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.Astragalin Regulates Autophagy and Apoptosis of Astrocytes in L4-5 Spinal Dorsal Horn of Mouse Inflammatory Pain Model
Weishan ZHANG ; Jiahong LIN ; Can WANG ; Runheng ZHANG ; Junhua YANG ; Jing LIU ; Guoying LI ; Yuxin MA
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):186-196
ObjectiveTo explore the effects of astragalin (AST) on autophagy and apoptosis of astrocytes in the L4-5 dorsal horn of the spinal cord in mice with inflammatory pain induced by complete Freund's adjuvant (CFA). MethodsTwenty-four male C57BL/6 mice, aged six months, were randomly assigned to four groups: control group, saline group, CFA model group, and CFA+AST group, six mice in each group. The inflammatory pain model was established by injection of 10 µL CFA into the right lateral malleolus fossa. The saline group were injected with an equal amount of normal saline at the same site. The inflammatory pain mice in CFA+AST group were further treated with AST (60 mg/kg) intraperitoneally once a day for 21 consecutive days. Multiplex immunofluorescence staining was used to detect the coexpression of autophagy-related factors including ATG 12 and Beclin-1, apoptosis-related factors including Cleaved-Caspase3 and Caspase9, and the astrocyte marker such as GFAP in the L4-5 spinal dorsal horn of the mice in each group. Western blot was used to examine the protein expression levels of autophagy-related proteins(ATG12, Beclin-1) and apoptosis-related proteins(Caspase 3, Caspase 9) in the L4-5 spinal dorsal horn of mice. ResultsImmunofluorescent staining showed that in the L4-5 dorsal horn of the spinal cord, the fluorescence intensity of ATG12 (P<0.000 1) and Beclin-1 (P<0.000 1) was significantly increased, while that of Cleaved-Caspase 3 (P<0.001) and Caspase 9 (P<0.000 1) was decreased in the CFA+AST group when compared to the CFA model group. Furthermore, AST could inhibit the activation of astrocytes. Western blot further confirmed that AST significantly upregulated the expression of ATG12 (P<0.000 1) and Beclin-1 (P<0.000 1) in the L4-5 spinal cord of CFA mice, and downregulated the expression of Caspase 3 (P<0.01) and Caspase 9 (P<0.001). ConclusionsAST promotes autophagy of astrocytes and inhibits their apoptosis in the L4-5 spinal dorsal horn of CFA mice.
3.Prognostic value of serum CD4+ and NK cells for the treatment response in children with aplastic anemia.
Chun-Can WU ; Mei YAN ; Hailiguli NURIDDIN ; Xu-Kai MA ; Yu LIU
Chinese Journal of Contemporary Pediatrics 2025;27(6):690-695
OBJECTIVES:
To evaluate the clinical value of CD4⁺ cell percentage (CD4⁺%) and NK cell percentage (NK%) in predicting treatment outcomes in children with aplastic anemia (AA), providing a reference for precise diagnosis and treatment.
METHODS:
This retrospective study analyzed the clinical data of AA children treated with cyclosporine A at the First Affiliated Hospital of Xinjiang Medical University from January 2019 to April 2024. The study involved 48 AA children as the observation group and 50 children undergoing medical check-ups during the same period as the control group. Lymphocyte subset data were collected from both groups to analyze differences and their relationship with treatment efficacy. Based on hematological responses, the observation group was divided into an effective group of 18 patients (HR group, including complete and partial remission) and an ineffective group of 30 patients (NHR group, including non-remission).
RESULTS:
Univariate analysis showed that NK% in the observation group was significantly lower than that in the control group (P<0.05). The observation group was followed up for 3 months. The HR group had a lower CD4⁺% than the NHR group (P=0.018) and a higher NK% than the NHR group (P=0.029). Multivariate logistic regression analysis indicated that a high CD4⁺% was a risk factor for poor treatment efficacy (OR=1.062), whereas a high NK% was a protective factor (OR=0.820). The area under the curve for the prediction of HR in pediatric AA by combining CD4⁺% and NK% was 0.812.
CONCLUSIONS
A higher CD4⁺% at diagnosis is a predictor of poor treatment response, whereas a higher NK% is associated with better outcomes.
Humans
;
Anemia, Aplastic/blood*
;
Male
;
Female
;
Killer Cells, Natural
;
Child
;
Retrospective Studies
;
Child, Preschool
;
Prognosis
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Adolescent
;
CD4-Positive T-Lymphocytes
;
Infant
4.Strengthening the prevention,treatment and rehabilitation of navy military training injuries:strategies and thinking
Xiaojing MA ; Can LÜ ; Lei SHI ; Wei GU ; Fanfu FANG ; Jintao JÜ
Academic Journal of Naval Medical University 2025;46(1):123-128
The prevention and research of military training injuries(MTI)are crucial for reducing non-battle casualties,ensuring combat readiness,and enhancing the effectiveness of military training.In-depth analyses of the prevention and treatment strategies of MTI and related research can provide concrete guidance for scientific training practices.As a critical component of national defense,the Chinese Navy has experienced rapid development in recent years,and the prevention and research of MTI in naval forces have become a key focus.In recent years,rehabilitation medicine has been increasingly recognized for its importance in areas such as physical capability enhancement and injury prevention.The comprehensive adoption of rehabilitation concepts and the early implementation of rehabilitation measures have been widely accepted.It has important guiding significance for further strengthening the application of rehabilitation in preventing and treating injuries in naval training.This article discusses how to further strengthen the rehabilitation strategies for the prevention and research of MTI in the Navy,so as to provide insights and prospects for this field.
5.Efficacy and safety of nicorandil and ticagrelor de-escalation after percutaneous coronary intervention for elderly patients with acute coronary syndrome
Xiang SHAO ; Ning BIAN ; Hong-Yan WANG ; Hai-Tao TIAN ; Can HUA ; Chao-Lian WU ; Bei-Xing ZHU ; Rui CHEN ; Jun-Xia LI ; Tian-Chang LI ; Lu MA
Medical Journal of Chinese People's Liberation Army 2024;49(1):75-81
Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.
6.Three-dimensional finite element analysis of effects of different bone densities on various intraarticular structures after unicompartmental knee arthroplasty
Mengfei LIU ; Pengcheng MA ; Can YIN ; Kan JIANG ; Xiaochen JU
Chinese Journal of Tissue Engineering Research 2024;28(24):3801-3806
BACKGROUND:Osteoporosis is a common comorbidity in patients with knee osteoarthritis.The impact of osteoporosis on the prognosis of unicompartmental knee arthroplasty is a trending topic of current research. OBJECTIVE:To investigate the effect of different bone densities on the stress value and stress distribution of each structure in the joint after unicompartmental knee arthroplasty using finite element analysis,and to evaluate the correlation between osteoporosis and complications. METHODS:CT and MRI were adopted to obtain the lower limb image data of a volunteer.Geomagic Studio,Ansys workbench,and Mimics were used to establish a finite element model of the knee joint with normal sclerotin condition(T-value≥-1.0).The finite element model of the knee joint with osteopenia(-2.5
7.The expression of System Xc-/ GSH / GPX4 ferroptosis pathway in peripheral blood mononuclear cells of rheumatoid arthritis patients and its effect on the secretion of inflammatory factors
Can Liu ; Wukai Ma ; Changming Chen ; Yang An ; Zong Jiang ; Hai Huang
Acta Universitatis Medicinalis Anhui 2024;59(1):64-70
Objective :
To investigate the expression of genes and proteins in the peripheral blood mononuclear cell ( PBMC) cystine / glutamate antiporter system (System Xc-) / glutathione ( GSH) / glutathione peroxidase 4 ( GPX4) ferroptosis pathway and its influence on inflammatory factors in patients with rheumatoid arthritis ( RA) .
Methods :
30 patients with RA and 30 healthy participants were enrolled.PBMCs were isolated using Ficoll-hypaque density gradient centrifugation.The cells were categorized into the healthy control,RA,ferroptosis inhibitor,ferroptosis in- ducer group.The cell viability was checked using the cell counting kit-8 ( CCK-8) method.Intracellular Fe2 + rela- tive fluorescence intensity and reactive oxygen species (ROS) levels were detected using the FerroOrange and Di- hydroethidium (DHE) fluorescent probes,respectively.Western blot and real-time quantitative PCR (qPCR) de- tected the expression of nuclear factor erythroid 2-related factor 2 ( Nrf2 ) ,solute carrier family 7 member 11 (SLC7A11) ,GPX4 proteins and mRNA.And the flow cytometry quantified the levels of tumor necrosis factor α (TNF-α) ,Interleukin (IL) -1,and IL-6 in the supernatant of each cell group.
Results :
Compared to the healthy control group,the RA group showed a significantly increased Fe2 + concentration and elevated ROS levels,reduced expression of Nrf2,SLC7A11 and GPX4 proteins and mRNA,and increased contents of TNF-α , IL-1 and IL-6 in PBMC supernatant,and the differences were statistically significant.The concentration of Fe2 + and ROS levels in the inhibitor group were lower than those in the RA group,the proteins expressions of Nrf2,SLC7A11 and GPX4 increased,the mRNA expressions of SLC7A11 and GPX4 increased,the content of IL-6 in the PBMC supernatant decreased but the content of TNF-α increased,and the differences were statistically significant.In contrast,the in- ducer group,when compared to the RA group,displayed increased ROS levels,reduced expression of SLC7A11 protein and mRNA and decreased expression of Nrf2 protein,and the contents of TNF-α and IL-1 in the PBMC su- pernatant increased,but the expression of GPX4 protein increased ,and the differences were statistically signifi- cant.The inducer group,compared to the RA group,showed increased cell viability,and the difference was statis-
tically significant (P<0. 000 1) .
Conclusion
The presence of ferroptosis in PBMC in RA patients,inhibiting or inducing PBMC ferroptosis in RA patients,will inhibit or promote the secretion of inflammatory factors.Inhibition of PBMC ferroptosis in RA patients may be helpful in the treatment of RA.
8.Synthesis of ornithine peptidomimetic efflux pump inhibitors and synergistic antibiotic activity against Pseudomonas aeruginosa
Xi ZHU ; Xi-can MA ; Xin-tong ZHANG ; Yi-shuang LIU ; Ning HE ; Yun-ying XIE ; Dan-qing SONG
Acta Pharmaceutica Sinica 2024;59(6):1720-1729
In order to solve the problem of resistance of
9.Study on the influencing factors and risk prediction model for proteinuria in patients with malignant tumors induced by apatinib
Can HUANG ; Shuan WANG ; Jun MA ; Yan GUO ; Lamei QI
China Pharmacy 2024;35(22):2779-2783
OBJECTIVE To study the influencing factors for proteinuria in patients with malignant tumors treated with apatinib, then establish and evaluate a risk prediction model based on it. METHODS A total of 120 patients with malignant tumors treated with apatinib in our hospital from January 2020 to December 2022 were selected as the training set, and the clinical data was collected. Univariate analysis and multivariate Logistic regression analysis were used to identify independent risk factors for proteinuria associated with apatinib and then construct a risk prediction model. The predictive value of the model was evaluated by using the receiver operator characteristic (ROC) curve. A total of 34 patients with malignant tumors treated with apatinib from January to December 2023 in our hospital were selected as the validation set, and their clinical data were obtained to cross-validate the accuracy of the prediction model. RESULTS The incidence of proteinuria in the training set of 120 patients was 26.67%. The proportions of patients with smoking history, combined hypertension, apatinib daily dose of ≥500 mg, and alanine aminotransferase level were significantly higher in proteinuria group than those in non-proteinuria group. At the same time,the neutrophilic granulocyte count was significantly lower than that in non-proteinuria group (P<0.05). Patients with smoking history and combined hypertension were the independent risk factors for apatinib-induced proteinuria (odds ratios were 5.005 and 5.342, respectively; with 95% confidence intervals of 1.806- 13.872 and 1.227-9.602, respectively; P<0.05). The binary Logistic regression model equation for the probability (P) of apatinib- induced proteinuria is expressed as LogitP=1.610XMH+1.233XSH-1.483 (MH for combined hypertension, SH for the smoking history), with a model accuracy of 80.0%. ROC curve analysis demonstrated the area under the ROC curve of 0.771, the maximum Youden’s index of 0.474, and the optimal cut-off value for LogitP was 0.159 9, with a sensitivity of 90.6% and specificity of 56.8%. Cross-validation results indicated an overall prediction accuracy of 88.24% for the 34 patients. CONCLUSIONS Combined hypertension and smoking history are independent risk factors for apatinib-induced proteinuria. The constructed risk prediction model has moderate predictive value and can be used to predict the risk of proteinuria in patients with malignant tumors induced by apatinib.
10.Four cases of occupational heatstroke among sanitation workers working in high temperature weather
Can MA ; Xin ZUO ; Ran SUN ; Yongmei ZHAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(8):621-623
Through the report of 4 cases of occupational heatstroke among sanitation workers working in high-temperature weather, this study analyzes the risk of occupational heatstroke among workers in the environmental sanitation industry working in high-temperature weather, and provides scientific suggestions for standardizing occupational health management, safeguarding the health rights and interests of workers, and preventing the occurrence of occupational heatstroke in summer. Through case analysis, we aim to raise high awareness of the occupational health of sanitation workers in the whole society, in order to provide a scientific and healthy working environment for sanitation workers and promote their physical and mental health.


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