Primary liver cancer is a common malignant tumor in China. The current main treatment methods include surgical resection, liver transplantation, interventional therapy, radiofrequency ablation, chemotherapy, targeted therapy, and immunotherapy. Yttrium-90 microsphere selective internal radiation therapy (⁹⁰Y-SIRT) represents a critical treatment option for converting unresectable intermediate to advanced hepatocellular carcinoma. This report details a case of a patient with a giant hepatocellular carcinoma in the right lobe treated with ⁹⁰Y resin microsphere at the Third Affiliated Hospital of Sun Yat-sen University. Post-treatment, the tumor showed significant necrosis and reduction in size, with a marked decrease in alpha fetoprotein (AFP) levels and notable improvement in clinical symptoms. The case highlights the substantial efficacy of ⁹⁰Y-SIRT in controlling tumor progression and enhancing patient quality of life.

This study aims to establish a high-performance size-exclusion chromatography (HPSEC) method for determining the content of the classical swine fever virus (CSFV) E2 protein and screen the optimal stabilizer to enhance the stability of this protein. The optimal detection conditions were determined by optimizing the composition of the mobile phase, and characteristic chromatographic peaks were identified by SDS-PAGE and Western blotting. The specificity, repeatability, precision, linearity, limit of detection (LOD), and limit of quantitation (LOQ) of the method were assessed. The method established was used to determine the content of CSFV E2 protein antigen and vaccine. Differential scanning fluorimetry (DSF) was employed to screen the buffer system, pH, and salt ion concentrations, and sugar, amino acid, and alcohol stabilizers were further screened. The results showed that using a 200 mmol/L phosphate buffer provided the best column efficiency. An antigen-specific chromatographic peak appeared at the retention time of 18 min, which was identified as the CSFV E2 protein by SDS-PAGE and Western blotting. The method exhibited high specificity for detecting the CSFV E2 protein, with no absorbance peak observed in the blank control. The relative standard deviation (RSD) of the peak area for six repeated injections of the CSFV E2 protein was 0.74%, indicating good repeatability of the method. The RSD for repeated detection of two different concentrations of CSFV E2 protein samples by different operators at different time points was less than 2%, suggesting good intermediate precision of the method. The peak area of the CSFV E2 protein was linearly related to its concentration, with the regression equation showing R² of 1.000. The LOD and LOQ of the method were 14.88 μg/mL and 29.75 μg/mL, respectively. Application of the developed method in the detection of three batches of CSFV E2 protein antigen and three batches of vaccine demonstrated results consistent with those from the bicinchoninic acid (BCA) assay, which meant that the method could accurately determine the content of CSFV E2 protein antigen and vaccine. The DSF method identified 50 mmol/L Tris-HCl at pH 8.0 as the optimal buffer, and the addition of sugar and alcohol stabilizers further improved the stability of the CSFV E2 protein. The HPSEC method established in this study is simple, fast, and exhibits good accuracy and repeatability, enabling precise measurement of the CSFV E2 protein content. It is expected to play a crucial role in the quality control of the CSFV E2 vaccine. Furthermore, the strategy for improving the CSFV E2 protein stability, identified through DSF screening, has significant implications for enhancing the stability of the CSFV E2 vaccine.
Classical Swine Fever Virus/chemistry* ; Chromatography, Gel/methods* ; Animals ; Swine ; Viral Envelope Proteins/immunology*

Objective To evaluate the cost-effectiveness of roxadustat and darbepoetin alfa on treating renal anemia in dialysis-dependent chronic kidney disease(DD-CKD)patients,thus providing health economics reference for treatment of renal anemia.Methods A Markov model simulating the development and treatment of anemia in DD-CKD patients in a lifetime horizon(20 years)was constructed.Total costs of roxadustat and darbepoetin alfa injection were estimated from the perspective of Chinese healthcare system,with health outcomes converted into quality-adjusted life year(QALY).The incremental cost-effectiveness ratio(ICER)was used to describe the results.The willingness-to-pay(WTP)threshold was set at 257 094 yuan,which was three times China's gross domestic product(GDP)per capita in 2023.Sensitivity analyses were performed to test the uncertainties of the results.Results The total treatment costs of roxadustat and darbepoetin alfa injection were 111 902.41 yuan and 52 927.92 yuan respectively,corresponding to QALY values of 4.76 and 4.74 life-years.The incremental cost-effectiveness(ICER)was 2 654 912.45 yuan/QALY,which exceeded 3 times GDP per capita.Therefore,compared with darbepoetin alfa injection,roxadustat has no cost-effectiveness for patients with DD-CKD.Conclusion In the context of current economic development in China,darbepoetin alfa injection is more cost-effective than roxadustatin for treating anemia in DD-CKD patients.

Objective To investigate the effect of ophiopogonin B(OP-B)on tumor growth in gastric tumor-bearing rats and its underlying mechanism.Methods Sixty-six SPF SD rats(half male and female,6 weeks old,180～200 g)were randomly divided into model group,low-,medium-and high-dose OP-B groups,and activator group,with 10 rats in each group.The gastric tumor-bearing model was established by orthotopic transplantation of Walker-256 tumor tissue.The rats in the 3 doses groups were given 17.5,35 and 70 mg/kg OP-B,respectively,by gavage and intraperitoneal injection of the same amount of normal saline,and the rats in the activator group were intragastrically administered with 70 mg/kg OP-B and intraperitoneally injected with 1 mg/kg Rho A/ROCK1 signaling pathway activator,lysophosphatidic acid(LPA).The weight and volume of transplanted tumor were recorded to calculate the tumor inhibitory rate.The morphology of tumor tissue was observed with HE staining.The apoptosis of tumor cells were detected by TdT-mediated dUTP-biotin nick end labeling(TUNEL)staining.The expression of proliferating cell nuclear antigen 67(Ki-67)and cleavage cysteine aspartic acid proteolytic enzyme-3(Cleaved Caspase-3)in tumor tissues were detected by immunohistochemical staining.RT-qPCR and Western blotting were utilized to measure the expression of Ras homologous gene family member A(Rho A)and Rho-associated coiled-coil forming protein kinasel(ROCK1)at mRNA and protein levels.Results Compared with the model group,the tumor weight and volume,mRNA and protein levels of Ki-67,Rho A and ROCK1 were significantly decreased,and the tumor inhibitory rate,tumor cell apoptotic rate and Cleaved Caspase-3 protein level were obviously increased in the low-,medium-and high-dose OP-B groups(P＜0.05).The activator group had heavier tumor weight and larger volume,increased mRNA and protein expression levels of Ki-67,Rho A and ROCK1,and lower tumor inhibitory rate and apoptotic rate and reduced Cleaved Caspase-3 expression when compared with the high-dose OP-B group(P＜0.05).Conclusion OP-B may suppress the tumor growth of gastric tumor-bearing rats by inhibiting the activation of Rho A/ROCK1 signaling pathway.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective: : The spontaneous intracerebral hemorrhage (ICH) remains a significant cause of mortality and morbidity throughout the world. The purpose of this retrospective study is to develop multiple models for predicting ICH outcomes using machine learning (ML). Methods: : Between January 2014 and October 2021, we included ICH patients identified by computed tomography or magnetic resonance imaging and treated with surgery. At the 6-month check-up, outcomes were assessed using the modified Rankin Scale. In this study, four ML models, including Support Vector Machine (SVM), Decision Tree C5.0, Artificial Neural Network, Logistic Regression were used to build ICH prediction models. In order to evaluate the reliability and the ML models, we calculated the area under the receiver operating characteristic curve (AUC), specificity, sensitivity, accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR). Results: : We identified 71 patients who had favorable outcomes and 156 who had unfavorable outcomes. The results showed that the SVM model achieved the best comprehensive prediction efficiency. For the SVM model, the AUC, accuracy, specificity, sensitivity, PLR, NLR, and DOR were 0.91, 0.92, 0.92, 0.93, 11.63, 0.076, and 153.03, respectively. For the SVM model, we found the importance value of time to operating room (TOR) was higher significantly than other variables. Conclusion : The analysis of clinical reliability showed that the SVM model achieved the best comprehensive prediction efficiency and the importance value of TOR was higher significantly than other variables.

Objective:To study the status of iodized salt consumption, iodine nutrition and thyroid nodules among adults in Wuhan City, so as to provide a basis for continuing implement the salt iodization policy in Wuhan City.Methods:From 2019 to 2021, a multi-stage cluster random sampling method was used in 13 districts of Wuhan City. Two communities or townships were selected from each district, and 100 permanent residents over 16 years old were selected from each community or township. Household salt samples and individual random urine samples were collected. Physical examination, salt iodine test, urinary iodine test and thyroid ultrasound examination were performed.Results:A total of 2 578 permanent residents over 16 years old in Wuhan City were surveyed, with an iodized salt coverage rate of 92.09% (2 374/2 578) and a qualified iodized salt consumption rate of 86.11% (2 220/2 578). The median adult urinary iodine was 185.32 μg/L. The detection rate of thyroid nodules was 35.49% (915/2 578). The detection rate of thyroid nodules was significantly lower in males than in females (χ 2 = 62.43, P < 0.001), with a trend of increasing with age (χ 2trend = 91.83, P < 0.001), with a lower detection rate in central urban areas than in remote urban areas (χ 2 = 23.17, P < 0.001). There were no statistically significant differences in the iodine content of edible salt, iodized salt coverage rate, qualified iodized salt consumption rate, and urinary iodine content between adults with and without thyroid nodule, as well as between the single nodule group and the multiple nodule group ( P > 0.05). According to Spearman correlation analysis, there was no correlation between the detection rate of thyroid nodules and the iodine content in edible salt and urine ( r = - 0.012, 0.017, P > 0.05). Conclusions:After the salt industry reform, the qualified iodized salt consumption rate among adults in Wuhan City has slightly decreased, and the iodine nutritional status is at an appropriate level. The prevalence of thyroid nodules is relatively high, and increases with age, which is higher in females than in males. Iodine nutrition and iodized salt consumption are not found to be associated with thyroid nodules.

Objective:To study the prevalence and epidemiological characteristics of adult thyroid nodules in Wuhan City, and to analyze the influencing factors of thyroid nodules, so as to provide basis for prevention and treatment of adult thyroid nodules in Wuhan City.Methods:From 2019 to 2021, two communities or towns were selected from each of the 13 districts in Wuhan City using multi-stage cluster random sampling method. One hundred permanent residents over the age of 16 were selected from each community or town according to the inclusion and exclusion criteria (age and sex ratio balanced), for questionnaire survey, physical examination, urinary iodine test and thyroid ultrasound examination. The influencing factors of thyroid nodules was analyzed using logistic regession and Spearman correlation.Results:A total of 2 578 adults were investigated, including 1 168 men and 1 410 women. The age was (41.79 ± 13.01) years. The prevalence of thyroid nodules was 35.49% (915/2 578). The prevalence of single nodules was 19.16% (494/2 578), which was higher than that of multiple nodules [16.33% (421/2 578), χ 2 = 2 577.00, P < 0.001]. Multivariate logistic regression analysis showed that female ( OR = 2.033, 95% CI: 1.631 - 2.535), older ( OR = 1.404, 95% CI: 1.290 - 1.528), history of thyroid disease ( OR = 1.351, 95% CI: 1.211 - 1.506) and diabetes ( OR = 1.449, 95% CI: 1.083 - 1.938) were independent risk factors for adult thyroid nodules ( P < 0.05). The median urinary iodine of residents in Wuhan City was 185.32 μg/L, at an appropriate level of iodine nutrition, there was no correlation between urinary iodine and thyroid nodules ( r = 0.02, P = 0.391). Conclusions:The prevalence of thyroid nodules of adults in Wuhan City is high. Women, older, a history of thyroid diseases and diabetes are all risk factors for thyroid nodules. No correlation is found between urinary iodine level and thyroid nodules.

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.
Chlorogenic Acid ; Drugs, Chinese Herbal/pharmacology* ; gamma-Aminobutyric Acid ; Interleukin-6 ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Tumor Necrosis Factor-alpha/genetics* ; Animals ; Mice ; RAW 264.7 Cells

As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.