ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer （NSCLC） based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/C/EBP homologous protein （CHOP） signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line （A549/cisplatin） were randomly divided into four groups： Blank control group （0.9% sodium chloride）， cisplatin group （5 µg·g^-1cisplatin）， Shenmai injection group （5.2 mg·g^-1 Shenmai injection）， and combination therapy group （5.2 mg·g^-1 Shenmai injection +5 µg·g^-1cisplatin）. The drug intervention lasted for 4 weeks， and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin （HE） staining was performed to observe tumor tissue pathology. Transmission electron microscopy （TEM） was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK， ATF4， and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein （BIP）， PERK， phosphorylated PERK （p-PERK）， eukaryotic translation initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， ATF4， CHOP， B-cell lymphoma -2 （Bcl-2）， and Bcl-2 Associated X protein （Bax）. A549/cis cells were divided into blank group： Blank control group （normal culture medium）， cisplatin group （23.3 µmol·L^-1 cisplatin）， Shenmai Injection group （20 g·L^-1 Shenmai injection）， and combination therapy group （20 g·L^-1 Shenmai injection+23.3 µmol·L^-1 cisplatin）. Cell counting kit-8 （CCK-8） method was used to detect cell viability， TEM was used to observe the morphology of endoplasmic reticulum， and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group， the combination therapy group showed increased body weight （P<0.05）， decreased tumor volume （P<0.05）， and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK， ATF4， and CHOP increased （P<0.05）. Western blot revealed elevated protein expression levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP， and Bax （P<0.05）， while Bcl-2 expression decreased （P<0.05）. As shown in the in vitro experiment， compared with the cisplatin group， the combination therapy group exhibited a reduced cell survival rate （P<0.05）. TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP and Bax （P<0.05）， with decreased Bcl-2 expression （P<0.05）. ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC， which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.

This article systematically analyzed the historical evolution of the name， origin， harvesting and others of Longan Arillus by referring to the ancient and modern literature， in order to provide a foundation for developing famous classical formulas containing this herb. After textual research， it indicated that Longan Arillus was first recorded under the name of longan in Shennong Bencaojing of the Han dynasty. During the Ming and Qing dynasties， Longan Arillus gradually replaced longan as the standard name recorded in the materia medica， with additional aliases including Yizhi， Lizhinu and Yuanyan. The source of Longan Arillus used in the past dynasties was the arillus of the Sapindaceae plant Dimocarpus longan. The production regions recorded in the past dynasties were mainly Fujian， Guangdong， Guangxi， Hainan， Sichuan and others. Since the Qing dynasty， Longan Arillus produced in Fujian， Guangdong and Guangxi have been regarded as the finest and authentic varieties， with Fujian， Guangxi， and Guangdong remaining the primary authentic production areas today. In ancient times， the fruits were primarily harvested in August of the lunar calendar. However， modern longan cultivation typically involves harvesting ripe fruits during summer and autumn. Post-harvest processing involves removing moisture through sun-drying or baking before drying for medicinal use. Throughout history， processing methods have primarily focused on raw product， though techniques such as wine soaking and powdering have also been employed. Since modern times， it has been concluded that its quality is the best one with thick flesh， sweet taste， brownish-yellow color and tender texture. Longan Arillus possesses a sweet and warm nature， entering the heart and spleen meridians. Its primary functions are tonifying the heart and spleen， nourishing the blood and calming the spirit， which is consistent in ancient and modern times. Based on the textual research， it is suggested to use the arillus of D. longan when developing the famous classical formulas containing Longan Arillus. Processing methods should be selected according to the formula requirements， where no specific processing is indicated， the raw products is recommended for medicinal use.

ObjectiveTo address the limitations of the current quality standard for Polygalae Radix（PR）， which relies on a single component for quality assessment and struggles to holistically control its intrinsic quality， by constructing a comprehensive quality evaluation system integrating "macro-characterization of chemical profile， synchronous quantification of multiple index components， and quantitative analysis of multi-components by single marker（QAMS） for key component groups". This study aims to facilitate the scientific revision of the quality standard for PR. MethodsHigh performance liquid chromatography（HPLC） characteristic chromatograms were established for 11 batches of PR medicinal materials（YZ）， 10 batches of PR decoction pieces（YP）， and 10 batches of licorice-processed PR decoction pieces（ZYZ）， followed by similarity evaluation and identification of common peaks. HPLC-QAMS was developed for xanthones（sibiricaxanthone B， polygalaxanthone Ⅺ， polygalaxanthone Ⅲ） in the characteristic chromatograms. Simultaneously， the external standard method（ESM） was used to determine the contents of the corresponding xanthones and 3，6'-disinapoyl sucrose in YZ， YP， and ZYZ， followed by multivariate statistical analysis and Spearman correlation analysis. ResultsThe similarity between the characteristic chromatograms of 31 batches of PR samples and the reference chromatogram was>0.9. A total of 13 common peaks were identified， and 10 of these peaks were characterized through reference standard comparison. The successfully constructed QAMS method showed that the relative correction factors（RCFs） of sibiricaxanthone B and polygalaxanthone Ⅺ to polygalaxanthone Ⅲ were 0.76 and 0.88， and their relative retention times（RRTs） were 0.85 and 0.97， respectively. The results calculated by the QAMS method showed no significant difference from those obtained by the ESM. According to the limit standard for polygalaxanthone Ⅲ in the 2020 edition of the Pharmacopoeia of the People's Republic of China（hereinafter referred to as the Chinese Pharmacopoeia）， the pass rate of 31 batches of samples was only 19.35%. Multivariate statistical analysis indicated certain compositional differences between different batches of YZ and YP， as well as between YP and ZYZ， with 3，6'-disinapoyl sucrose identified as the main differentiating component. Furthermore， correlation analysis revealed that the content of polygalaxanthone Ⅲ was positively correlated with the contents of sibiricaxanthone B and polygalaxanthone Ⅺ， but showed no association with the content of 3，6'-disinapoyl sucrose. ConclusionIt is recommended that the content limit for polygalaxanthone Ⅲ in YZ，YP and ZYZ be revised to not less than 0.07%， or the total content of polygalaxanthone Ⅲ， sibiricaxanthone B and polygalaxanthone Ⅺ be not less than 0.18%. The newly established triple quality control model of "holistic control via characteristic chromatograms， precise quantification of oligosaccharide esters， and efficient detection of xanthones by QAMS" provides a systematic and precise solution for quality evaluation of PR and similar Chinese herbal medicines.

ObjectiveTo investigate whether Shenmai injection （SMI） improves cisplatin resistance in non-small cell lung cancer （NSCLC） by modulating lipid metabolism and inducing ferroptosis. MethodsHuman lung adenocarcinoma cisplatin-resistant A549/DDP cells were divided into the following groups： Blank group， cisplatin group （23.3 μmol·L^-1 cisplatin）， SMI group （20 g·L^-1 SMI）， cisplatin combined with SMI group （23.3 μmol·L^-1 cisplatin + 20 g·L^-1 SMI）， cisplatin combined with ferroptosis inhibitor/inducer Ferrostatin-1/Erastin group （23.3 μmol·L^-1 cisplatin + 10 μmol·L^-1 Ferrostatin-1/5 μmol·L^-1 Erastin）， and cisplatin combined with SMI and Ferrostatin-1/Erastin group （23.3 μmol·L^-1 cisplatin + 20 g·L^-1 SMI + 10 μmol·L^-1 Ferrostatin-1/5 μmol·L^-1 Erastin）. Network pharmacology， transcriptomics and metabolomics， Cell Counting Kit-8 （CCK-8） assay， transmission electron microscopy （TEM）， colorimetric assays， and Western blot analysis were employed to evaluate the effects of these treatments on A549/DDP cell viability， lipid droplet formation， lipid metabolite levels， mitochondrial function， lipid peroxidation， glutathione （GSH） content， total and ferrous iron content， and effects on ferroptiosis and autophagy related protein expression levels. ResultsSMI improved cisplatin resistance in NSCLC mainly by targeting lipid metabolism-related pathways in A549/DDP cells， affecting tumor cell lipid metabolism via autophagy， ferroptosis， and glycerophospholipid metabolism pathways. Compared with the cisplatin group， the cisplatin combined with SMI group showed significantly decreased cell viability （P<0.01）， increased lipid droplet accumulation （P<0.01）， and reduced mitochondrial maximal respiration， basal respiration， mitochondrial membrane potential， GSH content， total iron， and ferrous iron （all P<0.01）. Mitochondrial reactive oxygen species （ROS） was significantly elevated（P<0.01）， and lipid peroxidation levels were significantly increased. Protein expression analysis showed significant downregulation of solute carrier family 7 member 11 （SLC7A11） and p62 （P<0.05，P<0.01） and upregulation of ferritin heavy chain （FTH） and microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） （P<0.05，P<0.01）. Compared with the cisplatin combined with SMI group， addition of Ferrostatin-1 significantly increased cell viability （P<0.05）， decreased mitochondrial ROS levels （P<0.05）， alleviated mitochondrial shrinkage， and reduced lipid peroxidation. Conversely， addition of Erastin further decreased cell viability （P<0.01）. ConclusionSMI improves cisplatin resistance in NSCLC by inducing oxidative stress， which may trigger ferroptosis through upregulation of lipophagy.

ObjectiveTo investigate the clinical application value of thromboelastographic parameters in assessing coagulation function by analyzing the thromboelastographic features of patients with primary liver cancer （PLC）， and to provide a basis for coagulation management and prognostic evaluation in liver cancer patients. MethodsA retrospective analysis was performed for 1 253 PLC patients who were admitted to The First Affiliated Hospital of Xi’an Jiaotong University from May 2015 to December 2022. According to the presence or absence of cirrhosis， the patients were divided into non-cirrhosis group with 262 patients and cirrhosis group with 991 patients， and according to the presence or absence of HBV infection， they were divided into HBV infection group with 1 055 patients and non-HBV infection group with 198 patients. The patients were stratified based on the severity of liver cirrhosis （Child-Pugh class and MELD score） and liver reserve function （indocyanine green retention rate at 15 minutes ［ICGR15］）， and thromboelastography was used to measure thromboelastographic parameters （reaction time ［R］， coagulation formation time ［K］， α-angle， maximum thrombosis amplitude ［MA］， and coagulation composite index ［CI］） and conventional coagulation markers. The t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Bonferroni correction method was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between grouips， and the Spearman test was used for correlation analysis. ResultsAmong the 991 patients in the cirrhosis group， 826 had Child-Pugh class A （5 — 6 points）， and 165 had Child-Pugh class B （7 — 9 points）； 812 had an MELD score of <10， and 179 had an MELD score of ≥10； 679 had an ICGR15 of <10%， and 294 had an ICGR15 of ≥10%. Compared with the patients with Child-Pugh class A， the patients with Child-Pugh class B had a significantly longer K time and significant reductions in α-angle， MA， and CI （all P <0.001）； compared with the MELD score <10 group， the MELD score ≥10 group had a significantly longer K time and significant reductions in α-angle， MA， and CI （all P<0.001）； compared with the ICGR15 <10% group， the ICGR15 ≥10% group had a significantly longer K time and a significant reduction in MA （both P <0.001）. Among the 1 253 patients， MA was strongly positively correlated with fibrinogen and platelet count （r=0.675 and 0.667， both P<0.001）； The MA had a weak correlation with Child-Pugh score， MELD score， and ICGR15 （r=-0.112， -0.250， and -0.117， all P<0.001）， while the K time，α-angle and CI were weakly correlated with the MELD score （r=0.222， -0.184， and -0.183， all P<0.001），R time was negatively correlated with ICGR15 （r=-0.080， P=0.005）. The HBV infection group had significantly higher MA and CI than the non-HBV infection group （P<0.05）. ConclusionThromboelastography can sensitively identify the hypocoagulable state associated with the progression of liver cirrhosis and the hypercoagulable tendency in HBV-related liver cancer， which provides an important reference for individualized anticoagulant therapy in clinical practice.

Depressive disorder is a prevalent mental illness characterized by pronounced and enduring symptoms of depression and cognitive impairment. The escalating pressures of modern society have led to a corresponding rise in the number of depressive disorder patients, particularly those exposed to adverse social, economic, political, and environmental factors which exacerbate the risk of this disorder. The pathogenesis of depressive disorder is multifaceted, encompassing oxidative stress, neuroplasticity alterations, neuroinflammation, neurotransmitter system imbalances, and intestinal microecological disruptions, among others. Clinically, conventional antidepressants are primarily predicated on the monoamine neurotransmitter hypothesis. This theory posits that depressive disorder can be ameliorated by regulating the levels of neurotransmitters within the body through a singular mechanism. However, the complex and multifaceted pathogenesis of depressive disorder results in limited selectivity for these drugs. Mitogen-activated protein kinase (MAPK) is a conserved serine/threonine kinase that plays a crucial role in various cellular physiological and pathological processes, including cell growth, differentiation, stress adaptation, and inflammatory response. It is instrumental in maintaining cellular homeostasis and regulating cellular responses. Numerous studies indicate that MAPK is involved in the pathogenesis and progression of depressive disorder through various pathogenesis. However, what deserves attention is that the interaction between the pathogenesis and dynamics of regulatory process remains unclear. Modulating MAPK has been shown to influence the onset and progression of depressive disorder, though the precise mechanism remains elusive. Within the MAPK family, aberrant activity of extracellular signal-regulated kinase (ERK) can damage hippocampal neurons and overactivate microglia, precipitating depressive disorder. Excessive activation of c-Jun N-terminal kinase (JNK) results in heightened neuronal apoptosis in the hippocampus and prefrontal cortex, and suppresses the expression of neurotrophic factors. p38, a key regulator in inflammatory reactions, can induce neuroinflammation when overactive, leading to depressive disorder. ERK, JNK, and p38 sub-pathways do not function in isolation but rather interact synergistically and/or antagonistically through shared activators and common target molecules. Consequently, these sub-pathways form a complementary and coordinated regulatory network. In addition, MAPK family members can jointly influence the process of depressive disorder by sharing upstream factors and regulating common downstream targets, and there is a lack of identification of their markers and screening for subgroups. The collective abnormal activities of these MAPK family members illuminate the underlying mechanisms of depressive disorder, suggesting that MAPK could serve as a potential therapeutic target for this disorder. As for the study of ERK, different models of depressive disorder have contradictory effects on its activity. The primary cause of these differences can be attributed to the distinct pathological environments utilized in the creation of depressive disorder models. In the future, it is suggested that we use the inducement of depressive disorder as a modeling standard to accurately simulate the onset of depressive disorder to carry out accurate treatment according to the causes of depressive disorder. Research shows that classic clinical drugs, novel MAPK inhibitors and certain traditional Chinese medicines can prevent and treat depressive disorder by regulating the MAPK signaling pathway. Research on MAPK remains limited, particularly concerning the permeability and cellular specificity across the blood-brain barrier and the identification of objective predictive markers. Although inhibitors face challenges, they also possess significant advantages and developmental potential. This paper systematically summarizes the current status of MAPK in the treatment of depressive disorder, in order to provide insights for researching the pathogenesis of depressive disorder and developing new antidepressant drugs.

Depressive disorder is a prevalent mental illness characterized by pronounced and enduring symptoms of depression and cognitive impairment. The escalating pressures of modern society have led to a corresponding rise in the number of depressive disorder patients, particularly those exposed to adverse social, economic, political, and environmental factors which exacerbate the risk of this disorder. The pathogenesis of depressive disorder is multifaceted, encompassing oxidative stress, neuroplasticity alterations, neuroinflammation, neurotransmitter system imbalances, and intestinal microecological disruptions, among others. Clinically, conventional antidepressants are primarily predicated on the monoamine neurotransmitter hypothesis. This theory posits that depressive disorder can be ameliorated by regulating the levels of neurotransmitters within the body through a singular mechanism. However, the complex and multifaceted pathogenesis of depressive disorder results in limited selectivity for these drugs. Mitogen-activated protein kinase (MAPK) is a conserved serine/threonine kinase that plays a crucial role in various cellular physiological and pathological processes, including cell growth, differentiation, stress adaptation, and inflammatory response. It is instrumental in maintaining cellular homeostasis and regulating cellular responses. Numerous studies indicate that MAPK is involved in the pathogenesis and progression of depressive disorder through various pathogenesis. However, what deserves attention is that the interaction between the pathogenesis and dynamics of regulatory process remains unclear. Modulating MAPK has been shown to influence the onset and progression of depressive disorder, though the precise mechanism remains elusive. Within the MAPK family, aberrant activity of extracellular signal-regulated kinase (ERK) can damage hippocampal neurons and overactivate microglia, precipitating depressive disorder. Excessive activation of c-Jun N-terminal kinase (JNK) results in heightened neuronal apoptosis in the hippocampus and prefrontal cortex, and suppresses the expression of neurotrophic factors. p38, a key regulator in inflammatory reactions, can induce neuroinflammation when overactive, leading to depressive disorder. ERK, JNK, and p38 sub-pathways do not function in isolation but rather interact synergistically and/or antagonistically through shared activators and common target molecules. Consequently, these sub-pathways form a complementary and coordinated regulatory network. In addition, MAPK family members can jointly influence the process of depressive disorder by sharing upstream factors and regulating common downstream targets, and there is a lack of identification of their markers and screening for subgroups. The collective abnormal activities of these MAPK family members illuminate the underlying mechanisms of depressive disorder, suggesting that MAPK could serve as a potential therapeutic target for this disorder. As for the study of ERK, different models of depressive disorder have contradictory effects on its activity. The primary cause of these differences can be attributed to the distinct pathological environments utilized in the creation of depressive disorder models. In the future, it is suggested that we use the inducement of depressive disorder as a modeling standard to accurately simulate the onset of depressive disorder to carry out accurate treatment according to the causes of depressive disorder. Research shows that classic clinical drugs, novel MAPK inhibitors and certain traditional Chinese medicines can prevent and treat depressive disorder by regulating the MAPK signaling pathway. Research on MAPK remains limited, particularly concerning the permeability and cellular specificity across the blood-brain barrier and the identification of objective predictive markers. Although inhibitors face challenges, they also possess significant advantages and developmental potential. This paper systematically summarizes the current status of MAPK in the treatment of depressive disorder, in order to provide insights for researching the pathogenesis of depressive disorder and developing new antidepressant drugs.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， harvesting and processing， and other aspects of Manjiao and Zanthoxyli Radix by referring to the herbal medicine， medical books， prescription books and other documents of the past dynasties， combined with the relevant modern research materials， in order to provide a basis for the development of famous classical formulas containing the two medicinal materials. According to the herbal textual research， Manjiao was first recorded in Shennong Bencaojing of the Han dynasty with aliases such as Zhujiao， Goujiao and Zhijiao. Throughout history， Manjiao was sourced from the stems and roots of Zanthoxylum armatum in the Rutaceae family， and its leaves and fruits can also be used in medicine. The traditional recorded production area was mainly in Yunzhong（now Tuoketuo region in Inner Mongolia）， with mentions in Zhejiang， Hunan， Fujian， Guangdong， Guangxi， Yunnan， Taiwan， and other provinces. Presently， this species is distributed from the south of Shandong， to Hainan， Taiwan， Tibet and other regions. The roots can be harvested year-round， while the fruits are harvested in autumn after maturity. In ancient times， the roots and stems were mostly used for brewing or soaking in wine， whereas nowadays， the roots are often sliced and then used as a raw material in traditional Chinese medicine， and the fruits should be stir-fried before use. Manjiao has a bitter taste and warm property， and was historically used to treat wind-cold dampness， joint pain， limb numbness， and knee pain. Modern researches have summarized its effects as dispelling wind， dispersing cold， promoting circulation， and relieving pain， and it is used for treating rheumatoid arthritis， toothache， bruises， as well as an anthelmintic. Zanthoxyli Radix initially known as Rudi Jinniugen， recorded in Bencao Qiuyuan of the Qing dynasty， with the alternate name of Liangbianzhen. In recent times， it is more commonly referred to as Liangmianzhen， sourced from the dried roots of Z. nitidum of the Rutaceae family， mainly produced in Guangxi and Guangdong. It can be harvested throughout the year， cleaned， sliced， and dried after harvesting. Zanthoxyli Radix is pungent， bitter， warm and slightly toxic， with the functions of promoting blood circulation， removing stasis， relieving pain， dispelling wind， and resolving swelling. Based on the results of herbal textual research， it is clarified that the ancient Manjiao and the modern Zanthoxyli Radix are not the same species. This article corrects the mistaken belief of by previous scholars that Zanthoxyli Radix is the same as ancient Manjiao， and suggests that formulas described as Manjiao should use Z. armatum as the medicinal herb， while those described as Liangmianzhen or Rudi Jinniu should use Z. nitidum. The processing was performed according to the processing requirements prescribed in the formulas， otherwise， the raw products are recommended for use.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， harvesting and processing， and other aspects of Manjiao and Zanthoxyli Radix by referring to the herbal medicine， medical books， prescription books and other documents of the past dynasties， combined with the relevant modern research materials， in order to provide a basis for the development of famous classical formulas containing the two medicinal materials. According to the herbal textual research， Manjiao was first recorded in Shennong Bencaojing of the Han dynasty with aliases such as Zhujiao， Goujiao and Zhijiao. Throughout history， Manjiao was sourced from the stems and roots of Zanthoxylum armatum in the Rutaceae family， and its leaves and fruits can also be used in medicine. The traditional recorded production area was mainly in Yunzhong（now Tuoketuo region in Inner Mongolia）， with mentions in Zhejiang， Hunan， Fujian， Guangdong， Guangxi， Yunnan， Taiwan， and other provinces. Presently， this species is distributed from the south of Shandong， to Hainan， Taiwan， Tibet and other regions. The roots can be harvested year-round， while the fruits are harvested in autumn after maturity. In ancient times， the roots and stems were mostly used for brewing or soaking in wine， whereas nowadays， the roots are often sliced and then used as a raw material in traditional Chinese medicine， and the fruits should be stir-fried before use. Manjiao has a bitter taste and warm property， and was historically used to treat wind-cold dampness， joint pain， limb numbness， and knee pain. Modern researches have summarized its effects as dispelling wind， dispersing cold， promoting circulation， and relieving pain， and it is used for treating rheumatoid arthritis， toothache， bruises， as well as an anthelmintic. Zanthoxyli Radix initially known as Rudi Jinniugen， recorded in Bencao Qiuyuan of the Qing dynasty， with the alternate name of Liangbianzhen. In recent times， it is more commonly referred to as Liangmianzhen， sourced from the dried roots of Z. nitidum of the Rutaceae family， mainly produced in Guangxi and Guangdong. It can be harvested throughout the year， cleaned， sliced， and dried after harvesting. Zanthoxyli Radix is pungent， bitter， warm and slightly toxic， with the functions of promoting blood circulation， removing stasis， relieving pain， dispelling wind， and resolving swelling. Based on the results of herbal textual research， it is clarified that the ancient Manjiao and the modern Zanthoxyli Radix are not the same species. This article corrects the mistaken belief of by previous scholars that Zanthoxyli Radix is the same as ancient Manjiao， and suggests that formulas described as Manjiao should use Z. armatum as the medicinal herb， while those described as Liangmianzhen or Rudi Jinniu should use Z. nitidum. The processing was performed according to the processing requirements prescribed in the formulas， otherwise， the raw products are recommended for use.

The combination of Aidi Injection(ADI) and doxorubicin(DOX) is a common strategy in the treatment of cancer, which can achieve synergistic anti-tumor effects while attenuating the cardiotoxicity caused by DOX. This study aims to investigate the mechanism of ADI in attenuating DOX-induced cardiotoxicity by multi-omics. DOX was used to induce cardiotoxicity in mice, and the cardioprotective effects of ADI were evaluated based on biochemical indicators and pathological changes. Based on the results, transcriptomics, proteomics, and metabolomics were employed to analyze the changes of endogenous substances in different physiological states. Furthermore, data from multiple omics were integrated to screen key regulatory pathways by which ADI attenuated DOX-induced cardiotoxicity, and important target proteins were selected for measurement by ELISA kits and immunohistochemical analysis. The results showed that ADI significantly reduced the levels of cardiac troponin T(cTnT) and N-terminal pro-B-type natriuretic peptide(NT-proBNP) and effectively ameliorated myocardial fibrosis and intracellular vacuolization, indicating that ADI showed therapeutic effect on DOX-induced cardiotoxicity. The transcriptomics analysis screened out a total of 400 differentially expressed genes(DEGs), which were mainly enriched in inflammatory response, oxidative stress, and myocardial fibrosis. After proteomics analysis, 70 differentially expressed proteins were selected, which were mainly enriched in the inflammatory response, cardiac function, and energy metabolism. A total of 51 differentially expressed metabolites were screened by the metabolomics analysis, and they were mainly enriched in multiple signaling pathways, including the inflammatory response, lipid metabolism, and energy metabolism. The integrated data of multiple omics showed that linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism pathways played an important role in DOX-induced cardiotoxicity, and ADI may exert therapeutic effects by modulating these pathways. Target validation experiments suggested that ADI significantly regulated abnormal protein levels of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), prostaglandin H2(PGH2), and prostaglandin D2(PGD2) in the model group. In conclusion, ADI may attenuate DOX-induced cardiotoxicity by regulating linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism, thus alleviating inflammation of the body.
Doxorubicin/toxicity* ; Animals ; Mice ; Cardiotoxicity/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Proteomics ; Metabolomics ; Injections ; Humans ; Multiomics