1.Development of a RP scoring system for predicting perioperative outcomes in robot-assisted partial nephrectomy by optimizing RENAL and MAP scores
Liang ZHENG ; Bohong CHEN ; Haoxiang HUANG ; Cong FENG ; Jin ZENG ; Wei CHEN ; Dapeng WU
Journal of Modern Urology 2025;30(1):53-58
[Objective] To establish a new scoring system to predict the perioperative outcomes (operation time, intraoperative blood loss, and trifecta achievement) in patients undergoing robot-assisted partial nephrectomy (RAPN) by integrating the RENAL and Mayo adhesive probability (MAP) scores. [Methods] Clinical data of 178 patients with renal cell carcinoma who underwent RAPN performed by the same surgeon in our hospital during Jan.2015 and Jan.2022 were retrospectively analyzed.The RENAL and MAP scores of all patients were calculated.Linear regression and logistic regression were used to evaluate the associations between the components of the RENAL and MAP scores (a total of 6 variables) and perioperative outcomes.The factors with significant associations were then included into logistic regression analysis to identify independent predictors for constructing an assessment system for perioperative outcomes, and the receiver operating characteristic (ROC) curve was plotted to calculate the area under the curve (AUC) to predict its efficacy. [Results] Multivariate linear regression analysis showed that tumor size (β=6.14, 95%CI: 1.93—10.34, P=0.004), exophytic rate (β=10.60, 95%CI: 3.44—17.76, P=0.004), and perinephric fat thickness (β=16.48, 95%CI: 8.52—24.45, P<0.001) were significantly associated with operation time.Tumor size (β=10.55 95%CI: 5.60—15.49, P<0.001) was associated with both intraoperative blood loss and trifecta achievement (OR=1.73, 95%CI: 1.26—2.36, P=0.001). Multivariate logistic regression analysis of these 3 factors identified tumor size (OR=9.07, 95% CI: 1.18—69.45, P=0.03) and perinephric fat thickness (OR=2.28, 95%CI: 1.86—6.04, P=0.01) as independent predictors of perioperative outcomes.Based on these findings, the tumor size and perinephric fat thickness (RP) scoring was constructed, which demonstrated better predictive ability than RENAL score or MAP score alone (RP vs.RENAL vs.MAP: 0.766 vs.0.548 vs.0.684). [Conclusion] The RP score includes fewer variables than the RENAL and MAP scores but outperforms them.
2.Inverse distance weight interpolation method for missing data of PM2.5 spatiotemporal series
Yurou LIANG ; Hongling WU ; Weipeng WANG ; Feng CHENG ; Ping DUAN
Journal of Environmental and Occupational Medicine 2025;42(2):171-178
Background Fine particulate matter (PM2.5) monitoring stations may generate missing data for a certain period of time due to various factors. This data loss will adversely affect air quality assessment and pollution control decision-making. Objective To propose an inverse distance weighted (IDW) spatiotemporal interpolation method based on particle swarm optimization (PSO) to interpolate and fill missing PM2.5 spatiotemporal sequence data and increase interpolation accuracy. Methods An interpolation experiment was designed into two parts. The first part used hourly PM2.5 observational data from four moments on January 1, 2017 in the Yangtze River Delta region. The second part employed daily PM2.5 observational data from the first 10 d of January 2017 in the Beijing-Tianjin-Hebei region. Interpolation accuracy was evaluated using four metrics: root mean square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE), and mean relative error (MRE). Results IDW spatiotemporal interpolation method optimized with PSO significantly improved the accuracy of filling missing PM2.5 spatiotemporal sequence data. In the hourly-scale experiment conducted in the Yangtze River Delta region, compared to a distance index of 2, the accuracy metrics RMSE, MAE, MAPE, and MRE generated by the proposed method improved on average by 0.17 μg·m−3, 0.27 μg·m−3, 0.17%, and 0.01%, respectively. The PM2.5 spatial field maps generated for four moments based on this method clearly illustrated the spatiotemporal distribution characteristics of hourly PM2.5 concentrations in the Yangtze River Delta region. In the daily-scale experiment conducted in the Beijing-Tianjin-Hebei region, the PSO-optimized distance index outperformed the traditional method, with interpolation accuracy improvements of approximately 0.215 μg·m−3, 0.283 μg·m−3, 0.174%, and 0.014%, respectively. Furthermore, the seasonal PM2.5 spatial field maps generated by this method revealed the spatiotemporal distribution characteristics of PM2.5 concentrations in the Beijing-Tianjin-Hebei region across different seasons, further validating the effectiveness and applicability of this method. Conclusion The IDW spatiotemporal interpolation method optimized with PSO is highly accurate and reliable for interpolating the missing data in the Yangtze River Delta region and the Beijing-Tianjin-Hebei region, providing valuable insights for air pollution control and public health protection.
3.Setup Error and Its Influencing Factors in Radiotherapy for Spinal Metastasis
Wenhua QIN ; Xin FENG ; Zengzhou WANG ; Shangnan CHU ; Hong WANG ; Shiyu WU ; Cheng CHEN ; Fukui HUAN ; Bin LIANG ; Tao ZHANG
Cancer Research on Prevention and Treatment 2025;52(5):400-404
Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.
4.Aerobic Exercise Improves Cognitive Function of Aging Mice by Regulating Intestinal Flora-metabolite Network
An-Feng WANG ; Tong WU ; Hu ZHANG ; Ji-Ling LIANG ; Ning CHEN
Progress in Biochemistry and Biophysics 2025;52(6):1484-1498
ObjectiveThis study aimed to explore the effects of aerobic exercise on cognitive function in aging mice and to elucidate the underlying molecular mechanisms by which aerobic exercise ameliorates cognitive decline through the regulation of gut microbiota-metabolite network. By providing novel insights into the interplay between exercise, gut microbiota, and cognitive health, this research seeks to offer a robust theoretical foundation for developing anti-aging strategies and personalized exercise interventions targeting aging-related cognitive dysfunction. MethodsUsing naturally aged C57BL/6 mice as the experimental model, this study employed a multi-omics approach combining 16S rRNA sequencing and wide-targeted metabolomics analysis. A total of 18 mice were divided into 3 groups: young control (YC, 4-month-old), old control (OC, 21-month-old), and old+exercise (OE, 21-month-old with 12 weeks of moderate-intensity treadmill training) groups. Behavioral assessments, including the Morris water maze (MWM) test, were conducted to evaluate cognitive function. Histopathological examinations of brain tissue sections provided morphological evidence of neuronal changes. Fecal samples were collected for gut microbiota and metabolite profiling via 16S rRNA sequencing and ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS). Data were analyzed using a combination of statistical and bioinformatics tools to identify differentially abundant microbial taxa and metabolites and to construct interaction networks between them. ResultsBehavioral tests revealed that 12 weeks of aerobic exercise significantly improved spatial learning and memory capacity of aged mice, as evidenced by reduced escape latency and increased target area exploration and platform crossings in the MWM. Histopathological analysis demonstrated that exercise mitigated aging-related neuronal damage in the hippocampus, enhancing neuronal density and morphology. 16S rRNA sequencing indicated that exercise increased gut microbiota α‑diversity and enriched beneficial bacterial genera, including Bifidobacterium, Parabacteroides, and Rikenella. Metabolomics analysis identified 32 differentially regulated metabolites between OC and OE groups, with 94 up-regulated and 30 down-regulated in the OE group when compared with OC group. These metabolites were primarily involved in energy metabolism reprogramming (e.g., L-homocitrulline), antioxidant defense (e.g., L-carnosine), neuroprotection (e.g., lithocholic acid), and DNA repair (e.g., ADP-ribose). Network analysis further revealed strong positive correlations between specific bacteria and metabolites, such as Parabacteroides with ADP-ribose and Bifidobacterium with lithocholic acid, suggesting potential neuroprotective pathways mediated by the gut microbiota-metabolite axis. ConclusionThis study provides comprehensive evidence that aerobic exercise elicits cognitive benefits in aging mice by modulating the gut microbiota-metabolite network. These findings highlight three key mechanisms: (1) the proliferation of beneficial gut bacteria enhances metabolic reprogramming to boost DNA repair pathways; (2) elevated neuroinflammation-inhibiting factors reduce neurodegenerative changes; and (3) enhanced antioxidant defenses maintain neuronal homeostasis. These results underscore the critical role of the “microbiota-metabolite-brain” axis in mediating the cognitive benefits of aerobic exercise. This study not only advances our understanding of the gut-brain axis in aging but also offers a scientific basis for developing personalized exercise and probiotic-based interventions targeting aging-related cognitive decline. Future research should further validate these mechanisms in non-human primates and human clinical trials to establish the translational potential of exercise-induced gut microbiota-metabolite modulation for combating neurodegenerative diseases.
5.Untargeted Metabolomics Analysis of Demyelination in the Brain of Balb/c Mice Infected by Angiostrongylus cantonensis
Zhen NIU ; Xiaojie WU ; Liang YANG ; Zhixuan MA ; Junxiong YANG ; Ying FENG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):293-300
ObjectiveTo investigate the demyelination induced by Angiostrongylus cantonensis (AC) infection in the brain of Balb/c mice and analyze the untargeted metabolomic changes in the corpus callosum, aiming to elucidate the underlying mechanisms. MethodsBalb/c mice were randomly assigned to a control group (n=6) and an infection group (n=6). The infection group was orally administered 30 third-stage larvae of AC, while the control group received an equal volume of saline. Body weight, visual function, and behavioral scores were measured on post-infection 3, 6, 9, 12, 15, 18, and 21 days to assess neurological alterations. After 21 days, brain tissues were harvested for immunofluorescence staining, hematoxylin-eosin (HE) staining, and transmission electron microscopy to examine morphological changes in brain myelin and retina. Metabolomics analysis was performed, and differential metabolites were identified using volcano plots and heatmaps. The distribution of fold changes and bar charts were used to profile the key metabolites. These differential metabolites were then subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and regulatory network analysis. ResultsOn the 9th day after AC infection, Balb/c mice showed a decline in neurological behavioral scores (P<0.05). By day 15, visual scores decreased (P<0.05), and by day 21, significant weight loss (P<0.001) and mortality were observed. Concurrently, transmission electron microscopy and immunofluorescence staining revealed significant myelin damage in the corpus callosum and a marked reduction in oligodendrocytes (P<0.001). HE staining showed severe retinal ganglion cell damage. Metabolomic analysis revealed that glycerophospholipids were the most abundant differential metabolites, with steroids and sphingolipids being relatively less abundant. Cholesteryl ester CE (20:2) was significantly upregulated (P<0.001), while phosphatidylmethanol (18:0_18:1) was significantly downregulated (P<0.01). KEGG enrichment and regulatory network analyses demonstrated that the differential metabolites were mainly enriched in metabolic pathways like steroid biosynthesis, bile secretion, and cholesterol metabolism, and were involved in key metabolic pathways such as sphingolipid metabolism, neural signal regulation, and glycerophospholipid metabolism. ConclusionsAC infection affects the metabolic state of mice via multiple pathways, modifying the levels of metabolites crucial for myelination and myelin stability. Demyelination may be closely linked to the disruption of these key metabolic pathways, particularly the dysregulation of cholesterol and sphingolipid metabolism, potentially playing a central role in demyelination onset. Furthermore, alterations in phospholipid metabolism and abnormal nerve signaling regulation may exacerbate myelin damage.
7.A national questionnaire survey on endoscopic treatment for gastroesophageal varices in portal hypertension in China
Xing WANG ; Bing HU ; Yiling LI ; Zhijie FENG ; Yanjing GAO ; Zhining FAN ; Feng JI ; Bingrong LIU ; Jinhai WANG ; Wenhui ZHANG ; Tong DANG ; Hong XU ; Derun KONG ; Lili YUAN ; Liangbi XU ; Shengjuan HU ; Liangzhi WEN ; Ping YAO ; Yunxiao LIANG ; Xiaodong ZHOU ; Huiling XIANG ; Xiaowei LIU ; Xiaoquan HUANG ; Yinglei MIAO ; Xiaoliang ZHU ; De'an TIAN ; Feihu BAI ; Jitao SONG ; Ligang CHEN ; Yingcai MA ; Yifei HUANG ; Bin WU ; Xiaolong QI
Chinese Journal of Digestive Endoscopy 2024;41(1):43-51
Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.
8.Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair.
Han XU ; Si-Cong XU ; Li-Yan LI ; Yu-Huang WU ; Yin-Feng TAN ; Long CHEN ; Pei LIU ; Chang-Fu LIANG ; Xiao-Ning HE ; Yong-Hui LI
Chinese journal of integrative medicine 2024;30(3):243-250
OBJECTIVE:
To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism.
METHODS:
Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis.
RESULTS:
DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01).
CONCLUSIONS
DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice
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Male
;
Animals
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Proto-Oncogene Proteins c-akt/metabolism*
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Lipopolysaccharides
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Interleukin-1beta/metabolism*
;
Vascular Endothelial Growth Factor A/metabolism*
;
Tumor Necrosis Factor-alpha/metabolism*
;
Claudin-5/metabolism*
;
Acute Lung Injury/chemically induced*
;
Lung/pathology*
;
Interleukin-6/metabolism*
;
Drugs, Chinese Herbal
9.Exploring Efficacy and Mechanism of Saffron Floral Bio-residues for Treatment of Hyperuricemia Combined with Gouty Arthritis Based on Compound Compatibility Environment
Jiping WU ; Qingqing LI ; Lan WANG ; Xiaojie YIN ; Shuyi FENG ; Zhihao WANG ; Rixin LIANG ; Bin YANG ; Zhiyong LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):129-140
ObjectiveTo investigate the efficacy and mechanism of saffron floral bio-residues(SFB) in the treatment of hyperuricemia(HUA) combined with gouty arthritis(GA) in a compound compatibility setting. MethodScreening candidate control Chinese medicines for compound and SFB based on network target distance calculation and data analysis. After adaptive feeding of 80 SD rats for 7 days, 10 rats were randomly selected as the blank group, while the remaining 70 rats were intraperitoneally injected with 3% potassium oxonate and orally administered with 1% adenine for 14 consecutive days. On the 13th day, rats were injected with 2.5% sodium urate solution into the right ankle joint cavity to induce swelling of the joint capsule on the opposite side, inducing a HUA combined with GA model. At the same time, the modeling rats were randomly divided into 7 groups, including the model group, benzbromarone group(positive drug, 0.02 g·kg-1), Tongfengshu tablets group(9 g·kg-1), Tongfengshu granules group(9 g·kg-1), SFB granules group(3.6 g·kg-1), Plantaginis Semen granules group(3.6 g·kg-1), and new formula group(SFB replacing Plantaginis Semen in Tongfengshu granules, 9 g·kg-1), with 10 rats in each group. Each treatment group was orally administered with the corresponding drugs according to body weight, while the control and model groups were given equal volume of distilled water by gavage once a day for 14 consecutive days. After 14 days of synchronous administration and modeling, changes in gait, ankle joint swelling and mechanical pain threshold in rats were observed, and serum uric acid, creatinine, urea nitrogen and xanthine oxidase(XOD) were measured. Enzyme-linked immunosorbent assay(ELSIA) was used to detect the levels of tumor necrosis factor(TNF)-α, interleukin(IL)-1β and IL-6 in rat serum, hematoxylin-eosin(HE) staining was used to observe the pathological changes in the liver, kidney and ankle joints of rats, Western blot was used to detect the expression levels of uric acid transporter 1(URAT1), glucose transporter 9 (GLUT9), organic anion transporter 1(OAT1), adenosine triphosphate(ATP) binding cassette transporter G2(ABCG2), and liver XOD proteins. ResultThrough network pharmacology analysis, Plantaginis Semen was selected as a candidate control herb, and Tongfengshu tablets was used as a compound compatibility environment to explore the efficacy of SFB in reducing blood uric acid levels and treating GA. Animal experiments showed that compared with the blank group, the gait score and joint swelling degree of the model group were significantly increased, and the mechanical pain threshold was significantly decreased(P<0.01). Compared with the model group, the gait score, joint swelling degree and mechanical pain threshold of rats in each medication group were improved to varying degrees. Biochemical indicators showed that compared with the blank group, the serum uric acid, creatinine, urea nitrogen and XOD levels of the model group were significantly increased(P<0.01). Compared with the model group, the serum uric acid and XOD levels of rats in each treatment group were significantly decreased(P<0.01). ELISA results showed that compared with the blank group, the levels of serum TNF-α, IL-1β and IL-6 in the model group were significantly increased(P<0.01). Compared with the model group, the levels of TNF-α, IL-1β and IL-6 in the benzbromarone group, Tongfengshu tablets group, Tongfengshu granules group and new formula group were significantly reduced(P<0.05,P<0.01). Western blot results showed that compared with the blank group, the expression levels of URAT1 and GLUT9 proteins in renal tissue and OXD protein in liver tissue of the model group were significantly increased, while the expression levels of renal OAT1 and ABCG2 were significantly decreased(P<0.01). Compared with the model group, the expression levels of renal URAT1 and GLUT9 in the SFB granules group, Tongfengshu granules group and new formula group were significantly decreased, while the expression levels of renal OAT1 and ABCG2 were significantly increased, and the expression of XOD protein in liver tissue was significantly decreased(P<0.05, P<0.01). Pathological analysis showed that focal infiltration of neutrophils, cell necrosis and nuclear fragmentation were observed in the liver tissue of the model group, sodium urate deposition crystals and tubular dilation appeared in renal tissue, synovial hyperplasia and inflammatory cell infiltration appeared in ankle joint. Compared with the model group, the abnormal degrees of liver, kidney and ankle joint tissue of rats in each treatment group were alleviated. ConclusionThe new formula of SFB replacing Plantaginis Semen has the same effect in the treatment of HUA combined with GA. This study proposes a new strategy to investigate the efficacy of new resources of Chinese medicine in a compound compatibility environment, which can provide a new demonstration for the research and development of new resources of Chinese medicine.
10.Exploring the risk "time interval window" of sequential medication of Reduning injection and penicillin G injection based on the correlation between biochemical indexes and metabolomics characteristics
Ming-liang ZHANG ; Yu-long CHEN ; Xiao-yan WANG ; Xiao-fei CHEN ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Wei-xia LI ; Jin-fa TANG
Acta Pharmaceutica Sinica 2024;59(7):2098-2107
Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

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