Objective:To evaluate the effects of chlorinated organophosphate flame retardants (Cl-OPFRs) via respiratory and digestive tract exposure on multiple organs in mice.Methods:A short-term repeated exposure model of tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP) and tris(1, 3-dichloro-2-propyl) phosphate (TDCIPP) in mice was established through intratracheal instillation and oral gavage administration. The exposure doses were 0.7, 1 and 2 mg·kg -1·day -1, respectively, with continuous administration for 14 days. The organs of the heart, liver, spleen, lung, kidney, stomach, large intestine, small intestine, bladder and testis were collected and weighed to calculate the organ coefficients. The pathological and histological changes were observed by hematoxylin-eosin staining to quantitatively assess the effects of the three Cl-OPFRs on the various organs by using the pathology score. Results:Analysis of organ coefficients in tracheal drip-treated mice showed that the organ coefficients in the testes of the TCEP, TCIPP and TDCIPP groups were lower than those in the control group ( PTCEP-testis=0.045, PTCIPP-testis=0.012 and PTDCIPP-testis<0.001). The organ coefficients were lower in the lungs and small intestines of the TCEP group ( PTCEP-lung=0.006, PTCEP-small intestine=0.042). The organ coefficients for the stomach and large intestine were higher in the TDCIPP group ( PTDCIPP-stomach=0.014, PTDCIPP-large intestine=0.049). Analyses of gavage-contaminated mice showed that the organ coefficients for liver, stomach and small intestine in the TCEP and TDCIPP groups were higher than those in the control group ( PTCEP-liver=0.007, PTCEP-stomach=0.003, PTCEP-small intestine<0.001, PTDCIPP-liver=0.001, PTDCIPP-stomach=0.004, and PTDCIPP-small intestine<0.001). Histopathological analyses of the organs of tracheal drip dyed mice showed significant pathological damage in the lung tissue of the TCIPP group, mainly in the form of thickening of the interstitium, infiltration of inflammatory cells and alveolar collapse. The results of the analysis of gavage poisoned mice showed that TCIPP exposure could lead to blurring of the red and white medullary boundaries of spleen tissues, destruction of white medullary structures, etc., and induce small intestinal cryptitis. TDCIPP induced significant pathological damage to the liver tissues of mice, which mainly included cytoplasmic washout, infiltration of inflammatory cells, acute inflammation, and other injurious effects. Significant pathological damage to the intestinal tissues of mice was also observed. Conclusions:This study demonstrates that the toxic effects of Cl-OPFRs are significantly associated with exposure routes and compound specificity. Respiratory exposure predominantly induces TCIPP-mediated pulmonary injury, while digestive exposure causes TDCIPP-driven hepatointestinal toxicity. These findings provide preliminary evidence for the toxicity screening of Cl-OPFRs.

Objective The purpose of writing the"expert consensus on humanistic care for patients in hospice care"(hereinafter referred to as the"consensus")aims to standardize the practice of humanistic care in the field of hospice care,ensuring that humanistic care is integrated throughout the entire service process for hospice care patients and their families.Methods A systematic search was conducted in domestic and foreign databases for literature related to hospice care and humanistic care,including guidelines,expert consensuses,systematic reviews or Meta-analyses,and evidence summaries.High-quality evidence was evaluated,extracted,and summarized to form the initial draft of the"consensus".From June to October 2024,20 experts from the fields of hospice care,nursing humanities,and evidence-based nursing were invited to participate in 1 round of expert consultation.Among them,13 experts were selected for 2 rounds of expert demonstration meetings.After collating and analyzing the experts' opinions,the initial draft was revised and refined,ultimately resulting in the final version of the"consensus".Results The effective response rate of the consultation questionnaire was 100％,with expert authority coefficient of 0.880,judgment coefficient of 0.935,and familiarity level of 0.825.The Kendall harmony coefficient of the expert consultation was 0.134(P＜0.05).The"consensus"consisted of 13 aspects,including the targets and objectives,principles,institutional guarantees,environmental requirements,etc.Conclusion This"consensus"possesses strong scientific rigor and practicality,which can provide guidance and references for the practice of humanistic care in the field of hospice care,promoting the standardization and humanization of hospice care services.

AIM To explore the Clinical effects of Pinggan Xifeng Huatan Tongluo Decoction on elderly patients with acute cerebral infarction complicated with hypertension.METHODS Eighty-six patients were randomly assigned into control group(43 cases)for intervention of conventional treatment,and observation group(43 cases)for intervention of both Pinggan Xifeng Huatan Tongluo Decoction and conventional treatment.The changes in clinical effects,TCM symptom effects,TCM symptom score,NIHSS score,FMA score,ambulatory blood pressure indices(SBP,DBP,pulse pressure difference,variation coefficient for systolic blood pressure,variation coefficient for diastolic blood pressure),cerebral hemodynamic indices(PSV,EDV,PI,RI),Leptin,RBP4 and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rates of clinic and TCM symptoms than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM symptom score,NIHSS score,ambulatory blood pressure indices,PSV,EDV,RI,Leptin,RBP4(P＜0.05),and increased FMA score,PI(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the elderly patients with acute cerebral infarction complicated with hypertension,Pinggan Xifeng Huatan Tongluo Decoction can safely and effectively relieve clinical symptoms,enhance anti-hypertensive effect,improve the perfusion of cerebral blood flow,and reduce the levels of serum leptin and RBP4.

Drug development encompasses multiple processes,wherein protein subcellular localization is essential.It promotes target identification,treatment development,and the design of drug delivery systems.In this research,a deep learning framework called LocPro is presented for predicting protein subcellular localization.Specifically,LocPro is unique in(a)combining protein representations from the pre-trained large language model(LLM)ESM2 and the expert-driven tool PROFEAT,(b)implementing a hybrid deep neural network architecture that integrates convolutional neural network(CNN),fully connected(FC)layer,and bidirectional long short-term memory(BiLSTM)blocks,and(c)developing a multi-label framework for predicting protein subcellular localization at multiple granularity levels.Additionally,a dataset was curated and divided using a homology-based strategy for training and validation.Compar-ative analyses show that LocPro outperforms existing methods in sequence-based multi-label protein subcellular localization prediction.The practical utility of this framework is further demonstrated through case studies on drug target subcellular localization.All in all,LocPro serves as a valuable complement to existing protein localization prediction tools.The web server is freely accessible at https://idrblab.org/LocPro/.

G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all mar-keted drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respi-ration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Ab-normalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alz-heimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.

Objective To study the correlation between the serum ferritin level and the pathological classification,tumor stage,PD-L1 expression,disease control rate(DCR),and survival period of patients with lung cancer.Methods A total of 85 patients with lung cancer admitted to our hospital from February 2020 to February 2021 were selected as the research subjects.All patients received immunotherapy,and the serum ferritin levels of patients before and after immunotherapy were detected.Meanwhile,according to the difference in serum ferritin levels before and after immunotherapy,the patients were divided into the increased group(31 cases)and the decreased group(54 cases).The correlation between the serum ferritin level and the pathological classification,tumor stage and PD-L1 expression level of patients was analyzed,and the DCRs and survival periods of patients with serum ferritin level≥300 ng/mL and<300 ng/mL before treatment were compared,as well as the increased group and the decreased group.The survival curve of patients in each group was analyzed by the Kaplan-Meier.Results Patients with tumor stage Ⅰ to Ⅲ showed significantly lower serum ferritin levels than patients with tumor stage Ⅳ(P<0.05).The DCR,3-year survival rate and progression-free survival(PFS)of patients with serum ferritin level≥300 ng/mL were significantly lower/shorter than those of patients with serum ferritin level<300 ng/mL(P<0.05).The DCR,3-year survival rate and PFS of patients in the increased group were significantly lower/shorter than those in the decreased group(P<0.05).Conclusion The increased serum ferritin level in lung cancer patients before treatment and the further increase after treatment are significantly associated with the reduced efficacy of immunotherapy and the shortened survival period.The combination of baseline serum ferritin levels before treatment and dynamic changes after treatment may serve as a clinical biomarker panel for predicting immunotherapy outcomes.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.