Latest Issue
      Vol. 29 ， Issue 10 ， 2023

        Original Article

      • XU Xiang-ru,ZHOU Shuang,JIN Guo-qiang,WU Hong-ze,LI Jin-hua,ZHOU Jing,PENG Wei,ZHANG Wen,SUN Ding,FANG Bang-jiang
        Vol. 29, Issue 10, Pages: 867-874(2023) DOI: 10.1007/s11655-023-3609-0
        Abstract：Objective:To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents.Methods:This is a prospective, open-label, randomized controlled trial. Patients aged 1–17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested.Results:A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5–6) vs. 7 days (IQR: 6–7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P=0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17–45.00) vs. 34.22 (IQR: 28.41–39.41), P=0.03; N gene: 34.97 (IQR: 28.50–45.00) vs. 33.51 (IQR: 27.70–38.25), P=0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72–45.00) vs. 35.81 (IQR: 29.96–45.00), P=0.003; N gene: 37.16 (IQR: 32.01–45.00) vs. 35.26 (IQR: 29.09–45.00), P=0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported.Conclusion:Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292)  
        Keywords：coronavirus diseases-2019;severe acute respiratory syndrome coronavirus 2;Omicron;children;Reyanning Mixture;randomized controlled trial;Chinese medicine   
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        Published：2023-09-26
      • WANG Ruo-lin,LIU Shu-hua,SHEN Si-heng,JIAN Lu-yong,YUAN Qi,GUO Hua-hui,HUANG Jia-sheng,CHEN Peng-hui,HUANG Ren-fa
        Vol. 29, Issue 10, Pages: 875-884(2023) DOI: 10.1007/s11655-023-3593-4
        Abstract：Objective:To investigate protective effect of Cordyceps sinensis (CS) through autophagy-associated adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in acute kidney injury (AKI)-induced acute lung injury (ALI).Methods:Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table, including the normal saline (NS)-treated sham group (sham group), NS-treated ischemia reperfusion injury (IRI) group (IRI group), and low- (5 g/kg•d) and high-dose (10 g/kg•d) CS-treated IRI groups (CS1 and CS2 groups), 12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12, 24, 48, and 72 h of reperfusion. The wet-to-dry (W/D) ratio of lung, levels of serum creatinine (Scr), blood urea nitrogen (BUN), inflammatory cytokines such as interleukin-β and tumor necrosis factor-α, and biomarkers of oxidative stress such as superoxide dismutase, malonaldehyde (MDA) and myeloperoxidase (MPO), were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 Ⅱ/light chain 3 Ⅰ (LC3-Ⅱ/LC3-Ⅰ), uncoordinated-51-like kinase 1 (ULK1), P62, AMPK and mTOR were measured by Western blot and immunohistochemistry, respectively.Results:The renal IRI induced pulmonary injury following AKI, resulting in significant increases in W/D ratio of lung, and the levels of Scr, BUN, inflammatory cytokines, MDA and MPO (P<0.01); all of these were reduced in the CS groups (P<0.05 or P<0.01). Compared with the IRI groups, the expression levels of P62 and mTOR were significantly lower (P<0.05 or P<0.01), while those of LC3-Ⅱ/LC3-Ⅰ, ULK1, and AMPK were significantly higher in the CS2 group (P<0.05 or P<0.01).Conclusion:CS had a potential in treating lung injury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-induced ALI.  
        Keywords：autophagy;ischemic reperfusion injury;acute kidney injury;acute lung injury;Cordyceps sinensis;Chinese medicine   
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        Published：2023-09-26
      • HONG Quan-long,DING Yi-hang,CHEN Jing-yi,SHI Song-sheng,LIANG Ri-sheng,TU Xian-kun
        Vol. 29, Issue 10, Pages: 885-894(2023) DOI: 10.1007/s11655-023-3596-1
        Abstract：Objective:To explore the effect and mechanism of schisandrin B (Sch B) in the treatment of cerebral ischemia in rats.Methods:The cerebral ischemia models were induced by middle cerebral artery occlusion (MCAO) and reperfusion. Sprague-Dawley rats were divided into 6 groups using a random number table, including sham, MCAO, MCAO+Sch B (50 mg/kg), MCAO+Sch B (100 mg/kg), MCAO+Sch B (100 mg/kg)+LY294002, and MCAO+Sch B (100 mg/kg)+wortmannin groups. The effects of Sch B on pathological indicators, including neurological deficit scores, cerebral infarct volume, and brain edema, were subsequently studied. Tissue apoptosis was identified by terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining. The protein expressions involved in apoptosis, inflammation response and oxidative stress were examined by immunofluorescent staining, biochemical analysis and Western blot analysis, respectively. The effect of Sch B on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling was also explored.Results:Sch B treatment decreased neurological deficit scores, cerebral water content, and infarct volume in MCAO rats (P<0.05 or P<0.01). Neuronal nuclei and TUNEL staining indicated that Sch B also reduced apoptosis in brain tissues, as well as the Bax/Bcl-2 ratio and caspase-3 expression (P<0.01). Sch B regulated the production of myeloperoxidase, malondialdehyde, nitric oxide and superoxide dismutase, as well as the release of cytokine interleukin (IL)-1β and IL-18, in MCAO rats (P<0.05 or P<0.01). Sch B promoted the phosphorylation of PI3K and AKT. Blocking the PI3K/AKT signaling pathway with LY294002 or wortmannin reduced the protective effect of Sch B against cerebral ischemia (P<0.05 or P<0.01).Conclusions:Sch B reduced apoptosis, inflammatory response, and oxidative stress of MCAO rats by modulating the PI3K/AKT pathway. Sch B had a potential for treating cerebral ischemia.  
        Keywords：cerebral ischemia;inflammation;neuroprotection;PI3K/AKT signaling;schisandrin B;Chinese medicine   
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        Published：2023-09-26
      • YI Jing,LI Li,YIN Zhu-jun,QUAN Yun-yun,TAN Rui-rong,CHEN Shi-long,LANG Ji-rui,LI Jiao,ZENG Jin,LI Yong,SUN Zi-jian,ZHAO Jun-ning
        Vol. 29, Issue 10, Pages: 895-904(2023) DOI: 10.1007/s11655-023-3598-z
        Abstract：Objective:To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice.Methods:The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively.Results:The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10–26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho- inhibitors of NF-κB (IκBs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck- like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs.Conclusion:PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.  
        Keywords：Moschus;polypeptide;inflammation;NLRP3 inflammasome;thioredoxin interacting protein;nuclear factor κB;Chinese medicine   
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        Published：2023-09-26
      • YANG Cheng-liu,WANG Shi-bo,HE Wen-ping,LIU Jin-juan
        Vol. 29, Issue 10, Pages: 905-913(2023) DOI: 10.1007/s11655-023-3602-7
        Abstract：Objective:To investigate the anti-oxidant and anti-inflammatory effects of ethanol extract of Polygala sibirica L. var megalopha Fr. (EEP) on RAW264.7 mouse macrophages.Methods:RAW264.7 cells were pretreated with 0–200 μg/mL EEP or vehicle for 2 h prior to exposure to 1 μg/mL lipopolysaccharide (LPS) for 24 h. Nitric oxide (NO) and prostaglandin (PGE2) production were determined by Griess reagent and enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), interleukin-1beta (IL-1β), and IL-6 were determined using reverse transcription polymerase chain reaction (RT-PCR). Western blot assay was used to determine the protein expressions of iNOS, COX-2, phosphorylation of extracellular regulated protein kinases (ERK1/2), c-Jun N-terminal kinase (JNK), inhibitory subunit of nuclear factor Kappa B alpha (IκB-α) and p38. Immunofluorescence was used to observe the nuclear expression of nuclear factor-κB p65 (NF-κB p65). Additionally, the anti-oxidant potential of EEP was evaluated by reactive oxygen species (ROS) production and the activities of catalase (CAT) and superoxide dismutase (SOD). The 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), superoxide anion (O2–) radical and nitrite scavenging activity were also measured.Results:The total polyphenol and flavonoid contents of EEP were 23.50±2.16 mg gallic acid equivalent/100 g and 43.78±3.81 mg rutin equivalent/100 g. With EEP treatment (100 and 150 μg/mL), there was a notable decrease in NO and PGE2 production induced by LPS in RAW264.7 cells by downregulation of iNOS and COX-2 mRNA and protein expressions (P<0.01 or P<0.05). Furthermore, with EEP treatment (150 μg/mL), there was a decrease in the mRNA expression levels of TNF-α, IL-1β and IL-6, as well as in the phosphorylation of ERK, JNK and p38 mitogen-activated protein kinase (MAPK, P<0.01 or P<0.05), by blocking the nuclear translocation of NF-κB p65 in LPS-stimulated cells. In addition, EEP (100 and 150 μg/mL) led to an increase in the anti-oxidant enzymes activity of SOD and CAT, with a concomitant decrease in ROS production (P<0.01 or P<0.05). EEP also indicated the DPPH, OH, O2– radical and nitrite scavenging activity.Conclusion:EEP inhibited inflammatory responses in activated macrophages through blocking MAPK/NF-κB pathway and protected against oxidative stress.  
        Keywords：Polygala sibirica L. var megalopha Fr.;anti-inflammatory;anti-oxidant;RAW264.7 cells;lipopolysaccharide;Chinese medicine   
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        Published：2023-09-26
      • WU Ming-hui,WU Kun,ZHU Yuan-bing,LI Da-chuan,YANG Huan,ZENG Hong
        Vol. 29, Issue 10, Pages: 914-923(2023) DOI: 10.1007/s11655-023-3595-2
        Abstract：Objective:To investigate the molecular mechanisms underlying the effect of baicalin on prostate cancer (PCa) progression both in vivo and in vitro.Methods:The in situ PCa stem cells (PCSCs)-injected xenograft tumor models were established in BALB/c nude mice. Tumor volume and weight were respectively checked after baicalin (100 mg/kg) treatment. Hematoxylin-eosin (HE) staining was used to observe the growth arrest and cell necrosis. mRNA expression levels of acetaldehyde dehydrogenase 1 (ALDH1), CD44, CD133 and Notch1 were determined by reverse transcription-polymerase chain reaction. Protein expression levels of ALDH1, CD44, CD133, Notch1, nuclear factor κB (NF-κB) P65 and NF-κB p-P65 were detected by Western blot. Expression and subcellular location of ALDH1, CD44, CD133, Notch1 and NF-κB p65 were detected by immunofluorescence analysis. In vitro, cell cycle distribution and cell apoptosis of PC3 PCSCs was assessed by flow cytometry after baicalin (125 μmol/L) treatment. The migration and invasion abilities of PCSCs were assessed using Transwell assays. Transmission electron microscopy scanning was utilized to observe the structure and autophagosome formation of baicalin-treated PCSCs. In addition, PCSCs were infected with lentiviruses expressing human Notch1.Results:Compared with the control group, the tumor volume and weight were notably reduced in mice treated with 100 mg/kg baicalin (P<0.05 or P<0.01). Histopathological analysis showed that baicalin treatment significantly inhibited cell proliferation and promoted cell apoptosis. Furthermore, baicalin treatment reduced mRNA and protein expression levels of CD44, CD133, ALDH1, and Notch1 as well as the protein expression of NF-κB p-P65 in the xenograft tumor (P<0.01). In vitro, the cell proliferation of PCSCs was significantly attenuated after treatment with 125 μmol/L baicalin for 72 h (P<0.01). The cell migration and invasion rates were decreased following treatment with baicalin for 48 and 72 h (P<0.01). Baicalin notably induced cell apoptosis and seriously damaged the structure of PCSCs. The mRNA and protein expressions of CD133, CD44, ALDH1 and Notch1 in PCSCs were significantly downregulated following baicalin treatment (P<0.01). Importantly, the inhibitory effects of baicalin on PCa progression and stemness were reversed by Notch1 overexpression (P<0.05 or P<0.01).Conclusion:Mechanistically, baicalin exhibited a potential therapeutic effect on PCa via inhibiting the Notch1/NF-κB signaling pathway and its mediated cancer stemness.  
        Keywords：baicalin;prostate cancer;cancer stemness;Notch1/nuclear factor κB signaling   
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        Published：2023-09-26

        Acupuncture Research

      • SHI Yun-zhou,YU Shu-guang,ZHENG Hui,ZHENG Qian-hua,ZHOU Si-yuan,HUANG Ying,ZHANG Lei-xiao,XIAO Xian-jun,CAO Wei,LI Ying
        Vol. 29, Issue 10, Pages: 924-931(2023) DOI: 10.1007/s11655-023-3741-x
        Abstract：Objective:To determine the feasibility of conducting a full-scale randomized controlled trial (RCT) and investigate the basic information and safety of acupuncture for patients with chronic spontaneous urticaria (CSU).Methods:A total of 80 participants with CSU from July 2018 to July 2019 were randomly assigned to receive active acupuncture (n=41) on a fixed prescription of acupoints or sham acupuncture (n=39) with superficial acupuncture on non-acupuncture points through the completely randomized design. Patients in both groups received 5 sessions per week for 2 weeks, and participants were followed for a further 2 weeks. Feasibility was assessed by recruitment and randomization rates, retention of participants, treatment protocol adherence, and the incidence of adverse events (AEs). The clinical primary outcome was the changes from baseline weekly urticaria activity scores (UAS7) after treatment at 2 weeks. Secondary outcomes included the Visual Analogue Scale (VAS) score of itching intensity, Dermatology Life Quality Index (DLQI), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA).Results:A total of 80 participants were enrolled. The recruitment rate of 24.02%, randomization rate of 100%, a loss rate of 6.25%, and no obvious AEs were observed in either group. The decrease from baseline in the mean UAS7 total score at week 2 in the active acupuncture group was –8.63 (95%CI, –11.78 to –5.49) and –6.21 (95%CI, –9.43 to –2.98) in the sham acupuncture group for a between-group difference of –2.42 (95% CI, –6.93 to 2.07). The change in the DLQI, VAS of itching intensity, HAMA, and HAMD were a slightly better improvement trend in the active acupuncture group than the sham acupuncture group, but the between-group difference was not significant.Conclusion:Active acupuncture had a better improvement trend in alleviating symptoms, improving quality of life and regulating the mood of anxiety and depression in patients with CSU than sham acupuncture. (Registration Nos. AMCTR-ICR-18000190 and ChiCTR2100054776)  
        Keywords：acupuncture;chronic spontaneous urticaria;randomized controlled trial;sham acupuncture   
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        Published：2023-09-26
      • LI Yong-ping,LI Meng-xin,WANG Chao,LI Yun-di,SA Yu-ping,GUO Yi
        Vol. 29, Issue 10, Pages: 932-940(2023) DOI: 10.1007/s11655-023-3597-0
        Abstract：Objective:To explore the protective effect of bloodletting acupuncture at twelve Jing-well points on hand (BAJP) on acute hypobaric hypoxia (AHH)-induced brain injury in rats and its possible mechanisms.Methods:Seventy-five Sprague Dawley rats were divided into 5 groups by a random number table (n=15), including control, model, BAJP, BAJP+3-methyladenine (3-MA), and bloodletting acupuncture at non-acupoint (BANA, tail tip blooding) groups. After 7-day pre-treatment, AHH models were established using hypobaric oxygen chambers. The levels of S100B, glial fibrillary acidic protein (GFAP), superoxide dismutase (SOD), and malondialdehyde (MDA) in serum were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method were used to assess hippocampal histopathology and apoptosis. Transmission electron microscopy assay was used to observe mitochondrial damage and autophagosomes in hippocampal tissues. Flow cytometry was used to detect mitochondrial membrane potential (MMP). The mitochondrial respiratory chain complexes Ⅰ, Ⅲ and Ⅳ activities and ATPase in hippocampal tissue were evaluated, respectively. Western blot analysis was used to detect the protein expressions of Beclin1, autophagy protein 5 (ATG5), microtubule-associated protein 1 light chain 3 beta (LC3B), phosphatase and tensin homolog induced kinase 1 (PINK1), and Parkin in hippocampal tissues. The mRNA expressions of Beclin1, ATG5 and LC3-Ⅱ were analyzed by quantitative real-time polymerase chain reaction.Results:BAJP treatment reduced hippocampal tissue injury and inhibited hippocampal cell apoptosis in AHH rats. BAJP reduced oxidative stress by decreasing S100B, GFAP and MDA levels and increasing SOD level in the serum of AHH rats (P<0.05 or P<0.01). Then, BAJP increased MMP, the mitochondrial respiratory chain complexes Ⅰ, Ⅲ and Ⅳ activities, and the mitochondrial ATPase activity in AHH rats (all P<0.01). BAJP improved mitochondrial swelling and increased the autophagosome number in hippocampal tissue of AHH rats. Moreover, BAJP treatment increased the protein and mRNA expressions of Beclin1 and ATG5 and LC3-Ⅱ/LC3-Ⅰ ratio in AHH rats (all P<0.01) and activated the PINK1/Parkin pathway (P<0.01). Finally, 3-MA attenuated the therapeutic effect of BAJP on AHH rats (P<0.05 or P<0.01).Conclusion:BAJP was an effective treatment for AHH-induced brain injury, and the mechanism might be through reducing hippocampal tissue injury via increasing the PINK1/Parkin pathway and enhancement of mitochondrial autophagy.  
        Keywords：acute hypobaric hypoxia;bloodletting acupuncture at Jing-well points;mitochondrial autophagy;PINK1/Parkin signaling;mitochondrial damage;Chinese medicine   
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        Published：2023-09-26

        Evidence-Based Integrative Medicine

      • XIONG Zhi-yi,LIU Xiao-yu,MA Pei-hong,SUN Chong-yang,SUN Cheng-yi,LIU Ting-lan,LIU Bao-yan,LIU Cun-zhi,YAN Shi-yan
        Vol. 29, Issue 10, Pages: 941-950(2023) DOI: 10.1007/s11655-023-3608-1
        Abstract：Background:Low back pain (LBP) is a prevalent and debilitating condition that poses a significant burden on healthcare systems. Acupuncture has been proposed as a promising intervention for LBP, but the evidence supporting its specific effect is insufficient, and the use of sham acupuncture as a control in clinical trials presents challenges due to variations in sham acupuncture techniques and the magnitude of the placebo effect.Objective:To investigate the magnitude of the placebo response of sham acupuncture in trials of acupuncture for nonspecific LBP, and to assess whether different types of sham acupuncture are associated with different responses.Methods:Four databases including PubMed, EMBASE, MEDLINE, and the Cochrane Library were searched through April 15, 2023, and randomized controlled trials (RCTs) were included if they randomized patients with LBP to receive acupuncture or sham acupuncture intervention. The main outcomes included the placebo response in pain intensity, back-specific function and quality of life. Placebo response was defined as the change in these outcome measures from baseline to the end of treatment. Random-effects models were used to synthesize the results, standardized mean differences (SMDs, Hedges'g) were applied to estimate the effect size.Results:A total of 18 RCTs with 3, 321 patients were included. Sham acupuncture showed a noteworthy pooled placebo response in pain intensity in patients with LBP [SMD –1.43, 95% confidence interval (CI) –1.95 to –0.91, I2=89%]. A significant placebo response was also shown in back-specific functional status (SMD –0.49, 95% CI –0.70 to –0.29, I2=73%), but not in quality of life (SMD 0.34, 95% CI –0.20 to 0.88, I2=84%). Trials in which the sham acupuncture penetrated the skin or performed with regular needles had a significantly higher placebo response in pain intensity reduction, but other factors such as the location of sham acupuncture did not have a significant impact on the placebo response.Conclusions:Sham acupuncture is associated with a large placebo response in pain intensity among patients with LBP. Researchers should also be aware that the types of sham acupuncture applied may potentially impact the evaluation of the efficacy of acupuncture. Nonetheless, considering the nature of placebo response, the effect of other contextual factors cannot be ruled out in this study. (PROSPERO registration No. CRD42022304416)  
        Keywords：low back pain;sham acupuncture;placebo response;meta-analysis;randomized controlled trial   
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        Published：2023-09-26

        Review

      • MAO Xi,XU Ding-qiao,YUE Shi-jun,FU Rui-jia,ZHANG Sai,TANG Yu-ping
        Vol. 29, Issue 10, Pages: 951-960(2023) DOI: 10.1007/s11655-022-3591-y
        Abstract：Diabetic kidney disease (DKD) is the primary cause of mortality among diabetic patients. With the increasing prevalence of diabetes, it has become a major concern around the world. The therapeutic effect of clinical use of drugs is far from expected, and therapy choices to slow the progression of DKD remain restricted. Therefore, research on new drugs and treatments for DKD has been a hot topic in the medical field. It has been found that rhein has the potential to target the pathogenesis of DKD and has a wide range of pharmacological effects on DKD, such as anti-nephritis, decreasing blood glucose, controlling blood lipids and renal protection. In recent years, the medical value of rhein in the treatment of diabetes, DKD and renal disease has gradually attracted worldwide attention, especially its potential in the treatment of DKD. Currently, DKD can only be treated with medications from a single symptom and are accompanied by adverse effects, while rhein improves DKD with a multi-pathway and multi-target approach. Therefore, this paper reviews the therapeutic effects of rhein on DKD, and proposes solutions to the limitations of rhein itself, in order to provide valuable references for the clinical application of rhein in DKD and the development of new drugs.  
        Keywords：rhein;diabetic kidney disease;rhein derivatives;toxicity;bioavailability   
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        Published：2023-09-26
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