BACKGROUND:Previous studies by our research group discovered that Jiawei Xiaoyao San has a significant anti-liver cancer effect,but the specific mechanism of action was unclear. OBJECTIVE:To investigate the regulatory effects of the traditional Chinese medicine formula Jiawei Xiaoyao San on the levels of miRNAs in plasma exosomes of rats with diethylnitrosamine chronically induced primary liver cancer,based on high-throughput sequencing combined with bioinformatics. METHODS:SD rats were randomly divided into a blank control group,a liver cancer model group,and a Jiawei Xiaoyao San treatment group.Liver cancer models were induced by continuous administration of diethylnitrosamine for 12 weeks.Starting from the 17th week,rats in the Jiawei Xiaoyao San treatment group were administered Jiawei Xiaoyao San once daily until the end of the 20th week,while rats in the blank control and liver cancer model groups were given an equivalent volume of saline.Anti-hepatocellular carcinoma effects were validated by assessing the morphological structure of rat liver tissues,along with the expression of the hepatocellular carcinoma markers,Glypican-3 protein and serum alpha-fetoprotein.Plasma exosomes from each group of rats were isolated using ultracentrifugation.High-throughput sequencing technology was used to screen for differentially expressed miRNAs in rat plasma exosomes.Bioinformatics was used to predict the potential biomarkers through which Jiawei Xiaoyao San exerts its anti-liver cancer effects via liver cancer-derived exosomal miRNAs,followed by functional analysis. RESULTS AND CONCLUSION:(1)Jiawei Xiaoyao San significantly improved the morphological structure of liver tissues in a rat model of liver cancer.Compared with the liver cancer model group,the expression of liver cancer markers Glypican-3 protein and serum alpha-fetoprotein was significantly reduced in the Jiawei Xiaoyao San treatment group.(2)Bioinformatics analysis showed that in the Jiawei Xiaoyao San group,upregulated miR-223-3p in the liver cancer model group had target binding sites with genes E2F1 and NCOA1,which were closely related to liver cancer survival and prognosis.Therefore,Jiawei Xiaoyao San has a therapeutic effect on liver cancer,possibly by targeting negative regulation of NCOA1/E2F1 through liver cancer plasma-derived exosomal miR-223-3p,thereby playing anti-liver cancer effect.

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

OBJECTIVE: Burning solid cooking fuel contributes to household air pollution and is associated with frailty. However, how solid cooking fuel use contributes to the development of frailty has not been well illustrated. METHODS: This study recruited 8,947 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study, 2011-2018. Group-based trajectory modeling was employed to identify frailty trajectories. Multinomial logistic regression was used to assess the association between solid cooking fuel use and frailty trajectories. Population-attributable fractions were used to estimate the frailty burden from solid fuel use. RESULTS: We identified three frailty trajectories: low-stable ( n = 5,789), moderate-increasing ( n = 2,603), and fast-increasing ( n = 555). Solid fuel use was associated with higher odds of being in the moderate-increasing ( OR: 1.24, 95% CI: 1.08-1.42) and fast-increasing ( OR: 1.48, 95% CI: 1.14-1.92) trajectories. These associations were strengthened by longer solid fuel use ( P for trend < 0.001). Switching to clean fuel significantly reduced the risk of being in these trajectories compared with persistent solid fuel users. Without solid fuel, 8% of moderate- and 19% of fast-increasing trajectories demonstrated frailty development like the low-stable group. CONCLUSION Solid cooking fuel use is associated with frailty trajectories in middle-aged and older Chinese populations.
Humans ; China/epidemiology* ; Cooking ; Male ; Female ; Middle Aged ; Aged ; Air Pollution, Indoor/adverse effects* ; Frailty/etiology* ; Longitudinal Studies ; Cohort Studies

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

A new method was developed for simultaneous detection of total 19 kinds of organophosphate esters(OPEs)and their diester metabolites(di-OPEs)in human serum(1.0 mL)and urine(1.5 mL)with low volume of samples.The target compounds were determined using ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)after acetonitrile liquid-liquid extraction combined with purification using an ENVI-18 solid-phase extraction(SPE)column.OPEs and di-OPEs were separated using a Shim-pack GIST C18 column(100 mm×2.1 mm,2 μm)with a Shim-pack GIST-HP(G)C18 guard column.An electrospray ionization source(ESI)was employed in mass spectrometry analysis,with positive/negative ion mode using the multiple reaction monitoring(MRM).All target compounds were separated within 15 min,and exhibited good linear relationships in the concentration range of 2-100 ng/mL,with correlation coefficients(R2)above 0.994.The method detection limits(MDL)in serum ranged from 0.001 to 0.178 ng/mL and the MDL in urine ranged from 0.001 to 0.119 ng/mL.The recoveries of the analytes spiked in serum and urine matrices at two concentration levels were 30.5%-126.8%,with the relative standard deviations(RSDs)ranged from 1%to 23%.In addition,paired serum and urine samples from 11 patients were analyzed.For all samples tested,the internal standards of OPEs exhibited recoveries between 61%and 114%,whereas the internal standards for di-OPEs had recoveries ranging from 43%to 103%.OPEs and di-OPEs exhibited high detection frequencies in 22 serum and urine samples.Triethyl phosphate(TEP),tributyl phosphate(TBP),tris(2-ethylhexyl)phosphate(TEHP),tris(2-butoxyethyl)phosphate(TBEP),tris(1-chloro-2-propyl)phosphate(TCIPP),triphenyl phosphate(TPHP),tri-m-tolyl-phosphate(TMTP)and 2-ethylhexyl diphenyl phosphate(EHDPP)were universally detected in all serum samples.TCIPP was identified at the highest concentrations(median 0.548 ng/mL)in serum samples.In urine samples,the detection frequency for 12 kinds of target compounds reached 100%.Notably,TBP emerged as the predominant OPE in urine,demonstrating a median concentration of 0.506 ng/mL.Regarding di-OPEs,bis(2-chloroethyl)phosphate(BCEP)and bis(2-butoxyethyl)hydrogen phosphate(BBOEP)were the most abundant in urine,with median concentrations of 6.404 and 2.136 ng/mL,respectively.The total concentrations of OPEs and di-OPEs in serum and urine were 1.580-3.843 ng/mL and 5.149-17.537 ng/mL,respectively.These results not only confirmed the effectiveness of the method in detection of OPEs and di-OPEs in biological matrices,but also revealed the widespread presence of OPE compounds in human body and pointed to potential exposure risks.

Objective To establish a risk model for lactate metabolism-related genes in soft tissue sarcomas,and to explore their correlation with tumor mutational burden,immune cells,immune related functions and immune checkpoints in the tumor microenvironment.Methods The differentially expressed genes associated with lactate metabolism in soft tissue sarcoma were obtained after intersecting the differentially expressed genes extracted by TCGA and GTEx database with lactate metabolism-related gene sets from the Msigdb database.The pathway enrichment analysis was carried out by gene ontology and Kyoto Encyclopedia of Genes and Genomes.By the univariate Cox regression and least absolute shrinkage and selection operator to construct a risk score model,and divided the soft tissue sarcomas samples into high-risk and low-risk groups.Finally,the differences of the tumor mutational burden and immunity in the tumor microenvironment between the two groups were analyzed.Results A total of 29 differentially expressed genes associated with lactate metabolism were screened,and the results of pathways enrichment analysis showed that they were mainly related to metabolic processes.By constructing a predictive risk score model,soft tissue sarcoma samples were divided into high-risk and low-risk groups.Tumor mutational burden analysis showed that the first mutated gene was tumor protein p53 in all soft tissue sarcoma samples.Missense mutation was the most common type of somatic mutations,and the frequency of mutation was higher in the high-risk group than that in the low-risk group.The analysis of tumor microenvironment indicated that the infiltration of M0 and M2 macrophage was more in the high-risk group,while the low-risk group had a higher percentage of infiltrating CD8+T cells and monocytes.The immune related functional response and immune checkpoints expression was higher in the low-risk group.Conclusion The lactate metabolism scoring model can better evaluate the prognosis of patients with soft tissue sarcoma and reflect the state of tumor microenvironment.

Objective:To compare the short-term effect and adverse reaction of venetoclax(VEN)combined with azacitidine(AZA)versus"7+3"regimen in newly diagnosed elder patients with acute myeloid leukemia(AML).Methods:From January 2021 to January 2022,the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed,including VEN+AZA group(41 cases)and"7+3"group(38 cases).The propensity score matching(PSM)method was used to balance confounding factors,then response,overall survival(OS),progression-free survival(PFS)and adverse reactions between the two groups were compared.Results:The ORR of VEN+AZA group and"7+3"group was 68％and 84％,respectively,and the CRc was 64％and 72％,respectively,the differents were not statistically significant(P＞0.05).In the VEN+AZA group,there were 5 non-remission(NR)patients,4 with chromosome 7 abnormality(7q-/-7),and 1 with ETV6 gene mutation.Median followed-up time between the two groups was 8 months and 12 months,respectively,and the 6-months OS was 84％vs 92％(P=0.389),while 6-months PFS was 84％vs 92％(P=0.258).The main hematological adverse reactions in two groups were stage Ⅲ-Ⅳmyelosuppression,and the incidence rate was not statistically different(P＞0.05).The median time of neutrophil recovery in two groups was 27(11-70)d,25(14-61)d(P=0.161),and platelet recovery was 27(11-75)d,25(16-50)d(P=0.270),respectively.The infection rate of VEN+AZA group was lower than that of"7+3"group(56％vs 88％,P=0.012).The rate of lung infections of two groups was 36％and 64％,respectively,the difference was statistically significant(P=0.048).Conclusion:The short-term effect of VEN+AZA group and"7+3"regimens in eldrly AML patients are similar,but the VEN+AZA regimen had a lower incidence of infection.The presence of chromosome 7 abnormality(7q-/-7)may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.