ObjectiveTo observe the changes in the levels of different subtypes of epidermal growth factor receptor （ErbB）， namely ErbB1， ErbB2， ErbB3， and ErbB4， in the spinal dorsal horn of inflammatory pain model rats， and to explore their mechanism of mediating hyperalgesia as well as the intervention mechanism of electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）". MethodsThe study was divided into five parts. In experiment 1， 14 Sprague Dawley （SD） rats were randomly divided into control and inflammatory pain group （7 rats each group） to observe the pain behavior and the protein expression of different ErbB receptor subtypes in the spinal dorsal horn. In experiment 2， 30 rats were randomly divided into control group 1， inflammatory pain group 1， and low-， medium-， and high-concentration TX1-85-1 groups， with 6 rats in each group， to observe the effect of inhibiting spinal ErbB3 on inflammatory pain. In experiment 3， 12 rats were randomly divided into control virus group and ErbB3 knockdown virus group， with 6 rats in each group， to observe the effect of knocking down ErbB3 in the spinal dorsal horn on inflammatory pain. In experiment 4， 44 rats were randomly divided into control group 2， inflammatory pain group 2， electroacupuncture group， and sham electroacupuncture group， with 11 rats in each group， to observe the effect of electroacupuncture. In experiment 5， 40 rats were randomly divided into control group 3， inflammatory pain group 3， electroacupuncture group 1， and electroacupuncture + NRG1 group， with 10 rats in each group， to observe the effect of activating ErbB3 on electroacupuncture. A rat model of inflammatory pain was established by subcutaneous injection of 100 μl of complete Freund's adjuvant into the sole of the unilateral hind foot of SD rats. Rats in the low-， medium-， and high-concentration TX1-85-1 groups were intrathecally injected with ErbB3 inhibitor TX1-85-1 on day 5 to day 7 after modeling. Rats in the ErbB3 knockdown virus group were injected with ErbB3 knockdown virus packaged with adenovirus vector-based short hairpin RNA （shRNA） into the spinal dorsal horn in situ 3 weeks before modeling. Rats in each electroacupuncture group received electroacupuncture at bilateral "Zusanli （ST 36）" and "Kunlun （BL 60）" from day 1 to day 7 after modeling， with dense-sparse waves at a frequency of 2 Hz/100 Hz and a current of 0.5-1.5 mA for 30 minutes once a day. Rats in the electroacupuncture + NRG1 group were intrathecally injected with ErbB3 ligand recombinant human neuregulin-1 （NRG1） after electroacupuncture intervention from day 5 to day 7 after modeling. The mechanical withdrawal threshold and thermal withdrawal latency of rats were measured on day 1， 3， 5， and 7 after modeling to evaluate behavior， and Western Blot was used to detect the protein and phosphorylation levels of each ErbB subtype in the spinal dorsal horn. ResultsCompared with the control group， rats in the inflammatory pain group showed decreased mechanical withdrawal threshold and thermal withdrawal latency of rats， and increased expression of phosphorylated ErbB3 （p-ErbB3） protein in the spinal dorsal horn on days 1， 3， 5， and 7 after modeling （P＜0.01）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 1， the mecha-nical withdrawal threshold and thermal withdrawal latency of rats in the medium- and high-concentration TX1-85-1 groups increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 1， 3， 5， and 7 after modeling， compared with the control virus group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the ErbB3 knockdown virus group increased （P＜0.05）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 2 and the sham electroacupuncture group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 5 and day 7 after modeling， compared with the electroacupuncture + NRG1 group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group 1 increased （P＜0.05）. ConclusionThe p-ErbB3 in the spinal dorsal horn involved in hyperalgesia in rats with inflammatory pain， and electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）" can alleviate inflammatory pain by inhibiting the expression of p-ErbB3 protein in the spinal dorsal horn of rats.

The Chinese Pharmacopoeia is the legal technical standard which should be followed during the research, production, use, and administration of drugs. At present, the new edition of the Chinese Pharmacopoeia is planned to be promulgated and implemented. This article summarizes and analyzes the main characteristics and the content of updates and amendments of the Chinese Pharmacopoeia 2025 Edition(Volume Ⅰ), to provide a reference for the correct understanding and accurate implementation the new edition of the pharmacopoeia.

Traditional Chinese medicine (TCM) has historically played a pivotal role in the prevention and treatment of warm diseases, establishing a comprehensive theoretical framework that underpins its practices. The distinctive and indispensable contributions of aromatic Chinese herbs in dispelling harmful influences and mitigating the spread of these diseases are well recognized; however, further investigation is warranted to elucidate their systematic properties and regularities, and the theory of aromatic Chinese herbs in preventing and treating warm diseases still needs to be comprehensively summarized. This study employs the principles rooted in TCM, with particular emphasis on the framework for warm diseases. An analysis of the disease mechanisms, transmission dynamics, and preventive strategies is conducted during the early stage of infection, throughout the course of the disease, and in the post-illness phase. Furthermore, the characteristics and applications of aromatic Chinese herbs are integrated with insights drawn from modern pharmacological research to explore their specific roles in the prevention and management of warm diseases. The utilization of aromatic Chinese herbs manifests in a variety of therapeutic effects: aromatic medicinals purging filth and dispelling pathogens for preventing epidemic disease, aromatic medicinals regulation for relieving superficies syndrome and dispersing evils, aromatic medicinals ventilation the lung to relieve cough and asthma, aromatic medicinals resolving the dampness to awaken the spleen and stomach, aromatic medicinals opening the orifices to restore consciousness, aromatic and pungent medicinals to regulate qi, aromatic medicinals dredging the vessels to activate blood circulation and dissipate blood stasis, and aromatic medicinals clearing latent heat from the yin level. These properties facilitate tailored approaches to address the diverse manifestations of warm diseases and their associated symptoms, providing clear guidance for clinical application to achieve pre-disease prevention, active disease treatment, complication prevention, and post-recovery relapse avoidance. The use of aromatic Chinese herbs in preventing and treating warm diseases demonstrates theoretical, practical, systematic, and regular characteristics. The theory of the properties of aromatic Chinese herbs has been expanded and sublimated in clinical practice, and its scientific connotation has been expounded in modern research. Under the guidance of the theory of treatment based on syndrome differentiation, and by taking into account the distinct stages and pathologies of warm diseases, the rational selection of aromatic Chinese herbs can improve the clinical efficacy.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Objective To investigate the effect of Danshen Baoxin Cha (DBC) on a rat model of coronary heart disease combined with cognitive impairment. Methods Male Sprague-Dawley(SD) rats were randomly assigned to two groups:normal group and model group. Streptozotocin was injected into the bilateral ventricles of rats in the model group to establish cognitive impairment model,then isoproterenol hydrochloride was injected subcutaneously to model myocardial ischemia. Behavioral experiments were conducted to verify the success of the model of cognitive dysfunction. The rats of the model group were randomly divided into five groups:model control group,Tongxinluo Capsule group (TXL group,1.6 g·kg-1),and low-(4 g·kg-1),medium-(8 g·kg-1),and high-(16 g·kg-1) dose DBC groups. These groups were received the respective treatments continuously for two weeks. Subsequently,the Y-maze,novel object recognition and Morris water maze experiment were employed to assess the learning and memory abilities of rats. A kit was utilized to quantify the level of oxidative stress in the brain and the adenosine triphosphate (ATP) content in the brain and mitochondria. Hematoxylin-eosin (HE) staining and Nissl staining were employed to observe the pathological changes of neurons in hippocampus CA1 region. Electron microscopy was utilized to observe the pathological changes of mitochondria in hippocampal CA1 region. The expression levels of peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),glucose transporter type 4(GLUT4),and optic atrophy 1(OPA1) were quantified by real-time fluorescence quantitative polymerase chain reaction (PCR),and the expression of proteins related to the AMPK/OPA1 signaling pathway was determined by Western Blot analysis. Results Compared with the normal group,the spontaneous alternating reaction rate,the novel object recognition index,number of crossing the original platform,and distance ratio in the model group were obviously decreased (P<0.01). Neuronal density in the CA1 region of the hippocampus was decreased,Nissl bodies were decreased,and nucleus consolidation was increased. The ATP level in mitochondria,and the levels of ATP,SOD,and GSH-PX in brain were significantly decreased(P<0.05,P<0.01),as well as the content of ROS and MDA were significantly increased (P<0.05,P<0.01). The mitochondria of hippocampus in CA1 region were swollen,with sparse and vacuolated cristae. The mRNA expression levels of GLUT4,PGC-1α,and OPA1 were significantly decreased (P<0.01). The protein expression levels of GLUT4,SIRT1,PGC-1α and OPA1,and p-AMPK/AMPK ratio were significantly decreased (P<0.05,P<0.01). Compared with the model group,the behavioral indexes of rats in the DBC groups were significantly improved (P<0.05,P<0.01),the number of neurons in the hippocampal CA1 area,Nissl bodies and nucleus consolidation were improved. The ATP level in mitochondria and the levels of ATP,SOD,and GSH-PX in brain were significantly increased (P<0.05,P<0.01). The levels of ROS and MDA were significantly decreased (P<0.05,P<0.01). The structure of mitochondrial cristae in hippocampal CA1 region were relatively intact. The mRNA expression levels of GLUT4,PGC-1α and OPA1 were increased (P<0.05,P<0.01),and the expression of proteins related to the AMPK/OPA1 signaling pathway was significantly increased(P<0.05,P<0.01). Conclusion DBC can enhance learning and memory abilities,reduce neuronal damage in a rat model of coronary heart disease combined with cognitive impairment. The mechanism may be related to the reduction of oxidative stress damage in the brain,the activation of the AMPK/OPA1 signaling pathway,and the restoration of energy levels.

AIM:To investigate the effect of Huangqi-Danggui decoction(HQDG)on the brain tissue of rats with cerebral ischemia/reperfusion(I/R)injury for 7 d by regulating macroautophagy and chaperone-mediated autophagy(CMA),and to explore its mechanism.METHODS:Male SD rats were randomly divided into sham group,model group,HQDG group and Xuesaitong(XST)group.Determination of main chemical components of HQDG by liquid chro-matography-mass spectrometry.The model of middle cerebral artery occlusion/reperfusion in rats was established by the left modified thread embolism method,and the changes of cerebral blood flow were observed by laser speckle blood flow imager.Zea Longa score was used to observe the neurological deficit.HE staining was used to observe the degree of nerve cell injury.The changes of neurovascular unit and autophagosomes in brain tissue were observed by transmission electron microscopy.Immunohistochemical method was used to detect the expression of LC3,P62,lysosome-associated membrane protein-2A(LAMP-2A),heat shock protein 70(HSP70)and myocyte enhancer factor 2D(MEF2D)proteins.Western blot was used to detect the expression of autophagy-related proteins P62 and LC3-Ⅱ/LC3-I.RESULTS:Compared with the sham group,the neurological deficit score in model group was significantly higher(P<0.01).A large number of nerve cells showed necrosis and nuclear dissolution,with the cell arrangement being disordered.The number of autophagosomes increased.The protein expression levels of LC3,LAMP-2A,HSP70 and MEF2D in brain tissue increased,while the ex-pression level of P62 protein decreased(P<0.05 or P<0.01).Compared with the model group,the scores of neurological deficit in brain tissue in HQDG and XST groups were significantly lower(P<0.01).Cell damage was significantly re-duced.The number of autophagosomes further increased.The expression levels of LAMP-2A,HSP70,MEF2D and P62 proteins in brain tissue decreased,while the expression levels of LC3-Ⅱ/LC3-I protein increased(P<0.05 or P<0.01).CONCLUSION:HQDG can alleviate cerebral ischemia/reperfusion injury in rats and exert neuroprotective effects by ac-tivating macroautophagy and reducing CMA.

Damage to organelles plays a significant role in myocardial ischemia/reperfusion injury,which results in the dysfunction of mitochondria and other related organelles.The communication between mitochondria and other organ-elles can also affect the development of myocardial ischemia/reperfusion injury.For instance,the mitochondria-associated endoplasmic reticulum membrane provides a"seamless connection"and regulates the exchange of organelles and metabolites(such as ions,lipids and proteins)between the mitochondria and the endoplasmic reticulum,which subse-quently affects myocardial ischemia/reperfusion injury.However,there is a lack of studies regarding the interaction be-tween mitochondria and related organelles,which is a critical component in triggering myocardial ischemia/reperfusion inju-ry.Therefore,this article describes the role of mitochondrial crosstalk with endoplasmic reticulum,lysosomes and nuclei in myocardial ischemia/reperfusion injury,and aims to provide a theoretical basis for targeting mitochondrial crosstalk with other organelles in the treatment of myocardial ischemia/reperfusion injury.

Objective To investigate the value of deep learning(DL)model based on integrated 18F-FDG PET/MRI for evaluating cerebral metabolic status around cerebral infarction.Methods A total of 46 patients with cerebral infarction caused by unilateral internal carotid artery(ICA)or middle cerebral artery(MCA)steno-occlusion were retrospectively collected.Based on integrated 18F-FDG PET/MRI,DL model was used to automatically segment cerebral infarction area.Asymmetry index(AI)was used to evaluate the volume of reduced metabolic areas in the segmented affected frontal lobe,temporal lobe,parietal lobe,occipital lobe and cerebral hemisphere of cerebral infarction area as well as their proportions,while their correlations with National Institutes of Health stroke scale(NIHSS)score of neurological function were analyzed.Results Among 46 patients,the volume of decreased metabolism in the affected temporal lobe,parietal lobe and cerebral hemisphere was(41.35±10.52)ml,(65.58±14.82)ml and(178.89±34.23)ml,respectively,all positively correlated with NIHSS scores(rs=0.359,0.343,0.362,all P＜0.05).The proportion of the reduced metabolic volume in the affected frontal lobe,temporal lobe,parietal lobe and cerebral hemisphere was(45.68±10.35)%,(42.32±10.19)%,(45.05±9.44)%and(44.11±8.63)%,respectively,all positively correlated with NIHSS scores(rs=0.344,0.340,0.439,0.393,all P＜0.05).Conclusion DL model based on integrated 18F-FDG PET/MRI was of important clinical value for evaluating cerebral metabolic state around cerebral infarction.

Objective To explore the effect and possible mechanism of aerobic exercise and empagliflozin(EMPA)on isoproterenol(ISO)-induced pathological cardiac remodeling.Methods Mice were divided randomly into control(Con),ISO,exercise(EX)+ISO,EMPA+ISO,and EX+EMPA+ISO groups.Mice in the EX groups were trained continuously for 6 weeks,mice in the EMPA groups were gavaged continuously for 4 weeks,and mice in the ISO groups were injected subcutaneously with ISO for 7 days before dissection.After euthanasia,the whole heart mass index,left heart mass index,heart mass to tibial length ratio,and left heart mass to tibial length ratio were calculated by weighing and measuring.Pathological changes,collagen fiber deposition,and myocardial cell cross-sectional area in the hearts were detected by hematoxylin and eosin,Sirius red,and wheat germ agglutinin staining.The expression levels of genes and proteins related to cardiac fibrosis and hypertrophy,macrophage infiltration,ferroptosis,and the phosphoinositide 3-kinase(PI3K)/AKT pathway were examined by quantitative reverse transcription-polymerase chain reaction,Western Blot,and immunofluorescence staining.Results(1)The whole heart mass index,left heart mass index,heart mass to tibial length ratio,and left heart mass to tibial length ratio showed downward trends in the EX+ISO group compared with the ISO group.The whole heart mass index and left heart mass index were significantly decreased in the EMPA+ISO group(P＜0.01,P＜0.05),and the heart mass to tibial length ratio and left heart mass to tibial length ratio were both down regulated.Mice in the EX+EMPA+ISO group had a significant decrease in whole heart mass index(P＜0.05),and the other three indicators were all down-regulated.(2)Myocardial cells were more orderly in the three intervention groups compared with the ISO group,with significant reductions in inflammatory cell infiltration(P＜0.01),the area of cardiac fibrosis,and the cross-sectional area of myocardial cells(P＜0.001).(3)The mRNA and protein expression levels of Col 1 and Anp were significantly reduced in the three intervention groups compared with the ISO group(P＜0.05,P＜0.01,P＜0.001).Col 3 mRNA expression significantly reduced in the EMPA+ISO and EX+EMPA+ISO groups(P＜0.05),and showed a downward trend in the EX+ISO group.(4)Macrophage infiltration and IL-6 mRNA levels were significantly reduced in the three intervention groups compared with the ISO group(P＜0.05,P＜0.01,P＜0.001).(5)Nrf2 and Gpx4 mRNA levels were upregulated in the three intervention groups compared with the ISO group,with a significant increase in GPX4 protein expression(P＜0.01,P＜0.001)and a significant decrease in HO-1 protein expression(P＜0.01,P＜0.001).(6)Pi3k mRNA levels were significantly increased in the EX+ISO group compared with the ISO group(P＜0.05),and Pi3k mRNA was upregulated in the EMPA+ISO and EX+EMPA+ISO groups.Akt mRNA levels showed an upward trend in the three intervention groups.PI3K and phospho-AKT protein levels were significantly increased in the EX+ISO group(P＜0.01,P＜0.05),and showed an increasing trend in the EMPA+ISO and EX+EMPA+ISO groups.Conclusions Moderate intensity aerobic exercise,the novel hypoglycemic drug EMPA,and their combination can alleviate ISO-induced pathological cardiac remodeling,possibly via a mechanism related to activation of the PI3K/AKT signaling pathway and inhibition of cardiac ferroptosis.

Objective:To evaluate the relationship between intracerebroventricular glial cell line-derived neurotrophic factor (GDNF)-induced improvement in long-term postoperative cognitive function and expression of PKMζ and Kalirin in the hippocampus of neonatal rats.Methods:Sixty 7-day old Sprague-Dawley rats, male or female, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), GDNF group (group G), surgery group (group S) and surgery plus GDNF group (group S+ G). Group C did not receive anesthesia, surgery or drug treatment. Group G received intracerebroventricular injection of 0.3 μg recombinant rat GDNF. Group S and group S+ G underwent right carotid artery exposure surgery under 3% sevoflurane anesthesia, and in addition group S+ G received intracerebroventricular injection of GDNF. The Barnes maze test and the fear conditioning test were performed starting from postnatal day 33. The animals were then sacrificed under sevoflurane anesthesia after behavioral testing, the brains were obtained and divided into 2 halves sagittally along the midline. The left half of the brain was used for Golgi staining to observe dendritic morphology and measure dendritic spine density. The hippocampal protein was extracted from the right half of the brain to detect the expression of PKMζ and Kalirin by Western blot. Results:Compared with group C, the time to identify the target box in the Barnes maze test was significantly prolonged, the context-related freezing time in the fear conditioning test was shortened, the total dendritic length, the number of branches, the number of intersections in sholl analysis and spinal density in the hippocampus were reduced, and the expression of PKMζ and Kalirin was down-regulated in group S ( P<0.05), and no significant change was found in the aforementioned parameters in group G ( P>0.05). Compared with group S, the time to identify the target box in the Barnes maze test was significantly shortened, the context-related freezing time in the fear conditioning test was prolonged, the total dendritic length, the number of branches, the number of intersections in sholl analysis and spinal density in the hippocampus were increased, and the expression of PKMζ and Kalirin was up-regulated in group S+ G ( P<0.05). Conclusions:The mechanism by which intracerebroventricular GDNF improves long-term postoperative cognitive function may be related to up-regulating the expression of PKMζ and Kalirin and promoting the development of dendrites and dendritic spines in the hippocampus of neonatal rats.