1.Exploration on Surrogate Outcome Measures in Clinical Trials of Traditional Chinese Medicine for Diabetic Kidney Disease
Can CAO ; Weiwei SUN ; Tong MA ; Yaoxian WANG
Journal of Traditional Chinese Medicine 2025;66(8):790-794
Traditional Chinese medicine (TCM) has unique advantages in alleviating the symptoms of diabetic kidney disease (DKD) and slowing its progression. However, traditional clinical trials often use the occurrence of end-stage renal disease as the end point, requiring long-term follow-up, which increases trial complexity and costs, thereby limiting the feasibility of TCM clinical studies. This paper suggested that in clinical trials of TCM for DKD, both the estimated glomerular filtration rate (eGFR) change rate (≥30%) and eGFR slope can serve as potential surrogate outcome measures. If the intervention course is short (<1 year), the eGFR change rate (≥30%) is recommended as a surrogate outcome measure, whereas in long-term interventional studies (≥1 year), the eGFR slope may be more appropriate. Furthermore, based on biochemical indicators such as eGFR slope and urinary albumin-to-creatinine ratio (UACR) change rate, integrating TCM symptom evaluation, TCM syndrome evaluation, and quality of life scales can help develop internationally recognized patient-reported outcome measures (PROMs) for TCM clinical trials, which will be a key step in enhancing the evaluation system for the effectiveness of TCM in treating DKD.
2.Comparison of anti-inflammatory, antibacterial and analgesic activities of formulated granules versus traditional decoction of Yinqiao Powder.
Zhuolin GUO ; Zhiheng ZHANG ; Xindeng GUO ; Weiwei YANG ; Zhiqing LIANG ; Jinying OU ; Huihui CAO ; Zibin LU ; Linzhong YU ; Junshan LIU
Journal of Southern Medical University 2025;45(5):1003-1012
OBJECTIVES:
To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction.
METHODS:
We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg.
RESULTS:
Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models.
CONCLUSIONS
The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals
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Mice
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Drugs, Chinese Herbal/pharmacology*
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Anti-Inflammatory Agents/pharmacology*
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Analgesics/pharmacology*
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RAW 264.7 Cells
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Zebrafish
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Anti-Bacterial Agents/pharmacology*
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Powders
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Tumor Necrosis Factor-alpha/metabolism*
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Acute Lung Injury/drug therapy*
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Interleukin-6/metabolism*
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Lipopolysaccharides
3.Study on the mechanism of Hongteng Decoction in inhibiting adenomyosis fibrosis from Hippo/YAP pathway
Weiwei ZENG ; Xinmin CHEN ; Lijuan LU ; Shenghui HUANG ; Yang CAO ; Tingting ZHANG
International Journal of Traditional Chinese Medicine 2024;46(7):867-873
Objective:To investigate the mechanism of Hongteng Decoction in inhibiting the adenomyosis (ADS) fibrosis by observing the effects on the key proteins of epithelial mesenchymal transformation (EMT), fibroblast-to-myofibroblast transformation (FMT) and Hippo pathway in uterine tissue of mice with ADS.Methods:ICR mice were divided into blank group, model group, Hongteng Decoction group, and verteporfin group according to random number table method, with 8 mice in each group. The day of birth of the mice was day 0, and from day 1, mice in model group, Hongteng Decoction group and verteporfin group were given 1 mg/kg tamoxifen solvent for gavage for 5 days. On the 42nd day after molding, HE staining verified that the molding was successful. Starting from the 43rd day, mice in the Hongteng Decoction group were given TCM solution of Hongteng Decoction 16.5 g/kg everyday, and intraperitoneally injected with 0.9%NaCl solution (100 μl/10 g) every 3 days. Mice in the verteporfin group were intraperitoneally injected with verteporfin solution of 100 mg/kg every 3 days, and intragastric with water of 100 μl/10 g everyday. Mice in blank group and model group were intragastric with constant volume of water daily and intraperitoneally injected with 0.9%NaCl solution every 3 days. The drugs were administered for 60 days. The fibrosis degree of mice in each group was evaluated by Masson staining. The expressions of E-cadherin, Vimentin, α-SMA, YAP and Snail in uterine tissue of mice in each group were detected by immunohistochemistry and Western blot.Results:Compared with the model group, the Masson staining expression in Hongteng Decoction group significantly decreased ( P<0.05). Immunohistochemical and Western blot analysis showed that the expression of E-cadherin in uterine tissue of mice in Hongteng Decoction group significantly increased ( P<0.05), while the expressions of Vimentin, α-SMA and YAP significantly decreased ( P<0.01, P<0.05) compared with the model group. Conclusion:Hongteng Decoction can inhibit the occurrence of EMT and FMT in ADS, thereby inhibiting fibrosis, and its mechanism is related to the regulation of Hipoo/YAP pathway.
4.Inhibition of prohibitin 2 enhances the sensitivity of non-small cell lung cancer cell line A549 to erlotinib
Jing ZHANG ; Zigeng YANG ; Wenqin CAI ; Weiwei CAO ; Hongmei WEI ; Xixi XUE ; Bin WU
Basic & Clinical Medicine 2024;44(3):325-332
Objective To explore the effects of prohibitin 2(PHB2)on sensitivity of non-small cell lung cancer cell line A549 to erlotinib(Erl)and its potential mechanisms.Methods RACK1-specific small interfering RNA was transfected in A549 cells for knocking-down of PHB2.The effects of PHB2 inhibition on cell proliferation and apop-tosis induced by Erl were observed.The colocalization of microtuble-associated protein light chain 3 alpha(LC3)and mitochondria was visualized by MitoTracker staining and green fluorescent protein-microtuble-associated protein light chain 3 alpha(GFP-LC3)transfection.Cell proliferation was detected by 5-ethynyl-2′-deoxyuridine(EdU)staining.Cell colony formation was evaluated by colony forming assay.Apoptotic index of A549 cells was evaluated by TUNEL.Western blot was used to measure the expressions of PHB2 and LC3Ⅱ.Mitochondrial transmembrane potential,cytochrome c and respiratory chain complexⅠ/Ⅱ/Ⅴactivity were analyzed by the commercially availa-ble kits.Results Compared with the siPHB2 and siCtrl+Erl group,the EdU-positive A549 cells and the number of cell colonies decreased significantly(P<0.05),while the TUNEL-positive A549 cells increased significantly(P<0.05)in the siPHB2+Erl group.In addition,compared with the siPHB2 and siCtrl+Erl group,mitochondrial transmembrane potential and respiratory chain complexⅠ/Ⅱ/Ⅴactivity decreased significantly(all P<0.05)and the levels of cytochrome c increased in mitochondrial fractions(P<0.05)and decreased in cytosolic fractions(P<0.05)in the siPHB2+Erl group.Conclusions PHB2 inhibition significantly improves sensitivity of A549 cells to Erl,which may be explained by inhibition of PHB2-mediated mitochondrial autophagy.
5.Application study of upper abdominal moxibustion combined with bedside ultrasound monitoring of gastric residual volume in pre-pyloric feeding of stroke patients
Bin XUE ; Meihua GAI ; Liming CAO ; Ruizhong YE ; Yanmei YU ; Yanping FU ; Weiwei ZHANG
China Modern Doctor 2024;62(32):7-10,15
Objective To explore the application effect of upper abdominal moxibustion combined with bedside ultrasound monitoring of gastric residual volume(GRV)in pre-pyloric feeding in stroke patients.Methods Eighty stroke patients admitted to the Department of Rehabilitation Medicine of Zhejiang Provincial People's Hospital from January 1,to December 31,2023 were selected as the study subjects.They were divided into control group(n=38)and observation group(n=42)using a random number table method.All patients had a nasogastric tube for pre-pyloric feeding.The control group used the traditional syringe aspiration method to monitor GRV,while the observation group used upper abdominal moxibustion combined with bedside ultrasound to monitor GRV.The study compared the differences between two groups in terms of enteral nutrition intolerance,feeding complications,enteral nutrition compliance rate within 7 days of admission,time to achieve enteral nutrition compliance,and changes in hemoglobin(Hb),serum prealbumin,serum albumin(ALB),and serum transferrin before and after 14 days of feeding.Results The incidence rates of vomiting,abdominal distention,intra-abdominal hypertension,reflux,and aspiration pneumonia in observation group were lower than those in control group(P<0.05).The rate of achieving intestinal nutrition standard within 7 days of hospitalization was significantly higher in observation group compared to the control group.The time to achieve intestinal nutrition standard was shorter in observation group compared to control group.Furthermore,after 14 days of feeding,the levels of Hb and ALB in observation group were higher than those in control group,and the differences were statistically significant(P<0.05).Conclusion Upper abdominal moxibustion combined with bedside ultrasonic monitoring of GRV can significantly reduce intestinal nutrition intolerance and feeding complications during pre-pyloric feeding in stroke patients,shorten the time to achieve nutritional benchmarks,and improve nutritional status.
6.Exploratory road of liver xenotransplantation:from scientific research to clinical application
Xiao LI ; Weiwei CAO ; Liang YU
Organ Transplantation 2024;15(5):758-763
With the advancement of surgical technologies and the improvement of perioperative management,the survival rates of organ transplant recipients and grafts have been significantly elevated.Shortage of donor organs has become the main obstacle to further development of organ transplantation.Recently,kidney and heart xenotransplantation with genetically modified pigs as donors have entered clinical trials and achieved favorable results.Xenotransplantation has repeatedly become a hot spot in biomedical research.Compared with heart and kidney,the survival time of liver grafts from genetically modified pigs in non-human primates is shorter.Besides,experimental results are dramatically different.Hence,it is not eligible for clinical trials.Consequently,recent research progress in xenotransplantation was reviewed from surgical pattern selection,coagulation dysfunction and acute vascular rejection,advances in liver xenotransplantation were summarized,and the main problems hindering xenotransplantation from entering clinical trials and potential solutions were illustrated,aiming to provide reference for xenotransplantation from scientific research to clinical application.
7.Endovascular therapy combined with laparoscopic surgery for acute mesentery artery occlusion
Keqiang ZHAO ; Peng ZHANG ; Junlai ZHAO ; Tong ZHANG ; Zhanjiang CAO ; Yu YANG ; Chao JIANG ; Rongrong ZHU ; Weiwei WU
Chinese Journal of General Surgery 2024;39(3):192-196
Objective:To explore the efficacy and safety of endovascular intervention combined with preoperative laparoscopic exploration in the treatment of patients with acute mesenteric artery ischemia.Methods:This was a prospective cohort study (NCT04686981). The study enrolled 31 patients with acute mesenteric artery ischemia from Oct 1, 2020 to Oct 1, 2022. Among them, 26 patients (84%) were male, with a mean age of (67±13) years and a mean time to onset of (21±8) hours. All patients underwent laparoscopic exploration in the hybrid operating room. If the presence of intestinal necrosis or suspected necrosis was clearly determined, the patient would undergo open surgery (mesenteric artery embolization, intestinal resection and intestinal double stoma) as the treatment by gastrointestinal surgeon. If intestinal necrosis or suspected necrosis was not found by laparoscopy, the patient would undergo endovascular intervention by vascular surgeon. The primary observational endpoints of this study were the proportion of patients who were not dependent on total parenteral nutrition and all-cause mortality within 30 days after operation. The secondary observational endpoints were the rate of mesenteric vascular patency within 30 days and the proportion of interventions that were converted to open surgery.Results:Six patients underwent open surgery and 25 patients underwent endovascular intervention, including 13 cases of thrombus reduction alone, 3 cases of stent implantation during the same period after reduction, and 9 cases of stent implantation alone. Twenty-four patients (77%) were completely weaned from the TPN within 30 days after the procedure, and all-cause mortality was observed in 3 cases (9.7%). The patency rate of the mesenteric artery within 30 days after the procedure was 82.1%. The rate of conversion to open surgery after intervention was 16%.Conclusions:Endovascular intervention combined with preoperative laparoscopic exploration can clarify intestinal ischemia in acute mesenteric patients as early as possible, and individualized treatment strategies for each patient by multidisciplinary care team can potentially improve the prognosis of such patients.
8.Influencing factors for unplanned re-hospitalization in adult renal transplant recipients after surgery
Weiwei CAO ; Minghuan ZHONG ; Zhou SUN ; Guofu LIANG ; Fu YAN ; Chao LIU ; Li MA ; Kejing ZHU ; Yanyan XU ; Bei DING ; Yulin NIU
Journal of Clinical Medicine in Practice 2024;28(18):117-122
Objective To investigate the influencing factors of unplanned rehospitalization within one year after surgery among adult renal transplant recipients. Methods The clinical data of 299 recipients who underwent renal transplant surgery in the Department of Organ Transplantation of the Affiliated Hospital of Guizhou Medical University from January 2020 to December 2022 were retrospectively analyzed. The recipients were divided into unplanned rehospitalization group and non-rehospitalization group based on whether they experienced unplanned rehospitalization within one year after surgery. Univariate analysis and binary Logistic regression analysis were performed to explore the influencing factors of unplanned rehospitalization within one year after renal transplantation. Results Among the 299 recipients, 102 experienced unplanned rehospitalization, with an incidence rate of 34.11%. Univariate analysis revealedstatistically significant differences were noted between the two groups in terms of gender, occupational status, preoperative underlying disease, rejection reactions, nosocomial infections, immunosuppressive medication regimens, serum creatinine, cystatin C, serum phosphorus, serum potassium, and initial hospitalization duration (
9.Long noncoding RNA MRAK088388 is involved in the progression of childhood allergic asthma via miR-30a/ATG5 axis
Weiwei SHE ; Tianshou SUN ; Chengfeng LONG ; Meiyu CHEN ; Xu CHEN ; Qinxue LIAO ; Mingdong WANG ; Wei CAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(5):764-772
【Objective】 To investigate the association between the long-stranded non-coding ribonucleic acid (lncRNA) MRAK088388 and allergic asthma in children. 【Methods】 A total of 15 healthy children and 15 children with asthma were monitored for disease progression over a 2-year period. Blood samples were collected from patients during the chronic phase of the disease for lncRNA/mRNA expression microarray analysis. Competing endogenous RNA networks (MRAK088388/miR-30a/ATG5) were identified by bioinformatics analysis. In vitro cultured bronchial epithelial (16HBE) cells were used to quantify gene and associated protein expression levels by real-time fluorescent quantitative polymerase chain reaction (qPCR) and protein blotting, respectively. Cell Counting Kit-8 and transwell assays were used to assess the proliferation and migration of 16HBE cells and verify the effects of MRAK088388, miR-30a and ATG5 on asthma. 【Results】 Six lncRNA-miRNA-mRNAs were identified by correlation analysis. By qRT-PCR analysis, MRAK088388/miR-30a/ATG5 was selected to construct the ceRNA network in this study. mRAK088388 and ATG5 expressions were high in the peripheral blood of children with asthma, while the expression of miR-30a was low (P<0.05). The expression level of E-cadherin was significantly higher in 16HBE cells after si-MRAK088388+TGF-β1 group, while the expression levels of Vimentin and α-SMA were significantly lower (P<0.05), indicating that knockdown of MRAK088388 inhibited the epithelial mesenchymal transition in 16HBE cells. Compared with si-NC+ TGF-β1 group, the cell morphology of si-MRAK088388+TGF-β1 group was similar to that of the control group, indicating that MRAK088388 knockdown attenuated TGF-β1-induced cell morphological changes; in addition, MRAK088388 knockdown inhibited TGF-β1-induced proliferation and migration of 16HBE cells. MRAK088388 was confirmed by qPCR and protein blotting to promote the progression of childhood asthma by targeting the miR-30a/ATG5 axis. 【Conclusion】 Childhood asthma is associated with the MRAK088388/miR-30a/ATG5 axis, and MRAK088388 is involved in the process of childhood allergic asthma by negatively regulating miR-30a expression and regulating elevated ATG5 expression levels to affect bronchial epithelial cell mesenchymal transition, proliferation, and migration.


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