Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
Hepatic Stellate Cells/cytology* ; Liver Cirrhosis/genetics* ; Artesunate/pharmacology* ; Cellular Senescence/drug effects* ; Membrane Proteins/genetics* ; Animals ; Humans ; Nerve Tissue Proteins/genetics* ; Tumor Suppressor Protein p53/genetics* ; Male ; Mice

Objective:To establish a model for the combined detection of serum copeptin and inflammatory markers in acute stroke (AS), and to explore the value of copeptin and inflammatory marker detection in the clinical diagnosis and prognosis assessment of AS.Methods:A total of 75 patients were diagnosed with acute ischemic stroke (AIS) [46 males, age (64.1±11.7) years] and 45 patients with acute intracerebral hemorrhage (ICH) [28 males, age (61.0±13.9) years] who were admitted to the First Affiliated Hospital of Hunan University of Chinese Medicine through the emergency department from January 1 to July 31, 2024, were included as the observation group. Meanwhile, 60 healthy individuals [39 males, age (64.4±8.2) years] were selected as the control group (HC). The differences in serum copeptin levels and inflammatory markers among different groups were compared. ROC curves were drawn to analyze the value of copeptin and inflammatory markers in the clinical diagnosis and prognosis assessment of AIS. The Kaplan-Meier method was used to draw survival curves to analyze the in-hospital survival rates of patients in different groups. Cox regression analysis was conducted to identify the risk factors affecting the prognosis of AIS patients.Results:The level of copeptin was significantly elevated in AS, with the results showing ICH>AIS>HC ( H=100.11, P<0.001). Copeptin demonstrated the highest efficacy in the early diagnosis of AIS and ICH (AUC=0.893, sensitivity 89.3%, specificity 75.0%; AUC=0.986, sensitivity 95.6%, specificity 93.3%) and the assessment of prognosis (AUC=0.997, sensitivity 100%, specificity 96.8%; AUC=0.907, sensitivity 86.7%, specificity 86.7%), outperforming other single indicators. The combined detection of copeptin with the neutrophil-to-lymphocyte ratio (NLR) and the systemic immune-inflammation index (SIIRI) was the best combination for the early diagnosis of AIS and ICH (AUC=0.937, sensitivity 77.3%, specificity 98.3%; AUC=0.989, sensitivity 95.6%, specificity 95.0%) and for the assessment of prognosis (AUC=0.996, sensitivity 100%, specificity 96.8%; AUC=0.944, sensitivity 86.7%, specificity 90.0%). Kaplan-Meier survival curves showed that AIS patients in the low-value group of copeptin and NLR had a higher survival rate during hospitalization than those in the high-value group ( HR 54.46, 7.608, P<0.01, respectively), and ICH patients in the low-value group of copeptin, SIIRI, SIRI, and SII had a higher survival rate during hospitalization than those in the high-value group ( HR 12.67, 7.923, 3.567, 5.925, P<0.05); Cox regression showed that copeptin, NLR, NIHSS, and mRS were independent risk factors affecting the prognosis of patients with AIS ( HR 1.421, 1.368, 1.158, and 1.188, respectively, P<0.05), copeptin and SIIRI were independent risk factors affecting the prognosis of ICH ( HR 1.308, 1.113, P<0.05), and GCS was a protective factor affecting ICH prognosis ( HR=0.741, P<0.05). Conclusion:Copeptin and inflammatory indicators can reflect the severity of different subtypes of stroke. The single or combined detection shows good value in the clinical application of AS. The combination of copeptin-NLR and copeptin-SIIRI is respectively the best comprehensive biomarker combination for the early diagnosis and prognosis assessment of AIS and ICH.

Objective To explore the related functional mechanism of Xihuang pill containing serum inter-vention in breast cancer cells based on microRNA(miR)21-5p targeting FAM13A gene.Methods Bioinfor-matics websites was used to predict potential miRNAs of FAM13A gene,double luciferase reporter experi-ments were conducted to verify the binding site relationship between FAM13A and predicted miRNAs.The Xihuang pill containing serum was prepared,and human breast cancer MDA-MB-231 cells were cultured.The proliferation of MDA-MB-231 cells was interfered by the Xihuang pill containing serum with different dilution ratios by CCK-8 test,and the best dilution ratio concentration of Xihuang pill containing serum to inhibit the proliferation of breast cancer cells was selected.Real time fluorescence quantitative PCR(RT-qPCR)was ap-plied to detect the relative expression levels of FAM13A mRNA,as well as the relative expression levels of miR21-5p,in MDA-MB-231 cells after intervention with Xihuang pill containing serum.Cell proliferation(Edu)assay and cell apoptosis detection(TUNEL)assay were used to detect the effects of Xihuang pill con-taining serum intervention on cell proliferation and apoptosis function in MDA-MB-231 cells.The siRNA lentiviral transfection on MDA-MB-231 cells was performed to knock down the FAM13A gene,and Edu assay and TUNEL assay were used to detect changes in proliferation and apoptosis ability of MDA-MB-231 cells af-ter lentiviral transfection.The expression level of miR21-5p in MDA-MB-231 cells after FAM13A gene knock-out was detected by RT-qPCR technology.Results Target Scan online website predicted the potential miR-21-5p binding sequence in the 3'UTR of FAM13A mRNA,and dual luciferase reporter assay confirmed the in-teraction between miR-21-5p and FAM13A.After intervention of MDA-MB-231 cells with Xihuang pill drug containing serum,RT-qPCR results showed that compared with the control group(NC group),the Xihuang pill drug containing serum group(XHW group)downregulated the expression levels of FAM13A mRNA(P＜0.05),and upregulated the expression level of miR21-5p(P＜0.05).Compared with the NC group,the XWH group showed reduced cell proliferation ability and promoted cell apoptosis.(P＜0.05).After silencing the FAM13A gene in MDA-MB-231 cells,compared with the control group(shCtrl group),the shFAM13A group showed a significant decrease in cell proliferation ability and promoted cell apoptosis.The RT-qPCR re-sults showed that compared with the shCtrl group,the expression level of miR21-5p was significantly upregu-lated in the shFAM13A group(P＜0.05).Conclusion Xihuang pill could participate in the anti-tumor treat-ment of breast cancer by regulating miR21-5p to affect the expression level of FAM13A gene.

Objective:To establish a model for the combined detection of serum copeptin and inflammatory markers in acute stroke (AS), and to explore the value of copeptin and inflammatory marker detection in the clinical diagnosis and prognosis assessment of AS.Methods:A total of 75 patients were diagnosed with acute ischemic stroke (AIS) [46 males, age (64.1±11.7) years] and 45 patients with acute intracerebral hemorrhage (ICH) [28 males, age (61.0±13.9) years] who were admitted to the First Affiliated Hospital of Hunan University of Chinese Medicine through the emergency department from January 1 to July 31, 2024, were included as the observation group. Meanwhile, 60 healthy individuals [39 males, age (64.4±8.2) years] were selected as the control group (HC). The differences in serum copeptin levels and inflammatory markers among different groups were compared. ROC curves were drawn to analyze the value of copeptin and inflammatory markers in the clinical diagnosis and prognosis assessment of AIS. The Kaplan-Meier method was used to draw survival curves to analyze the in-hospital survival rates of patients in different groups. Cox regression analysis was conducted to identify the risk factors affecting the prognosis of AIS patients.Results:The level of copeptin was significantly elevated in AS, with the results showing ICH>AIS>HC ( H=100.11, P<0.001). Copeptin demonstrated the highest efficacy in the early diagnosis of AIS and ICH (AUC=0.893, sensitivity 89.3%, specificity 75.0%; AUC=0.986, sensitivity 95.6%, specificity 93.3%) and the assessment of prognosis (AUC=0.997, sensitivity 100%, specificity 96.8%; AUC=0.907, sensitivity 86.7%, specificity 86.7%), outperforming other single indicators. The combined detection of copeptin with the neutrophil-to-lymphocyte ratio (NLR) and the systemic immune-inflammation index (SIIRI) was the best combination for the early diagnosis of AIS and ICH (AUC=0.937, sensitivity 77.3%, specificity 98.3%; AUC=0.989, sensitivity 95.6%, specificity 95.0%) and for the assessment of prognosis (AUC=0.996, sensitivity 100%, specificity 96.8%; AUC=0.944, sensitivity 86.7%, specificity 90.0%). Kaplan-Meier survival curves showed that AIS patients in the low-value group of copeptin and NLR had a higher survival rate during hospitalization than those in the high-value group ( HR 54.46, 7.608, P<0.01, respectively), and ICH patients in the low-value group of copeptin, SIIRI, SIRI, and SII had a higher survival rate during hospitalization than those in the high-value group ( HR 12.67, 7.923, 3.567, 5.925, P<0.05); Cox regression showed that copeptin, NLR, NIHSS, and mRS were independent risk factors affecting the prognosis of patients with AIS ( HR 1.421, 1.368, 1.158, and 1.188, respectively, P<0.05), copeptin and SIIRI were independent risk factors affecting the prognosis of ICH ( HR 1.308, 1.113, P<0.05), and GCS was a protective factor affecting ICH prognosis ( HR=0.741, P<0.05). Conclusion:Copeptin and inflammatory indicators can reflect the severity of different subtypes of stroke. The single or combined detection shows good value in the clinical application of AS. The combination of copeptin-NLR and copeptin-SIIRI is respectively the best comprehensive biomarker combination for the early diagnosis and prognosis assessment of AIS and ICH.

To introduce a strategy for a case of severe pneumonia complicated with lung abscess caused by Fusobacterium necrotum.The pathogen was not identified,but the patient was still coughing up feverish bloody sputum after being treated with meropenem,linezolid and ornidazole.The results of detection of pathogen metagenomes in bronchoalveolar lavage fluid by posterior bronchoscopy suggested that the pathogen was Fusobacterium necrophorum,according to the characteristics of bacteria,the dynamic changes of clinical symptoms,liver and kidney function,body temperature and blood picture infection index,combined with the results of bacterial culture/drug sensitivity test,bronchoalveolar lavage fluid NGS and the pharmacokinetic/pharmacodynamic characteristics of antimicrobial agents,to propose an anti-infective regimen that is strategically adjusted to imipenem cilastatin(1.0 g,ivd,q8h)plus ornidazole(0.5 g,ivd,q12h)for the implementation of pharmaceutical care after adoption by physicians.After 21 days,the patient's severe infection and lung abscess was controlled and patient was discharged.In this case,clinical pharmacists study the bacterial characteristics of Fusobacterium necrotum,review a large number of domestic and foreign literature to track the frontier knowledge of antimicrobial agents,and use their own expertise to provide effective pharmaceutical support for the clinical team,to assist clinical team in the diagnosis and treatment of rare infections,to achieve professional value.

Respiratory viral infections are an important public health problem worldwide, with complex mechanisms of infection, and the key to infection lies in the specific binding between respiratory viruses and receptors. This article provides an overview of the progress in the study of receptors for respiratory viruses, such as coronavirus and influenza virus (IV), with a focus on the binding sites of receptors such as angiotensin-converting enzyme 2 (ACE2) and sialic acid (SA) to respiratory viruses and the role of receptor diversity in respiratory viral infections. An in-depth study of the binding sites between viruses and receptors will help to understand the molecular mechanism of respiratory viral infections and provide a theoretical basis for disease prevention and control and the development of new therapeutic targets.

Objective:To analyze genioglossus (GG) activation responses to the negative pressure of upper airway cavity during awake and different sleep stages in patients with different obstructive sleep apnea (OSA) graduation.Methods:This prospective cohort study started from August 2019 to January 2021, recruited 42 male OSA patients aged from 21 to 59 (38.77±8.42) years. After completing whole night polysomnography (PSG) and upper airway CT, each subject underwent drug-induced sleep with simultaneous monitoring of genioglossal electromyography (GGEMG) and pressure of epiglottis (P epi). Subjects were divided into three groups of mild OSA(7 males), moderate OSA(12 males), and severe OSA(23 males). The differences in upper airway CT measurements, parameters of GGEMG and P epi during awake and induced sleep were compared. Statistical analysis was conducted by SPSS 21.0. Results:There was no significant difference in the GGEMG parameters between the mild and moderate groups. In wakefulness, the peak phasic GGEMG of the severe group was higher than the mild group ( t=1.249, P=0.025), with no statistically difference in the corresponding P epi. In the sleep onset, the GGEMG parameters and P epi in severe group were higher than the other two groups. Linear regression analysis of the maximum GGEMG and maximum P epi at the end of obstructive apnea (OA) in all moderate plus severe patients ( n=35) was shown nonlinear correlation ( r=0.28, P=0.694). The airway length of the glossopharyngeal cavity was linearly correlated with the maximum P epi of OA ( r=0.468, R2=0.219, P=0.005). Conclusions:The individual difference of GG activation in OSA patients is related to the severity of the disease (frequency of respiratory events) and negative pressure stimulation. In moderate and severe OSA patients, GG activity is not in harmony with the corresponding negative pressure stimulation, which may be one of the mechanisms leading to the aggravation of OSA.

Respiratory viral infections are an important public health problem worldwide, with complex mechanisms of infection, and the key to infection lies in the specific binding between respiratory viruses and receptors. This article provides an overview of the progress in the study of receptors for respiratory viruses, such as coronavirus and influenza virus (IV), with a focus on the binding sites of receptors such as angiotensin-converting enzyme 2 (ACE2) and sialic acid (SA) to respiratory viruses and the role of receptor diversity in respiratory viral infections. An in-depth study of the binding sites between viruses and receptors will help to understand the molecular mechanism of respiratory viral infections and provide a theoretical basis for disease prevention and control and the development of new therapeutic targets.

Objective:To investigate the characteristics of functional limitation and associated factors in patients with rheumatoid arthritis (RA).Methods:Consecutive patients with RA were recruited from August 2015 to June 2019 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. Demographic and clinical characteristics including age, gender, erythrocyte sedimentation rate (ESR), visual analogue scale (VAS) of pain, clinical disease activity index (CDAI), modified total Sharp score were collected. Physical function was assessed by the Stanford health assessment questionnaire disability index (HAQ-DI).Ordered logistic regression was used to analyze the related factors of HAQ-DI.Results:A total of 643 RA patients were finally recruited including 114 males and 529 females with mean age (49.7±12.9) years. There were 399 (62.1%) patients having different degrees of functional limitation, who were classified as mild (293, 45.6%), moderate (73, 11.4%) and severe (33, 5.1%). The prevalence of functional limitation was positively correlated with age and disease activity. The most restricted activity was walking [43.5% (280/643)], followed by gripping [36.1% (232/643)], reaching [35.5% (228/643)], daily activities [33.4% (215/643)], hygiene [33.0% (212/643)], dressing and grooming [29.7% (191/643)] and arising [29.1% (187/643)], and the last eating [18.4% (118/643)]. Multivariate ordered logistic regression analysis showed that age ( OR=1.019, 95% CI 1.004-1.035),pain VAS ( OR=1.820, 95% CI 1.616-2.050), ESR ( OR=1.009, 95% CI 1.001-1.017), CDAI ( OR=1.080, 95% CI 1.059-1.102) and modified total Sharp score ( OR=1.010, 95% CI 1.004-1.015) were associated factors of functional limitation. Conclusion:The majority RA patients have functional limitation. Age, pain and active disease are independent associated factors. Therefore, target treatment and control of pain should be emphasized in RA patients.

Objective:To explore the diagnostic value of radiomics based on arterial-venous mixed images derived from dual-energy CT (DECT) data in diagnosis of cervical lymph nodes (LNs) metastasis of papillary thyroid cancer (PTC).Methods:From June 2017 to December 2018, eighty-four patients with preoperatively DECT scanning and pathologically confirmed PTC (129 non-metastatic LNs and 97 metastatic LNs) in the First Affiliated Hospital of Nanjing Medical University were included in this study. The clinical and imaging data of all patients were retrospectively analyzed. The training cohort consisted of 62 PTC cases with 156 LNs (91 non-metastatic LNs and 65 metastatic LNs). An independent validation cohort consisted of 22 PTC patients with 70 LNs (38 non-metastatic LNs and 32 metastatic LNs). Semi-automatic LNs segmentation was conducted on arterial-venous mixed images derived from DECT using Syngo.via Frontier Radiomics software. Totally 1 226 radiomics features were extracted from arterial-venous mixed images for each LN. The least absolute shrinkage and selection operator (LASSO) regression was applied for radiomics features selection and signature building. The logistic regression modeling was used to construct diagnostic models based on the CT image features of LNs (model 1), the radiomics signature (model 2) and the combination of the CT image features and radiomics signature (model 3). An intuitive nomogram was plotted for model 3. The ROC curve analyses and area under the curve (AUC) were performed to evaluate the diagnostic efficiency of the three models, with the performances compared using the Delong test.Results:Model 1 was developed with LNs shape, degree of enhancement, pattern of enhancement, calcification and extra nodal extension. Three arterial phase radiomics features were selected and used to establish radiomics signature using LASSO regression (model 2). Model 3 was developed with LNs size, shape, degree of enhancement and radiomics signature. In both the training and validation cohort, model 3 showed the best diagnostic performance (AUC=0.965, 0.933), followed by model 2 (AUC=0.947, 0.910), and both these two models significantly outperformed model 1 (AUC=0.850, 0.846) (training cohort, Z=4.066 and 3.758, P both<0.001; validation cohort, Z=2.871 and 1.998, P=0.017 and 0.042) respectively. Conclusion:The radiomics model based on arterial-venous mixed images derived from DECT data can realize effective diagnosis of LNs metastasis in patients with PTC; and the combination model of radiomics signature with CT image features can further improve the diagnostic accuracy.