1.Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics
Yu-long CHEN ; You ZHAI ; Xiao-yan WANG ; Wei-xia LI ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Xiao-fei CHEN ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Kun LI ; Jin-fa TANG ; Ming-liang ZHANG
Acta Pharmaceutica Sinica 2024;59(2):382-394
Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. 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). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and
2.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.
3.Treatment of hypoxia-induced ED in high-altitude areas by transcutaneous low-frequency electrical stimulation based on the parameters obtained from visualized precision electrophysiological diagnosis
Rong-Rong YANG ; Ji-Xiong YAN ; Qi-Wei CHEN ; Fa-Ming WANG ; Zhan-Hu YE ; Wei GUO
National Journal of Andrology 2024;30(2):132-138
Objective:To investigate the effects of visualized precision electrophysiological diagnosis and transcutaneous low-frequency electrical stimulation(TES)on hypoxia-induced ED in high-altitude areas.Methods:This study included 152 ED pa-tients from high-altitude hypoxic areas treated by TES based on the parameters obtained from visualized precision electrophysiological diagnosis.We followed up the patients for 1 to 3 months and compared their ⅡEF-5 scores,nocturnal penile tumescence and rigidity(NPTR)and infrared thermal metabolic technology(TMT)-based temperature of the whole body and diseased parts before and after treatment.Results:All the patients successfully completed 1 to 3 courses of TES.There were no statistically significant differences in the ⅡEF-5 scores(P<0.05)and penile tip optimal erection rigidity and duration(P<0.01)of the patients before and after treat-ment.TMT images indicated a temperature change of>1.5 ℃ in the penis and bilateral inguinal regions after treatment,suggesting the effectiveness of electrical stimulation.No recurrence was observed during the follow-up.Conclusion:TES based on the parame-ters obtained from visualized precision electrophysiological diagnosis has a definite effect on hypoxia-induced ED by enhancing oxygen supply to the penile corpus cavernosum and improving its function and structure.
4.Virtual preoperative planning and 3D-printed templates for pre-contoured plates in treatment of acetabular posterior wall fractures
Chen HUANG ; Wei XU ; Mei-Ming XIE ; Cai-Ru WANG ; Shao-Lin DENG ; Dong-Fa LIAO
China Journal of Orthopaedics and Traumatology 2024;37(2):135-141
Objective To evaluate the feasibility and accuracy of virtual preoperative planning and 3D-printed templates for pre-contoured plates for the treatment of posterior wall fractures of the acetabulum.Methods A retrospective analysis of 29 patients with posterior acetabular wall fractures treated between August 2017 and March 2021 were divided into 2 groups based on whether to use preoperative virtual planning and 3D printed template.In 3D-printing group,there were 14 patients,includ-ing 10 males and 4 females;aged from 21 to 53 years old;CT-based virtual surgical planning was done using Mimics and 3-Matic software and 3D-printed templates for pre-contoured plates were adopted.In conventional group,there were 15 patients,including 10 males and 5 females;aged from 19 to 55 years old;conventional method of intra-operative contouring to adapt the plate to the fracture region was adopted.Blood loss,surgical time,radiographic quality of reduction,and hip function were compared between groups.Results The difference in operation time and intraoperative blood loss was significant(P<0.05).Twenty-three patients were followed up from 12 to 30 months,and the fractures in both groups healed with a healing time of 3 to 6 months.At the last follow-up,the Merle d'Aubign-Postel score of the 3D printed group was lower than that of the conven-tional group(P<0.05),with no significant differences in walking ability,hip mobility and total score(P>0.05).In 3D printing group,6 cases were excellent,5 cases were good,3 cases were fair;in conventional group,5 cases were excellent,5 cases were good,4 cases were fair,1 case was worse;no significant difference between two groups(P>0.05).Conclusion Virtual preopera-tive planning and 3D-printed templates for pre-contoured plates can reduce operative time and the blood loss of surgery,im-prove the quality of reduction.This method is efficient,accurate and reliable to treat acetabular posterior wall fractures.
5.Event-related potential study on vigilant attention in children with sleep disordered breathing
Ye HE ; Huijie HAN ; Ming FA ; Chaoqun WANG ; Haitian MEI ; Fangqiao ZHAO ; Yang YI
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(6):500-504
Objective:To explore the vigilant attention function and behavioral changes in sleep disordered breathing(SDB) children.Methods:Thirty SDB children (SDB group) and 30 normal children (control group) were selected from June 2022 to August 2023. All participants underwent continuous performance test(CPT-AX) (Go/Nogo) and behavioral test. The latency and amplitude of contingent negative variation(CNV) components under cue/uncue conditions in leads F3, Fz and F4 were measured. The t-test and Mann-Whitney U test were used to conduct statistical analysis by SPSS 25.0 software. Results:(1) There were no statistically significant differences in the number of correct responses, reaction time and number of false alarms between the SDB group and the control group (all P>0.05).(2) The latencies of cue-CNV in the SDB group(F3: 618.00(582.50, 644.50)ms, Fz: 603.00(579.50, 634.00)ms, F4: (606.87±25.07)ms) were longer than those in the control group(F3: (508.47±25.82)ms, Fz: 502.00(470.00, 520.50)ms, F4: 514.00(487.00, 536.50)ms) in leads F3, Fz and F4. The latency of cue-CNV of lead F4 in the SDB group was higher than that in the control group, and the difference was statistically significant ( P<0.05). The latencies of uncue-CNV in lead F3 and Fz in the SDB group were higher than those in the control group, and the differences were statistically significant (both P<0.05). Conclusion:SDB children have shown activation in the right brain area during attentional tasks, and the prolonged CNV latency may be a sensitive neuroelectrophysiological marker for early clinical assessment of vigilant attention dysfunction.
6.Mechanism of Shenkang injection in treatment of renal fibrosis based on bioinformatics and in vitro experimental verification
Gao-Quan MENG ; Ming-Liang ZHANG ; Xiao-Fei CHEN ; Xiao-Yan WANG ; Wei-Xia LI ; Dai ZHANG ; Lu JIANG ; Ming-Ge LI ; Xiao-Shuai ZHANG ; Wei-Ting MENG ; Bing HAN ; Jin-Fa TANG
Chinese Pharmacological Bulletin 2024;40(10):1953-1962
Aim To explore the mechanism and mate-rial basis of Shenkang injection(SKI)in the treatment of renal fibrosis(RF)by bioinformatics and in vitro experiments.Methods The differentially expressed genes of RF were screened by GEO database.With the help of CMAP database,based on the similarity princi-ple of gene expression profile,the drugs that regulated RF were repositioned,and then the components of SKI potential treatment RF were screened by molecular fin-gerprint similarity analysis.At the same time,the core targets and pathways of SKI regulating RF were predic-ted based on network pharmacology.Finally,it was verified by molecular docking and cell experiments.Results Based on the GEO database,two RF-related data sets were screened,and CMAP was relocated to three common RF therapeutic drugs(saracatinib,da-satinib,pp-2).Molecular fingerprint similarity analysis showed that RF therapeutic drugs had high structural similarity with five SKI components such as salvianolic acid B and hydroxysafflor yellow A.Molecular docking results showed that salvianolic acid B,hydroxysafflor yellow A and other components had good binding abili-ty with MMP1 and MMP13,which were the core targets of SKI-regulated potential treatment of RF.Network pharmacology analysis suggested that the core targets of SKI were mainly enriched in signaling pathways such as Relaxin and AGE-RAGE.Cell experiments showed that SKI could significantly reduce the mRNA expres-sion levels of AGER,NFKB1,COL1A1,SERPINE1,VEGFC in AGE-RAGE signaling pathway and MMP1 and MMP13 in Relaxin signaling pathway in RF model cells,and significantly increase the mRNA expression level of RXFP1.Conclusions SKI can play a role in the treatment of RF by regulating Relaxin and AGE-RAGE signaling pathways,and its material basis may be salvianolic acid B,hydroxysafflor yellow A and other components.
7.hiPSCs and organoids: prediction of arrhythmogenic risks for optimized traditional Chinese medicine.
Hao-Kun SUN ; Yuan GAO ; Ming-Jun ZHU ; Jin-Fa TANG ; Ying WU ; Bin LI ; Rui YU ; Yan WANG ; Lu-Ye ZHOU
China Journal of Chinese Materia Medica 2023;48(20):5404-5409
Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.
Animals
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Humans
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Medicine, Chinese Traditional/adverse effects*
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Cardiotoxicity
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Induced Pluripotent Stem Cells
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Arrhythmias, Cardiac/chemically induced*
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Myocytes, Cardiac
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Organoids
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Drugs, Chinese Herbal/adverse effects*
8.Comparison of distribution of eight components from Liangxue Tuizi Mixture between normal and Henoch-Schonlein purpura rats.
Li-Ling SI ; Lu NIU ; Xiao-Yan WANG ; Hui ZHANG ; Ming-Liang ZHANG ; Shuang XU ; Xian-Qing REN ; Jin-Fa TANG ; Wei-Xia LI
China Journal of Chinese Materia Medica 2023;48(21):5915-5931
This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.
Rats
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Animals
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IgA Vasculitis/drug therapy*
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Monoterpenes
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Administration, Oral
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Liquid Chromatography-Mass Spectrometry
9.Preliminary experience of gasless transoral vestibular robotic thyroidectomy.
Fa Ya LIANG ; Pei Liang LIN ; Xi Jun LIN ; Ping HAN ; Ren Hui CHEN ; Jing Yi WANG ; Xin ZOU ; Xiao Ming HUANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(6):596-601
Objective: To explore the feasibility and safety of the gasless transoral vestibular robotic thyroidectomy using skin suspension. Methods: The clinical data of 20 patients underwent gasless transoral vestibular robotic thyroidectomy in the Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from February 2022 to May 2022 were retrospectively analyzed. Among them, 18 were females and 2 were males, aged (38.7±8.0) years old. The intraoperative blood loss, operation time, postoperative hospital stay, postoperative drainage volume, postoperative pain visual analogue scale (VAS) score, postoperative swallowing function swallowing impairment score-6 (SIS-6), postoperative aesthetic VAS score, postoperative voice handicap index-10 (VHI-10) voice quality, postoperative pathology and complications were recorded. SPSS 25.0 was used for statistical analysis of the data. Results: The operations were successfully completed without conversion to open surgery in all patients. Pathological examination showed papillary thyroid carcinoma in 18 cases, retrosternal nodular goiter in 1 case, and cystic change in goiter in 1 case. The operative time for thyroid cancer was 161.50 (152.75, 182.50) min [M (P25, P75), the same below] and the average operative time for benign thyroid diseases was 166.50 minutes. The intraoperative blood loss 25.00 (21.25, 30.00) ml. In 18 cases of thyroid cancer, the mean diameter of the tumors was (7.22±2.02) mm, and lymph nodes (6.56±2.14) were dissected in the central region, with a lymph node metastasis rate of 61.11%. The postoperative pain VAS score was 3.00 (2.25, 4.00) points at 24 hours, the mean postoperative drainage volume was (118.35±24.32) ml, the postoperative hospital stay was 3.00 (3.00, 3.75) days, the postoperative SIS-6 score was (4.90±1.58) points at 3 months, and the postoperative VHI-10 score was 7.50 (2.00, 11.00) points at 3 months. Seven patients had mild mandibular numbness, 10 patients had mild cervical numbness, and 3 patients had temporary hypothyroidism three months after surgery and 1 patient had skin flap burn, but recovered one month after surgery. All patients were satisfied with the postoperative aesthetic effects, and the postoperative aesthetic VAS score was 10.00 (10.00, 10.00). Conclusion: Gasless transoral vestibular robotic thyroidectomy using skin suspension is a safe and feasible option with good postoperative aesthetic effect, which can provide a new treatment option for some selected patients with thyroid tumors.
Male
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Female
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Humans
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Adult
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Middle Aged
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Thyroidectomy/adverse effects*
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Robotic Surgical Procedures/adverse effects*
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Retrospective Studies
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Blood Loss, Surgical
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Hypesthesia/surgery*
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Neck Dissection/adverse effects*
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Thyroid Neoplasms/surgery*
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Pain, Postoperative/surgery*
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Postoperative Complications/etiology*
10.Analysis of Gene Recombination between HLA-B and -DRB1, HLA-DQB1 and -DPB1 Loci.
Chen CHEN ; Wei WANG ; Nan-Ying CHEN ; Li-Na DONG ; Wei ZHANG ; Fa-Ming ZHU
Journal of Experimental Hematology 2023;31(3):855-859
OBJECTIVE:
To investigate the recombinations within the human leukocyte antigen (HLA) region in two families.
METHODS:
Genomic DNA was extracted from the peripheral blood specimens of the different family members. HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci were genotyped using polymerase chain reaction-sequence specific oligonucleotide probing technique (PCR-SSO) and next-generation sequencing technique. HLA haplotype was determined by genetic analysis of the pedigree.
RESULTS:
The haplotypes of HLA-A*11:01~C*03:04~B*13:01~DRB1*12:02~DQB1*03:01~DPB1*05:01:01G and HLA-A*03:01~C*04:01~B*35:03~DRB1*12:01~DQB1*03:01~DPB1*04:01:01G in the family 1 were recombined between HLA-B and HLA-DRB1 loci, which formed the haplotype of HLA-A*11:01~C*03:04~B*13:01~DRB1* 12:01~DQB1*03:01~DPB1*04:01:01G. The haplotypes of HLA-A *02:06~C*03:03~B*35:01~DRB1*08:02~DQB1*04:02~ DPB1*13:01:01G and HLA-A *11:01~C*07:02~B*38:02~DRB1*15:02~DQB1*05:01~DPB1*05:01:01G in the family 2 were recombined between HLA-DQB1 and HLA-DPB1 loci, which formed the haplotype of HLA-A*02:06~C*03:03~B*35:01~ DRB1*08:02~DQB1*04:02~DPB1*05:01:01G.
CONCLUSION
The gene recombination events between HLA-B and -DRB1, HLA-DQB1 and -DPB1 loci were found respectively in two Chinese Han families.
Humans
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Gene Frequency
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HLA-DQ beta-Chains/genetics*
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HLA-B Antigens/genetics*
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Histocompatibility Antigens Class I/genetics*
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Haplotypes
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HLA-A Antigens/genetics*
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HLA-DRB1 Chains/genetics*
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Recombination, Genetic
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Alleles

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