Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Wound cleansing is an essential step in skin wound management. It can prevent local infection and optimize healing micro-environment by removing necrotic tissue and foreign matter, reducing microbial load, breaking bacterial biofilm formation and so on. Many randomized controlled trials and meta-analysis abroad have concluded that there is no significant difference in the incidence of wound infection and healing rate between the wounds irrigated with tap water and with sterile normal saline for skin wound cleansing. Considering the current requirements of medical fee policies in China, we recommend the use of tap water instead of saline or other wound cleansing solutions for cleansing skin wounds.

Decabromodiphenyl ether(BDE-209)and decabromodiphenyl ethane(DBDPE)are widely used brominated flame retardants,which have been detected in the atmosphere,water,soil,and various organisms.In this study,a method based on high-performance liquid chromatography-inductively coupled plasma-mass spectrometry(HPLC-ICP-MS)was developed for determination of BDE-209 and DBDPE in sediment.Firstly,the target compounds in the sediments were extracted by accelerated solvent extraction(ASE),and the extraction solvent was hexane/dichloromethane(1∶1,V/V).The extract was concentrated by rotary evaporation and purified by a composite silica gel column(6 g neutral silica gel,8 g acidic silica gel,and 4 g anhydrous sodium sulfate),concentrated by nitrogen blowing,and then re-dissolved with 1 mL of toluene for instrumental determination.The chromatographic separation was carried out on a TC-C18(2)column(250 mm×4.6 mm)with isocratic elution using methanol-isopropanol-water(89∶6∶5,V/V)as the mobile phase,and the samples were separated within 20 min.Further,the Br element was quantified by ICP-MS to realize the detection of the target.The results showed that the method established in this study exhibited good linearity(R2>0.999)in the range of 100-10000 ng/mL,and the limits of quantification(LOQs)of the method were 2.0 ng/g for BDE-209 and 10.0 ng/g for DBDPE,with the relative standard deviations(RSDs,n=3)lower than 10%,and the recoveries were in the acceptable range(80.9%-120.7%).The matrix effect was effectively controlled within 10%.In addition,by analyzing the actual sediment samples from Guangxi,a background point,and Taizhou,Zhejiang,a typical contaminated area,it was found that neither BDE-209 nor DBDPE was detected in the sediment from Guangxi,while the concentrations of BDE-209 and DBDPE in the sediment from Zhejiang ranged from 1591.8 to 3362.9 ng/g,which further demonstrated the applicability and reliability of the method for analyzing actual environmental samples.This study provided a strong technical support for the accurate detection of POPs in the environment.

Objective To detect the expression changes of citrullinated histone H3(CitH3)during the development of deep vein thrombosis(DVT)in mice,and to explore its value in estimating the time to thrombosis.Methods The inferior vena cava(IVC)of mice was ligated to establish a thrombosis model induced by congestion.Mice were sacrificed under excessive anesthesia at 0 h,1 d,3 d,5 d,7 d,10 d,14 d and 21 d after the modeling,respectively.The congested IVC segments(0 h after modeling)and the thrombosed IVC segments(1-21 days after modeling)were extracted.Immunohistochemistry and double immunofluorescence staining were used to observe the number of neutrophils and the ex-pression of CitH3 during thrombosis.Western blotting was used to detect the protein expression level of CitH3.Results During thrombosis,CitH3 was mainly expressed in neutrophils within the thrombus.A small number of neutrophils and a few CitH3-positive cells were observed at 0 h after modeling in the congested IVC.Between 1 d and 21 d after modeling,the number of neutrophils reached a peak at 1 d and gradually decreased.The number of CitH3-positive cells and their ratio to neutrophils began to increase at 1 d,reached a peak at 5 d after modeling,and then decreased.The expression level of CitH3 protein began to increase at 1 d and reached a peak at 5 d after modeling.Conclusion The expres-sion of CitH3 during DVI shows temporal changes,and is expected to become a biological marker for estimating the formation time of thrombosis.

Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of Chlamydomonas reinhardtii (CR) microalgae with alginate lyase (Alg) via biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo, showing huge promise for the active treatment of biofilm-associated infections.

This study aimed to explore the pharmacological mechanism of Yourenji Capsules(YRJ) in improving osteoporosis by combining network pharmacology and proteomics technologies. The SD rats were randomly divided into a blank control group and a 700 mg·kg~(-1) YRJ group. The rats were subjected to gavage administration with the corresponding drugs, and the blank serum, drug-containing serum, and YRJ samples were compared using ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) to analyze the main components absorbed into blood. Network pharmacology analysis was conducted based on the YRJ components absorbed into blood to obtain related targets of the components and target genes involved in osteoporosis, and Venn diagrams were used to identify the intersection of drug action targets and disease targets. The STRING database was used for protein-protein interaction(PPI) network analysis of potential target proteins to construct a PPI network. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed using Enrichr to investigate the potential mechanism of action of YRJ. Ovariectomy(OVX) was performed to establish a rat model of osteoporosis, and the rats were divided into a sham group, a model group, and a 700 mg·kg~(-1) YRJ group. The rats were given the corresponding drugs by gavage. The femurs of the rats were subjected to label-free proteomics analysis to detect differentially expressed proteins, and GO functional enrichment and KEGG pathway enrichment analyses were performed on the differentially expressed proteins. With the help of network pharmacology and proteomics results, the mechanism by which YRJ improves osteoporosis was predicted. The analysis of the YRJ components absorbed into blood revealed 23 bioactive components of YRJ, and network pharmacology results indicated that key targets involved include tumor necrosis factor(TNF), tumor protein p53(TP53), protein kinase(AKT1), and matrix metalloproteinase 9(MMP9). These targets are mainly involved in osteoclast differentiation, estrogen signaling pathways, and nuclear factor-kappa B(NF-κB) signaling pathways. Additionally, the proteomics analysis highlighted important pathways such as peroxisome proliferator-activated receptor(PPAR) signaling pathways, mitogen-activated protein kinase(MAPK) signaling pathways, and β-alanine metabolism. The combined approaches of network pharmacology and proteomics have revealed that the mechanism by which YRJ improves osteoporosis may be closely related to the regulation of inflammation, osteoblast, and osteoclast metabolic pathways. The main pathways involved include the NF-κB signaling pathways, MAPK signaling pathways, and PPAR signaling pathways, among others.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Osteoporosis/metabolism* ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Network Pharmacology ; Female ; Protein Interaction Maps/drug effects* ; Capsules ; Humans ; Signal Transduction/drug effects*

This study aimed to investigate the underlying mechanisms of Duhuo Jisheng Decoction(DJD) in the prevention and treatment of knee osteoarthritis(KOA). Forty SPF New Zealand rabbits were randomly divided using SPSS 26.0 software into five groups: blank group, model group, low-dose DJD group, high-dose DJD group, and high-dose DJD+phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway activator group(high-dose DJD+740Y-P group), with eight rabbits in each group. Except for the blank group, the KOA model was established in the other groups using papain injection into the knee joint cavity combined with forced flexion of the knee joint. The day after modeling, the blank group and model group were given normal saline at 10 mL·kg~(-1) by gavage, the low-dose DJD group received DJD at 8.8 g·kg~(-1) by gavage, the high-dose DJD group received DJD at 35.2 g·kg~(-1) by gavage, and the high-dose DJD+740Y-P group received DJD at 35.2 g·kg~(-1) by gavage along with 740Y-P at 0.15 μmoL·kg~(-1) injected via the auricular vein. All groups received treatment continuously for four weeks. After modeling and intervention, behavioral observations were performed for all groups, and after the intervention, imaging assessments of the knee joints were conducted. Cartilage from the knee joints was collected, and gross morphological changes were observed. Pathological changes in cartilage tissue were examined using hematoxylin-eosin(HE) staining. The results of these observations were quantitatively evaluated using the Lequesne MG score, Kellgren-Lawrence(K-L) grading, Pelletier score, and Mankin score. ELISA was used to measure the levels of interleukin-1β(IL-1β), interleukin-18(IL-18), and matrix metalloproteinase 13(MMP13) in cartilage tissue. Real-time RT-PCR was used to detect the mRNA expression levels of PI3K, Akt, mTOR, Nod-like receptor protein 3(NLRP3), cysteine protease 1(caspase-1), and gasdermin D(GSDMD) in cartilage tissue. Western blot was employed to measure the protein expression levels of PI3K, Akt, mTOR, NLRP3, caspase-1, and GSDMD. The results showed that compared with the blank group, the model group exhibited significant knee joint degeneration, increased Lequesne MG score, K-L grading, Pelletier score, and Mankin score, elevated levels of IL-1β, IL-18, and MMP13 in cartilage tissue, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression levels, and elevated protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. Compared with the model group, these indicators were reversed in both the low-dose and high-dose DJD groups, with the high-dose group showing greater decline degree than the low-dose DJD group. However, compared with the high-dose DJD group, the improvements in knee joint degeneration were less pronounced in the high-dose DJD+740Y-P group, with increased Lequesne MG score, K-L grading, Pelletier score, Mankin score, elevated levels of IL-1β, IL-18, and MMP13, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression, and increased protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. In conclusion, DJD is effective and safe in the treatment of KOA, and its mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway-mediated pyroptosis in cartilage tissue, thereby improving knee joint bone structure, reducing the inflammatory response, and preventing cartilage matrix degradation.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rabbits ; TOR Serine-Threonine Kinases/genetics* ; Osteoarthritis, Knee/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Signal Transduction/drug effects* ; Male ; Disease Models, Animal ; Pyroptosis/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Humans ; Female