Objective : To identify autophagy-related genes involved in pulmonary infection caused by the highly drug-resistant and virulent methicillin-resistant Staphylococcus aureus strain USA300 ( USA300) ，and to explore the underlying molecular mechanisms ， thereby providing potential targets for immunotherapy． Methods: The GSE220943 dataset of a USA300-induced pulmonary infection mouse model was obtained from the GEO database． Differentially expressed genes ( DEGs ) were identified using the DESeq2 package． Autophagy-related genes ( ARGs) were retrieved from the MSigDB and Autophagy databases．Weighted gene co-expression network analysis ( WGCNA) was performed to construct gene co-expression modules．Genes overlapping among DEGs，ARGs，and WGCNA modules were identified as autophagy-related DEGs．Gene Ontology ( GO) enrichment analysis was con- ducted using the clusterProfiler R package，while Kyoto Encyclopedia of Genes and Genomes ( KEGG) pathway en- richment analysis was performed via the Metascape platform．Immune cell infiltration was analyzed using the Immu- CellAI-mouse website．A protein - protein interaction ( PPI) network was constructed using the STRING database， and hub genes were identified through topological analysis in Cytoscape． Receiver operating characteristic curve ( ROC) curves were plotted via the website https: / /www．bioinformatics．com．cn． Finally，key gene expression was validated in mouse lung tissues by real-time quantitative reverse transcription PCR ( RT-qPCR) ． Results: A total of 6 135，4 075，3 680，and 2 342 differentially expressed genes ( DEGs) were identified at 12，24，48，and 96 hours post-infection，respectively．By integrating DEGs，autophagy-related genes ( ARGs) ，and WGCNA mod- ules，19 autophagy-related DEGs were identified． GO and KEGG enrichment analyses indicated that these genes were mainly involved in CD4 + T cell activation and regulation，innate immune responses，and autophagosome mem- brane formation．Immune infiltration analysis revealed that innate immune cells such as neutrophils and dendritic cells predominated during the early phase of infection，while γδ T cells and M2 macrophages became more promi- nent in the later stages．PPI network analysis identified 12 hub autophagy-related genes，among which three upreg- ulated key genes ( Eif2ak2，Ikbke，and Nfkbiz) were further confirmed．The area under the ROC curve for all three genes was 1. 000．RT-qPCR validation demonstrated significantly elevated expression of these three genes in lung tissues at 24 hours post-infection ( all P＜0. 05) ． Conclusion Eif2ak2，Ikbke，and Nfkbiz may be involved in the pulmonary infection caused by USA300 by promoting autophagy and hold promise as potential targets for immuno- therapy．

Objective:To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis.Methods:The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software.Results:Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP.Conclusion:The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.

OBJECTIVE To evaluate the consistency between the quetiapine LC-MS/MS kit and the laboratory-built method(reference method) in the detection results of quetiapine therapeutic drug monitoring. METHODS A total of 120 remaining plasma samples were collected from patients receiving quetiapine therapeutic drug monitoring from March to October in 2021. The plasma concentration of quetiapine was detected by kit and reference method respectively. The analysis of correlations and consistency was performed by outlier analysis, linear regression and Bland-Altman method. RESULTS No outliers were detected. The linear regression equation was Y=1.018X+4.400(r=0.998), indicating a good correlation. The Bland-Altman plot analysis showed good agreement between the two measurements. CONCLUSION The detection results of quetiapine LC-MS/MS kit and reference method are in good agreement. The kit can be used for clinical quetiapine treatment drug monitoring.

Objective:To explore the efficacy and safety of tetrandrine in the treatment of rheumatoid arthritis.Methods:Randomized controlled studies of tetrandrine in the treatment of rheumatoid arthritis were searched in CNKI,VIP,Wanfang database,SinoMed,PubMed,Springer,Web of Science and Cochrane Central Register of Controlled Trails databases.A meta-analysis was conducted using R 3.5.3 software to evaluate the clinical outcomes,including the total effective rate,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),rheumatoid factor(RF),visual analogue scale(VAS),disease activity score(DAS),tender joint count(TJC),swollen joint count(SJC),and morning stiffness duration,as well as adverse events of rheumatoid arthritis patients.Results:A total of 10 articles were included in the study.The meta-analysis indicated that tetrandrine significantly improved the total effective rate(OR=3.27,95%CI:2.01-5.37,P<0.01),ESR(SMD=1.12,95%CI:0.06-2.19,P<0.05),CRP(SMD=0.75,95%CI:0.28-1.22,P<0.01),VAS(SMD=0.64,95%CI:0.29-1.00,P<0.01),TJC(SMD=1.16,95%CI:0.58-1.74,P<0.01),SJC(SMD=0.85,95%CI:0.40-1.31,P<0.01),and morning stiffness(SMD=1.09,95%CI:0.68-1.50,P<0.01).However,no statistical significance was found in RF(SMD=1.70,95%CI:-1.10-4.51,P>0.05)and DAS(SMD=0.26,95%CI:-0.59-1.11,P>0.05).The overall incidence of adverse events associated with tetrandrine treatment for rheumatoid arthritis was 20%(95%CI:12%-27%,I2=60%,P<0.05),with mild severity and favorable outcomes.Conclusion:Tetrandrine is effective in the treatment of RA patients with a mild degree of adverse events.

Objective To analyze the stresses in implanted titanium solid and bone trabecular prosthesis hip replacements.Methods A femur model was built inversely based on Mimics software,and optimized using Geomagic software,and then materialized by SolidWorks software.The osteotomized femur was assembled with the metal femoral stem to form a model,and then the model was imported into ABAQUS for finite element calculation.The upper femur was divided into four regions in different states of integration:medial proximal point(small trochanter region),lateral proximal region(large trochanter region),proximal point of the femoral stem(region around the mid-portion of the styloid process)and distal region(around the end of the styloid process and distal portion).Calculations were carried out over the femoral stresses before and after implantation of titanium solid and trabecular prostheses under gait and stair-climbing loads and the interfacial stresses when the region was unintegrated.The type of deformation at the bone interface was analyzed by means of a stress ellipsoid.Results At the small trochanter region,the stress shielding rates of the trabecular prosthesis under gait and stair climbing loads were reduced by 20.5％and 14.7％compared to the titanium solid prosthesis,respectively.In case of different integration states of the titanium solid prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 10.842 MPa and 12.900 MPa,and the shear stresses reached 7.050 MPa and 6.805 MPa,respectively;in case of different integration states of the trabecular prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 3.858 MPa and 4.389 MPa,and the shear stresses reached 4.156 MPa and 3.854 MPa,respectively.Under the 2 different loads,the inboard shear stress ellipsoid of the interface opened toward the sides and the bone interface showed tensile deformation;the outboard shear stress ellipsoid of the interface opened up and down and had compressive deformation.Conclusion After total hip arthroplasty,the overall performance of the trabecular prosthesis is better than that of the titanium solid prosthesis.The unintegrated edges of the prosthesis-bone interface are susceptible to stress concentrations and distortion which may result in occurrence of failures.[Chinese Medical Equipment Journal,2024,45(3):29-35]

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m² group (P_interaction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.
Humans ; Male ; Arsenic/urine* ; Creatinine ; East Asian People ; Testosterone/blood* ; Urinalysis ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged

We reviewed the data of an 18-year-old male patient complained of weakness of limbs and hypokalemia for 6 months. CT scan revealed left adrenal adenoma. He was diagnosed as primary aldosteronism(PA). Laboratory tests showed hypokalemia and hyperaldosteronemia. After potassium supplement and blood pressure lowering treatment, laparoscopic resection of the left adrenal adenoma was performed, and severe hyperkalemia occured 2 hours after surgery(maximum serum potassium 7.02 mmol/L). After hyperrisotonic glucose+ insulin(10% glucose 200 ml+ 50% glucose 40 ml+ insulin 8U)+ cation exchange resin(Sodium Polystyrene Sulfonate 20 g) treatment, serum potassium returned to normal range within 12 hours. The plasma aldosterone, blood potassium and blood pressure returned to normal during the 5-month follow-up. According to the experience of this case report, after resection of aldosteronoma, the changes of serum electrolyte should be closely monitored, the occurrence of hyperkalemia should be vigilant.

As the main active ingredient of the orchidaceous herb Bletilla striata, B. striata polysaccharide(BSP) has pharmacological activities such as promoting coagulation, anti-inflammation, anti-oxidation, promoting wound healing, anti-tumor, and immunomodulation, and is biodegradable and non-toxic. Additionally, it has the material properties of suspension thickening, film-forming adhesion, coating and solubilizing, targeting and slow releasing, effect-enhancing and toxicity-reducing, etc., playing the role of unification of medicines and excipients. Therefore, BSP has a wide application prospect in the fields of drug delivery system and trauma repair. This paper reviews the research progress of BSP application in new drug delivery systems and biomaterials based on the related li-terature in recent years, with the aim of providing reference for the further research and application of BSP.
Biocompatible Materials ; Drug Delivery Systems ; Orchidaceae ; Polysaccharides ; Wound Healing

OBJECTIVE: To investigate the associations between mean arterial pressure (MAP) and mortality in patients with peritoneal dialysis (PD). METHODS: A total of 1737 patients with terminal renal diseases under PD in the First Affiliated Hospital of Zhejiang University from 2008 to 2016 were enrolled. Patients were followed up for 33.0(19.3, 52.4) months. The mean arterial pressure over the first 3 months of PD therapy were calculated. All-cause death and cardiovascular death were assessed using Cox regression models adjusted for demographics, laboratory measurements, comorbid conditions and antihypertensive medications. RESULTS: During the follow-up, 208 patients died, among which 95(45.7%) patients died of cardiovascular causes. Compared with patients with MAP >95-<120 mmHg, patients with MAP ≤ 95 mmHg were associated with significantly higher risk of all-cause death (=1.40,95%:1.01-1.93,<0.05); patients with MAP ≥ 120 mmHg were associated with significantly higher risk of all-cause (=2.12,95%:1.32-3.40, <0.01) and cardiovascular morality (=2.55, 95%:1.38-4.70, <0.01). MAP presents a U-shaped association with all-cause mortality and a J-shaped association with cardiovascular mortality. CONCLUSIONS Both high MAP and low MAP are associated with higher risk of mortality in PD patients.
Arterial Pressure ; Humans ; Kidney Failure, Chronic ; mortality ; pathology ; Peritoneal Dialysis ; Renal Dialysis ; Risk Factors