To introduce the general thinking, guidelines, work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition, and to summarize and figure out the main characteristics on dosage forms, physico-chemical testing, microbial and biological testing, reference standards and guidelines The newly revised general chapters of pharmacopoeia give full play to the normative and guiding role of the Chinese Pharmacopoeia standard, track the frontier dynamics of international drug regulatory science and the elaboration of monographs, expand the application of state-of-the-art technologies, and steadily promote the harmonization and unification with the ICH guidelines； further enhance the overall capacity of TCM quality control, actively implement the 3 R principles on animal experiments, and practice the concept of environmental-friendly； replace and/or reduce the use of toxic and hazardous reagents, strengthen the requirements of drug safety control This paper aims to provide a full-view perspective for the comprehensive, correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.

Mitochondria are semi-self-service organelles in eukaryotes. Their main function is to synthesize adenosine triphosphate (ATP), provide energy to cells through this pathway, and participate in a variety of activities within cells. These functions rely on the unique genetic material inside the mitochondria, known as mitochondrial DNA (mtDNA). Mitochondrial DNA abundance is the amount of mitochondrial DNA in a cell and is measured by the mitochondrial DNA copy number (mtDNA-CN). In recent years, as the scientific research community continues to deepen research on mitochondrial DNA abundance, and considering that blood mtDNA is relatively easier to obtain, researchers have begun to explore the potential relationship between blood mtDNA abundance and human health conditions and various diseases. Blood mtDNA abundance is increasingly considered as a possible biomarker for a variety of diseases. Research evidence has shown that blood mitochondrial DNA abundance is significantly correlated with diseases of human nervous system, kidney system and cardiovascular system, and can be used as a new biomarker for diagnosis and treatment. This review focuses on recent advances in the study of the association between blood mitochondrial DNA abundance and various human diseases.

AIM: To explore the therapeutic effect of oral Xuefu Zhuyu Pill combined with intravitreal injection of aflibercept in the treatment of retinal vein occlusion(RVO).METHODS: A total of 80 patients(80 eyes)with RVO admitted to our hospital from January 2021 to March 2024 were prospectively selected. According to the treatment method, they were divided into a control group of 40 patients treated with intravitreal injection of aflibercept, and an observation group of 40 patients treated with oral Xuefu Zhuyu Pill combined with intravitreal injection of aflibercept. The efficacy, TCM syndrome score, retinal microcirculation parameters, macular edema(ME), and adverse reactions were compared between the two groups of patients in the treatment of RVO.RESULTS: All patients have completed follow-up. The clinical effective rate of the observation group after treatment was 95%, obviously higher than that of the control group(80%; χ2=4.114, P=0.043). After treatment for 3 mo, the traditional Chinese medicine syndrome scores, foveal avascular area(FAZ)area, FAZ circumference, macular central retinal thickness, and neovascularization leakage area of both groups decreased, the overall blood flow density of the superficial capillary plexus(SCP)and deep capillary plexuses(DCP)increased, and the observation group showed better results than the control group(all P<0.05). There was no statistically significant difference in the occurrence of adverse reactions between the two groups during the treatment period(P>0.05).CONCLUSION: Oral administration of Xuefu Zhuyu Pill combined with intravitreal injection of aflibercept in the treatment of RVO can improve retinal microcirculation, enhance vision, restore ocular blood circulation, improve bleeding, promote ME absorption, and improve clinical efficacy.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

BACKGROUND:In clinical practice,Cibotium barometz and Epimedium have shown significant efficacy in the treatment of rheumatoid arthritis,but the complex active ingredients contained in the two have an unclear mechanism of action at the molecular level for the treatment of rheumatoid arthritis. OBJECTIVE:Based on network pharmacology and molecular docking technology,to establish a collagen-induced arthritis model and to verify the potential targets and pathways of Cibotium barometz and Epimedium in the treatment of rheumatoid arthritis,providing reliable experimental evidence for the use of clinical formulas with Cibotium barometz and Epimedium as the main components. METHODS:Utilizing traditional Chinese medicine research platforms,traditional Chinese medicine encyclopedias,and databases of traditional Chinese medicine and chemical components from the Shanghai Institute of Organic,effective ingredients were retrieved and identified.3D molecular formulas were obtained from the PubChem platform and target predictions were made using PharmMapper and SwissTargetPrediction.Disease targets for rheumatoid arthritis were obtained from gene databases such as DrugBank,GeneCards,and OMIM.The intersections of targets and Cibotium barometz and Epimedium were plotted using VENNY 2.1 after calibration with the Uniport database.A protein-protein interaction network graph was constructed using the STRING platform.Gene Ontology function analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the Metascape platform for data visualization.A four-layered network model of traditional Chinese medicine,ingredients,targets,diseases,and pathways was constructed using Cytoscape 3.9.0.The main effective ingredients were docked with core targets using AutoDock-Vina software to explore the best binding targets.A type II collagen+adjuvant-induced arthritis rat model was established,and the effects of Cibotium barometz and Epimedium on relevant pathway targets and inflammatory cell factors were observed after 21 days of intervention. RESULTS AND CONCLUSION:A total of 28 active ingredients from Cibotium barometz and Epimedium were selected,yielding 288 intersection targets for rheumatoid arthritis.The main ingredients included isobavachalcone,cibotium,and epimedium.The main targets included protein kinase 1 for serine/threonine(AKT1),tumor necrosis factor,and vascular endothelial growth factor A.Gene ontology analysis yielded 2 232 biological processes,mainly related to serine protein phosphorylation,positive regulation of serine/threonine protein kinase,and reactive oxygen metabolism.Kyoto Encyclopedia of Genes and Genomes enrichment analysis yielded 202 pathways,mainly involving the PI3K/AKT signaling pathway and epidermal growth factor receptor signaling pathway,which may exert therapeutic effects by regulating synovial cell apoptosis and proliferation and suppressing inflammatory factors.Molecular docking results showed the strongest binding activity and stable structure of Cibotium barometz and Epimedium with AKT1 and estrogen receptor transcription factor 1,which was closely related to apoptosis and proliferation and inflammatory signaling pathways such as PI3K/AKT.Cibotium barometz and Epimedium reduced the expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the serum of collagen-induced arthritis rat models.Cibotium barometz and Epimedium reduced the expression of p-PI3K,p-AKT,and p-FOXO1 in the synovium of collagen-induced arthritis rat models.The results indicate that the combination of Cibotium barometz and Epimedium may exert therapeutic effects by inhibiting the proliferation of synovial cells and suppressing the expression of inflammatory factors via the PI3K/AKT/FOXO1 signaling pathway.This may be closely related to the occurrence of inflammation and bone destruction in rheumatoid arthritis,and provides a reference for the rational use and development of new drugs in clinical practice.

Based on the species-specific peptides of Pheretima and its common counterfeit (Metaphire magna), an identification method was established using ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) for quality evaluation of Pheretima and its preparations. Separation was performed on a CORTECS T3 C18 column with 0.1% formic acid and acetonitrile as the mobile phases. Mass spectrometry with multiple reaction monitoring (MRM) using ESI⁺ mode was used to simultaneously monitor three ion pairs. The results indicated that the method was specific and could distinguish Guang Dilong, Hu Dilong, and M. magna, which were consistent with those of DNA barcode identification. The adulteration test showed that the LOD of peptide M was 1 μg·g^-1. Peptide M could be detected when 1% M. magna was added to Guang Dilong, indicating the high sensitivity of the method. Fifty-four batches of commercially available samples contained 35% Guang Dilong, 35% Hu Dilong, and 15% M. magna. No ions were detected in 15% of the samples, and DNA barcode identification revealed that they were mainly from Amynthas, with similar appearance to Hu Dilong. The analysis results of the formulation showed that no peptide ions were detected in 3 batches of Xiaohuoluo pills (3/6) and M. magna were detected in 2 batches of Shenjindan capsules (2/4). The developed method in the study has good specificity, sensitivity, and feasibility, and could be used for quality control of Pheretima and its related preparations. It is of great significance for improving quality standards and regulating the medicinal market of Pheretima.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Naturally derived metabolites are valuable resources for drug research and development, and play an important role in the treatment of diseases. As the "second genome" of the body, gut microbiota is rich in metabolic enzymes, which interacts with external substances such as drugs, thus affecting the progression of diseases. This article summarizes the interaction between gut microbiota-producing enzymes and natural medicines, and focuses on the impact of this interaction on disease progression, hoping to provide new ideas for the development and pharmacological mechanism of natural medicines.

OBJECTIVE To explore the effects of different concentrations of aconitine on the ventricular electrophysiology of the rat heart when applied to the heart. METHODS By optical mapping technology, the effects of different concentrations of aconitine on ventricular action potential and calcium signal in rats before and 15 min after administration were observed by in vitro administration of aconitine 0.3, 1, 3 ng·mL−1. RESULTS Compared with the blank group, aconitine could be concentration-dependent to delay the conduction of action potentials under both spontaneous and 6 Hz stimulation rhythms, and there was a significant difference at a concentration of 3 ng·mL−1(P<0.05 or P<0.01). Compared with blank group, when the concentration of aconitine was 1 and 3 ng·mL−1, the action potential duration(APD) of the ventricle was significantly prolonged(P<0.01). Aconitine could also increase the dispersion of action potential conduction(P<0.05) and reduce the ratio of effective refractory period(ERP) to APD90(P<0.01). In addition, aconitine could also be concentration-dependent delay of calcium signal conduction, reduce the speed of calcium conduction(P<0.05 or P<0.01), increase the dispersion of calcium conduction and calcium transient duration(P<0.05 or P<0.01), and reduce the amplitude of calcium signal(P<0.01). CONCLUSION Using the optical labeling technique, it can be visualized that aconitine induces arrhythmia by concentration-dependent delay of ventricular action potential and calcium signaling in rats.To explore the effects of different concentrations of aconitine on the ventricular electrophysiology of the rat heart when applied to the heart. METHODS By optical mapping technology, the effects of different concentrations of aconitine on ventricular action potential and calcium signal in rats before and 15 min after administration were observed by in vitro administration of aconitine 0.3, 1, 3 ng·mL−1. RESULTS Compared with the blank group, aconitine could be concentration-dependent to delay the conduction of action potentials under both spontaneous and 6 Hz stimulation rhythms, and there was a significant difference at a concentration of 3 ng·mL−1(P<0.05 or P<0.01). Compared with blank group, when the concentration of aconitine was 1 and 3 ng·mL−1, the action potential duration(APD) of the ventricle was significantly prolonged(P<0.01). Aconitine could also increase the dispersion of action potential conduction(P<0.05) and reduce the ratio of effective refractory period(ERP) to APD90(P<0.01). In addition, aconitine could also be concentration-dependent delay of calcium signal conduction, reduce the speed of calcium conduction(P<0.05 or P<0.01), increase the dispersion of calcium conduction and calcium transient duration(P<0.05 or P<0.01), and reduce the amplitude of calcium signal(P<0.01). CONCLUSION Using the optical labeling technique, it can be visualized that aconitine induces arrhythmia by concentration-dependent delay of ventricular action potential and calcium signaling in rats.

Objective To study the traditional Chinese medicine(TCM)constitution characteristics of overweight/obese patients in Shanghai region and to investigate the correlation of TCM constitution with body composition.Methods Relevant data were collected from the patients with complete information of TCM constitution and human body composition analysis who visited the specialized outpatient clinic of acup-moxibustion catgut embedding therapy in the Department of Endocrinology,Shanghai Tenth People's Hospital from August 2020 to December 2022.The patients were divided into a normal body mass group(BMI＜24 kg/m2),an overweight group(24 kg/m2≤BMI＜28 kg/m2)and obesity group(BMI≥28 kg/m2),and then the distribution of TCM constitution types in the three groups of patients were analyzed.After that,the correlation between TCM constitution and body composition were explored with multiple regression analysis.Results(1)A total of 315 patients were included,of which 43 patients had normal body mass,85 patients were overweight and 187 patients were obese.(2)The TCM constitution types in descending order of the composition ratio in the normal body mass group and in the overweight group were spleen deficiency constitution,liver stagnation constitution,damp-heat constitution,yang deficiency constitution,and yin deficiency constitution,in the obese group were spleen deficiency constitution,yang deficiency constitution,damp-heat constitution,liver stagnation constitution,and yin deficiency constitution,and in the overweight/obese group were spleen deficiency constitution,damp-heat constitution,yang deficiency constitution,liver stagnation constitution,and yin deficiency constitution.No statistically significant differences of the distribution of TCM constitution types were shown between normal body bass population and overweight/obese population(P＞0.05).In both normal body mass population and overweight/obese population,the single body constitution type was common,and biased constitution was rare,and there was no statistically significant difference when comparing between the two groups(P＞0.05).(3)The results of multiple regression analysis showed that the basal metabolism of all patients was positively correlated with yang deficiency constitution and was negatively correlated with damp-heat constitution,and the differences were statistically significant(P＜0.01).It is indicated that if the score of yang deficiency constitution rose by one point,the basal metabolism would increase by 0.54 kcal,and if the score of damp-heat constitution decreased by one point,the basal metabolism would decrease by 1.005 kcal.Conclusion In Shanghai region,obesity may be the main indication of the variation of the body constitution.In addition to spleen deficiency constitution,the proportions of yang deficiency constitution,damp-heat constitution and liver stagnation constitution are also higher in obese patients.In terms of the correlation between TCM constitution and body composition,basal metabolism is positively correlated with yang deficiency constitution and is negatively correlated with damp-heat constitution.Therefore,for the patients with yang deficiency constitution and damp-heat constitution,the influence of the basal metabolism level on the development of the disease should be taken into account.