1.Interpretation and thoughts on the formulation and revision of the standards for exogenous harmful residues in traditional Chinese medicinal materials in the Chinese Pharmacopoeia 2025 Edition
WANG Ying ; SHEN Mingrui ; LIU Yuanxi ; ZUO Tiantian ; WANG Dandan ; HE Yi ; CHENG Xianlong ; JIN Hongyu ; LIU Yongli ; WEI Feng ; MA Shuangcheng
Drug Standards of China 2025;26(1):083-092
As people’s attention to health continues to increase, the market demand for traditional Chinese medicine (TCM) is growing steadily. The quality and safety of Chinese medicinal materials have attracted unprecedented social attention. In particular, the issue of exogenous harmful residue pollution in TCM has become a hot topic of concern for both regulatory authorities and society. The Chinese Pharmacopoeia 2025 Edition further refines the detection methods and limit standards for exogenous harmful residues in TCM. This not only reflects China’s high-level emphasis on the quality and safety of TCM but also demonstrates the continuous progress made by China in the field of TCM safety supervision. Basis on this study, by systematically reviewing the development history of the detection standards for exogenous harmful residues in TCM and analyzing the revisions and updates of these detection standards in the Chinese Pharmacopoeia 2025 Edition, deeply explores the key points of the changes in the monitoring standards for exogenous harmful residues in TCM in the Chinese Pharmacopoeia 2025 Edition. Moreover, it interprets the future development directions of the detection of exogenous residues in TCM, aiming to provide a reference for the formulation of TCM safety supervision policies.
2.Diabetes-associated sleep fragmentation impairs liver and heart function via SIRT1-dependent epigenetic modulation of NADPH oxidase 4.
Yuanfang GUO ; Jie WANG ; Dongmei ZHANG ; Yufeng TANG ; Quanli CHENG ; Jiahao LI ; Ting GAO ; Xiaohui ZHANG ; Guangping LU ; Mingrui LIU ; Xun GUAN ; Xinyu TANG ; Junlian GU
Acta Pharmaceutica Sinica B 2025;15(3):1480-1496
Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.
3.Melatonin receptor 1a alleviates sleep fragmentation-aggravated testicular injury in T2DM by suppression of TAB1/TAK1 complex through FGFR1.
Xiaohui ZHANG ; Xinyu TANG ; Ting GAO ; Yuanfang GUO ; Guangping LU ; Qingbo LIU ; Jiahao LI ; Jie WANG ; Mingrui LIU ; Dongmei ZHANG ; Yufeng TANG ; Junlian GU
Acta Pharmaceutica Sinica B 2025;15(7):3591-3610
A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO +/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.
4.Efficacy and safety of mini-track,mini-nephroscopy and mini-ultrasonic probe per-cutaneous nephrolithotomy for the treatment of 1.5-2.5 cm kidney stones
Mingrui WANG ; Jun LIU ; Liulin XIONG ; Luping YU ; Hao HU ; Kexin XU ; Tao XU
Journal of Peking University(Health Sciences) 2024;56(4):605-609
Objective:To investigate the efficacy and safety of mini-track,mini-nephroscopy and mini-ultrasonic probe percutaneous nephrolithotomy(3mPCNL)for the treatment of 1.5-2.5 cm kidney stones.Methods:The perioperative data and postoperative follow-up data of a total of 25 patients with about 1.5-2.5 cm kidney stones who underwent 3mPCNL under ultrasound guidance in Peking Univer-sity People's Hospital from November 2023 to January 2024 were retrospectively analyzed.During the matching period,the 25 patients with 1.5-2.5 cm kidney stones receiving standard percutaneous neph-rolithotomy(sPCNL)were matched one-to-one according to the criterion that the absolute difference of the maximum diameter of stones between the two groups was less than 1 mm.The operative time,renal function changes,postoperative stone-free rate,hemoglobin changes,and complication rate of the two treatments were compared,and then the effectiveness and safety of 3mPCNL were preliminarily analyzed.Results:There were no significant differences in mean age,preoperative median creatinine,preoperative mean hemoglobin,preoperative mean hematocrit,median stone maximum diameter,and median stone CT density between the 3mPCNL group and the sPCNL group.The median operation time in the 3mPCNL group was 60.0(45.0-110.0)min,with no statistical significance compared with the sPCNL group,and all the patients underwent single-channel operations.The mean hemoglobin after operation in the 3mPCNL group was(115.3±15.5)mmol/L,and there was no significant difference between the preoperative group and the sPCNL group,and the mean hemoglobin decreased significantly between the sPCNL group and the sPCNL group[(9.5±2.2)mmol/L vs.(10.1±1.9)mmol/L].The mean hematocrit after operation was(28.0±5.2)%,and the difference was statistically significant compared with that before operation(t=2.414,P=0.020).The mean hematocrit drop was not statistically signi-ficant compared with the sPCNL group(2.3%vs.2.7%).The median serum creatinine in the 3mPCNL group was 74.0(51.0-118.0)μmol/L after operation,and the difference was statistically significant compared with that before operation(Z=-2.980,P=0.005).The stone-free rate in the 3mPCNL group and the sPCNL group was 96.0%and 97.3%,respectively,and the mean hospital stay was(4.3±1.4)d and(5.5±2.0)d,respectively,with the statistical significance(t=0.192,P=0.025).After the operation,one patient in sPCNL group had massive hemorrhage after the nephrostomy tube was re-moved,which was improved after selective renal artery embolization.One patient in the 3mPCNL group developed mild perirenal hematoma,which was improved after conservative treatment,and no complica-tions were observed in the other patients.Conclusion:3mPCNL in the treatment of 1.5-2.5 cm kidney stones can achieve an effective rate comparable to sPCNL,and can achieve the ideal stone-free rate in a shorter operative time with a lower rate of surgery-related complications.
5.Meta-analysis of the efficacy and safety of febuxostat in the treatment of hyperuricemia with hypertension
Ruilin LIU ; Jigao LI ; Mingrui DU ; Quan ZHOU
Chinese Journal of Rheumatology 2024;28(10):738-742
Objective:To evaluate the efficacy and safety of febuxostat in the treatment of hyperuricemia with hypertension.Methods:Randomized controlled trials (RCT) on the treatment of hyperuricemia with hypertension using febuxostat were retrieved from Medline, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database from January 2013 to July 2023, according to the retrieval strategy. Two trained researchers completed the literature screening, quality evaluation, and data extraction. Meta-analysis was performed using RevMan 5.3. The fixed-effect model or random-effects model was used to analyze the research data, and subgroup analysis was conducted to identify the source of heterogeneity.Results:A total of 5 RCTs involving 456 patients (228 in the experimental group and 228 in the control group) were included in the meta-analysis, all of which were English-language literatures and foreign studies. In the treatment of hyperuricemia with hypertension, febuxostat showed a statistically significant difference in reducing serum uric acid (sUA) levels compared to control drugs [MD(95% CI)=-1.31(-2.55, -0.07), P=0.040]; there was no statistically significant difference in reducing systolic blood pressure (SBP) [SMD(95% CI)=-0.12(-0.51, 0.27), P=0.540] or diastolic blood pressure (DBP) [SMD(95% CI)=-0.15(-0.40, 0.09), P=0.220]. Subgroup analysis showed that the difference in intervention drugs in the control group may be the cause of heterogeneity in sUA levels, and the difference in intervention time may be the cause of heterogeneity in SBP levels among different studies. There was no statistically significant difference in the incidence of adverse reactions between the febuxostat group and the control group [RD (95% CI) =-0.01(-0.08, 0.06), P=0.770]. Conclusion:Febuxostat has a significant advantage in improving sUA levels and is relatively safe in the treatment of hyperuricemia with hypertension, but it does not show significant advantages in blood pressure control.
6.Study on the Construction of the Intelligent Hospital Evaluation Index System in China
Zhiyong LIU ; Mingrui GUO ; Xiaohang CHEN ; Jing LONG ; Yuxin PENG
Journal of Medical Informatics 2024;45(5):1-7
Purpose/Significance To build an evaluation index system of hospital intelligence in line with China's national conditions,so as to provide references for the quantitative evaluation of the degree of hospital intelligence,and to help the orderly development of hospi-tal intelligence construction.Method/Process Based on the review of the existing evaluation standard system of hospital informatization con-struction,Delphi method and analytic hierarchy process are used to discuss the construction process of hospital intelligence evaluation index system from four processes:construction of an evaluation index system,selection of experts in letter consultation,evaluation of indicator im-portance and verification of letter consultation results,and determination of the evaluation index weight.Result/Conclusion The construc-tion of hospital intelligence evaluation index system,which includes 3 first-level indexes,8 second-level indexes and 33 third-level in-dexes,is complementary to the existing evaluation system of smart hospitals,can reflect the construction foundation and development goals of the current intelligent hospitals,and has certain applicability and guidance for the future construction of smart hospitals.
7.Study on the Conceptual Model of Hospital Intelligence Index
Zhiyong LIU ; Jing LONG ; Xiaohang CHEN ; Xinyang ZHANG ; Mingrui GUO ; Yuxin PENG
Journal of Medical Informatics 2024;45(5):8-13
Purpose/Significance To construct the conceptual model of hospital intelligence index,so as to lay the foundation for the quantitative evaluation of hospital intelligence degree,and help the intelligent construction of hospital.Method/Process The paper intro-duces the connotation of intelligence,expounds the evaluation standard system of hospital informatization construction,and considers the application of intelligence in hospital from the perspective of structure-function-effect.Result/Conclusion The conceptual model of hospital intelligence index is built.That conceptual model includes 3 first-level indicators,8 second-level indicators and 33 third-level indicators of intelligence basis,intelligence capacity and intelligence effect.As a tool for continuous improvement of medical serv-ices,regular assessment of hospital intelligence level can promote the improvement of medical quality and patient experience,and help the high-quality development of hospitals.
8.METTL3/DUXAP8 axis promotes proliferation,migration and invasion of salivary adenoid cystic carci-noma cells
Qi ZHAO ; Wanpeng GAO ; Jiale WANG ; Rong LIU ; Mingrui SHI ; Chenghao REN ; Zihui YANG ; Zhenqing BAI ; Xinjie YANG
Journal of Practical Stomatology 2024;40(3):337-343
Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P<0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P<0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P<0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P<0.05)and enzyme-encoding genes in SACC-LM cells(P<0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P<0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.
9.Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy.
Yue ZHANG ; Jingwen GAO ; Na LI ; Peng XU ; Shimeng QU ; Jinqian CHENG ; Mingrui WANG ; Xueru LI ; Yaheng SONG ; Fan XIAO ; Xinyu YANG ; Jihong LIU ; Hao HONG ; Ronghao MU ; Xiaotian LI ; Youmei WANG ; Hui XU ; Yuan XIE ; Tianming GAO ; Guangji WANG ; Jiye AA
Acta Pharmaceutica Sinica B 2024;14(2):667-681
Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.
10.Recent advance in role of resolvin D1 in inflammatory injury of major neurological diseases
Xiaoyu LYU ; Ziyou ZHANG ; Zhuang LI ; Dandan LI ; Mingrui LIU ; Yangyang ZHONG ; Yusong HE ; Yannan SHAO ; Yan YU ; Bensi ZHANG
Chinese Journal of Neuromedicine 2024;23(11):1172-1178
Neurodegenerative diseases are often associated with inflammatory mechanisms, where persistent or excessive inflammatory responses can lead to neuronal damage and subsequent pathological changes. In acute neurological conditions such as stroke or traumatic brain injury, inflammation is a key factor that triggers acute neuronal injury and long-term sequelae. In chronic neurodegenerative diseases, including Alzheimer's disease, cognitive dysfunction, Parkinson's disease, and multiple sclerosis, the chronic activation of inflammation is closely related to gradual degeneration of neurons. Resolvin D1 (RvD1), an endogenous pro-resolving mediator, plays a crucial role in controlling the intensity and duration of inflammation by inhibiting excessive activation of immune cells, modulating the release of pro-inflammatory cytokines, and maintaining the integrity of the blood-brain barrier. This review focuses on the mechanisms of RvD1 in mediating inflammatory damage in major neurological diseases, aiming to provide theoretical support for a deeper understanding of disease mechanism, optimized therapeutic strategies, and enhanced outcome.

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