 in the placebo group; 61.7±12.1 years; 50 males (46.7%)] were included in the intention-to-treat analysis. The patients in the WDG group had a significantly shorter time to first defecation and flatus [between-group difference –11.01 h (95% CI –20.75 to –1.28 h), P=0.012 for defecation; –5.41 h (–11.10 to 0.27 h), P=0.040 for flatus] than the placebo group. Moreover, the extent of improvement in postoperative gastrointestinal-related symptoms in the WDG group was significantly better than that in the placebo group (P<0.05). Subgroup analyses revealed that the benefits of WDG were significantly superior in patients who were male, or under 60 years old, or surgical time less than 3 h, or having no history of basic disease or no history of abdominal surgery. There were no serious adverse events.Conclusion:The addition of WDG to an ERAS postoperative care may be a viable strategy to enhance gastrointestinal function recovery after laparoscopic bowel resection surgery. (Registry No. ChiCTR2100046242)  
        Keywords：laparoscopic bowel resection;gastrointestinal function;postoperative ileus;Wuda Granule;enhanced recovery after surgery;randomized double-blind controlled trial;Chinese medicine   
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        Published：2024-11-25
      • TAO Zhu,XU Zi-ming,GUO Yan,YU Hui-yong
        Vol. 30, Issue 12, Pages: 1068-1079(2024) DOI: 10.1007/s11655-024-3816-3
        Abstract：Objective:To explore the effects of Tai Chi on body mass index (BMI), exercise capacity, and mental health of overweight/obese adults, and investigate factors influencing adherence to enhance adherence of Tai Chi as a sustainable exercise method.Methods:A randomized, controlled, exploratory clinical trial was conducted paired with a qualitative study of adherence management. A total of 20 overweight/obese participants were randomly assigned to a standard Tai Chi group (experimental) and a simplified Tai Chi group (control) for an 8-week intervention, 10 patients in each group, with a 12-month follow-up. BMI was calculated and exercise capacity including an isokinetic muscle strength and balance ability test were evaluated. Mental health was assessed using the General Well-Being Schedule (GWB), Pittsburgh Sleep Quality Index (PSQI), and Coping Self Efficacy Scale (CSES) at baseline, 4th week, and 8th week, respectively. The qualitative research included open-interviews with Tai Chi practitioners and semi-structured interviews with subjects.Results:The intervention was conducted in Haidian Park, Beijing, China from October 6, 2022, to January 1, 2023, without dropouts. After an 8-week intervention, the participants in the experimental group exhibited a significant decrease in BMI (P<0.05). Both groups demonstrated significant improvements in exercise capacity (P<0.05). The experimental group exhibited a significant enhancement in the GWB, PSQI and CSES (P<0.05). Only GWB had significant difference in the control group (P<0.05). The experimental group surpassed the control group in GWB and CSES (P<0.05). The adherence rate was 87.5% in the experimental group and 57.9% in the control group after 8 weeks intervention. Analysis on adherence identified 15 themes, the top 3 themes mentioned were as follows: mind-body effects, online and on-site guidance, training schedule (for subjects); mind-body effects, difficulties in practicing, and understanding of Tai Chi (for practitioners).Conclusions:Both interventions were effective in improving exercise capacity. Standard Tai Chi, integrating both physical and mental conditioning, reduced weight, improved exercise capacity and mental happiness, and increased adherence, providing a sustainable exercise program (ChiCTR2200063599).  
        Keywords：Tai Chi;overweight;obesity;exercise capacity;mental health;adherence;interview   
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        Published：2024-11-25
      • QI Ying,WU Xin-jie,SHI Jing-bin,SHI Xiao-wei,ZHAO Na,XIONG Yang,WANG Li-pei
        Vol. 30, Issue 12, Pages: 1080-1089(2024) DOI: 10.1007/s11655-023-3555-x
        Abstract：Objective:To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triplenegative breast cancer (TNBC) in mice and its underlying mechanism.Methods:The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×105 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice.Results:Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice.Conclusion:SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism.  
        Keywords：Sanhuang Xiexin Decoction;Janus kinase 2-signal transducer and activator of transcription 3;lipid metabolism;triple-negative breast cancer;epithelial-mesenchymal transition   
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        Published：2024-11-25
      • Nageh Ahmed El-Mahdy,Thanaa Ahmed El-Masry,Ahmed Mahmoud El-Tarahony,Fatemah A. Alherz,Enass Youssef Osman
        Vol. 30, Issue 12, Pages: 1090-1100(2024) DOI: 10.1007/s11655-024-3808-3
        Abstract：Objective:To explore the prophylactic and therapeutic effects of Alhagi maurorum ethanolic extract (AME) in concanavalin A (Con A)-induced hepatitis (CIH) as well as possible underlying mechanisms.Methods:Polyphenols in AME were characterized using high performance liquid chromatography (HPLC). Swiss albino mice were divided into 4 groups. Normal group received intravenous phosphate-buffered saline (PBS); Con A group received 40 mg/kg intravenous Con A. Prophylaxis group administered 300 mg/(kg • d) AME orally for 5 days before Con A intervention. Treatment group received intravenous Con A then administered 300 mg/kg AME at 30 min and 3 h after Con A intervention. After 24 h of Con A injection, hepatic injury, oxidative stress, and inflammatory mediators were assessed. Histopathological examination and markers of apoptosis, inflammation, and CD4+ cell infiltration were also investigated.Results:HPLC analysis revealed that AME contains abundant polyphenols with pharmacological constituents, such as ellagic acid, gallic acid, ferulic acid, methylgallate, and naringenin. AME alleviated Con A-induced hepatic injury, as manifested by a significant reduction in alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase (P<0.01). Additionally, the antioxidant effect of AME was revealed by a significant reduction in oxidative stress markers (nitric oxide and malondialdehyde) and restored glutathione (P<0.01). The levels of proinflammatory cytokines (tumor necrosis factor-α, interferon-γ, and interleukin-6) and c-Jun N-terminal kinase (JNK) activity were reduced (P<0.01). Histopathological examination of liver tissue showed that AME significantly ameliorated necrotic and inflammatory lesions induced by Con A (P<0.01). Moreover, AME reduced the expression of nuclear factor kappa B, pro-apoptotic protein (Bax), caspase-3, and CD4+ T cell hepatic infiltration (P<0.01). The expression of anti-apoptotic protein Bcl-2 was increased (P<0.01).Conclusions:AME has hepatoprotective and ameliorative effects in CIH mice. These beneficial effects are likely due to the anti-inflammatory, antioxidant, and anti-apoptotic effects of the clinically important polyphenolic content. AME could be a novel and promising hepatoprotective agent for managing immune-mediated hepatitis.  
        Keywords：concanavalin A-induced hepatitis;Alhagi maurorum ethanolic extract;hepatoprotective effect   
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        Published：2024-11-25
      • LIU Yi-yan,BAO Dai-qin,ZHANG Zi-sen,ZHU Yu,LIU Liang-ming,LI Tao
        Vol. 30, Issue 12, Pages: 1101-1112(2024) DOI: 10.1007/s11655-023-3550-2
        Abstract：Objective:To investigate whether Radix Sanguisorbae (RS, Diyu) could restore intestinal barrier function following sepsis using a cecal ligation and puncture (CLP)-induced septic rat model and lipopolysaccharide (LPS)-challenged IEC-6 cell model, respectively.Methods:Totally 224 rats were divided into 4 groups including a control, sham, CLP and RS group according to a random number table. The rats in the control group were administrated with Ringer's lactate solution (30 mL/kg) with additional dopamine [10 μg/(kg • min)] and given intramuscular injections of cefuroxime sodium (10 mg/kg) 12 h following CLP. The rats in the RS group were administrated with RS (10 mg/kg) through tail vein 1 h before CLP and treated with RS (10 mg/kg) 12 h following CLP. The rats in the sham group were only performed abdominal surgery without CLP. The rats in the CLP group were performed with CLP without any treatment. The other steps were same as control group. The effects of RS on intestinal barrier function, mesenteric microvessels barrier function, multi-organ function indicators, inflammatory response and 72 h survival window following sepsis were observed. In vitro, the effects of RS on LPS-challenged IEC-6 cell viability, the expressions of zona occludens-1 (ZO-1) and ferroptosis index were evaluated by cell counting kit-8, immunofluorescence and Western blot analysis. Bioinformatic tools were applied to investigate the pharmacological network of RS in sepsis to predict the active compounds and potential protein targets and pathways.Results:The sepsis caused severe intestinal barrier dysfunction, multi-organ injury, lipid peroxidation accumulation, and ferroptosis in vivo. RS treatment significantly prolonged the survival time to 56 h and increased 72-h survival rate to 7/16 (43.75%). RS also improved intestinal barrier function and relieved intestinal inflammation. Moreover, RS significantly decreased lipid peroxidation and inhibited ferroptosis (P<0.05 or P<0.01). Administration of RS significantly worked better than Ringer's solution used alone. Using network pharmacology prediction, we found that ferroptosis and hypoxia inducible factor-1α (HIF-1α) signaling pathways might be involved in RS effects on sepsis. Subsequent Western blot, ferrous iron measurements, and FerroOrange fluorescence of ferrous iron verified the network pharmacology predictions.Conclusion:RS improved the intestinal barrier function and alleviated intestinal injury by inhibiting ferroptosis, which was related in part to HIF-1α/heme oxygenase-1/Fe2+ axis.  
        Keywords：Radix Sanguisorbae;sepsis;ferroptosis;intestinal barrier function;network pharmacology;Chinese medicine   
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        Published：2024-11-25
      • HE Xiao-yan,XIONG Xiao-jiao,LIU Mei-jun,LIANG Jing-tao,LIU Fu-you,XIAO Jing-yi,WU Li-juan
        Vol. 30, Issue 12, Pages: 1113-1120(2024) DOI: 10.1007/s11655-024-3801-x
        Abstract：Objective:To explore the effect and mechanism of Dahuang Zhechong Pill (DHZCP) on liver fibrosis.Methods:Liver fibrosis cell model was induced by transforming growth factor-β (TGF-β) in hepatic stellate cells (HSC-T6). DHZCP medicated serum (DMS) was prepared in rats. HSC-T6 cells were divided into the control (15% normal blank serum culture), TGF-β (15% normal blank serum + 5 ng/mL TGF-β), DHZCP (15% DMS + 5 ng/mL TGF-β), DHZCP+PDTC [15% DMS + 4 mmol/L ammonium pyrrolidine dithiocarbamate (PDTC)+ 5 ng/mL TGF-β], and PDTC groups (4 mmol/L PDTC + 5 ng/mL TGF-β). Cell activity was detected by cell counting kit 8 and levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the cell supernatant were determined by enzyme-linked immunosorbnent assay. Western blot was used to measure the expressions of p38 mitogen-activated protein kinase/nuclear factor kappa B/transforming growth factor-β1 (p38 MAPK/NF-κB/TGF-β1) pathway related proteins, and the localization and expressions of these proteins were observed by immunofluorescence staining.Results:DHZCP improved the viability of cells damaged by TGF-β and reduced inflammatory cytokines and ALT and AST levels in the supernatant of HSC-T6 cells induced with TGF-β (P<0.05 or P<0.01). Compared with the TGF-β group, NF-κB p65 levels in the DHZCP group were decreased (P<0.05). p38 MAPK and NF-κB p65 levels in the DHZCP+PDTC were also reduced (P<0.01). Compared with the TGF-β group, the protein expression of Smad2 showed a downward trend in the DHZCP, DHZCP+PDTC, and PDTC groups (all P<0.01), and the decreasing trend of Samd3 was statistically significant only in DHZCP+PDTC group (P<0.01), whereas Smad7 was increased (P<0.05 or P<0.01).Conclusion:DHZCP can inhibit the process of HSC-T6 cell fibrosis by down-regulating the expression of p38 MAPK/NF-κB/TGF-β1 pathway.  
        Keywords：liver fibrosis;Dahuang Zhechong Pill;inflammation;p38 mitogen-activated protein kinase/nuclear factor kappa B/transforming growth factor-β1 pathway;Chinese medicine   
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        Published：2024-11-25
      • WANG Jun,ZHANG Xue-ying,KANG Yan-hong,ZHANG Yun,CHEN Xin-yi,ZHOU Jia-li,MA Wei
        Vol. 30, Issue 12, Pages: 1121-1127(2024) DOI: 10.1007/s11655-023-3567-6
        Abstract：Objective:To investigate the hemostatic effect of modified Sijunzi Granules (MSG) in primary immune thrombocytopenia (ITP) zebrafish model and explore the potential mechanism.Methods:AB strain wild type zebrafish were treated with simvastatin (6 μmol/L) for 24 h to establish the hemorrhage model (model control group). The zebrafish were treated with MSG at different doses (55.6, 167, and 500 μg/mL), respectively. The hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate. 5-hydroxytryptamine (5-HT) content was determined using enzyme-linked immunosorbent assay (ELISA) assay. The expressions of 5-HT2aR, 5-HT2bR, and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR). The protein expressions of protein kinase B (Akt), p-Akt, extracellular regulated protein kinases (Erk), and p-Erk were examined using Western blot analysis.Results:The intestinal bleeding rate was 37%, 40%, and 80% in the 55.6, 167, and 500 μg/mL dose of MSG, respectively, in which 55.6 and 167 μg/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group (70%, P<0.05). Significantly higher hemostatic rates were also observed in the 55.6 μg/mL (54%) and 167 μg/mL (52%) MSG dose groups (P<0.05). MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR, 5-HT2bR, and SERT (P<0.05). In addition, caspase3/7 activity was inhibited (P<0.05). Significant increase in p-Akt and p-Erk was also detected after treatment with MSG (P<0.05).Conclusions:MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors, which may provide evidence for the treatment of ITP.  
        Keywords：modified Sijunzi Granules;Chinese medicine;primary immune thrombocytopenia;zebrafish;5-hydroxytryptamine;5-hydroxytryptamine receptor;mitogen-activated protein kinase/extracellular regulated protein kinases signal pathway;phosphoinositide3-kinases/ protein kinase B signal pathway   
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        Published：2024-11-25

        Literature Research

      • QIAN Jia-nan,KANG Yan-lan,HE You-cheng,HU Hong-yi
        Vol. 30, Issue 12, Pages: 1128-1136(2024) DOI: 10.1007/s11655-024-3800-y
        Abstract：Objective:To analyze Chinese medicine (CM) prescriptions for gastroesophageal reflux disease (GERD), we model topics on GERD-related classical CM literature, providing insights into the potential treatment.Methods:Clinical guidelines were used to identify symptom terms for GERD, and CM literature from the database "Imedbooks" was retrieved for related prescriptions and their corresponding sources, indications, and other information. BERTopic was applied to identify the main topics and visualize the data.Results:A total of 36,207 entries are queried and 1,938 valid entries were acquired after manually filtering. Eight topics were identified by BERTopic, including digestion function abate, stomach flu, respiratory-related symptoms, gastric dysfunction, regurgitation and gastrointestinal dysfunction in pediatric patients, vomiting, stroke and alcohol accumulation are associated with the risk of GERD, vomiting and its causes, regurgitation, epigastric pain, and symptoms of heartburn.Conclusions:Topic modeling provides an unbiased analysis of classical CM literature on GERD in a time-efficient and scale-efficient manner. Based on this analysis, we present a range of treatment options for relieving symptoms, including herbal remedies and non-pharmacological interventions such as acupuncture and dietary therapy.  
        Keywords：gastroesophageal reflux disease;BERTopic;prescription;topic modeling;Chinese medicine   
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        Published：2024-11-25

        Herbal and Botanical Review

      • LIU Yu-quan,WU Hui-li,ZHANG Zhi-qiang,WANG Wen-le,HAN Guo-qing,ZHANG Chun-hong,LYU Xin-liang,MA Chun-jie,LI Min-hui
        Vol. 30, Issue 12, Pages: 1137-1147(2024) DOI: 10.1007/s11655-024-3815-4
        Abstract：Persicae Semen (Taoren), the seed of mature peaches consumed as both food and medicine, is native to the temperate regions of China, distributed in the provinces of North and East China, and currently cultivated worldwide. The primary components of Persicae Semen include volatile oil, protein, amino acids, amygdalin, and prunasin, all of which have pharmacological properties, such as anti-inflammatory, antioxidant, and immune regulatory effects, and are clinically used in the treatment of gynecological, cardiovascular, cerebrovascular, orthopedic, and digestive system diseases. This review provides a comprehensive perspective on the resource status, ethnopharmacology, phytochemistry, pharmacology, and toxicology, as well as the trend of Persicae Semen patent, global distribution, and clinical applications. This review will help facilitate the development and utilization of Persicae Semen in clinical settings.  
        Keywords：Persicae Semen;pharmacology;clinical applications;food-medicine homology;phytochemistry;review   
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        Published：2024-11-25
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