ObjectiveThis study aims to explore the effects of Huangqin Qingre Chubi capsules-containing serum on the expression of CircRNA_0001543/nuclear factor-kappa B （NF-κB） in co-cultured peripheral blood mononuclear cells （PBMCs） and human fibroblast-like synoviocytes （FLSs） from patients with ankylosing spondylitis （AS）. MethodsVenous blood was collected from patients with AS to isolate PBMCs. FLSs were co-cultured with AS patients' PBMCs， and FLSs were harvested after co-culture for subsequent experiments. The normal control group consisted of normal FLSs， while the model group comprised co-cultured AS PBMCs and FLSs to simulate AS pathology. The Huangqin Qingre Chubi capsules group involved adding Huangqin Qingre Chubi capsules-containing serum to the co-cultured cells（6.48 g·kg^-1）. To investigate the effect of HQC-containing serum on the viability of co-cultured cells， and the experiment was divided into the following groups based on the dilution concentration： blank group， 10% HQC group， 20% HQC group， and 30% HQC group.To study the influence of the optimal concentration of HQC-containing serum on cytokine and pathway indicators in each group， the experiment was divided into three groups： normal group， model group， and optimal concentration HQC-containing serum group.For the validation of the transfection efficiency of the CircRNA_0001543 interference plasmid， the experiment was divided into the following groups： blank group， si-NC group （with transfection reagent）， si-circ_0001543-1 group （with transfection reagent and interference plasmid No. 1 targeting circ_0001543）， si-circ_0001543-2 group （with transfection reagent and interference plasmid No. 2 targeting circ_0001543）， and si-circ_0001543-3 group （with transfection reagent and interference plasmid No. 3 targeting circ_0001543）.For the validation of the transfection efficiency of the CircRNA_0001543 overexpression plasmid， the experiment was divided into the following groups： blank group， OE-NC group （with transfection reagent）， and OE-circ_0001543 group （with transfection reagent and overexpression plasmid targeting circ_0001543）.To study the effects of CircRNA_0001543 interference/overexpression on cytokine and pathway indicators in each group， the experiment was divided into the following groups： si-NC group， si-CircRNA_0001543 group， OE-NC group， and OE-CircRNA_0001543 group. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of interleukin-1β （IL-1β）， IL-10， IL-37， and tumor necrosis factor-α （TNF-α）. Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to measure the expression of CircRNA_0001543， IκBα， and NF-κB p65. ResultsAfter 48 hours， 30% Huangqin Qingre Chubi Capsules-containing serum significantly inhibited the proliferation of co-cultured PBMCs and FLSs， which was determined to be the optimal experimental drug-containing serum concentration. Compared with those in the normal group， the expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α in the model group were significantly increased （P<0.01）， while the expressions of CircRNA_0001543 mRNA， IL-10， and IL-37 were significantly decreased （P<0.01）. Compared with those in the model group， the expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α in the Huangqin Qingre Chubi Capsules-containing serum group were significantly decreased （P<0.05）， and the expressions of CircRNA_0001543 mRNA， IL-10， and IL-37 were significantly increased （P<0.05）， with the most prominent changes in the 30% drug-containing serum group （P<0.01）. Compared with that in the si-NC group， the expression of CircRNA_0001543 was significantly reduced in the si-CircRNA_0001543 group （P<0.01）. Compared with that in the OE-NC group， the expression of CircRNA_0001543 was significantly increased in the OE-CircRNA_0001543 group （P<0.01）， indicating that the si-CircRNA_0001543 and OE-CircRNA_0001543 plasmids were successfully transfected. Based on the optimal drug-containing serum of Huangqin Qingre Chubi Capsules， si-CircRNA_0001543 transfection led to significantly increased expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α and decreased the expressions of IL-10 and IL-37 （P<0.01）. In contrast， OE-CircRNA_0001543 transfection significantly decreased the expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α （P<0.01） and increased the expressions of IL-10 and IL-37 （P<0.01）. ConclusionHuangqin Qingre Chubi capsules-containing serum can improve immune inflammation in AS by increasing the expression of CircRNA_0001543， regulating the NF-κB pathway， suppressing pro-inflammatory cytokines， and enhancing anti-inflammatory cytokine expression.

Objective To evaluate the effects of fasting and high-fat diet on the pharmacokinetics of rabeprazole sodium enteric-coated tablets in healthy Chinese subjects.Methods A single-center,randomized,open,two-agent,two-sequence,four-cycle,fully repeated crossover,single-dose trial design was used in this study,healthy subjects were assigned to receive single dose of rabeprazole sodium enteric-coated tablets 0.1 g in either fasting or high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of rabeprazole sodium enteric-coated in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),the model method of the non-compartmental was used to calculate the pharmacokinetic parameters by Phoenix WinNonlin 8.2.Results The main pharmacokinetic parameters of rabeprazole sodium enteric-coated tablets in fasting state and high-fat diet state were as follows:Cmax were(339.63±156.47)and(318.86±132.13)ng·mL-1;t1/2 were(2.34±0.68)and(3.60±2.40)h;AUC0_t were(556.62±251.65)and(528.50±201.78)ng·mL-1·h;AUC0-∞ were(563.39±255.69)and(535.15±203.24)ng·mL-1·h;tmax were 3.65 and 6.99 h.After high-fat diet,the Cmax and AUC of rapeprazole sodium after high-fat and high-calorie diet decreased,Cmax decreased by 6.12％,AUC0-t decreased by 5.05％,AUC0-∞ decreased by 5.01％,andtmaxwas delayed by about 3.34 h.Cmax,AUC0-t and AUC0-∞ 90％confidence interval were 73.13％-115.10％,83.22％-112.28％and 83.40％-112.13％,respectively.Neither was between 85.00％-125.00％.Conclusion High-fat diet affects the absorption rate and degree of rabeprazole sodium enteric-coated,so it is suitable to be administered on an empty stomach.

Objective:To explore the clinicopathological characteristics and prognosis of fumarate hydratase-deficient uterine leiomyoma (FH-dUL).Methods:Clinical data and follow-up information for 117 patients with FH-dUL diagnosed through surgical pathology and immunohistochemistry in the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2024, were collected. A control group of 130 patients with common uterine leiomyomas was also included. The differences between the two groups in clinical, imaging, and pathological characteristics were compared. Additionally, recurrence rates, fertility outcomes for FH-dUL patients, and the incidence of renal cancer in FH germline mutation carriers were monitored.Results:(1) Comparison of clinicopathological characteristics: the median age of 117 FH-dUL patients was 35 years, and the median age at first diagnosis of uterine leiomyomas was 29 years, both significantly younger than the control group (41 and 36 years; both P<0.01). The FH-dUL group showed significantly higher incidences of uterine myomectomy, multiple leiomyomas, diffusion restriction on pelvic magnetic resonance imaging diffusion weighted imaging, and typical pathological features (candelabra-like vessels, bizarre nuclei, cytoplasmic eosinophilic globules, perinuclear halo, cellular atypia) and higher ultrasound blood flow score (all P<0.05). Of the 30 FH-dUL patients who underwent genetic testing, 9 had germline mutations, 3 had somatic mutations, and 6 had mutations of unclear origin. Among the 9 FH gene germline mutation patients, 2 had already developed renal cell carcinoma. (2) Recurrence analysis: among the 56 patients who underwent uterine myomectomy, 22 (39.3%, 22/56) experienced recurrence during follow-up, compared to 12 (21.8%, 12/55) of the 55 patients in the control group, the difference between the two groups was statistically significant ( P=0.046). Multivariate binary logistic regression analysis showed that cellular leiomyomas ( OR=9.489, 95% CI: 1.740-51.755; P=0.009) and multiple uterine leiomyomas ( OR=10.709, 95% CI: 1.354-84.683; P=0.025) were significant risk factors for recurrence in FH-dUL. (3) Fertility analysis: among the 66 FH-dUL patients who underwent fertility-preserving surgery, 16 had the intention to have fertility desire, only 2 (2/16) completed their fertility plans during follow-up. Conclusions:Clinicopathological features and imaging features help to differentiate FH-dUL from common type uterine fibroids, but lack specificity, and the diagnosis of FH-dUL is based on immunohistochemistry. The recurrence rate after resection of FH-dUL is high, and cellular and multiple leiomyomas are important predictors of recurrence. It is crucial to perform genetic testing, genetic counseling, drug treatment to prevent recurrence, fertility guidance, and long-term comprehensive management after surgery for FH-dUL management.

Objectives:To explore the value of non-invasive myocardial work combined with myocardial contrast echocardiography(MCE)in the early diagnosis of coronary artery disease and its efficacy in stratifying the severity of coronary vessel lesions.Methods:A total of 130 patients with suspected coronary artery disease admitted to the First Affiliated Hospital of Dalian Medical University from June 2024 to January 2025 were enrolled in this study.All patients underwent echocardiography and MCE after admission,and coronary angiography(CAG).Based on CAG results,patients were divided into non-CAD group(n=45,coronary artery stenosis<50%)and CAD group(n=85,coronary artery stenosis≥50%).Patients in CAD group were further divided into low-score CAD group(≤49 points,n=43)and high-score CAD group(>49 points,n=42)according to the median of Gensini score(49 points).Non-invasive MW indices and quantitative MCE parameters were assessed.A binary logistic regression model was used to construct a combined diagnostic model,and the value of each parameter in diagnosing CAD and evaluating the severity of coronary lesions was calculated.The receiver operating characteristic(ROC)curve of subjects was estimated,and the area under the curve(AUC)was calculated to evaluate its sensitivity and specificity for early diagnosis of coronary heart disease.Results:Compared with the non-CAD group,the global longitudinal strain,global work index(GWI),and global constructive work(GCW)in both low-score and high-score CAD groups were significantly lower(all P<0.05),and the global work efficiency in the high-score CAD group was significantly reduced(P<0.05).MCE indices in both low-score and high-score CAD groups were significantly lower than those in the non-CAD group(all P<0.05).The multivariate logistic stepwise regression analysis and ROC curve showed that GWI(OR=0.997,95%CI:0.995-0.999,P=0.003)and A value(representing the peak intensity of the curve,reflecting myocardial blood volume(OR=0.415,95%CI:0.246-0.698,P=0.001)were independent predictors of low-score CAD.The combined diagnostic sensitivity and specificity for low-score coronary artery disease were 72.1%and 88.9%respectively,with an AUC of 0.851.GCW(OR=0.997,95%CI:0.995-1.000,P=0.019)and β-value(OR=0.000,95%CI:0.000-0.003,P<0.001)were independent predictors of high-score CAD.The combined diagnostic sensitivity and specificity for high-score coronary artery disease were 88.1%and 88.9%respectively,with an AUC of 0.934.Conclusions:Both non-invasive myocardial work parameters and MCE parameters have high diagnostic efficacy for coronary artery lesions of various degrees.The combined application of the two methods significantly improves the accuracy of coronary artery disease diagnosis,with improved sensitivity and specificity than single technique.Our results provide a new non-invasive comprehensive diagnostic model for clinical early diagnosis and risk stratification of coronary artery disease.

Objective To analyze the age-related changes in proximal pulmonary artery(PPA)based on computed tomography pulmonary angiography(CTPA)images.Methods A total of 327 patients who underwent CTPA were retrospectively selected.Participants were stratified into six age groups by decade:20-29,30-39,40-49,50-59,60-69,and≥70 years.The main pul-monary artery(MPA),right pulmonary artery(RPA),and left pulmonary artery(LPA)were segmented.A cross-section within 1.5 mm of the vascular bifurcation was selected to measure the cross-sectional area(A)and perimeter(P).The hydraulic diameter(Dh)was calculated by 4A/P,and the diameter of a circle of equal area was calculated as the fitted diameter(Dfit).Results Correlation analy-sis revealed positive correlations between age and the diameters of the MPA(r=0.260-0.340,P＜0.01),RPA(r=0.414-0.494,P＜0.01),and LPA(r=0.405-0.478,P＜0.01).For the MPA,the Dfit and Dh showed no significant increase in the first three age groups(P＞0.05);the Dh in the 50-59,60-69,and≥70 age groups was significantly higher than that in the first three age groups(P＜0.05).In the RPA,the Dh and Dfit of the 30-39 age group were significantly higher than those of the 20-29 age group(P＜0.05);the Dh and Dfit of the 50-59 age group were significantly higher than those of the first three age groups(P＜0.05).In the LPA,the Dh and Dfit of the 60-69 age group were significantly higher than those of the first three age groups(P＜0.05).The Dh of both the RPA and LPA was independent predictors of age.Conclusion Pulmonary artery stiffness shows no significant changes in the 20-29,30-39,and 40-49 age groups,but becomes significant starting from the 50-59 age group.The Dh of the bilateral pulmonary artery trunks are age-related predictors.

Objective:To investigate the utility of a computational pathology-based tumor microenvironment(TME)score derived from whole slide images(WSIs)in predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)in patients with EGFR mutation-positive non-small cell lung cancer(NSCLC).Methods:This retrospective study collected 240 EGFR-mutant NSCLC pa-tients treated with EGFR-TKIs at The First Affiliated Hospital of Wannan Medical College and analyzed hematoxylin-eosin(H&E)-stained WSIs of biopsy specimens,along with clinical and imaging data.The patients were randomly assigned into a training cohort(n=160)and an inde-pendent validation cohort(n=80)in a 2:1 ratio.Treatment response was assessed based on CT findings at 3 months after EGFR-TKIs initi-ation.Computational pathology was employed to automatically quantify the proportions of four TME components(tumor epithelium,stroma,lymphocytes,and vasculature)within the tumor regions of WSIs.Multivariate Logistic regression in the training cohort identified TME components independently predictive of treatment response(P<0.05),which were then integrated into a TME-score.The predictive performance was evaluated using receiver operating characteristic(ROC)curve analysis and area under the curve(AUC).The TME-score model was compared with a clinical-feature-based model and a combined model(TME-score+clinical features).Finally,the models were val-idated in the independent cohort.Results:In the training cohort,the TME-score,incorporating epithelial and stromal proportions,achieved an AUC of 0.827(95%CI:0.749-0.892)for predicting treatment response,while the validation cohort yielded an AUC of 0.845(95%CI:0.735-0.937).Both outperformed the clinical model(AUCs=0.730[95%CI:0.645-0.804]and 0.712[95%CI:0.586-0.824],respectively).The combined model(TME-score+clinical features,including cytokeratin 19 fragment and non-contrast CT values)further improved predictive performance(AUCs=0.884[95%CI:0.827-0.932]and 0.882[95%CI:0.798-0.950],respectively).Delong's test for pairwise model comparis-ons showed significant differences(all P<0.05)except TME-score and the combined model in the validation cohort(P=0.289).Conclusions:TME-score outperformed clinical models in predicting EGFR-TKIs efficacy in EGFR mutation-positive NSCLC patients and may serve as a novel tool for identifying patients likely to benefit from targeted therapy.

BACKGROUND:The decreased postural control ability due to mild cognitive impairment in elderly people leads to the increased risk of falls.Dual-task is the primary research paradigm for evaluating the relationship between cognition and postural control in the scenes close to real life.The sample entropy of the plantar center of pressure(COP)displacement during standing can represent the complexity of postural control. OBJECTIVE:Based on the COP displacement sample entropy,to analyze the differences in postural stability characteristics and control strategies between older adults with mild cognitive impairment and cognitively normal older adults during the dual-task with postural control and spatial working memory,aiming to explore the impact of cognitive impairment on the postural control ability during standing. METHODS:Sixteen older adults with mild cognitive impairment and 17 cognitively normal older adults were eligible and selected for the study.They completed five test tasks,including spatial working memory,double-feet balance stance,Romberg stance,double-feet balance stance-spatial working memory dual-task,and Romberg stance-spatial working memory dual-task,with three valid completions of each task.The plantar COP data were collected by the Kistler 3D force platform.The indicators included cognitive behavior(cognitive score and reaction time)and kinematic indexes(COP displacement and sample entropy). RESULTS AND CONCLUSION:The older adults with mild cognitive impairment performed the spatial working memory task with the greatest cognitive score and the shortest reaction time,the double-feet balance stance-spatial working memory dual-task with moderate cognitive score and reaction time,and the Romberg stance-spatial working memory dual-task with the smallest cognitive score and the longest reaction time,where the differences were significant among the tasks(P<0.05).In the older adults with mild cognitive impairment,the anterior-posterior and medial-lateral COP displacements were significantly greater,and their sample entropy values were significantly smaller in the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task than in the double-feet balance stance and Romberg stance tasks(P<0.05).In the spatial working memory task,there were no significant differences in cognitive score and reaction time between the both groups(P>0.05);however,in the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task,cognitive scores were significantly smaller and reaction times were longer in the older adults with mild cognitive impairment compared with the cognitively normal older adults(P<0.05).In the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task,the older adults with mild cognitive impairment exhibited significantly greater anterior-posterior and medial-lateral COP displacements and significantly smaller sample entropy values compared with the cognitively normal older adults(P<0.05).All findings indicate that compared with cognitively normal older adults,older adults with mild cognitive impairment exhibit smaller complexity,poorer systematic adaption and decreased automatic regulation of the postural control during performing the dual-tasks,who are more susceptible to spatial working memory interference,leading to the increased risk of falls.

ObjectiveTo assess the efficiency of a Sophora flavescens Ait (S. flavescens, Ku Shen)-soluble microneedle (SFA-MN) for improving skin lesion symptoms in mice with psoriasis.MethodsSFA-MNs were prepared using a two-mold molding process with 20% w/v polyvinylpyrrolidone and 15% w/v polyvinyl alcohol. The SFA-MNs were assessed for morphology, mechanical properties, in vitro dissolution, identification of components, and skin lesion improvement in imiquimod-induced psoriasis mice.ResultsThe SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis, facilitating efficient drug delivery. Furthermore, they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differentiation 3 and tumor necrosis factor-α. In addition, this system alleviated skin inflammation, splenic swelling, and thymic atrophy in the psoriasis-like mouse model. Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios (m/z) of the secondary fragments N-methylcytisine, 5α, 9α-dihydroxymatrine, sophoramine, matrine, oxysophocarpine, oxymatrine, and kushenol O.ConclusionThe drug delivery strategy combining traditional herbal S. flavescens with soluble microneedle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models, enabling enhanced therapeutic effects compared with the control group.

This study aims to explore the mechanism of Huanglian Jiedu Decoction(HJD) in treating acute liver injury(ALI) in the mouse model of sepsis induced by lipopolysaccharide(LPS). Fifty-four male C57BL/6 mice were randomized into six groups: blank group, model group, low-, medium-, and high-dose group HJD, and dexamethasone group. The mouse model of sepsis was established by intraperitoneal injection of LPS after 7 days of gavage with HJD, and dexamethasone(0.2 mL) was injected intraperitoneally 1.5 h after modeling. The murine sepsis score(MSS) was recorded 12 h after modeling. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver tissue and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the serum were measured by ELISA. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of the mouse liver. The content of light chain 3 of microtubule-associated protein 1(LC3) was detected by immunofluorescence, and that of sirtuin 1(SIRT1) was detected by immunohistochemistry. The mRNA levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), LC3, and P62 were detected by RT-PCR. Western blot was employed to determine the protein levels of AMPK, p-AMPK, and SIRT1 in the liver tissue. The results showed that compared with model group, drug interventions decreased the MSS and liver injury indicators, lowered the levels of inflammatory cytokines, improved the liver tissue structure, upregulated the protein levels of of p-AMPK/AMPK and SIRT1 and the mRNA levels of AMPK and LC3, and downregulated the mRNA level of P62. To sum up, HJD can regulate the autophagy level and reduce inflammation to ameliorate acute liver injury in septic mice by activating the AMPK/SIRT1 autophagy pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Sirtuin 1/genetics* ; Male ; Mice ; Sepsis/metabolism* ; Mice, Inbred C57BL ; Autophagy/drug effects* ; AMP-Activated Protein Kinases/genetics* ; Liver/metabolism* ; Humans ; Signal Transduction/drug effects* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/genetics*

In patients with chronic kidney disease(CKD),the incidence of cardiovascular events and the mortality rate are significantly higher than those in the general population.Approximately 85% of end-stage CKD patients develop hyperhomocysteinemia(HHcy)due to impaired renal function.It is not yet fully determined whether HHcy merely acts as a biomarker of CKD or plays a role in the pathogenesis.Although supplementation with folic acid and other B vitamins(B6 and B12)has been proven to lower the plasma level of total homocysteine,their effectiveness in slowing CKD progression or reducing cardiovascular complications remains uncertain.This article reviews the latest research progress in the relationship between HHcy and CKD,aiming to give new insights into the prevention and treatment of CKD and its complications.
Humans ; Hyperhomocysteinemia/complications* ; Renal Insufficiency, Chronic/complications*