Objective To observe the effects of Daizong Prescription on glycogen metabolism in adipose tissue of obese mice;To explore its regulatory mechanism in activating browning in the white adipose tissue.Methods A obesity model was established by feeding high-fat diet to C57BL/6J mice.The obese mice were divided into model group,metformin group(0.15 g/kg),and Daizong Prescription low-(0.20 g/kg)and high-dosage(0.40 g/kg)groups.Mice fed a standard diet were set as the normal group,with 12 mice in each group.Each medication group was given corresponding drugs by gavage for 6 consecutive weeks.Body mass and fasting blood glucose were monitored,serum triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)contents were measured.Brown adipose tissue from the interscapular region and white adipose tissue from the inguinal,perirenal and epididymal region were collected,the adipose tissue mass was measured,and the body fat coefficient was calculated.HE staining was performed to observe morphological changes in adipose tissue,PAS staining was used to observe glycogen distribution in adipose tissue,immunohistochemistry staining was performed to detect the expressions of Gys2,Ppp1r3c,and GSK-3β in inguinal white adipose tissue.Results Compared with the normal group,the body mass and fasting blood glucose in different time points of the model group significant increase(P<0.05,P<0.01),and serum TC and HDL-C contents significantly increased(P<0.01);the mass and body fat coefficient of white adipose tissue in inguinal,perirenal,and epididymis significantly increased(P<0.01),the cells in white adipose tissue in inguinal were hypertrophic and appeared as large vacuoles,with less glycogen accumulation,the expressions of Gys2 and Ppp1r3c significantly decreased(P<0.01).Compared with the model group,the mice in Daizong Prescription high-dosage group showed a significant decrease in body mass and fasting blood glucose at 4 and 6 weeks of administration(P<0.05,P<0.01),and the contents of serum TG,TC,HDL-C,and LDL-C were significantly decreased(P<0.01);the mass and body fat coefficient in white adipose tissue of perirenal and epididymal significantly decreased(P<0.05,P<0.01),and the mass of inguinal white adipose tissue significantly decreased(P<0.05),multiple irregularly shaped small vacuoles could be seen in inguinal white adipose tissue,accompanied by nuclear aggregation and increased glycogen accumulation,the expressions of Gys2 and Ppp1r3c significantly increased(P<0.01).There was no significant difference in the expression of GSK-3β inguinal white adipose tissue of mice among the groups.Conclusion Daizong Prescription can increase the activity of Gys2 by upregulating the expression of Ppp1r3c,promote glycogen synthesis,induce browning of adipose tissue,increase fat heat production,and improve obesity and related disorders of glycolipid metabolism.

ObjectiveTo investigate the possible mechanism of Huatan Sanjie Formula （化痰散结方， HSF） in treating Graves' disease （GD） from the perspective of thyroid angiogenesis. MethodsThirty-six BALB/c female mice were randomly divided into a normal control group （n=9） and a modeling group （n=27）. Mice in the modeling group were injected with 2.0×10⁹ PFU/ml of Ad-TSHR289 adenovirus into the tibialis anterior muscle to build GD model. Nine weeks after immunization， the successfully modeled mice were randomly divided into model group， methimazole （MMI） group and HSF group， with 9 mice in each group. The MMI group was given 5.2 mg/（kg·d） of methimazole tablets by gavage， while the HSF group was given HSF at a relative crude drug dosage of 7.02 g/（kg·d） by gavage. The normal control group and the model group were given 0.1 ml/10 g of pure water by gavage. All groups were administered intragastrically once a day for a total of 4 weeks. The levels of thyroxine （T4） and thyrotropin receptor autoantibodies （TRAb） in serum were detected by radioimmunoassay， while the pathological changes of the thyroid gland were assessed by HE staining. The vascular morphology of thyroid tissue was observed by CD34 immunohistochemical staining， and the microvessel density （MVD） was counted. The protein expression of vascular endothelial growth factor A （VEGFA） and vascular endothelial growth factor receptor 2 （VEGFR2） in thyroid was detected by Western-blot. ResultsCompared to those in the normal control group， the thyroid volume of the mice in the model group significantly increased with excessive congestion， and the pathology showed significant thyroid follicular hyperplasia， columnar and proliferated epithelial cells， and enlarged follicle size； serum T4 and TRAb significantly increased， as well as the count of thyroid MVD， and the protein expressions of thyroid VEGFA and VEGFR2 （P＜0.01）. Compared to those in the model group， the thyroid glands of the mice in the MMI group and the HSF group were significantly reduced， and the congestion was improved； pathology showed that thyroid follicular hyperplasia and epithelial cell proliferation were reduced， with smooth edges of the follicles and the significantly reduced inward protrusion； serum T4 and TRAb significantly decreased， as well as the thyroid MVD， thyroid VEGFA and VEGFR2 protein expressions （P＜0.05 or P＜0.01）. There was no significant difference in all indicators between the MMI group and the HSF group （P＞0.05）. ConclusionHSF may inhibit thyroid angiogenesis by down-regulating thyroid VEGFA/VEGFR2 signaling pathway， thereby improving goitre and hyperfunction in GD mice.

This study was designed to investigate the effects of TNFSF14 on mitochondrial function in ischemia/reperfusion-induced acute kidney injury(I/R-AKI)and its mechanism.TNFSF14-/-and TNFSF14+/+mice underwent renal ischemia-reperfusion operation to establish I/R-AKI models,and their histopathology changes were compared by using Periodic Acid-Schiff stain,transmission electron microscopy.Immunohistochemistry(IHC)was used to detect levels of TNFSF14,HVEM,LT[3R,mitochondrial activity related proteins(Dpr1 and Mfn2)and inflammatory cells infiltration in kidney tissues of mice and relevant patients.In vitro cell experiments,immunofluorescence and immunoblotting were used to observe the effects of exogenous recombinant TNFSF14 factor on the damage and mitochondrial activity of renal tubular epithelial cell line HK-2 cells.Data showed that the expression of TNFSF14 and its receptors were significantly increased in kidney tissues of I/R-AKI mice and clinical human renal tissues of acute tubular injury.Compared with the sham group,I/R mice showed significantly higher levels of renal tubular injury score,inflammatory cells infiltration,cell apoptosis,mitochondrial damage,and Drp1 expression,while knocking out the TNFSF14 gene,the above indicators were significantly reduced.In vitro,exogenous TNFSF14 stimulation could aggravate the hypoxia-induced apoptosis and the decrease of mitochondrial membrane potential in HK-2 cells,while increasing phosphorylation of Drp1 at Se616 to promote its transfer from cytoplasm to mitochondria,leading to an abnormal increase in mitochondrial fission.In conclusions,TNFSF14 may mediate the pathological process of I/R-AKI by promoting mitochondrial damage.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Objective:To explore the predictive value of deep learning (DL)-based coronary artery calcification score (CACS) for obstructive coronary artery disease (CAD) and noncalcified plaque/mixed plaque in type 2 diabetes mellitus (T2DM).Methods:Forty hundred and twenty-four consecutive T2DM patients who accepted CACS scan and coronary CT angiography (CCTA) from December 2012 to December 2019 were included retrospectively, with clinical risk factors and plaque features collected. Plaque composition was classified as calcified, non-calcified or mixed plaque. Obstructive CAD was defined as maximum diameter stenosis≥50%. CACS was calculated with a fully automated method based on DL. Univariate and multivariate logistic regressions were applied to select statistically significant factors and the odds ratios(ORs) were measured. Receiver operating characteristic (ROC) curve was evaluated to assess the predictive performance.Results:Increased CACS was associated with a significantly higher odds of obstructive CAD in CCTA (adjusted ORs were 2.22, 6.18 and 16.98 for CACS=1-99, 100-299, 300-999 vs. CACS=0, and P values were 0.009,<0.001,<0.001 respectively). The area under ROC curve (AUC) of CACS to predict obstructive CAD was 0.764. Compared with 0, increased CACS was associated with increased risk of non-calcified/mixed plaque (adjusted ORs were 2.75, 4.76, 5.29 for CACS=1-99, 100-299, 300-999 respectively and P values were 0.001,<0.001,<0.001 respectively). The AUC of CACS to predict non-calcified/mixed plaque was 0.688. It took 1.17 min to perform automated measurement of CACS based on DL in total, which was significantly less than manual measurement of 1.73 min ( P<0.001). Conclusion:DL-based CACS can predict obstructive CAD and non-calcified plaque/mixed plaque in T2DM, which is economical and efficient, and has important value for clinical diagnosis and treatment.

BACKGROUND: Pneumonia-like primary pulmonary lymphoma (PPL) was commonly misdiagnosed as infectious pneumonia, leading to delayed treatment. The purpose of this study was to establish a computed tomography (CT)-based radiomics model to differentiate pneumonia-like PPL from infectious pneumonia. METHODS: In this retrospective study, 79 patients with pneumonia-like PPL and 176 patients with infectious pneumonia from 12 medical centers were enrolled. Patients from center 1 to center 7 were assigned to the training or validation cohort, and the remaining patients from other centers were used as the external test cohort. Radiomics features were extracted from CT images. A three-step procedure was applied for radiomics feature selection and radiomics signature building, including the inter- and intra-class correlation coefficients (ICCs), a one-way analysis of variance (ANOVA), and least absolute shrinkage and selection operator (LASSO). Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and construct a clinical factor model. Two radiologists reviewed the CT images for the external test set. Performance of the radiomics model, clinical factor model, and each radiologist were assessed by receiver operating characteristic, and area under the curve (AUC) was compared. RESULTS: A total of 144 patients (44 with pneumonia-like PPL and 100 infectious pneumonia) were in the training cohort, 38 patients (12 with pneumonia-like PPL and 26 infectious pneumonia) were in the validation cohort, and 73 patients (23 with pneumonia-like PPL and 50 infectious pneumonia) were in the external test cohort. Twenty-three radiomics features were selected to build the radiomics model, which yielded AUCs of 0.95 (95% confidence interval [CI]: 0.94-0.99), 0.93 (95% CI: 0.85-0.98), and 0.94 (95% CI: 0.87-0.99) in the training, validation, and external test cohort, respectively. The AUCs for the two readers and clinical factor model were 0.74 (95% CI: 0.63-0.83), 0.72 (95% CI: 0.62-0.82), and 0.73 (95% CI: 0.62-0.84) in the external test cohort, respectively. The radiomics model outperformed both the readers' interpretation and clinical factor model ( P <0.05). CONCLUSIONS The CT-based radiomics model may provide an effective and non-invasive tool to differentiate pneumonia-like PPL from infectious pneumonia, which might provide assistance for clinicians in tailoring precise therapy.
Humans ; Retrospective Studies ; Pneumonia/diagnostic imaging* ; Analysis of Variance ; Tomography, X-Ray Computed ; Lymphoma/diagnostic imaging*

Objective: Recent studies have highlighted the active and potential role of perivascular adipose tissue (PVAT) in atherosclerosis and aneurysm progression, respectively. This study explored the link between PVAT attenuation and abdominal aortic aneurysm (AAA) progression using computed tomography angiography (CTA). Materials and Methods: This multicenter retrospective study analyzed patients with AAA who underwent CTA at baseline and follow-up between March 2015 and July 2022. The following parameters were obtained: maximum diameter and total volume of the AAA, presence or absence of intraluminal thrombus (ILT), maximum diameter and volume of the ILT, and PVAT attenuation of the aortic aneurysm at baseline CTA. PVAT attenuation was divided into high (> -73.4 Hounsfield units [HU]) and low (≤ -73.4 HU). Patients who had or did not have AAA progression during the follow-up, defined as an increase in the aneurysm volume > 10 mL from baseline, were identified. Kaplan–Meier and multivariable Cox regression analyses were used to investigate the association between PVAT attenuation and AAA progression. Results: Our study included 167 participants (148 males; median age: 70.0 years; interquartile range: 63.0–76.0 years), of which 145 (86.8%) were diagnosed with AAA accompanied by ILT. Over a median period of 11.3 months (range: 6.0–85.0 months), AAA progression was observed in 67 patients (40.1%). Multivariable Cox regression analysis indicated that high baseline PVAT attenuation (adjusted hazard ratio [aHR] = 2.23; 95% confidence interval [CI], 1.16–4.32; P = 0.017) was independently associated with AAA progression. This association was demonstrated within the patients of AAA with ILT subcohort, where a high baseline PVAT attenuation (aHR = 2.23; 95% CI, 1.08–4.60; P = 0.030) was consistently independently associated with AAA progression. Conclusion Elevated PVAT attenuation is independently associated with AAA progression, including patients of AAA with ILT, suggesting the potential of PVAT attenuation as a predictive imaging marker for AAA expansion.

Objective:To investigate the prognostic value of baseline peripheral blood inflammatory biomarkers for prognosis in patients with advanced hepatocellular carcinoma (HCC) receiving immunotherapy combined with targeted therapy.Methods:The clinical data of a total of 120 patients with advanced HCC who received immunotherapy combined with targeted therapy at Cancer Center of Renmin Hospital of Wuhan University from December 2019 to March 2022 were analyzed retrospectively. Receiver operating characteristic (ROC) curve was used to calculate the optimal cut-off values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII) and prognostic nutritional index (PNI). According to the optimal cut-off values, the study objects were divided into high value group and low value group. The Kaplan-Meier method was used for survival analysis. Cox proportional hazard regression model was applied to analyze the factors associated with prognosis.Results:By the end of follow-up, 74 patients died and 46 survived. The median follow-up time was 23.0 months, the median overall survival (mOS) was 15.6 months, and the median progression-free survival (mPFS) was 13.1 months. ROC curve analysis showed that the optimal cut-off values of NLR, PLR, SII, LMR and PNI were 3.45, 131.87, 626.21, 2.12 and 43.30, respectively. The mPFS (18.3 months vs. 8.7 months) and mOS (26.6 months vs. 10.9 months) of patients in the low-NLR group ( n=75) were longer than those of the high-NLR group ( n=45), and there were statistically significant differences ( χ2=55.64, P<0.001; χ2=64.14, P<0.001). The mPFS (17.9 months vs. 10.9 months) and mOS (24.5 months vs. 13.5 months) of patients in the low-PLR group ( n=55) were longer than those of the high-PLR group ( n=65), and there were statistically significant differences ( χ2=5.27, P=0.023; χ2=11.84, P<0.001). The mPFS (18.0 months vs. 10.7 months) and mOS (25.7 months vs. 12.8 months) of patients in the low-SII group ( n=75) were longer than those of the high-SII group ( n=45), and there were statistically significant differences ( χ2=24.46, P<0.001; χ2=25.42, P<0.001). The mPFS (18.2 months vs. 10.9 months) and mOS (26.6 months vs. 13.2 months) of patients in the high-LMR group ( n=56) were longer than those of the low-LMR group ( n=64), and there were statistically significant differences ( χ2=19.25, P<0.001; χ2=19.92, P<0.001). The mPFS (17.9 months vs. 10.9 months) and mOS (25.4 months vs. 13.4 months) of patients in the high-PNI group ( n=62) were longer than those of the low-PNI group ( n=58), and there were statistically significant differences ( χ2=13.69, P<0.001; χ2=19.07, P<0.001). Univariate analysis showed that Barcelona clinic liver cancer (BCLC) stage ( HR=1.83, 95% CI: 1.17-2.87, P=0.008), Child-Pugh grade ( HR=2.21, 95% CI: 1.47-3.34, P<0.001), modified albumin-bilirubin (mALBI) grade ( HR=1.35, 95% CI: 1.01-1.81, P=0.045), extrahepatic metastases ( HR=2.18, 95% CI: 1.47-3.25, P<0.001), NLR ( HR=1.40, 95% CI: 1.28-1.54, P<0.001), PLR ( HR=1.00, 95% CI: 1.00-1.01, P=0.001), SII ( HR=1.00, 95% CI: 1.00-1.00, P<0.001), LMR ( HR=0.64, 95% CI: 0.51-0.79, P<0.001) and PNI ( HR=0.95, 95% CI: 0.93-0.98, P=0.001) were correlated with PFS; BCLC stage ( HR=2.18, 95% CI: 1.21-3.91, P=0.009), Child-Pugh grade ( HR=2.57, 95% CI: 1.61-4.09, P<0.001), Eastern Cooperative Oncology Group performance status score ( HR=1.59, 95% CI: 1.01-2.51, P=0.044), mALBI grade ( HR=1.60, 95% CI: 1.17-2.17, P=0.003), extrahepatic metastasis ( HR=2.51, 95% CI: 1.59-3.96, P<0.001), NLR ( HR=1.45, 95% CI: 1.32-1.60, P<0.001), PLR ( HR=1.01, 95% CI: 1.01-1.01, P<0.001), SII ( HR=1.01, 95% CI: 1.01-1.01, P<0.001), LMR ( HR=0.57, 95% CI: 0.40-0.72, P<0.001) and PNI ( HR=0.92, 95% CI: 0.89-0.96, P<0.001) were correlated with OS. Multivariate analysis showed that extrahepatic metastasis ( HR=1.78, 95% CI: 1.10-2.87, P=0.018) and NLR ( HR=1.46, 95% CI: 1.24-1.73, P<0.001) were independent influencing factors for PFS; extrahepatic metastasis ( HR=2.09, 95% CI: 1.21-3.61, P=0.009), NLR ( HR=1.56, 95% CI: 1.29-1.88, P<0.001), SII ( HR=1.00, 95% CI: 1.00-1.00, P=0.025), LMR ( HR=0.59, 95% CI: 0.45-0.78, P=0.008) and PNI ( HR=0.93, 95% CI: 0.88-0.99, P=0.013) were independent influencing factors for OS. Conclusion:NLR and extrahepatic metastasis can be regarded as important indicators to predict PFS in patients with advanced HCC receiving immunotherapy combined with targeted therapy, and NLR, SII, LMR, PNI and extrahepatic metastasis can be regarded as important indicators to predict OS in patients with advanced HCC receiving immunotherapy combined with targeted therapy. High NLR, high SII, low LMR, low PNI and extrahepatic metastasis indicate poor prognosis of HCC patients.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, with a high incidence and fatality rate in China. Since sorafenib opened up a new era of targeted therapy for HCC, drug developers around the world have made a lot of efforts and contributions to the exploration of systematic therapy for HCC. In recent years, novel molecular targeted agents, immune checkpoint inhibitors and their combined treatment regimens in advanced HCC have been implemented for many large samples, international multi-center clinical trials. The results show that the therapeutic effect of immunotherapy combined with targeted therapy and dual immunotherapy have significant advantages compared with that of targeted or immune monotherapy, and have satisfactory safety while prolonging survival and improving the quality of life of patients.

Medical rescue bases for nuclear or radiological emergencies are mostly composed of institutions that have obtained the qualification of radiological health technical service (Class A) or the qualification of radiation-induced disease diagnosis. Institutions of radiological health have accumulated the technical capabilities of radiation monitoring, contamination detection, dose estimation, and health effects evaluation in their daily work, which can play an important role in the response to nuclear or radiological emergencies and realize the “combination of non-emergency and emergency use” in capacity building. It is suggested that institutions of radiological health at all levels should continue to take advantage of their strengths, improve their capabilities through participating in radiation monitoring projects, and actively participate in the assessment of assay capabilities of institutions of radiological health, so as to provide personnel and technical reserves for the health response to nuclear or radiological emergencies.