Aconiti Lateralis Radix Praeparata (Fuzi) represents a significant traditional Chinese medicine (TCM) that exhibits both notable pharmacological effects and toxicity. Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components, primarily diterpenoid alkaloids. To comprehensively analyze the chemical variations between different Fuzi products, ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) was employed to systematically characterize Shengfuzi, Heishunpian and Baifupian. A total of 249 diterpenoid alkaloids present in Shengfuzi were identified, while only 111 and 61 in Heishunpian and Baifupian were detected respectively, indicating substantial differences among these products. An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers. Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples, 8 robust markers distinguishing these products were identified, including AC1-propanoic acid-3OH, HE-glucoside, HE-hydroxyvaleric acid-2OH, dihydrosphingosine, N-dodecoxycarbonylvaline and three unknown compounds. Additionally, the MS imaging (MSI) technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi, revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian. The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products. This research provides valuable insights into the material basis for future investigations of different Fuzi products.
Diterpenes/chemistry* ; Alkaloids/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Aconitum/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Metabolomics ; Mass Spectrometry/methods* ; Plant Roots/chemistry* ; Molecular Structure

Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety, particularly concerning the composition and content levels of trace ingredients. Panax notoginseng Saponins Injection (PNSI), widely used in China for treating acute cardiovascular diseases, contains low-abundance (10%-25%) and trace saponins in addition to its five main constituents (notoginsenoside R₁, ginsenoside Rg₁, ginsenoside Re, ginsenoside Rb₁, and ginsenoside Rd). This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation types. To achieve this, a liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method employing multiple ions monitoring (MIM) was developed. A "post-column valve switching" strategy was implemented to eliminate highly abundant peaks (NR₁, Rg₁, and Re) at 26 min. A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards, with digoxin as the internal standard. This study evaluated 119 batches of PNSI from seven vendors, revealing significant variability in trace saponin levels among different vendors and formulation types. These findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical safety. Standardization of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases.
Ginsenosides ; Saponins ; Chemometrics ; Panax notoginseng ; Cardiovascular Diseases ; Chromatography, Liquid ; Tandem Mass Spectrometry

Achyranthes bidentata Blume is widely used as a traditional Chinese medicine with the effects of nourishing the liver and kidneys and strengthening muscles and bones. In this work, a rapid and simple strategy was developed for characterizing phytoecdysteroids by ultra-high-performance liquid chromatography coupled with liner ion trap-Orbitrap mass spectrometry using electrospray ionization in the negative mode. As a result, 47 phytoecdysteroids were unambiguously or tentatively characterized. Among them, seven known compounds were identified according to the reference standards along with molecular formula, retention time and fragmentation patterns, while others were mostly potential new compounds. Through targeted isolation, the structures of three new compounds were determined by NMR spectra, which were consistent with LC-MS characterization. The present study provides an efficient method to deeply characterize phytoecdysteroids.
Achyranthes/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Gas Chromatography-Mass Spectrometry ; Mass Spectrometry ; Medicine, Chinese Traditional ; Spectrometry, Mass, Electrospray Ionization/methods*

Objective:To understand the clinical features and outcomes of chronic liver diseases overlapping with CMV infection.Methods:Clinical characteristics, treatment and outcome of patients of chronic liver diseases overlapping with CMV infection were analyzed retrospectively. T-test was used for measurement data and χ2 test was used for count data. All measurement data were expressed by ( ± s). P > 0.05 was not determined as significant. P < 0.05 was regarded as statistically significant. Results:Chronic liver diseases overlapping with CMV infections had similar clinical features. Etiopathogenic treatment + symptomatic supportive treatment + CMV overlapping infection treatment (including antiviral therapy, corticosteroids consideration, clearing heat and traditional Chinese choleretic medicine, etc) were the primary principles of therapy. The incidence of cytomegalovirus infection accounted for 4.125% during the corresponding hospitalization period. Cytomegalovirus infection had relatively caused liver function damage in patients with milder clinical symptoms and signs. Biochemical indicators before and after treatment showed that there was no significant difference in total bilirubin (TBil) before (262.93 ± 178.944) μmol/L and after one week of treatment (245.08 ± 179.332) μmol/L ( P > 0.05). However, when TBIL was compared with three (156.58 ± 147.461) μmol/L and four weeks (103.39 ± 102.218) μmol/L) of treatment, the decrease was significant ( P < 0.05, P < 0.01). Alanine aminotransferase (ALT) after one week (293.57 ± 467.438) U/L ( P < 0.01) of treatment was significantly lower than before treatment (782.34 ± 828.801) U/L. Gamma-glutamyl transferase (GGT) after treatment (202.52 ± 155.174)U/L was significantly lower than before treatment(280.69 ± 205.619)U/L). Total bile acid (TBA) was increased after treatment (198.04 ± 155.174)μmol/L, when compared with that of before treatment (62.93 ± 178.944)μmol/L. Biochemical indicators of liver diseases had shown typical features of cholestasis, and the slow and reduced flow of bile acid was tracked and observed. Compared with the advanced group (182.45 ± 214.169) umol/L, the total bilirubin in inflammation group (50.36 ± 26.282) umol/L was decreased ( P < 0.05). Moreover, advanced group (122.18 ± 106.780) umol/L ( P < 0.05) had elevated total bile acid normalization rate than that of bile acid group (54.82 ± 56.123) umol/L, and the inflammatory phase had significantly better outcome than those with advanced-stage. Conclusion:Chronic liver diseases overlapping with cytomegalovirus infection has a good therapeutic outcome in the inflammatory phase, but in the advanced-stage; the therapeutic efficacy and outcome is poor and perilous.

Objective: To investigate the clinical characteristics of extremely severe burn patients complicated with severe inhalation injury caused by dust explosion. Methods: The medical records of 13 extremely severe burn patients complicated with severe inhalation injury in August 2nd Kunshan factory aluminum dust explosion accident, who were admitted to the First Affiliated Hospital of Soochow University on August 2nd, 2014, were retrospectively analyzed. The following indicators were collected: (1) Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score and Sequential Organ Failure Assessment (SOFA) score at post admission hour (PAH) 24. (2) Prognosis, death time, causes of death, and the mortality of patients with different sexes. (3) The number of times of airway electronic bronchoscopy, airway characteristics, and the corresponding onset time. (4) The number and result of microorganism culture of lesion tissue during the leukoplakia formation stage. Detection of Pseudomonas aeruginosa in patients with and without leukoplakia in airway mucosa. Fisher′s exact probability test was used to detect the mortality of patients with different sexes. Kappa test was used to detect the relevancy between leukoplakia and Pseudomonas aeruginosa. Results: (1) The APACHE Ⅱ score of patients of this group at PAH 24 was (19±3) points, and the SOFA score was (12±3) points. (2) Eight patients survived, while 5 patients died, and the time of death was 19-46 (34±10) d after injury. The main cause of death was multiple organ dysfunction syndrome, which was secondary to severe infection. One of the 7 male patients and 4 of the 6 female patients died, but there was no significantly statistical difference in mortality between patients of the two sexes (P>0.05). (3) Airway electronic bronchoscopy was performed 4-25 (10±5) times among patients of this group. Hyperemia and edema were found in the airway mucosa of all the 13 patients 2-3 weeks after injury; ulcer was found in the airway mucosa of 5 patients 2-4 weeks after injury; leukoplakia was found in the airway mucosa of 7 patients 4-14 weeks after injury; granulation formed in the airway mucosa of 7 patients 10-15 weeks after injury, and airway patency was affected, which was solved after local clamping or replacement of lengthened tracheal cannula. (4) During the leukoplakia formation stage, 19 cases of microorganism culture were performed basing on airway lesion tissue, and the results were 15 cases of Pseudomonas aeruginosa, 5 cases of Acinetobacter baumannii, 2 cases of Serratia marcescens, as well as 1 case of Stenotrophomonas maltophilia, Burkholderia cepacia, and Proteus mirabilis each. Among 7 patients with airway mucosa leukoplakia, 6 patients were detected with Pseudomonas aeruginosa. Among 6 patients without airway mucosa leukoplakia, 1 patient was detected with Pseudomonas aeruginosa. The appearance of leukoplakia was consistent with the detection of Pseudomonas aeruginosa (Kappa=0.69, P<0.05). Conclusions Most of these extremely severe burn patients complicated with severe inhalation injury caused by dust explosion survived, and there was no significant gender difference in mortality. Electronic bronchoscopy showed that the early manifestations of airway mucosa were hyperemia and edema, followed by varying degrees of erosion, ulcer, leukoplakia, and granulation formation, etc. Leukoplakia may be relevant to Pseudomonas aeruginosa infection.

Objective To detect the small molecular metabolite profiles of urine from patients with acute pancreatitis (AP) in different severity,and screen the differential metabolites that have potential diagnostic value for AP and its severity.Methods Urine samples were collected from 65 AP patients (MSAP and SAP 29,MAP 36) in the First Affiliated Hospital of Soochow University,and 25 healthy volunteers served as controls.The liquid chromatograph mass spectrometer (LC-MS) combined method was used to detect urine small molecule metabolites of AP patients and healthy controls.Multivariate statistical analysis was used to establish and validate the principal component analysis (PCA) model and partial least squares discriminate analysis (PLS-DA) model to select the differential metabolites.Results PCA model had a good degree of interpretation (R2X ＞0.5),and each group of urine samples showed a good distinction between clustering trends,and good classification models were obtained.In the PLS-DA model,the differences among groups were further highlighted,and samples of each group showed distinct differentiation between clusters,with high predictability (Q2 ＞ 0.7).The model was reliable and effective indicated by the PLS-DA permutation test.17 differential metabolites were screened out by comparing AP with control.A diagnostic model constructed with 7 differential metabolites including nonanedioic acid,succinic acid semialdehyde,D-beta-hydroxy butyric acid,acetylcarnitine,angelic acid,sebacic acid and hippuric acid had a high diagnostic value for AP,with the sensitivity of 100％ and the specificity of 94％.Then control,MAP and MSAP + SAP group were compared with each other,and it was found that the model integrating urine succinic acid semialdehyde,angelic acid,D (-)-beta-hydroxy butyric acid,malic acid and acetylcarnitine had a good diagnostic value for SAP,with the sensitivity and specificity of both 90％.Conclusions LC-MS metabolomics can effectively identify the changes of urine metabolism in patients with different severity of AP.The screened differential metabolites have the potential clinical value in the diagnosis and classification of AP.

Euphorbia kansui is a commonly used traditional Chinese medicine for the treatment of edema, pleural effusion, and asthma, etc. According to the previous researches, terpenoids in E. kansui possess various biological activities, e.g., anti-virus, anti-allergy, antitumor effects. In this work, twenty five terpenoids were isolated from E. kansui, including thirteen ingenane- and eight jatrophane-type diterpenoids (with two new compounds, kansuinin P and Q) and four triterpenoids. Eighteen of them were analyzed by MTS assay for in vitro anticancer activity in five human cancer cell lines. Structure-activity relationship for 12 ingenane-type diterpenoids in colorectal cancer Colo205 cells were preliminary studied. Significant anti-proliferation activities were observed in human melanoma cells breast cancer MDA-MB-435 cells and Colo205 cells. More than half of the isolated ingenane-type diterpenoids showed inhibitory activities in MDA-MB-435 cells. Eight ingenane- and one jatrophane-type diterpenoids possessed much lower IC values in MDA-MB-435 cells than positive control staurosporine. Preliminary structure-activity relationship analysis showed that substituent on position 20 was important for the activity of ingenane-type diterpenoids in Colo205 cells and substituent on position 3 contributed more significant biological activity of the compounds than that on position 5 in both MDA-MB-435 and Colo205 cells.
Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Euphorbia ; chemistry ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; physiopathology ; Structure-Activity Relationship ; Terpenes ; chemistry ; pharmacology

Arisaema heterophyllum Blume is one of the three medicinal plants known as traditional Chinese medicine Rhizoma Arisaematis (RA). RA has been popularly used to treat patients with convulsions, inflammation, and cancer for a long time. However, the underlying mechanisms for RA effects are still unclear. The present study was designed to determine the cytotoxicity of agglutinin isolated from Arisema heterophyllum Blume (AHA) and explore the possible mechanisms in human non-small-cell lung cancer A549 cells. AHA with purity up to 95% was isolated and purified from Arisaema heterophyllum Blume using hydrophobic interaction chromatography. AHA dose-dependently inhibited the proliferation of A549 cells and induced G phase cell cycle arrest. AHA induced apoptosis by up-regulating pro-apoptotic Bax, decreasing anti-apoptotic Bcl-2, and activating caspase-9 and caspase-3. In A549 cells treated with AHA, the PI3K/Akt pathway was inhibited. Furthermore, AHA induced increase in the levels of ER stress markers such as phosphorylated eukaryotic initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), inositol-requiring enzyme 1α (IRE1α), and phosphorylated c-Jun NH-terminal kinase (p-JNK). AHA also induced autophagy in A549 cells. Staining of acidic vesicular organelles (AVOs) and increase in the levels of LC3II and ATG7 were observed in AHA-treated cells. These findings suggested that AHA might be one of the active components with anti-cancer effects in Arisaema heterophyllum Blume. In conclusion, cytotoxicity of AHA on cancer cells might be related to its effects on apoptosis and autophagy through inhibition of PI3K/Akt pathway and induction of ER stress.
A549 Cells ; Agglutinins ; pharmacology ; Apoptosis ; drug effects ; Arisaema ; chemistry ; Autophagy ; drug effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; metabolism ; physiopathology ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Endoplasmic Reticulum Stress ; drug effects ; Humans ; MAP Kinase Signaling System ; drug effects ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism

Objective To analyze the changes in serum procalcitonin (PCT) in patients with extremely severe burn and sepsis,and to evaluate its clinical significance in the prognosis of patients.Methods Thirteen patients with extremely severe burn and sepsis injured in the aluminum dust explosion accident,which occurred in Kunshan of Jiangsu province,were admitted to our unit on August 2nd,2014.They were involved in this retrospective study and divided into death group (n =5) and survival group (n =8) according to the outcome.Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score and Sequential Organ Failure Assessment (SOFA) score at post admission hour (PAH) 24 were compared among the patients between two groups.Serum level of PCT,serum level of C-reactive protein (CRP),white cell count,neutrophils,platelet count,level of aspartate transaminase (AST),level of prealbumin (PA),level of creatinine,level of urea nitrogen,and level of blood sodium were compared among the patients between two groups in post admission week (PAW) 1,2,3,and 4.Data were processed with Fisher's exact test,analysis of variance for repeated measurement,t test,and Mann-Whitney test.Receiver operating characteristic (ROC) curves of serum PCT values were plotted to evaluate the predictive value for death of 13 patients in PAW 3 and 4.Results The differences in APACHE Ⅱ score and SOFA score at PAH 24 and serum level of CRP,white cell count,level of AST,level of creatinine,level of urea nitrogen,and level of blood sodium from PAW 1 to 4 of the patients between two groups were not statistically significant (with t values from-1.164 to0.587,Zvalues from-1.872 to-0.442,Pvalues above0.05).The serum levels of PCT in patients of death group in PAW 3 and 4 were respectively (15.8 ± 14.9) and (13.6 ± 5.6) ng/mL,which were significantly higher than those of survival group [(2.4 ± 1.8) and (4.9 ± 6.1) ng/mL,with Z values respectively-2.635 and-2.208,P ＜ 0.05 or P ＜0.01].The serum levels of PCT of patients in death group and survival group in PAW 1 and 2 were close (with Z values respectively-0.732 and -1.025,P values above 0.05).Compared with those of survival group,neutrophils in PAW 4 was significantly increased (t =-3.690,P ＜ 0.01),the platelet count in PAW 4 was significantly decreased (t =4.858,P ＜ 0.01),and the level of PA in PAW 2 was significantly increased in patients of death group (t =-2.320,P ＜ 0.05).There were no statistically significant differences in neutrophils,platelet count,and the level of PA at the other time points of patients between death group and survival group (with t values from-1.562 to 1.904,P values above 0.05).The total areas under ROC curves of serum level of PCT for predicting death of 13 patients with extremely severe burn and sepsis in PAW 3 and 4 were respectively 0.938 and 0.906,and 7.45 ng/mL and 8.77 ng/mL were respectively chosen as the optimal threshold values,with sensitivity of 75.0％ and 100.0％ and specificity of 100.0％ and 87.5％.Conclusions Serum level of PCT in PAW 3 and 4 can be used as the vital prognostic indicators for patients with extremely severe burn and sepsis,and it can be considered as a guide for rational treatment in clinic.

Over the past 30 years, China has significantly improved the drug development environment by establishing a series of policies for the regulation of new drug approval. The regulatory system for new drug evaluation and registration in China was gradually developed in accordance with international standards. The approval and registration of TCM in China became as strict as those of chemical drugs and biological products. In this review, TCM-based new drug discovery and development are introduced according to the TCM classification of nine categories.
China ; Drug Discovery ; legislation & jurisprudence ; standards ; Drugs, Chinese Herbal ; analysis ; standards ; Medicine, Chinese Traditional ; standards