Objective To investigate the role of the neutrophil-to-lymphocyte ratio(NLR)in predicting the in-hospital mortality risk of patients with acute aortic dissection(AAD)in multicenter hospitals.Methods A multicenter retrospective cohort study was conducted.Clinical data were collected from 2642 AAD patients who were hospitalized in five teaching hospitals:Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Henan Provincial People's Hospital,Fuwai Central China Cardiovascular Hospital,the Third Affiliated Hospital of Xinxiang Medical University,and the Second Affiliated Hospital of Chongqing Medical University between August 2010 and December 2021.According to the quartiles of serum NLRlevels,the patients were divided into four groups:first quartile(Q1,n=660),second quartile(Q2,n=661),third quartile(Q3,n=661),and fourth quartile(Q4,n=660).The clinical characteristics and biochemical indicators of each group were compared.Partial correlation analysis was used to assess the relationship between NLR and cardiovascular parameters.Restricted cubic splines,Kaplan-Meier survival analysis,and Cox regression models were employed to evaluate the association between NLR levels and in-hospital mortality risk in AAD patients.Results The median age of all patients was 54[interquartile range(IQR):46-63]years,including 2096 males and 546 females.Compared with Q1-Q3 groups,patients inQ4group had a lower incidence of smoking history and diabetes history,and were more likely to have DeBakey type Ⅰ AAD(P＜0.05).Additionally,the levels of aspartate aminotransferase,high-density lipoprotein cholesterol,creatinine,and D-dimer in Q4 group were higher,while the levels of triglycerides and C-reactive protein(CRP)were lower(P＜0.01).The results of partial correlation analysis showed that the plasma NLR level was positively correlated with D-dimer(r=0.43,P＜0.01)and creatinine(r=0.16,P＜0.01).The restricted cubic spline function in the Cox model revealed a significant non-linear relationship between the plasma NLR level and clinical outcomes in AAD patients(P＜0.01).Kaplan-Meier survival analysis indicated that patients in Q4 group had the highest in-hospital mortality rate compared with Q1-Q3 groups(P＜0.0001).Furthermore,multivariate Cox regression analysis demonstrated that compared with Q1 group,the hazard ratio(HR)of NLR in Q4 group was 1.77(95％CI 1.33-2.37,P＜0.001),which was an independent risk factor for the primary endpoint events.Conclusion A higher plasma NLR level is significantly associated with the occurrence of cardiovascular events in AAD patients,and this association remains significant even after adjusting for potential confounding factors such as the multicenter visiting hospitals.

Objective To establish a method for determining the concentration of contezolid in human cerebro spinal fluid(CSF)using ultra high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS).Methods Linezolid as the internal standard(IS)and acetonitrile as the protein precipitant.Waters ACQUITY UPLC? BEH C18(2.1 mm × 50.0 mm,1.7 μm)chromatographic column was used for separation,with a mobile phase of 0.1％formic acid aqueous solution-0.1％formic acid acetonitrile solution,gradient elution method,flow rate was 0.4 mL·min-1,column temperature was 40 ℃,automatic sampler temperature was 10 ℃,the analysis time was 4 minutes.Electrospray ion source,positive ion mode,and multi-reaction monitoring scanning mode were used.The monitoring and analysis ion pairs for contezolid were m/z 409.15→269.14,and the monitoring ion pairs for linezolid were m/z 338.14 → 195.10.The specificity,standard curve and lower limit of quantification(LLOQ),precision and recovery rate,matrix effect,residual effect,dilution effect and stability of the method were investigated.Results The endogenous substances in CSF do not interfere with the determination of the analyte contezolid and the internal standard linezolid,and the method has good specificity.Satisfactory linearity was observed within the concentration range of 20-5 000 ng·mL-1 for contezolid in CSF,the calibration curve was y=8.97 × 10-4x+1.95 × 10-2(r=0.999 1),and the LLOQ was 20 ng·mL-1.Precision of the intra-batch and inter-batch relative standard deviation(RSD)＜15％,and the extraction recovery were 90.96％-98.71％.The average normalized matrix effect factor of the quality control CSF sample were 94.39％-100.25％.The RSD of dilution effect＜15％.The CSF samples of contezolid were stored at room temperature,in the automatic sampler for 72 hours,-20 ℃ and-80 ℃ for 90 days,and subjected to repeated freezing and thawing three times,were stable with all of which the RSD＜10％.Conclusion This method is high sensitivity,rapid,simple and accurate,which is very suitable for the therapeutic drug monitoring of contezolid in human CSF.

This study explores the antiviral effects of Lopinavir on porcine hemagglutinating en-cephalomyelitis virus(PHEV)in vitro and in vivo.Using PHEV-infected N2a cells as an in vitro experimental model,the impact of varying concentrations of Lopinavir on PHEV replication was analyzed through Western blot and qRT-PCR techniques.The results demonstrated that Lopinavir was beneficial to PHEV replication at low-concentration,but as the concentration increased,Lopi-navir began to exert an inhibitory effect,with the most pronounced effect observed at a concentra-tion of 8 μmol/L.PHEV-infected 3-week-old male BALB/c mice were utilized in vivo experi-ments,with Lopinavir(10 mg/kg)administered intragastrically three days post-infection.Follow-ing the onset of illness in the control group,all mice were euthanized,and brain tissues were col-lected for histopathological examination.The findings indicated that Lopinavir significantly reduced the distribution of PHEV and ameliorated the pathological damage in brain tissue,and prolonged the survival time of the mice.In conclusion,Lopinavir exhibits an antiviral effect against PHEV both in vitro and in vivo,offering a theoretical basis for the prevention and treatment of PHEV in-fections in clinical practice.

This study explores the antiviral effects of Lopinavir on porcine hemagglutinating en-cephalomyelitis virus(PHEV)in vitro and in vivo.Using PHEV-infected N2a cells as an in vitro experimental model,the impact of varying concentrations of Lopinavir on PHEV replication was analyzed through Western blot and qRT-PCR techniques.The results demonstrated that Lopinavir was beneficial to PHEV replication at low-concentration,but as the concentration increased,Lopi-navir began to exert an inhibitory effect,with the most pronounced effect observed at a concentra-tion of 8 μmol/L.PHEV-infected 3-week-old male BALB/c mice were utilized in vivo experi-ments,with Lopinavir(10 mg/kg)administered intragastrically three days post-infection.Follow-ing the onset of illness in the control group,all mice were euthanized,and brain tissues were col-lected for histopathological examination.The findings indicated that Lopinavir significantly reduced the distribution of PHEV and ameliorated the pathological damage in brain tissue,and prolonged the survival time of the mice.In conclusion,Lopinavir exhibits an antiviral effect against PHEV both in vitro and in vivo,offering a theoretical basis for the prevention and treatment of PHEV in-fections in clinical practice.

In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*

Dipeptidyl peptidase 4(DPP4)is one of the binding receptors for the spike(S)protein of porcine hemagglutinating encephalomyelitis virus(PHEV).To identify the key amino acid binding sites at the interface of DPP4 protein and PHEV spike protein and explore the impact of their mu-tations on viral infection,recombinant plasmids of porcine DPP4,murine DPP4 and human DPP4(pDPP4,mDPP4,hDPP4)and spike protein truncations(S311-608,S13-298)were constructed and co-transfected into HEK293T cells to detect the protein binding by co-immunoprecipitation(CoIP).Simultaneously,the expression of PHEV proteins and genes was detected in DPP4-over-expressing HeLa cells infected by PHEV using Western blot and RT-qPCR.homologues were overexpressed in HeLa cells which were not susceptible to and then inoculated with the virus,and.Subsequently,the important pDPP4 amino acid sites at the interaction interface were mutated one by one using a point mutation kit to construct mutant overexpression plasmids.The mutant and wild-type pDPP4 were co-transfected into HEK293T cells with the spike protein truncations re-spectively to assay the protein interaction ability by co-immunoprecipitation.After HeLa cells over-expressing the mutant and wild-type pDPP4 were infected by PHEV,the replication level of PHEV was detected by Western blot and RT-qPCR.Compared with hDPP4,the pDPP4 and mDPP4 had significantly stronger binding to PHEV spike protein,which significantly promote PHEV infection.Moreover,mutation of pDPP4 glycosylation sites significantly enhanced the inter-action with PHEV spike protein,and the mutation of glycosylation sites(N229,N321)dramatical-ly promoted PHEV infection.The above results indicated that DPP4 glycosylation modification plays an important shielding role in the process of PHEV invading target cells mediated by spike protein.

Objective To establish a method for determining the concentration of contezolid in human cerebro spinal fluid(CSF)using ultra high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS).Methods Linezolid as the internal standard(IS)and acetonitrile as the protein precipitant.Waters ACQUITY UPLC? BEH C18(2.1 mm × 50.0 mm,1.7 μm)chromatographic column was used for separation,with a mobile phase of 0.1％formic acid aqueous solution-0.1％formic acid acetonitrile solution,gradient elution method,flow rate was 0.4 mL·min-1,column temperature was 40 ℃,automatic sampler temperature was 10 ℃,the analysis time was 4 minutes.Electrospray ion source,positive ion mode,and multi-reaction monitoring scanning mode were used.The monitoring and analysis ion pairs for contezolid were m/z 409.15→269.14,and the monitoring ion pairs for linezolid were m/z 338.14 → 195.10.The specificity,standard curve and lower limit of quantification(LLOQ),precision and recovery rate,matrix effect,residual effect,dilution effect and stability of the method were investigated.Results The endogenous substances in CSF do not interfere with the determination of the analyte contezolid and the internal standard linezolid,and the method has good specificity.Satisfactory linearity was observed within the concentration range of 20-5 000 ng·mL-1 for contezolid in CSF,the calibration curve was y=8.97 × 10-4x+1.95 × 10-2(r=0.999 1),and the LLOQ was 20 ng·mL-1.Precision of the intra-batch and inter-batch relative standard deviation(RSD)＜15％,and the extraction recovery were 90.96％-98.71％.The average normalized matrix effect factor of the quality control CSF sample were 94.39％-100.25％.The RSD of dilution effect＜15％.The CSF samples of contezolid were stored at room temperature,in the automatic sampler for 72 hours,-20 ℃ and-80 ℃ for 90 days,and subjected to repeated freezing and thawing three times,were stable with all of which the RSD＜10％.Conclusion This method is high sensitivity,rapid,simple and accurate,which is very suitable for the therapeutic drug monitoring of contezolid in human CSF.

This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history* ; Humans ; Medicine, Chinese Traditional/history* ; History, Ancient ; Astragalus Plant/chemistry* ; China ; Astragalus propinquus

This study investigates the effect and underlying mechanism of Guizhi Tongluo Tablets(GZTL) in treating atherosclerosis(AS) in a mouse model. Apolipoprotein E-knockout(ApoE~(-/-)) mice were randomly assigned to the following groups: model, high-, medium-, and low-dose GZTL, and atorvastatin(ATV), and age-matched C57BL/6J mice were selected as the control group. ApoE~(-/-) mice in other groups except the control group were fed with a high-fat diet for the modeling of AS and administrated with corresponding drugs via gavage for 8 weeks. General conditions, signs of blood stasis, and body mass of mice were monitored. Aortic plaques and their stability were assessed by hematoxylin-eosin, Masson, and oil red O staining. Serum levels of total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) were measured by biochemical assays, and those of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) were determined via enzyme-linked immunosorbent assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL). Single-cell RNA sequencing(scRNA-seq) was employed to analyze the differential expression of CD72hi macrophages(CD72hi-Mφ) in the aortas of AS patients and mice. The immunofluorescence assay was employed to visualize CD72hi-Mφ expression in mouse aortic plaques, and real-time fluorescence quantitative PCR was utilized to determine the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. The results demonstrated that compared with the control group, the model group exhibited significant increases in body mass, aortic plaque area proportion, necrotic core area proportion, and lipid deposition, a notable decrease in collagen fiber content, and an increase in apoptosis. Additionally, the model group showcased elevated serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6, alongside marked upregulations in the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. In comparison with the model group, the GZTL groups and the ATV group showed a reduction in body mass, and the medium-and high-dose GZTL groups and the ATV group demonstrated reductions in aortic plaque area proportion, necrotic core area proportion, and lipid deposition, an increase in collagen fiber content, and a decrease in apoptosis. Furthermore, the treatment goups showcased lowered serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6. The data of scRNA-seq revealed significantly elevated CD72hi-Mφ signaling in carotid plaques of AS patients compared with that in the normal arterial tissue. Animal experiments confirmed that CD72hi-Mφ expression, along with several pro-inflammatory cytokines, was significantly upregulated in the aortas of AS mice, which were downregulated by GZTL treatment. In conclusion, GZTL may alleviate AS by inhibiting CD72hi-Mφ activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atherosclerosis/immunology* ; Mice ; Mice, Inbred C57BL ; Macrophages/immunology* ; Male ; Humans ; Apolipoproteins E/genetics* ; Tablets ; Tumor Necrosis Factor-alpha/genetics* ; Apoptosis/drug effects* ; Interleukin-1beta/genetics* ; Interleukin-6/genetics* ; Disease Models, Animal ; Mice, Knockout

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires