ObjectiveTo investigate the therapeutic effect and mechanism of Huatan Qushi Huoxue prescription on rats with metabolic dysfunction-associated steatohepatitis （MASH）. MethodsA total of 60 specific pathogen-free Sprague-Dawley rats were randomly divided into blank control group， model A group， model B group， Western medicine group （polyene phosphatidylcholine， 143.64 mg/kg）， high-dose Chinese medicine group （Huatan Qushi Huoxue prescription， 20.16 g/kg）， and middle-dose Chinese medicine group （Huatan Qushi Huoxue prescription， 10.08 g/kg）. All rats except those in the blank control group were given high-fat diet. Samples were collected from the model A group at week 8， and since week 12， the other groups were given the corresponding drug once a day for 8 consecutive weeks， with samples collected at week 20. Body weight， liver wet weight， and liver index were measured for all rats； the microplate method was used to measure the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and free fatty acids （FFA）； ELISA was used to measure the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and soluble triggering receptor expressed on myeloid cells 2 （sTREM2）； HE staining and oil red O staining were performed to observe liver histopathological changes； immunofluorescence assay was used to measure CD68⁺TREM2⁺ cells in liver tissue and calculate the phagocytosis rate of macrophages； quantitative real-time PCR was used to measure the mRNA expression levels of sphingosine 1-phosphate （S1P）， sphingosine 1-phosphate receptor 1 （S1PR1）， a disintegrin and metalloproteinase 17 （ADAM17）， and triggering receptor expressed on myeloid cells 2 （TREM2） in liver tissue， and immunohistochemistry was used to measure the protein expression levels of S1P， S1PR1， ADAM17， and TREM2 in liver tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between groups， and the least significant difference t-test was used for further comparison between two groups； the Welch’s test was used for comparison of normally distributed continuous data with heterogeneity of variance between groups， and the Tamhane’s test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the blank control group， the model A group and the model B group had significant increases in body weight and liver wet weight， and the model B group had a significant increase in liver index （all P<0.05）. HE staining showed diffuse macrovesicular steatosis of liver tissue in the model A group and a large number of hepatocytes with ballooning degeneration in liver tissue in the model group B， with the presence of mixed inflammatory cell infiltration and mild perisinusoidal fibrosis in the lobules and the portal area. Compared with the blank control group， the model A group and the model B group had significant increases in NAS score and oil red O-positive area （all P<0.05）， and the model B group had significant increases in these two indicators than the model A group （both P<0.05）. Compared with the blank control group， the model A group and the model B group had significant increases in the serum levels of TC， TG， LDL-C， FFA， IL-1β， IL-6， and sTREM2 and a significant reduction in the serum level of HDL-C， and the model B group had significant increases in the serum levels of ALT， AST， and TNF-α （all P<0.05）； compared with the model A group， the model B group had significant increases in the serum levels of ALT， AST， TC， TG， FFA， TNF-α， IL-1β， IL-6， and sTREM2 and a significant reduction in the serum level of HDL-C （all P<0.05）. Immunofluorescence assay showed that compared with the blank control group， the model A group had a significant increase in the phagocytosis rate of macrophages （P<0.05）， while the model B group had a significantly lower phagocytosis rate of macrophages than the model A group （P<0.05）. Quantitative real-time PCR showed that compared with the blank control group， the model A group and the model B group had a significant increase in the mRNA expression level of TREM2， and the model B group had significant increases in the mRNA expression levels of S1P and S1PR1 （both P<0.05）； moreover， compared with the model A group， the model B group had significant increases in the mRNA expression levels of S1PR1 and TREM2 （both P<0.05）. Immunohistochemistry showed that compared with the blank control group， the model A group and the model B group had significant increases in the protein expression levels of S1P， S1PR1， and ADAM17， and the model A group had a significant increase in the protein expression level of TREM2 （all P<0.05）； compared with the model A group， the model B group had significant increases in the protein expression levels of S1P， S1PR1， and ADAM17 and a significant reduction in the protein expression level of TREM2 （all P<0.05）. Compared with the model B group， each medication group had significant reductions in body weight， liver wet weight， and liver index （all P<0.05）； each medication group had significant improvements in hepatic steatosis and inflammatory damage， with significant reductions in NAS score and oil red O-positive area （all P<0.05）； each medication group had significant reductions in the serum levels of ALT， AST， TC， TG， FFA， IL-1β， and IL-6 （all P<0.05） and a significant increase in the serum level of HDL-C （P<0.05）， and the high-dose Chinese medicine group had a significant reduction in the serum level of TNF-α （P<0.05）； each medication group had a significant increase in the phagocytosis rate of macrophages （all P<0.05）； the high- and middle-dose Chinese medicine groups had a significant reduction in the protein expression level of ADAM17， and the high-dose Chinese medicine group had a significant increase in the protein expression level of TREM2 （all P<0.05）. ConclusionHuatan Qushi Huoxue prescription improves lipid metabolism and inflammation in the liver of MASH rats by regulating hepatic macrophage phagocytosis.

OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

OBJECTIVE To explore the mechanism by which Qingre antai decoction improves pregnancy outcomes of threatened abortion rats with blood heat syndrome. METHODS The pregnant rats were randomly divided into normal group， model group， dydrogesterone group （0.002 g/kg）， and Qingre antai decoction group （44.1 g/kg）， with 13 rats in each group. Except for normal group， other groups were given warming-yang Chinese medicine and corresponding drugs intragastrically， once a day， for 12 consecutive days. On the 13th day of pregnancy， a single intragastric administration of mifepristone （5 mg/kg） was performed to establish a model of threatened abortion with blood heat syndrome. On the 14th day of pregnancy， the abortion rate and uterine coefficient were calculated； the pathological morphology of pregnant uterine was observed； the serum levels of 3，5，3′-triiodothyronine （T3）， thyroid hormone （T4）， thyroid stimulating hormone （TSH）， as well as the levels of vascular endothelial growth factor （VEGF） and nitric oxide （NO） in the pregnant uterus were all determined； the expressions of mRNA and protein related to Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） pathways were detected. RESULTS Compared with normal group， the model group exhibited endometrial tissue damage， a reduced number of decidual cells， and a significant presence of blood stasis within the uterus； abortion rate， the serum levels of T3， T4 and TSH， the mRNA expressions of JAK2， STAT3 and suppressor of cytokine signaling 3 （SOCS3） as well as protein expressions of p-JAK2， p-STAT3 and SOCS3 in the pregnant uterus were increased significantly （ P ＜0.05）； uterine coefficient， the levels of VEGF and NO in pregnant uterus， mRNA expressions of VEGFR2， PI3K， AKT and endothelial nitric oxide synthase（eNOS）， protein expressions of VEGFR2， PI3K and eNOS as well as phosphorylation level of AKT in the pregnant uterus were significantly reduced （ P ＜0.05）. Compared with model group， the endometrial tissue damage and congestion in the Qingre antai decoction group were significantly improved， and the levels of the aforementioned quantitative indicators were significantly reversed （ P ＜0.05）. CONCLUSIONS Qingre antai decoction can improve the pregnancy outcomes in rats with threatened abortion of blood heat syndrome， the mechanism of which may be associated with inhibiting JAK2/STAT3 pathway and activating PI3K/AKT pathway.

ObjectiveTo investigate the association between body roundness index （BRI） and the risk of metabolic dysfunction-associated fatty liver disease （MAFLD） based on the National Health and Nutrition Examination Survey （NHANES） database， as well as the clinical value of BRI as a noninvasive tool for risk prediction. MethodsBased on the NHANES data in 2015—2020， the 4 573 individuals were divided into MAFLD group with 2 508 individuals and non-MAFLD group with 2 065 individuals， and BRI was calculated for each individual. In order to ensure data quality and reduce the impact of abnormal values on analytical results， the boxplot method was used to remove abnormal levels of BRI and improve the robustness of data. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The multivariate Logistic regression model was established to investigate the association between BRI and MAFLD. BRI was divided into four groups based on quantiles， and with the first quantile （Q1） as reference， odds ratio （OR） and 95% confidence interval （CI） were calculated for the other three models. Restricted cubic spline was used to investigate the dose-effect relationship between BRI and MAFLD. The receiver operating characteristic （ROC） curve was plotted and the area under the ROC curve （AUC） was calculated to assess the efficacy of BRI in the diagnosis of MAFLD. The decision curve analysis was used to investigate the potential clinical value of the model in clinical practice. The interaction analysis and the subgroup analysis were performed to investigate the difference in the association between BRI and MAFLD between different populations. The Lasso regression analysis was conducted for the screening and analysis of characteristic variables. ResultsCompared with the non-MAFLD group， the MAFLD group had a significantly higher BRI （Z=36.29， P<0.001）. After adjustment for the variables including age， sex， ethnicity， educational level， the proportion of individuals with poor income， marital status， smoking， hypertension， diabetes， alanine aminotransferase， aspartate aminotransferase， gamma-glutamyl transpeptidase， and high-density lipoprotein cholesterol， the fully adjusted Logistic regression model showed that BRI was significantly positively associated with the risk of MAFLD （OR=2.53， 95%CI： 2.28 — 2.80， P<0.001）. In addition， the highest BRI quartile （Q4） group had a significantly higher risk of MAFLD than the lowest quartile （Q1） group （OR=83.45， 95%CI： 51.87 — 134.26， P<0.001）. The restricted cubic spline analysis further confirmed the significant nonlinear association between BRI and MAFLD （P for nonlinear<0.001）. The interaction analysis and the subgroup analysis showed that the interaction between hypertension and BRI had statistical significance （P for interaction=0.003）， and compared with the individuals without hypertension， the individuals with hypertension had a stronger association between BRI and MAFLD （OR=1.60， 95%CI： 1.23 — 2.08， P<0.001）. The ROC curve analysis showed that the fully adjusted model based on BRI had a strong discriminatory ability in differentiating MAFLD from non-MAFLD， with an AUC of 0.887 （95%CI： 0.877 — 0.896）. The decision curve analysis showed that the fully adjusted model had good net benefits within the risk threshold of 0.10 — 0.75， which was commonly used in clinical practice. The model based on the key variables identified by the Lasso regression analysis had an AUC of 0.882 （95%CI： 0.872 — 0.892）， which confirmed the robustness of the prediction results. ConclusionThere is a significant positive correlation between BRI and the risk of MAFLD， with a stronger association observed in the hypertensive population. As a body index reflecting abdominal obesity and visceral fat accumulation， BRI shows promising application prospects in the risk assessment of MAFLD.

Objective: To identify the phenotypes, antibodies and explore the molecular mechanisms of a patient who carries antibodies to RBC high-frequency antigens and his family members. Methods: The antibody identification test was performed for the proband by serological methods, and targeted NGS was subsequently used to detect mutations that occurred in blood group genes. Blood samples were collected from the proband and his family members. Sanger sequencing was used to verify the mutation of the XK gene. The expression of Kell blood group antigens was detected by serological methods and flow cytometry. K cells were used to detect the antibody specificity of the proband. The morphology of red blood cells was detected by the scanning electron microscopy. The serum creatine kinase levels of the proband and his family members were analyzed by colorimetric methods. Results: The results of the antibody identification test suggested that the proband might have antibodies to high-frequency antigens. NGS results suggested a homozygous mutation (c. 107G>A) in exon 1 of the XK gene in the proband, resulting in a truncated XK protein. The Sanger sequencing results of the proband were consistent with the NGS results, and the mutation was not found in other family members. The expression of Kell blood group antigens of the proband was not found by serological methods and flow cytometry. The results of the antibody specificity test showed that the proband had anti-Km antibodies. Spike-like changes were identified on red blood cells, and serum creatine kinase level was elevated in the proband. Conclusion: In this study, the McLeod phenotype caused by homozygous mutation (c. 107G>A) of XK gene was identified in Chinese individuals for the first time by the phenotype and molecular mechanism studies. The results of genotyping and phenotyping suggested that the McLeod phenotype caused by the mutation was compatible with the phenotypes of McLeod and K .

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans ; China/epidemiology* ; Hearing Loss/epidemiology* ; Prevalence ; Middle Aged ; Male ; Female ; Adult ; Aged ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Aged, 80 and over ; Cost of Illness

Siwu Decoction is a classic formula for tonifying the blood and activating blood circulation and is characterized by its ability to tonify the blood without leaving stasis and promote blood circulation without harming the vital energy of the body.It is widely used in clinical practice for the treatment of various conditions related to blood deficiency and poor blood circulation,such as anemia,menstrual disorders,and dysmenorrhea.The liver is responsible for governing the free flow of Qi and storing blood,and abnormalities in liver function are associated with various acute and chronic liver injuries.Siwu Decoction can restore liver homeostasis by tonifying the blood,activating blood circulation,nourishing the blood,and soothing the liver.Based on its unique prescription formulation and multiple pharmacological mechanisms,Siwu Decoction has become an important prescription for enhancing liver microcirculation,facilitating hepatocyte repair and regeneration,and alleviating liver injury.This article reviews the effect and mechanism of Siwu Decoction in the prevention and treatment of various liver injuries(including alcoholic liver disease,nonalcoholic fatty liver disease,nonalcoholic fatty liver disease,liver fibrosis,and liver cirrhosis)and discusses existing problems and future research directions.

Objective:Periprosthetic joint infection (PJI) is one of the most severe complications following hip and knee arthroplasty and is a leading cause of revision surgery. Pathogens and their antibiotic susceptibility are key factors in the successful treatment of PJI. This study retrospectively analyzes the pathogen characteristics and antimicrobial susceptibility of PJI patients treated at our center, aiming to establish an empirical antibiotic regimen for PJI in the region, providing a reference for empirical antibiotic therapy in the clinical management of PJI.Methods:This study retrospectively reviewed PJI patients treated at our center from January 2018 to October 2024. In each case, preoperative arthrocentesis fluid, and synovium tissue from at least three sites during surgery were collected for aerobic and anaerobic blood culture. The positive culture rate, distribution of pathogens based on Gram staining, methicillin resistance, mixed infections, and multidrug resistance were analyzed. Effective coverage parameters were constructed based on antimicrobial sensitivity and coverage rates, and appropriate empirical antimicrobial regimens were proposed.Results:A total of 233 PJI patients were included in the analysis. There were 99 males and 134 females with an average age of 67.0±10.1 years (ranging from 32 to 93 years). The study included 130 hip and 103 knee arthroplasty patients. Among the patients, 202 (86.7%) had positive cultures, with a total of 301 pathogen strains isolated: 268 Gram-positive bacteria (89.4%), 25 Gram-negative bacteria (8.3%), and 7 fungal strains (2.3%). The most common Gram-positive bacteria were coagulase-negative staphylococci (196 strains, 65.1%), epidermal staphylococci (77 strains, 25.6%), Staphylococcus aureus (39 strains, 13.0%), and Streptococcus spp. (19 strains, 6.3%). The most common Gram-negative bacteria were Enterobacteriaceae (14 strains, 4.7%). In hip joint infections, the most prevalent pathogens were epidermal Staphylococci (48 strains, 28.1%) and Staphylococcus aureus (27 strains, 15.8%), while in knee joint infections, epidermal Staphylococci (29 strains, 22.3%) were most common. Regarding antibiotic resistance, 48.5% of staphylococcal strains were methicillin-resistant Staphylococcus, and 51.5% were multidrug-resistant strains. Staphylococci were 100% susceptible to vancomycin, teicoplanin, daptomycin, linezolid, and tigecycline, but exhibited high resistance to β-lactams and quinolone antibiotics. Analysis of empirical antibiotic regimens revealed that vancomycin combined with meropenem, linezolid combined with meropenem, vancomycin combined with imipenem, vancomycin combined with piperacillin/tazobactam, and vancomycin combined with ceftriaxone had effective coverage rates of 97.0%, 97.0%, 96.0%, 94.9%, and 90.9%, respectively.Conclusion:The main pathogens in PJI in this region are Gram-positive bacteria, with high rates of methicillin resistance and multidrug resistance. Based on antimicrobial susceptibility data, we recommend vancomycin combined with meropenem as the empirical treatment regimen for culture-negative PJI in this region, with linezolid combined with meropenem as an alternative.

In this study, we propose an automatic contour outlining method to measure the spatial resolution of homemade automatic tube current modulation (ATCM) phantom by outlining the edge contour of the phantom image, selecting the region of interest (ROI), and measuring the spatial resolution characteristics of computer tomography (CT) phantom image. Specifically, the method obtains a binarized image of the phantom outlined by an automated fast region convolutional neural network (AFRCNN) model, measures the edge spread function (ESF) of the CT phantom with different tube currents and layer thicknesses, and differentiates the ESF to obtain the line spread function (LSF). Finally, the values passing through the zeros are normalized by the Fourier transform to obtain the CT spatial resolution index (RI) for the automatic measurement of the modulation transfer function (MTF). In this study, this algorithm is compared with the algorithm that uses polymethylmethacrylate (PMMA) to measure the MTF of the phantom edges to verify the feasibility of this method, and the results show that the AFRCNN model not only improves the efficiency and accuracy of the phantom contour outlining, but also is able to obtain a more accurate spatial resolution value through automated segmentation. In summary, the algorithm proposed in this study is accurate in spatial resolution measurement of phantom images and has the potential to be widely used in real clinical CT images.
Phantoms, Imaging ; Tomography, X-Ray Computed/instrumentation* ; Algorithms ; Neural Networks, Computer ; Image Processing, Computer-Assisted/methods* ; Humans ; Polymethyl Methacrylate