AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.

Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.

AIM To evaluate the chemical constituent consistency in formula granules and traditional decoctions of Gouteng Jiangya Formula.METHODS HPLC characteristic chromatograms were established,the analysis was performed on a 30 ℃ thermostatic YMC-Triart C18 column(4.6 mm× 250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2％phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.Puerarin was used as an internal standard to calculate the relative correction factors of 3'-methoxy puerarin,puerarin apioside,magnolflorine,paeoniflora,daidzin,baicalin,palmatine,berberine,wogonoside and benzoylpaeoniflorin,after which the content detemination was made by quantitative analysis of multi-components by single-marker(QAMS).RESULTS The characteristic chromatograms of 9 batches of formula granules and 15 bacthes of traditional decoctions demonstrated the similarities of more than 0.90 at the detection wavelengths of 192,210,240,260,280,300,320,360 nm,along with similar total peak areas.Eleven constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 97.27％-101.64％with the RSDs of 0.36％-1.11％,the result obtained by QAMS and external standard method demonstrated no significant differences(P＞0.05).The contents of various constituents in the formula granules approximated those in the traditional decoctions.CONCLUSION The consistent kinds and contents of various constituents are obversable in formula granules and traditional decoctions of Gouteng Jiangya Formula,which can provide a reference for the reasonable clinical application of this formula.

OBJECTIVE: To explore the clinical significance of preoperative neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP) to albumin (ALB) ratio in spinal surgery patients with postoperative incision infection. METHODS: A total of 373 patients who underwent spinal surgery were collected and devided into two groups according to the postoperative incision infection situation. Among them, 65 cases in the incision infection group included 34 males and 31 females with a mean age of (56.01±9.78) years old;308 cases in the non incision infection group included 157 males and 151 females with a mean age of (55.54±10.19) years old. Blood cell analyzer was applied to detect neutrophils, lymphocytes, and platelets, and calculate NLR and PLR;immunoturbidimetry was applied to measure serum CRP and ALB levels and calculate CRP/ALB ratio;receiver operating characteristic (ROC) curve was applied to analyze the predictive value of preoperative NLR, PLR, and CRP/ALB ratio for postoperative spinal incision infection;Logistic multivariate regression was applied to analyze the influencing factors of incision infection after spinal surgery. RESULTS: The NLR(4.92±1.13), PLR (119.32±22.74), CRP/ALB ratio (10.19±2.51), operation time (3.02±0.64) h, history of diabetes 38.46%(25/65), and the proportion of patients with implant 32.31%(21/65) in the incision infection group were higher than those in the non incision infection group 3.72±0.81, 90.58±20.16, 7.23±2.21, (2.26±0.51) h, 16.88%(53/308), 11.69%(36/308), there were statistical differences(P<0.05). The AUC of preoperative NLR, PLR, and CRP/ALB ratio alone and in combination for predicting postoperative incision infection after spinal surgery was 0.786, 0.806, 0.839, and 0.926, respectively. Preoperative NLR, PLR, and CRP/ALB ratio were independent risk factors for postoperative incision infection in spinal surgery(P<0.05). CONCLUSION The determination of preoperative NLR, PLR, and CRP/ALB ratio is beneficial for early prediction of postoperative spinal incision infection, and the combined detection of the three can further improve the accuracy of the prediction results.
Humans ; Male ; Female ; Middle Aged ; Aged ; C-Reactive Protein/metabolism* ; Surgical Wound Infection/etiology* ; Adult ; Spine/surgery* ; Inflammation ; Preoperative Period

Fusion variations of neurotrophic receptor tyrosine kinase (NTRK) are oncogenic drivers in various solid tumors such as breast cancer, salivary gland carcinoma, infant fibrosarcoma, etc. Gene rearrangements involving NTRK1/2/3 lead to constitutive activation of the tropomyosin receptor kinase (TRK) domain, and the expressed fusion proteins drive tumor growth and survival. NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1% in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are prevalent in NSCLC, but the frequency of EGFR G719A mutation is relatively low (about 2%), and EGFR mutations are typically mutually exclusive with NTRK fusion variants. The study presented the first documented case of lung adenocarcinoma harboring both EGFR G719A mutation and LMNA-NTRK1 fusion. A review of the literature was conducted to elucidate the role of NTRK fusion mutations in NSCLC and their relationship with EGFR mutations, aiming to enhance the understanding of NTRK fusion mutations in NSCLC.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Lamin Type A/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Receptor, trkA/metabolism*

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

The mechanism of L-perilla alcohol(L-POH) in intervening hypoxic pulmonary hypertension(HPAH) was discussed based on network pharmacology, and experimental verification. The active components and potential targets of the volatile oil of Rhodiola tangutica(VORA) in the intervention of HPAH were screened by network pharmacology. The biological process of Gene Ontology(GO) and the signaling pathway enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG) were analyzed for the core targets, and a "component-common target-disease" network was constructed. Four active components were screened from VORA: L-POH, linalool, geraniol, and(-)-myrtenol. The core targets for treating HPAH were HSP90AA1, AKT1, ESR1, PIK3CA, EP300, EGFR, and JAK2. GO enrichment analysis mainly involved biological processes such as reaction to hypoxia, heme binding, and steroid binding. KEGG enrichment analysis mainly involved hypoxia-inducing factor 1(HIF-1) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and Janus kinase/activator of signal transduction and transcription(JAK/STAT) signaling pathway. The vasodilation effects of the four active components were screened by perfusion experiment of extracorporeal vascular rings, and the mechanism of the main active component L-POH was studied by channel blockers. The inhibitory effects of the four active components on the proliferation of pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia were screened by cell proliferation experiment, and the mechanism of the main active component L-POH was studied by flow cytometry, cell cycle experiment, and Western blot. The results showed that L-POH could directly act on vascular smooth muscle to relax pulmonary arterioles, induce ATP-sensitive potassium channels to open, and inhibit extracellular Ca~(2+) influx through voltage-gated calcium channels to relax blood vessels. In addition, L-POH could inhibit the abnormal proliferation of PASMCs induced by hypoxia and promote its apoptosis, and its mechanism may be related to the increase in Bax protein expression and the decrease in p-JAK2, p-STAT3, Bcl-2, and cyclinA2 protein expression. In summary, L-POH can interfere with HPAH by relaxing pulmonary arterioles and inhibiting the proliferation of smooth muscle cells.
Network Pharmacology ; Animals ; Hypertension, Pulmonary/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Hypoxia/metabolism* ; Rhodiola/chemistry* ; Signal Transduction/drug effects* ; Humans ; Monoterpenes/chemistry* ; Male ; Cell Proliferation/drug effects* ; Rats, Sprague-Dawley

Objective To analyze the correlation between venous thromboembolism(VTE)and traditional Chinese medicine(TCM)constitution types in elderly frail patients.Methods A retrospective study was conducted on 1 428 elderly frail patients admitted to the Second Comprehensive Department of Guangdong Provincial Hospital of Chinese Medicine from January 2019 to June 2023.Patients were divided into a venous thrombsis(VT)group(n=187)and a non-VT group(n=1 241)based on VTE occurrence.Baseline data,including age distribution,Padua scores,Wells scores,and TCM constitution types,were compared between the two groups.Multivariate logistic regression analysis was performed to identify factors for influencing VTE in elderly frail patients.Results(1)Compared with the non-VT group,the VT group had significantly higher total hospitalization costs,length of stay,age,Fried scores,Padua scores,and Wells scores,with statistically significance(P＜0.001).(2)Compared with the non-VT group,the VT group had a higher proportion of high VTE-risk individuals and those with Wells scores of 2 points,with statistically significance(P＜0.001).(3)The age distribution of VTE patients showed an increasing trend in the age groups of 60-69,70-79,80-89,and ≥90-year-old,with a significant difference compared to the non-VT group(P＜0.001).(4)The VT group had a higher proportion of qi-deficiency,blood-stasis,and qi-depression constitutions than the non-VT group(P＜0.05 or P＜0.001).(5)Multivariate logistic regression analysis(after adjusting age,gender,frailty,and other scores)showed that qi-deficiency and yang-deficiency constitutions were non-susceptible,while damp-heat,blood-stasis,and qi-depression constitutions were susceptible to VTE in elderly frail patients(P＜0.05 or P＜0.01).Conclusion VTE in elderly frail patients is significantly correlated with TCM constitution types.Deviated constitutions are characteristic of TCM constitution types in elderly frail patients,and damp-heat,blood-stasis,and qi-depression constitutions are risk factors for VTE in this population.

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats