OBJECTIVE To investigate a suspected hospital-acquired infection cluster of Enterococcus faecium(Efm)in a neonatal intensive care unit(NICU)of the First Medical Center of Chinese PLA General Hospital,identify the source of infection and transmission routes,and provide a reference for precise prevention and control of hospital-acquired infections.METHODS Epidemiological investigations and environmental microbiological sam-pling were conducted for two neonates with Efm bloodstream infections in the NICU in Jul.2024 to detect Efm in the ward environment.Whole-genome average nucleotide identity(ANI)and multilocus sequence typing(MLST)were used to analyze the homology,drug resistance,and virulence factors of Efm isolates from patients and envi-ronments.Targeted intervention measures were proposed.RESULTS Two cases of Efm bloodstream infection were detected.A total of 37 environmental specimens were collected,and 2 were cultured Efm(the wipe dispenser o-pening and incubator handle of the patients).The drug susceptibility testing results of 2 environmental specimens were consistent with those of the two patient specimens.Genomic analysis confirmed high homology(ANI＞99.99％)among the four Efm isolates.After implementing a series of measures including centralized isolation,strict hand hygiene,thorough environmental cleaning and disinfection,strict disinfection and management of inva-sive devices,enhanced grouping of medical staff for diagnosis and treatment,the incident was effectively con-trolled.CONCLUSIONS This incident can be determined as cluster of hospital-acquired infection with Enterococcus faecium in the neonatal intensive care unit.The wet wipes are the source or transmission medium of contamina-tion.Inadequate disinfection of items and the environment,and insufficient hand hygiene of medical staff are the main reasons for this infection outbreak.Early identification of abnormal cluster of infection,investigation of the source of infection and transmission routes and timely implementation of targeted measures are the keys for preventing infection outbreaks.

Objective To identify the cuproptosis genes associated with prognosis and immune microenvironment in lung cancer with the use of bioinformatics.Methods The lung cancer dataset used in this study was obtained from the TCGA database.The cuproptosis-related genes(CRGs)were obtained from the previously reported literature.The R software Deseq2 package was used to identify the differentially expressed genes(DEGs)in lung cancer.The intersection of DEGs and CRGs was taken to obtain the differentially expressed CRGs(DE-CRGs).COX analysis and R software rms package were used to identify DE-CRGs associated with the prognosis of lung cancer.Estimate and Cibersort algorithms were applied to identify the correlation of DE-CRGs with the immune microenvironment.Results Compared to the normal tissues,a total of 5,269 DEGs were present in lung cancer tissues in the TCGA database,and there were 11 shared genes between DEGs and CRGs.The 11 DE-CRGs mainly regulated the energy metabolism,carbon metabolism and amino acid metabolism.In the DE-CRGs,LIPT1 was an independent risk factor for lung cancer,and the column chart constructed with the clinical features(age,TNM staging,and residual tumor)predicted the survival of lung cancer patients in a manner similar to their actual outcomes.LIPT1 showed a positive correlation with the infiltration of M1 and M2 type macrophages,activated natural killer cells cells and CD8+T cells,and showed a significant negative correlation with M0 type macrophages,activated mast cells,neutrophils and Treg cells(P<0.05).Conclusion LIPT1 may serve as a prognostic and immune microenvironment-associated cuproptosis gene,which is a novel biomarker for lung cancer therapy.

The growth and atrophy of bones are closely related to the mechanical stress they experience. Mechanotransduction, a fundamental biological signal transmission mechanism, enables cells to convert external mechanical forces into intracellular signaling responses through the secretion of protein factors and activation of signaling pathways. Piezo1 is a mechanosensitive ion channel that detects mechanical stress (such as pressure, stretch, and shear force), induces Ca 2+ influx, and transduces these signals into intracellular responses, playing a crucial role in bone homeostasis. Encoded by the Fam38A gene, Piezo1 possesses a distinctive 38-transmembrane helical structure that forms a bowl-shaped, trimeric propeller-like configuration. This unique structure allows it to function as a mechanical transducer, sensing mechanical stimuli at the cell membrane and transmitting mechanical signals. In the skeletal system, Piezo1 contributes to maintaining the dynamic balance between bone formation and resorption by regulating the functions of macrophages, bone marrow mesenchymal stem cells, chondrocytes, osteocytes, osteoblasts, and osteoclasts, as well as through signaling pathways such as Akt, Wnt/β-catenin, TGF-β, and MAPK. Additionally, studies have demonstrated a significant association between Piezo1 gene polymorphisms and bone mineral density, highlighting its potential therapeutic applications in osteoporosis treatment via the osteogenic-angiogenic coupling mechanism. This review summarizes the mechanisms and recent research progress on the Piezo1 mechanosensitive ion channel in bone homeostasis. By elucidating Piezo1’s role in bone metabolism, this review aims to provide a theoretical foundation and potential strategies for the prevention and treatment of osteoporosis and other bone-related diseases in clinical practice.

Objective To explore the impact of Metformin(Met)on the balance of type 17 helper T cells(Th17)/regulatory T cells(Treg)in DM rats by regulating the C-C motif chemokine ligand 2(CCL2)-C-C motif chemokine receptor 2(CCR2)axis.Methods A total of 50 SD rats were randomly divided into normal control(NC)group,model(Mod)group,Met(100 mg/kg)group,Met+empty vector(Met+oe-NC)group,and Met+CCL2 overexpression(Met+oe-CCL2)group,with 10 rats in each group.The changes of FBG evaluated in each group,and the pathological changes of pancreatic islet tissue were assessed using hematoxylin-eosin(HE)staining followed by histological scoring.The ratio of Th17/Treg in peripheral blood was detected by flow cytometry.ELISA was used to measure the serum levels of IL-17,TNF-α,TGF-β and IL-10.Immunofluorescence was used to detect the proportion of Th17 and Treg in pancreatic tissue.RT-PCR and Western blot were used to detect the mRNA and protein expression of ROR-γt,forkhead box P3(FOXP3),CCL2 and CCR2 in pancreatic tissue.Results The islet structure was intact and the boundary was clear,and there was no pathological damage in the NC group.In the Mod group,the islet tissue exhibited significant pathological damage,characterized by disrupted architecture,reduced volume,and blurred boundaries with surrounding tissues.Additionally,the cells in the islet displayed marked disorganization and substantial loss.Compared with the Mod group,the pathological damage of the islet tissue was alleviated in the Met and Met+oe-NC group.Compared with the Met group,the pathological damage was aggravated in the Met+oe-CCL2 group.Compared with the NC group,the levels of FBG,Th17/Treg ratio,IL-17,TNF-α,Th17 infiltration rate,ROR-γt,CCL2,and CCR2 mRNA and protein expression were higher(P<0.05),while TGF-β,IL-10,Treg infiltration rate,FOXP3 mRNA and protein expression were lower in the Mod group(P<0.05).Compared with the Mod group,the levels of FBG,Th17/Treg ratio,IL-17,TNF-α,Th17 infiltration rate,ROR-γt,CCL2,and CCR2 mRNA and protein were lower(P<0.05),while TGF-β,IL-10,Treg infiltration rate,FOXP3 mRNA and protein expression were higher in the Met and Met+oe-NC groups(P<0.05).Compared with the Met group,the levels of FBG,Th17/Treg ratio,IL-17,TNF-α,Th17 infiltration rate,ROR-γt,CCL2,and CCR2 mRNA and protein were higher(P<0.05),and TGF-β,IL-10,Treg infiltration rate,FOXP3 mRNA and protein expression were higher in the Met+oe-CCL2 group(P<0.05).Conclusions Metformin can promote Th17/Treg cell balance drift towards Treg direction by inhibiting the activation of CCL2-CCR2 signal axis,thereby preventing the occurrence and development of inflammatory reactions,alleviating pancreatic islet damage,and improving the glucose metabolism in DM rats.

The growth and atrophy of bones are closely related to the mechanical stress they experience. Mechanotransduction, a fundamental biological signal transmission mechanism, enables cells to convert external mechanical forces into intracellular signaling responses through the secretion of protein factors and activation of signaling pathways. Piezo1 is a mechanosensitive ion channel that detects mechanical stress (such as pressure, stretch, and shear force), induces Ca 2+ influx, and transduces these signals into intracellular responses, playing a crucial role in bone homeostasis. Encoded by the Fam38A gene, Piezo1 possesses a distinctive 38-transmembrane helical structure that forms a bowl-shaped, trimeric propeller-like configuration. This unique structure allows it to function as a mechanical transducer, sensing mechanical stimuli at the cell membrane and transmitting mechanical signals. In the skeletal system, Piezo1 contributes to maintaining the dynamic balance between bone formation and resorption by regulating the functions of macrophages, bone marrow mesenchymal stem cells, chondrocytes, osteocytes, osteoblasts, and osteoclasts, as well as through signaling pathways such as Akt, Wnt/β-catenin, TGF-β, and MAPK. Additionally, studies have demonstrated a significant association between Piezo1 gene polymorphisms and bone mineral density, highlighting its potential therapeutic applications in osteoporosis treatment via the osteogenic-angiogenic coupling mechanism. This review summarizes the mechanisms and recent research progress on the Piezo1 mechanosensitive ion channel in bone homeostasis. By elucidating Piezo1’s role in bone metabolism, this review aims to provide a theoretical foundation and potential strategies for the prevention and treatment of osteoporosis and other bone-related diseases in clinical practice.

Objective To explore the impact of Metformin(Met)on the balance of type 17 helper T cells(Th17)/regulatory T cells(Treg)in DM rats by regulating the C-C motif chemokine ligand 2(CCL2)-C-C motif chemokine receptor 2(CCR2)axis.Methods A total of 50 SD rats were randomly divided into normal control(NC)group,model(Mod)group,Met(100 mg/kg)group,Met+empty vector(Met+oe-NC)group,and Met+CCL2 overexpression(Met+oe-CCL2)group,with 10 rats in each group.The changes of FBG evaluated in each group,and the pathological changes of pancreatic islet tissue were assessed using hematoxylin-eosin(HE)staining followed by histological scoring.The ratio of Th17/Treg in peripheral blood was detected by flow cytometry.ELISA was used to measure the serum levels of IL-17,TNF-α,TGF-β and IL-10.Immunofluorescence was used to detect the proportion of Th17 and Treg in pancreatic tissue.RT-PCR and Western blot were used to detect the mRNA and protein expression of ROR-γt,forkhead box P3(FOXP3),CCL2 and CCR2 in pancreatic tissue.Results The islet structure was intact and the boundary was clear,and there was no pathological damage in the NC group.In the Mod group,the islet tissue exhibited significant pathological damage,characterized by disrupted architecture,reduced volume,and blurred boundaries with surrounding tissues.Additionally,the cells in the islet displayed marked disorganization and substantial loss.Compared with the Mod group,the pathological damage of the islet tissue was alleviated in the Met and Met+oe-NC group.Compared with the Met group,the pathological damage was aggravated in the Met+oe-CCL2 group.Compared with the NC group,the levels of FBG,Th17/Treg ratio,IL-17,TNF-α,Th17 infiltration rate,ROR-γt,CCL2,and CCR2 mRNA and protein expression were higher(P<0.05),while TGF-β,IL-10,Treg infiltration rate,FOXP3 mRNA and protein expression were lower in the Mod group(P<0.05).Compared with the Mod group,the levels of FBG,Th17/Treg ratio,IL-17,TNF-α,Th17 infiltration rate,ROR-γt,CCL2,and CCR2 mRNA and protein were lower(P<0.05),while TGF-β,IL-10,Treg infiltration rate,FOXP3 mRNA and protein expression were higher in the Met and Met+oe-NC groups(P<0.05).Compared with the Met group,the levels of FBG,Th17/Treg ratio,IL-17,TNF-α,Th17 infiltration rate,ROR-γt,CCL2,and CCR2 mRNA and protein were higher(P<0.05),and TGF-β,IL-10,Treg infiltration rate,FOXP3 mRNA and protein expression were higher in the Met+oe-CCL2 group(P<0.05).Conclusions Metformin can promote Th17/Treg cell balance drift towards Treg direction by inhibiting the activation of CCL2-CCR2 signal axis,thereby preventing the occurrence and development of inflammatory reactions,alleviating pancreatic islet damage,and improving the glucose metabolism in DM rats.

OBJECTIVE To investigate a suspected hospital-acquired infection cluster of Enterococcus faecium(Efm)in a neonatal intensive care unit(NICU)of the First Medical Center of Chinese PLA General Hospital,identify the source of infection and transmission routes,and provide a reference for precise prevention and control of hospital-acquired infections.METHODS Epidemiological investigations and environmental microbiological sam-pling were conducted for two neonates with Efm bloodstream infections in the NICU in Jul.2024 to detect Efm in the ward environment.Whole-genome average nucleotide identity(ANI)and multilocus sequence typing(MLST)were used to analyze the homology,drug resistance,and virulence factors of Efm isolates from patients and envi-ronments.Targeted intervention measures were proposed.RESULTS Two cases of Efm bloodstream infection were detected.A total of 37 environmental specimens were collected,and 2 were cultured Efm(the wipe dispenser o-pening and incubator handle of the patients).The drug susceptibility testing results of 2 environmental specimens were consistent with those of the two patient specimens.Genomic analysis confirmed high homology(ANI＞99.99％)among the four Efm isolates.After implementing a series of measures including centralized isolation,strict hand hygiene,thorough environmental cleaning and disinfection,strict disinfection and management of inva-sive devices,enhanced grouping of medical staff for diagnosis and treatment,the incident was effectively con-trolled.CONCLUSIONS This incident can be determined as cluster of hospital-acquired infection with Enterococcus faecium in the neonatal intensive care unit.The wet wipes are the source or transmission medium of contamina-tion.Inadequate disinfection of items and the environment,and insufficient hand hygiene of medical staff are the main reasons for this infection outbreak.Early identification of abnormal cluster of infection,investigation of the source of infection and transmission routes and timely implementation of targeted measures are the keys for preventing infection outbreaks.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

Objective:A high-throughput assay for the detection of five common clinical Candidaemia pathogens was established by combining polymerase chain reaction (PCR) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS).Method:Establishment of methodology. We selected Candida albicans, Candida parapsilosis, Candida glabrata, Candida krusei, Candida tropicalis to be the target pathogens and the internal transcribed spacer (ITS) region as the target gene. Specific single base extension primers were designed to perform single base extension reaction in the same reaction system. MALDI-TOF MS was used to detect the characteristic peaks of each target pathogen. The sensitivity and specificity of the detection system were verified by using spiked blood samples. Totally 108 blood samples from proven or suspected candidaemia patients were collected from October 2021 to September 2022 in a hospital in Beijing. The results of nucleic acid mass spectrometry were compared with those of clinical blood culture. Results:The established nucleic acid mass spectrometry detection system can simultaneously detect five common clinical Candida species. Each strain can produce specific product peaks and there is no mutual interference between the strains. The detection limit of Candida albicans was 100 CFU/ml. The detection limit of Candida parapsilosis, Candida glabrata, Candida krusei and Candida tropicalis was 10 CFU/ml. For the 108 blood samples, the sensitivity, specificity, positive predictive value and negative predictive value of nucleic acid mass spectrometry were 94.74% (36/38), 97.14% (68/70), 92.31% (36/39) and 98.55% (68/69), respectively. The McNemar χ 2 test showed no significant difference between the two methods ( P>0.05), and the Kappa consistency test showed good consistency between the two methods ( Kappa=0.9, P<0.05). Conclusion:A nucleic acid mass spectrometry detection system suitable for clinical candida detection was successfully constructed, and the method validation results were consistent with the clinical blood culture.

BackgroundThe comorbidity rate of bipolar disorder and borderline personality disorder （BPD） is high， and the cognitive impairment of comorbidity patients is more serious. ObjectiveTo explore the difference of cognitive function between bipolar disorder patients with BPD or not， so as to provide references for clinical diagnosis and treatment. MethodsUsing simple random sampling， 60 patients with bipolar disorder comorbidity BPD treated in the First Hospital of Hebei Medical University from April 2021 to April 2022 were selected as the research group， including 33 patients with bipolar depression and 27 patients with bipolar mania. At the same time， 60 patients with bipolar disorder were randomly selected as the control group， including 35 patients with bipolar depression and 25 patients with bipolar mania. The cognitive function of patients was evaluated by the Chinese version of Repeatable Battery for the Assessment of Neuropsychological Status （RBANS） and the Stroop Color Word Test. ResultsThe immediate memory， visual span， speech function and total score of RBANS in the comorbid group were lower than those in the non-comorbid group， and the differences were statistically significant （t=-2.356， -2.138， -3.306， -2.729， P<0.05 or 0.01）. The single word time， single color time， double word time and double color time in Stroop Color Word Test in comorbid group were longer than those in non-comorbid group， and the differences were statistically significant （t=4.808， 3.341， 5.249， 5.167， P<0.01）. The immediate memory， visual span， speech function and total score in RBANS of bipolar depression patients with comorbid BPD were lower than those of bipolar depression patients without comorbid BPD （t=-2.446， -2.407， -2.231， -2.078， P<0.05）， and the time of single word， single color， double word and double color in Stroop Color Word Test were longer than those of non-comorbid BPD patients （t=-3.652， 3.035， 4.406， 5.016， P<0.01）. The speech function and total score of RBANS in bipolar manic patients in comorbid group were higher than those in non-comorbid group （t=-2.777， -2.347， P<0.05 or 0.01）， and the time of single word， single color， double word and double color in Stroop Color Word Test were longer than those in non-comorbid group （t=3.600， 2.658， 2.943， 4.337， P<0.05 or 0.01）. ConclusionThe cognitive impairment of bipolar disorder patients comorbid with BPD is more severe than that of patients without comorbid with BPD. ［Funded by Medical Science Research Project of Hebei Province in 2022 （number， 20221407）］