1.Zuoguiwan Mitigates Oxidative Stress in Rat Model of Hyperthyroidism Due to Kidney-Yin Deficiency via DRD4/NOX4 Pathway
Ling LIN ; Qianming LIANG ; Changsheng DENG ; Li RU ; Zhiyong XU ; Chao LI ; Mingshun SHEN ; Yueming YUAN ; Muzi LI ; Lei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):43-51
ObjectiveTo decipher the mechanism by which Zuoguiwan (ZGW) treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 (DRD4)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone (0.35 mg·kg-1). After successful modeling, the rats were randomized into model, methimazole (positive control, 5 mg·kg-1), low-, medium-, and high-dose (1.85, 3.70, 7.40 g·kg-1, respectively) ZGW, and normal control groups. After 21 days of continuous gavage, the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones [triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH)], renal function indexes [serum creatine (Scr) and blood urea nitrogen (BUN)], energy metabolism markers [cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)], and oxidative stress-related factors [superoxide dismutase (SOD), malondialdehyde (MDA), and NADPH)] were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was employed to analyze the expression of DRD4, NOX4, mitochondrial respiratory chain complex proteins [NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) and cytochrome C oxidase subunit 4 (COX4)], and inflammation-related protein [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), p38 mitogen-activated protein kinase (MAPK)] pathway in the renal tissue. ResultsCompared with the normal group, the model group showed mental malaise, body weight decreases (P<0.01), inflammatory cell infiltration in the renal tissue, a few residual parotid glands in the thyroid, elevations in serum levels of T3, T4, Scr, BUN, cAMP, cAMP/cGMP, MDA, and NADPH (P<0.01), down-regulation in protein levels of TSH, SOD, and DRD4 (P<0.05, P<0.01), and up-regulation in expression of NOX4, p-p38 MAPK/p38 MAPK, and inflammatory factors (P<0.01). Compared with the model group, ZGW increased the body weight (P<0.05, P<0.01), reduced the infiltration of renal interstitial inflammatory cells, restored the thyroid structure and follicle size, lowered the serum levels of T3, T4, Scr, BUN, cAMP, cAMP/cGMP, MDA and NADPH (P<0.05, P<0.01), up-regulated the expression of TSH, SOD and DRD4 (P<0.05, P<0.01), and down-regulated the expression of NOX4, p-p38 MAPK/p38 MAPK, and inflammatory factors (P<0.05, P<0.01). Moreover, high-dose ZGW outperformed methimazole (P<0.05). ConclusionBy activating DRD4, ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway, reduce oxidative stress and inflammatory response, thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.
2.Perioperative immune dynamics and clinical outcomes in patients undergoing on-pump cardiac surgery
Zhiyuan CHENG ; Xinyi LIAO ; Juan WU ; Ping YANG ; Tingting WANG ; Qinjuan WU ; Wentong MENG ; Zongcheng TANG ; Jiayi SUN ; Jia TAN ; Jing LIN ; Dan LUO ; Hao WANG ; Chaonan LIU ; Jiyue XIONG ; Liqin LING ; Jing ZHOU ; Lei DU
Chinese Journal of Blood Transfusion 2026;39(1):31-43
Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10
/L vs preoperative 3.07×10
/L, P<0.001), with significant upregulation of CD11b (7.30×10
/L vs preoperative 3.05×10
/L, P<0.001) and CD54 (7.15×10
/L vs preoperative 2.99×10
/L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10
/L vs preoperative 1.12×10
/L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10
/L vs preoperative 1.12×10
/L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.
3.Diabetic vascular calcification inhibited by soluble epoxide hydrolase gene deletion via regressing NID2-mediated IGF2-ERK1/2 signaling pathway.
Yueting CAI ; Shuiqing HU ; Jingrui LIU ; Jinlan LUO ; Wenhua LI ; Jiaxin TANG ; Siyang LIU ; Ruolan DONG ; Yan YANG ; Ling TU ; Xizhen XU
Chinese Medical Journal 2025;138(20):2657-2668
BACKGROUND:
Epoxyeicosatrienoic acids (EETs), which are metabolites of arachidonic acid catalyzed by cytochrome P450 epoxygenase, are degraded into inactive dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Many studies have revealed that sEH gene deletion exerts protective effects against diabetes. Vascular calcification is a common complication of diabetes, but the potential effects of sEH on diabetic vascular calcification are still unknown.
METHODS:
The level of aortic calcification in wild-type and Ephx2-/- C57BL/6 diabetic mice induced with streptozotocin was evaluated by measuring the aortic calcium content through alizarin red staining, immunohistochemistry staining, and immunofluorescence staining. Mouse vascular smooth muscle cell lines (MOVAS cells) treated with β-glycerol phosphate (0.01 mol/L) plus advanced glycation end products (50 mg/L) were used to investigate the effects of sEH inhibitors or sEH knockdown and EETs on the calcification of vascular smooth muscle cells, which was detected by Western blotting, alizarin red staining, and Von Kossa staining.
RESULTS:
sEH gene deletion significantly inhibited diabetic vascular calcification by increasing levels of EETs in the aortas of mice. EETs (especially 11,12-EET and 14,15-EET) efficiently prevented the osteogenic transdifferentiation of MOVAS cells by decreasing nidogen-2 (NID2) expression. Interestingly, suppressing sEH activity by small interfering ribonucleic acid or specific inhibitors did not block osteogenic transdifferentiation of MOVAS cells induced by β-glycerol phosphate and advanced glycation end products. NID2 overexpression significantly abolished the inhibitory effect of sEH gene deletion on diabetic vascular calcification. Moreover, NID2 overexpression mediated by adeno-associated virus 9 vectors markedly increased insulin-like growth factor 2 (IGF2) and phospho-ERK1/2 expression in MOVAS cells. Overall, sEH gene knockout inhibited diabetic vascular calcification by decreasing aortic NID2 expression and, then, inactivating the downstream IGF2-ERK1/2 signaling pathway.
CONCLUSIONS
sEH gene deletion markedly inhibited diabetic vascular calcification through repressed osteogenic transdifferentiation of vascular smooth muscle cells mediated by increased aortic EET levels, which was associated with decreased NID2 expression and inactivation of the downstream IGF2-ERK1/2 signaling pathway.
Animals
;
Mice
;
Vascular Calcification/metabolism*
;
Mice, Inbred C57BL
;
Epoxide Hydrolases/metabolism*
;
Diabetes Mellitus, Experimental/genetics*
;
Male
;
Gene Deletion
;
MAP Kinase Signaling System/genetics*
;
Cell Line
;
Immunohistochemistry
;
Muscle, Smooth, Vascular/metabolism*
;
Signal Transduction/genetics*
;
Mice, Knockout
4.Spicy food consumption and risk of vascular disease: Evidence from a large-scale Chinese prospective cohort of 0.5 million people.
Dongfang YOU ; Dianjianyi SUN ; Ziyu ZHAO ; Mingyu SONG ; Lulu PAN ; Yaqian WU ; Yingdan TANG ; Mengyi LU ; Fang SHAO ; Sipeng SHEN ; Jianling BAI ; Honggang YI ; Ruyang ZHANG ; Yongyue WEI ; Hongxia MA ; Hongyang XU ; Canqing YU ; Jun LV ; Pei PEI ; Ling YANG ; Yiping CHEN ; Zhengming CHEN ; Hongbing SHEN ; Feng CHEN ; Yang ZHAO ; Liming LI
Chinese Medical Journal 2025;138(14):1696-1704
BACKGROUND:
Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association.
METHODS:
This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results.
RESULTS:
During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037).
CONCLUSIONS
Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans
;
Male
;
Female
;
Prospective Studies
;
Middle Aged
;
Aged
;
Vascular Diseases/etiology*
;
Risk Factors
;
China/epidemiology*
;
Adult
;
Proportional Hazards Models
;
Cerebrovascular Disorders/epidemiology*
;
East Asian People
5.Clinical effects of Yifei Tongluo Decoction combined with azithromycin on patients with childern severe Mycoplasma pneumoniae pneumonia due to Toxic Heat Blocking Lung
Shu-ling WANG ; Yu-qing GUO ; Xiao-yang TANG ; Yan ZHANG ; Yan-rong GUO ; Xiao-song CHEN
Chinese Traditional Patent Medicine 2025;47(4):1162-1167
AIM To investigate the clinical effects of Yifei Tongluo Decoction combined with azithromycin on patients with childern severe Mycoplasma pneumoniae pneumonia due to Toxic Heat Blocking Lung.METHODS One hundred and fifty-six patients were randomly assigned into control group(78 cases)for 7-day administration of azithromycin,and observation group(78 cases)for 7-day administration of both Yifei Tongluo Decoction and azithromycin.The changes in clinical effects,disappearance time of local symptoms,mycoplasmas,pulmonary imaging score,Toxic Heat Blocking Lung score,pulmonary function indices(PEF,VPTEF,MMF,TPTEF),inflammatory factors(sB7-H3,Cgp-39,sICAM-1,CCL5),immune function indices(RBC-C3bR,RBC-ICR,CD3+,CD4+)and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05),along with shorter disappearance time of local symptoms(P<0.05).After the treatment,the two groups displayed decreased mycoplasmas,pulmonary imaging score,Toxic Heat Blocking Lung score,inflammatory factors,RBC-ICR(P<0.05),and increased pulmonary function indices,RBC-C3bR,CD3+,CD4+(P<0.05),especially for the observation group(P<0.05).No obvious difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with childern severe Mycoplasma pneumoniae pneumonia due to Toxic Heat Blocking Lung,Yifei Tongluo Decoction combined with azithromycin can safely and effectively alleviate clinical symptoms,improve pulmonary functions,and reduce body inflammatory responses.
6.Analysis of risk factors on 90-day mortality in critically ill patients undergoing continuous renal replacement therapy
Renli MAO ; Xue TANG ; Zhiwen CHEN ; Yingying YANG ; Bo WANG ; Zhongwei ZHANG ; Ling ZHANG
Chinese Journal of Nephrology 2025;41(7):507-515
Objective:To investigate the risk factors associated with 90-day mortality in critically ill patients receiving continuous renal replacement therapy (CRRT), with a particular focus on the association between hypotension within the first hour of CRRT initiation and 90-day mortality after hospital admission.Methods:This study was a post hoc analysis of a prospective cohort study investigating the impact of colloid versus crystalloid priming solutions on early hemodynamics in critically ill patients undergoing CRRT. The study enrolled intensive care unit patients who received CRRT at West China Hospital of Sichuan University from January 2024 to May 2024. The data were collected including demographic characteristics, laboratory tests, CRRT-related parameters, blood pressure, heart rate, sequential organ failure assessment scores, and vasoactive-inotropic score, etc. The 90-day survival outcome after hospital admission of critically ill patients aged 18-80 years who received continuous veno-venous hemodiafiltration was used as the primary outcome indicator. A Cox proportional hazards model analysis was conducted, and the predictive ability of the model was evaluated along with the test of the proportional hazards assumption. The risk factors associated with the 90-day mortality after hospital admission of critically ill patients receiving CRRT were explored, with a particular focus on whether hypotension occurring within the first hour of CRRT initiation was one of these risk factors.Results:A total of 208 patients were included in this study. Within 90 days after hospital admission, 141 patients (67.8%) died, among whom 102 were male (72.3%) and the median age was 61.0 (50.0, 71.5) years; 67 patients (32.2%) survived, among whom 53 were males (79.1%) and the median age was 56.0 (47.0, 68.0) years. The incidence of hypotension within the first hour of CRRT initiation was significantly higher in the death group than in the survival group [29.8% (42/141) vs. 16.4% (11/67), χ2=4.275, P=0.039]. Moreover, The mortality rate of the group with hypotension within the first hour of CRRT initiation was higher than that of the group without hypotension [79.2% (42/53) vs. 63.9% (99/155), χ2=4.275, P=0.039]. The Kaplan-Meier survival analysis showed that the median survival time of patients without hypotension within the first hour of CRRT initiation [39.0 d (95% CI 23.2-54.8)] was longer than that of patients with hypotension [26.0 d (95% CI 18.9-33.1)], and the 90-day cumulative survival rate after hospital admission of patients without hypotension was significantly higher than that of patients with hypotension (Log-rank test, χ2=5.100, P=0.024). Univariate and multivariate Cox proportional hazards analyses demonstrated that serum albumin ( HR=0.964, 95% CI 0.933-0.997, P=0.030), sequential organ failure assessment score ( HR=1.064, 95% CI 1.012-1.118, P=0.015), and the use of mechanical ventilation ( HR=8.272, 95% CI 1.145-59.743, P=0.036) were significantly associated with 90-day mortality in critically ill patients undergoing CRRT. In contrast, the vasoactive-inotropic score ( HR=1.004, 95% CI 0.999-1.008, P=0.079) and the presence of hypotension within the first hour of CRRT initiation ( HR=1.236, 95% CI 0.833-1.835, P=0.293) were not significantly associated with 90-day mortality in critically ill patients undergoing CRRT. The consistency index of this model was 0.654 (95% CI 0.617-0.691), the area under the receiver operating characteristic curve was 0.724 (95% CI 0.658-0.800), and the calibration curve showed that the predicted values of the model were well fitted to the actual observations, suggesting that the predictive effect of this model was relatively ideal. Conclusions:In critically ill patients undergoing CRRT, the occurrence of hypotension within the first hour of CRRT initiation was not significantly associated with 90-day mortality after hospital admission. Lower serum albumin levels, higher sequential organ failure assessment scores, and the use of mechanical ventilation may be the risk factors for 90-day mortality in this population.
7.Correlation between net ultrafiltration intensity of continuous renal replacement therapy and survival prognosis in critically ill patients with acute kidney injury
Youli TANG ; Lu JIN ; Peiyun LI ; Fang WANG ; Yingying YANG ; Ling ZHANG
Chinese Journal of Nephrology 2025;41(9):651-659
Objective:To explore the correlation between the intensity of net ultrafiltration in continuous renal replacement therapy (CRRT) and the survival prognosis in critically ill patients with acute kidney injury (AKI), and provide evidence-based references for establishing optimal net ultrafiltration target during CRRT.Methods:This was a retrospective observational study. Demographic and clinical data of critically ill AKI patients who received CRRT in the Intensive Care Unit of West China Hospital, Sichuan University from May 2021 to September 2023 were collected. Net ultrafiltration was defined as the hourly fluid clearance volume in the 72 hours prior of CRRT. This variable was converted into a categorical variable, including low net ultrafiltration <1.01 ml·kg -1·h -1, moderate net ultrafiltration 1.01-1.38 ml·kg -1·h -1 and high net ultrafiltration >1.38 ml·kg -1·h -1, and the differences of baseline characteristics and clinical treatment conditions among the three groups were compared. Kaplan-Meier survival curve and log-rank test were used to compare the survival conditions among the three groups in patients at 28 days and 60 days after CRRT. Logistic regression analysis method was used to analyze the related factors of mortality in patients 28 days and 60 days after CRRT. Results:This study included a total of 661 critically ill AKI patients who underwent CRRT for more than 72 hours. The age was 56.00 (43.00, 68.00) years, and 488 patients (73.83%) were males. The net ultrafiltration rate was 1.36 (0.94, 1.89) ml·kg -1·h -1. Among them, 188 patients (28.44%) were in the low net ultrafiltration group, 152 patients (23.00%) were in the medium net ultrafiltration group, and 321 patients (48.56%) were in the high net ultrafiltration group. There were statistically significant differences among the three groups in terms of gender distribution ( χ2=17.81, P<0.001), body mass index ( H=32.37, P<0.001), urine volume 24 hours before admission ( H=9.41, P=0.009), fluid overload ( H=6.02, P=0.049), platelets ( H=13.49, P=0.001), pro-B type natriuretic peptide ( H=14.18, P<0.001), serum creatinine ( H=9.66, P=0.008), lactate ( H=9.83, P=0.007), AKI stage distribution ( χ2=15.51, P=0.004), admission indication ( P<0.001), total CRRT duration ( H=8.45, P=0.015), ultrafiltration ( H=456.10, P<0.001), net ultrafiltration ( H=561.20, P<0.001), and vasoactive-inotropic score at 72 hours of CRRT treatment ( H=10.42, P=0.005). Kaplan-Meier survival analysis showed that there were statistically significant differences in the 28-day (Log-rank test, χ2=10.89, P=0.004) and 60-day (Log-rank test, χ2=8.55, P=0.014) survival rates among the three groups in patients after CRRT. Multivariate logistic regression analysis showed age ( OR=1.03, 95% CI 1.02-1.04, P<0.001), mean arterial pressure ( OR=0.98, 95% CI 0.97-1.00, P=0.011), bilirubin ( OR=3.02,95% CI 1.39-5.59, P=0.006), 72-hour vasoactive-inotropic score ( OR=1.01, 95% CI 1.00-1.02, P=0.004), low net ultrafiltration group (medium net ultrafiltration group as a reference, OR=1.66, 95% CI 1.02-2.72, P=0.042), and high net ultrafiltration group (medium net ultrafiltration group as a reference, OR=1.78, 95% CI 1.14-2.78, P=0.011) were independent correlated factors of 28-day mortality after CRRT. Age ( OR=1.02,95% CI 1.01-1.04, P<0.001), mean arterial pressure ( OR=0.98,95% CI 0.97-1.00, P=0.016), fluid overload ( OR=1.10, 95% CI 1.02-1.19, P=0.012), bilirubin ( OR=4.96,95% CI 1.00-17.80, P=0.013), 72-hour vasoactive-inotropic score ( OR=1.02,95% CI 1.01-1.03, P=0.003), and high net ultrafiltration group (medium net ultrafiltration group as a reference, OR=1.91,95% CI 1.22-3.00, P=0.005) were independent correlated factors of 60-day mortality after CRRT. Conclusions:During the first 72 hours of CRRT, net ultrafiltration > 1.38 ml·kg -1·h -1 and net ultrafiltration < 1.01 ml·kg -1·h -1 are associated with a higher mortality rate at 28 days or 60 days after CRRT. Net ultrafiltration of 1.01-1.38 ml·kg -1·h -1 may be a relatively safe range.
8.Clinical characteristics of juvenile dermatomyositis in anti-nuclear matrix protein 2 antibody-positive patients and risk factors for severity: a national multicenter retrospective study
Huiyuan YANG ; Wanzhen GUAN ; Ling2 YANG ; Haimei LIU ; Xiaoqing3 LI ; Haiguo YU ; Meiping LU ; Jun YANG ; Xiaohui LIU ; Hongxia ZHANG ; Wei ZHANG ; Jihong XIAO ; Xiaozhong LI ; Guomin LI ; Hong CHANG ; Sheng HAO ; Yue DU ; Daliang XU ; Ling WU ; Wenjie ZHENG ; Li LIU ; Xinhui JIANG ; Shaohui ZHU ; Dongmei ZHAO ; Xuemei TANG ; Li SUN
Chinese Journal of Pediatrics 2025;63(12):1299-1305
Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.
9.Safety evaluation of new drugs of traditional Chinese medicine based on human use experience.
Zhong-Qi YANG ; Ya-Qin TANG ; Hui-Min TANG ; Yan LING ; Yan-Ping DU
China Journal of Chinese Materia Medica 2025;50(3):812-816
Because of the unclear active substances, metabolic pathways, and targets of new drugs of traditional Chinese medicine(TCM), non-clinical safety evaluation often fails to accurately locate the target organs and tissue exposed to medicinal toxicity. The human use experience(HUE) contains important safety information of TCM, while the clinical safety data in the past HUE are few and have not been effectively applied. Standardized prospective HUE studies should be carried out to collect the clinical safety data, in which appropriate physical and chemical indicators(including blood, urine, and stool routine), liver biochemical indicators, kidney biochemical indicators, and cardiovascular biochemical indicators should be selected for safety evaluation, and the detection time point and sample size should be rationally designed. Importance should be attached to the observation of symptoms and signs of adverse events/reactions in patients as well as the safety information of special groups such as the elderly, children, and pregnant women. The adverse events of TCM should be observed, judged, and treated according to the theory and the diagnosis and treatment mode of TCM. The clinical safety information about the HUE should be comprehensively collected for new drugs of TCM to make up for the lack of extrapolation of toxicological test results to humans. The unique advantages of clinical origin of new drugs of TCM should be given full play for cross-reference of the results of toxicological research and the conclusions of HUE safety evaluation. In addition, benefit-risk assessment should be conducted based on HUE, and a panoramic safety evaluation system characterized by macro and micro combination and in line with the characteristics of TCM should be established to improve the success rate in the research and development of new drugs of TCM.
Humans
;
Drugs, Chinese Herbal/adverse effects*
;
Medicine, Chinese Traditional/adverse effects*
;
Drug-Related Side Effects and Adverse Reactions
;
Female
10.Expert consensus on evaluation index system construction for new traditional Chinese medicine(TCM) from TCM clinical practice in medical institutions.
Li LIU ; Lei ZHANG ; Wei-An YUAN ; Zhong-Qi YANG ; Jun-Hua ZHANG ; Bao-He WANG ; Si-Yuan HU ; Zu-Guang YE ; Ling HAN ; Yue-Hua ZHOU ; Zi-Feng YANG ; Rui GAO ; Ming YANG ; Ting WANG ; Jie-Lai XIA ; Shi-Shan YU ; Xiao-Hui FAN ; Hua HUA ; Jia HE ; Yin LU ; Zhong WANG ; Jin-Hui DOU ; Geng LI ; Yu DONG ; Hao YU ; Li-Ping QU ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2025;50(12):3474-3482
Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards*
;
Humans
;
Consensus
;
Drugs, Chinese Herbal/therapeutic use*
;
Surveys and Questionnaires

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