The differences in chemical quality characteristics between Xinjiang Rehmannia glutinosa and R. glutinosa were analyzed to provide a theoretical basis for the introduction and quality control of R. glutinosa. In this study, the high performance liquid chromatography(HPLC) fingerprints of 6 batches of Xinjiang R. glutinosa and 10 batches of R. glutinosa samples were established. The content of iridoid glycosides, phenylethanoid glycosides, monosaccharides, oligosaccharides, and polysaccharides in Xinjiang R. glutinosa and R. glutinosa was determined by high performance liquid chromatography-diode array detection(HPLC-DAD), high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD), and ultraviolet-visible spectroscopy(UV-Vis). The determination results were analyzed with by chemical pattern recognition and entropy weight TOPSIS method. The results showed that there were 19 common peaks in the HPLC fingerprints of the 16 batches of R. glutinosa, and catalpol, aucubin, rehmannioside D, rehmannioside A, hydroxytyrosol, leonuride, salidroside, cistanoside A, and verbascoside were identified. Hierarchical cluster analysis(HCA) and principal component analysis(PCA) showed that Qinyang R. glutinosa, Mengzhou R. glutinosa, and Xinjiang R. glutinosa were grouped into three different categories, and eight common components causing the chemical quality difference between Xinjiang R. glutinosa and R. glutinosa in Mengzhou and Qinyang of Henan province were screened out by orthogonal partial least squares discriminant analysis(OPLS-DA). The results of content determination showed that there were glucose, sucrose, raffinose, stachyose, polysaccharides, and nine glycosides in Xinjiang R. glutinosa and R. glutinosa samples, and the content of catalpol, rehmannioside A, leonuride, cistanoside A, verbascoside, sucrose, and glucose was significantly different between Xinjiang R. glutinosa and R. glutinosa. The analysis with entropy weight TOPSIS method showed that the comprehensive quality of R. glutinosa in Mengzhou and Qinyang of Henan province was better than that of Xinjiang R. glutinosa. In conclusion, the types of main chemical components of R. glutinosa and Xinjiang R. glutinosa were the same, but their content was different. The chemical quality of R. glutinosa was better than Xinjiang R. glutinosa, and other components in R. glutinosa from two producing areas and their effects need further study.
Rehmannia/classification* ; Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Quality Control

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To investigate the effect and mechanism of hypericin on osteoporosis(OP)in rats with chronic obstructive pulmonary disease(COPD).Methods COPD combined with OP rat model was established by cigarette combined with bacteria.The rats were randomly divided into control group,model group(COPD combined with OP model was constructed),experimental-L group(50 mg·kg-1 hypericin was given by intragastric administration after constructing COPD combined with OP model),experimental-H group(100 mg·kg-1 hypericin was given intragastric administration after constructing COPD combined with OP model),positive group(subcutaneous injection of 16 U·kg-1 salmon calcitonin after constructing COPD combined with OP model);each group was given 12 rats for 90 days.The lung function of rats was detected by pulmonary function apparatus;bone mineral density(BMD)was detected by micro-computed tomography(CT);serum bone metabolism and inflammatory factors were detected by enzyme-linked immunosorbent assay(ELISA);Western blot assay was used to detect the relevant indicators of the pathway.Results The levels of forced vital capacity(FVC)in control group,model group,experimental-H group and positive group were(10.42±1.40),(4.10±0.60),(6.75±0.37),(4.18±0.33)mL,respectively;BMD levels were(0.31±0.04),(0.12±0.02),(0.28±0.03),(0.29±0.04)g·mm-3,respectively;bone alkaline phosphatase(BALP)levels were(200.04±20.03),(80.80±6.00),(148.16±14.23),(173.97±23.55)U·L1,respectively;interleukin-1β(IL-1β)levels were(122.60±8.70),(695.59±74.84),(422.41±44.86),(527.90±39.36)pg·mL-1,respectively;phosphorylated p38 mitogen-activated protein kinase(p-P38)protein expression levels were 0.99±0.11,0.36±0.05,0.79±0.08,0.36±0.04,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P＜0.05);the above indexes in experimental-H group were significantly different from those in model group(all P＜0.05).Conclusion Hypericin can inhibit inflammatory response,improve bone metabolism and biomechanics.

The NiFe2O4-graphene oxide nanocomposite modified with polyethylenimine(GO@PEI-NiFe2O4)was prepared to purify and enrich phosphopeptides from biosamples.The Ni2+and Fe3+ions on its surface could coordinate with phosphate groups and then selectively adsorb phosphopeptides.PEI was conducive to the above combination due to its high hydrophilicity.The material showed good magnetic response properties and could be rapidly separated from samples with the aid of magnet.With tryptic digest of β-casein as sample,the enrichment property of the material to phosphopeptides was studied,which was compared with the results of GO@NiFe2O4,revealing the adsorption mechanism of GO@PEI-NiFe2O4.The static and dynamic binding properties of GO@PEI-NiFe2O4 were investigated using pTyr as a representative phosphopeptide,and the adsorption capacity was 36.2 μg/mg.The results showed that the material could remove the interference of nonphosphopeptides and effectively enrich phosphopeptides in complex matrix.After enrichment by GO@PEI-NiFe2O4,1535 phosphopeptides were identified from the tryptic digest of rat liver by mass spectrum and the enrichment effect of GO@PEI-NiFe2O4 greatly outperformed commercial Fe3+-IMAC kits.This work provided an efficient material for the enrichment of phosphopeptides,showing potential applications in phosphoproteomics research.

An analytical method based on ultra high performance liquid chromatography-high resolution tandem mass spectrometry(UHPLC-HRMS/MS)and high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-TQ MS)was established to reveal the characteristics of various sulfur mustard analogs with different active thiol molecules in CWC Schedule 1.A.04.Firstly,the toxic agents were prepared by micro-directed synthesis,and then the differences of the reactivity and abundance of formed adducts between different sulfur mustards and glutathione(GSH),cysteine(Cys)and N-acetylcysteine(NAC)in incubation solution,plasma and cell were investigated,respectively.The results indicated that all target sulfur mustards could react with three kinds of thiol molecules.The content of Cys and sulfur mustard adducts in plasma was higher than that of GSH and sulfur mustard adducts,while NAC and sulfur mustard adducts might have fewer types of adducts due to low content or poor mass spectrometry response.Additionally,the content of GSH and sulfur mustard adducts in exposed cells was higher than that of Cys,which should be due to the significant difference in the content of thiol molecules in plasma and cells.

Objective To develop a biological safety protection third-level(BSL-3)laboratory based on folding-modular shelters to solve the problems of the existing laboratories in space and function expansion,large-scale deployment and low-cost transportation.Methods The BSL-3 laboratory was composed of a folding combined shelter module,a ventilation and purification module,a power supply and distribution module,a monitoring and communication module,a control system module and an equipment module.The folding combined shelter module used a leveling base frame as the foundation and a lightweight panel as the enclosure mechanism,and was divided into an auxiliary area and a protection protected area;the ventilation and purification module was made up of an air supply unit and an air exhaust unit,the air supply unit was integrated with a fresh-air air conditioner and the exhaust unit was equipped with a main fan,a standby fan and a bag in/bag out filter;the control system module adopted a supervision mode of decentralized control and centralized management,which executed communication with the data server as the center and Profinet protocol and MODBUS-TCP.Results The BSL-3 laboratory proved to meet the requirements of relevant standards in internal microenvironment,airflow direction,airtightness,working condition and disinfection effect.Conclusion The BSL-3 laboratory is compatible with large-scale transport and deployment and facilitates reliable and safe experiments for epidemic prevention and control and cross-regional support.[Chinese Medical Equipment Journal,2024,45(3):41-46]

This study focuses on the microbial quality control of the Chinese herbal decoction pieces. In view of the shortcomings of traditional culture methods such as slow detection speed and inability to detect unculturable microorganisms, a new method based on ATP bioluminescence technology combined with statistical analysis methods was established to rapidly predict and quantitatively detect the total aerobic microbial count (TAMC) and total yeast and mold count (TYMC) contaminated Bupleurum chinense DC. decoction pieces. Based on the optimized ATP bioluminesence detection system, accurate detection of pure bacterial solution of Escherichia coli, Bacillus subtilis and Staphylococcus aureus can be achieved, with detection limits of 47.86, 89.13 and 1 862.09 CFU·mL^-1, respectively. The detection time was 6.5 h, and the detection cost was as low as 2 yuan/time. The upper and lower warning limits of TAMC were determined by the misjudgment rates of 10% and 20%, respectively. And the warning limit of TYMC was determined by the misjudgment rate of 20%. The proposed crossing method could quickly predict the amount of microbial contamination in Bupleurum chinense DC. decoction pieces. The constructed partial least squares regression (PLSR) model could accurately quantify the quantity of microbial contamination in Bupleurum chinense DC. decoction pieces. The optimal PLSR prediction model for TAMC had a correction coefficient (R²) of 0.826, a root mean square error of correction set (RMSE_E) of 0.468 and a root mean square error of cross-validation set (RMSE_CV) of 0.465. The R², RMSE_E and RMSE_CV in the prediction model of TYMC were 0.778, 0.543 and 0.541, respectively. The aim of this study is to establish a kind of rapid detection method and prediction models for the microbial limit of traditional Chinese medicine and Chinese herbal decoction pieces, and to provide a more convenient and sensitive detection technology for the microbial quality process control of traditional Chinese medicine products.

OBJECTIVE To provide references for the clinical safe use of axitinib. METHODS Adverse drug event （ADE） data for axitinib were collected from the US FDA Adverse Event Reporting System （FAERS） database from the first quarter of 2012 to the fourth quarter of 2022. The data were mined and analyzed by utilizing the ratio-of-reporting-ratio （ROR） method and comprehensive standard method of the United Kingdom’s Medicines and Healthcare Products Regulatory Agency （MHRA） of proportional imbalance measurement. RESULTS A total of 13 962 reports of axitinib-related ADEs were obtained， with patients’ age concentrated in 65-85 years （43.25%）， gender predominantly male （65.23%）， country of reporting predominantly US （60.01%）， and serious ADE outcomes mostly hospitalization or prolonged hospitalization （31.51%）. A total of 172 ADE risk signals were detected， involving 18 system and organ classifications （SOC）， mainly systemic diseases and various reactions at the site of administration （3 749 cases， 30.84%） and gastrointestinal system diseases （2 067 cases， 17.00%）. ADE risk signals that occurred more frequently were generally consistent with the drug instruction， such as diarrhea， fatigue， and hypertension； new ADE risk signals requiring clinical attention were death， immune-mediated nephritis， and PT signals contained in the SOC of various benign， malignant， and tumors of undetermined nature （including cysts and polyps）. CONCLUSIONS For ADEs that occur frequently with axitinib and are already contained in the drug instruction （e.g. hypertension， diarrhea）， they should be adequately evaluated before administration， especially for patients with combined use of immune checkpoint inhibitors and patients with underlying hypertension； for ADEs with stronger signals and newer ADEs （e. g. death， disease progression， tumor progression）， the patient’s disease progression should be closely monitored during the treatment period for potentially fatal ADEs； for its rare ADEs （e. g.immune-mediated nephritis， scrotal ulcer， non-infectious encephalitis）， clinical validation should be further strengthened.