ObjectiveTo investigate the contamination status, transmission risk and drug resistance of Klebsiella pneumoniae (KP) on the object surfaces in the surrounding environment of hospitalized patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) , so as to provide a scientific guidance for the prevention and control of healthcare-associated infection. MethodsSamples from the surfaces of objects in the surrounding environment of CRKP infected patients living in the intensive care unit (ICU) and hand specimens from healthcare workers were collected for KP isolation and identification, as well as drug susceptible test in a medical institution located in Minhang District, Shanghai from 2021 to 2023. Additionally, both univariate and multivariate logistic regression analyses were used to identify the influencing factors associated with KP contamination in the hospital environment. ResultsA total of 546 surface samples were collected from the surrounding environment objects of 15 patients infected with CRKP, with a KP detection rate of 6.59% (36/546).The KP detection rate in the ICU of general ward (10.22%) was higher than that in the ICU of emergency department (2.94%) (χ²=12.142, P<0.001). Moreover, the KP detection rate on the surfaces of patient-contacted items (15.66%) was higher than that on shared-use items (6.25%), cleaning items (10.00%), and medical supplies (3.30%) (χ²=17.943, P<0.001). Besides, the detection rate of KP in items sent out of hospital for disinfection (15.38%) was higher than that in those self-disinfected (4.20%) (χ²=19.996, P<0.001).The highest detection rate of KP was observed in high-temperature washing (15.13%, 18/119) (χ²=21.219, P<0.001), while the lowest detection rate was observed in antibacterial hand sanitizer with trichlorohydroxydiphenyl ether sanitizing factor (0, 0/60) ( χ²=21.219, P<0.001).The detection rate of KP in samples taken more than 24 hours after the last disinfection (23.08%) was higher than that in those taken at 4 to24 hours (12.90%) and less than 4 hours (4.22%) (χ²=23.398,P<0.001).ICU of general ward (OR=4.045, 95%CI: 2.206‒7.416), patient-contacted items (OR=3.113, 95%CI: 1.191‒8.141), and self-disinfection ( OR=0.241, 95%CI:0.144‒0.402) were influencing factors for KP contamination in environmental surface. From 2021 to 2023, the drug resistance rates of hospital environmental KP isolates showed an upward trend (P<0.001) to antibiotics such as ceftazidime and gentamicin. Furthermore, high drug resistance rates of KP (>90%) were observed to ciprofloxacin, levofloxacin, cefotaxime, ceftriaxone, and cefepime. ConclusionCRKP can be transmitted outward through the surfaces of objects in the patients’ surroundings, and the drug resistance situation is severe. In clinical settings, it is necessary to implement isolation measures for CRKP infection patients, to increase the frequency of disinfection for objects in their surroundings, to strengthen hand hygiene practices, and to use antibiotics appropriately.

Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.

OBJECTIVE: Benzylisoquinoline alkaloids (BIAs) have pharmacological functions and clinical use. BIAs are mainly distributed in plant species across the order Ranunculales and the genus Phellodendron from Sapindales. The BIA biosynthesis has been intensively investigated in Ranunculales species. However, the accumulation mechanism of BIAs in Phellodendron is largely unknown. The aim of this study is to unravel the biosynthetic pathways of BIAs in Phellodendron amurens. METHODS: The transcriptome and metabolome data from 18 different tissues of P. amurense were meticulously sequenced and subsequently subjected to a thorough analysis. Weighted gene co-expression network analysis (WGCNA), a powerful systems biology approach that facilitates the construction and subsequent analysis of co-expression networks, was utilized to identify candidate genes involved in BIAs biosynthesis. Following this, recombinant plasmids containing candidate genes were expressed in Escherichia coli, a widely used prokaryotic expression system. The purpose of this genetic engineering endeavor was to express the candidate genes within the bacteria, thereby enabling the assessment of the resultant enzyme activity. RESULTS: The synonymous substitutions per synonymous site for paralogs indicated that at least one whole genome duplication event has occurred. The potential BIA biosynthetic pathway of P. amurense was proposed, and two PR10/Bet v1 members, 14 CYP450s, and 33 methyltransferases were selected as related to BIA biosynthesis. One PR10/Bet v1 was identified as norcoclaurine synthase, which could catalyze dopamine and 4-hydroxyphenylacetaldehyde into (S)-norcoclaurine. CONCLUSION Our studies provide important insights into the biosynthesis and evolution of BIAs in non-Ranunculales species.

Objective:To evaluate the predictive performance of machine learning methods for predicting the risk of death in traumatic hemorrhage, and address the low prediction accuracy of traditional trauma scores, provide a reference for developing a more robust prediction method for severe trauma patients.Methods:Clinical data of severe trauma patients from the National Trauma Medical Center between April 1, 2023, and March 31, 2024 were collected. ElasticNet, Recursive Feature Elimination, and Mutual Information-based feature selection methods were used to screen variables and compared with traditional hypothesis testing methods. Built the prediction models for mortality risk in traumatic hemorrhage using Logistic Regression, ElasticNet, and Support Vector Machine (SVM) and compared the predictive performance.Results:The study included 5,601 trauma patients, the results of the variable screening and importance ranking were consistent with three feature selection methods. The classification accuracy and AUC values for the three models were as follows: Overall accuracy was 83.2%, survival accuracy was 84.0%, death accuracy was 76.3%, and an AUC was 0.86 in logistic regression; Overall accuracy was 78.9%, survival accuracy was 78.5%, death accuracy was 81.7%, and an AUC was 0.88 in ElasticNet; Overall accuracy was 84.7%, survival accuracy was 86.1%, death accuracy was 72.4%, and an AUC was 0.86 in SVM. The prediction performance of three models is quite little.Conclusion:Machine learning methods can effectively improve the prediction of death risk for traumatic hemorrhage,and has wide applications.

Objective: To identify ferroptosis-related genes associated with gastric cancer prognosis and investigate their potential molecular functions. Methods: Gene expression profiles and clinical information of gastric cancer tissues and adjacent normal tissues were obtained from TCGA database. Differential expression analysis of ferroptosis-related genes was performed using the "DESeq2" package in R software. Key genes were identified and a prognostic model for gastric cancer was constructed through Cox regression analysis based on the LASSO algorithm. Patients were stratified into high-risk and low-risk groups according to the median risk score. The accuracy of the model was evaluated using Kaplan-Meier survival analysis and ROC curve analysis. Immune cell infiltration in gastric cancer patients was assessed with the "CIBERSORT" package. The mRNA expression of differentially expressed genes(DEGs) with prognostic significance was examined in both gastric cancer and adjacent normal tissue samples. In vitro experiments were conducted to validate the impact of hydroxycarboxylic acid receptor 1(HCAR1) on the malignant biological behavior of gastric cancer. Results: Based on ferroptosis-related genes from the TCGA database, a novel prognostic model was constructed. It demonstrated robust predictive power for survival in both training and validation cohorts. RT-qPCR analysis of 8 pairs of gastric cancer and normal tissues revealed that the expression patterns of 6 prognostic DEGs in cancer tissues were consistent with those predicted by the model. In vitro experiments confirmed that downregulation of the key gene HCAR1 could inhibit the proliferation, invasion, and metastasis of gastric cancer cells. Conclusion The ferroptosis-related gene based prognostic model exhibits robust predictive capability, allowing for accurate determination of prognosis and survival in individuals with gastric cancer.

Objective:To analyze the causes of out-of-hospital cardiac arrest (OHCA) and the differences in outcomes of pre-hospital first-aid measures and cardiopulmonary resuscitation for different etiologies, improved the success rate of rescue.Methods:A retrospective study was conducted on OHCA patients admitted to Beijing Emergency Medical Centre from January to December 2021. The pre-hospital emergency medical records and rescue results within medical institutions were collected. Compared the basic situation between patients with cardiogenic and non-cardiogenic cardiac arrest, the differences of rescue measures and CPR outcomes between the groups were compared by non-parametric test and χ 2 test. Results:A total of 7 517 patients were included in this study. Cardiogenic arrest patients were older, more underlying diseases (84.2%), and cardiac arrest mainly occurred at home. The cause of non-cardiogenic arrest included disease (85.1%), trauma (2.9%), suicide (5.0%), traffic accidents (1.7%), poisoning (1.1%), and so on. In terms of first-aid measures, after the emergency doctor arrived at the scene, the proportion of first-aid measures used for cardiogenic patients was high (22.3%), and the first aid measures include cardiopulmonary resuscitation, tracheal intubation, defibrillation, oxygen inhalation, injection of adrenaline and use of other drugs. All the proportions of first-aid measures for cardiogenic patients were significantly higher than non-cardiogenic patients (all P<0.001). In terms of clinical outcomes, there were no statistical differences in return of spontaneous circulation ( P=0.072) and 24-hour survival ( P=0.093) between cardiogenic and non-cardiogenic patients. Conclusions:Cardiogenic cardiac arrest was the main cause of OHCA. Cardiogenic arrest patients were more underlying diseases, and older in age, the main clinical feature was onset at home. The comprehensive treatment measures for pre-hospital first-aid cardiac arrest should continue to be strengthened to improve the success rate of rescue for OHCA.

Objective:To explore the association between cognitive function and the level of gamma-amino-butyric acid(GABA)in anterior cingulate cortex(ACC)before and after treatment in patients with major depres-sion disorder.Methods:Totally 31 medication-naive patients with major depression disorder meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)and 33 normal controls were col-lected.Each eligible patient received treatment with selective serotonin reuptake inhibitor agents for 8 weeks.The MATRICS Consensus Cognitive Battery(MCCB)was used to evaluate the cognitive function.By means of 1H magnetic resonance spectroscopy,anterior cingulate cortex GABA concentrations were measured.Results:At base-line,the concentration of ACC GABA relative to water(GABA+/W)was lower in the patient group than in the control group(P＜0.05)and increased after treatment(P＜0.05).ACC GABA+/W was negatively associated with verbal learning and visual memory score in patient group at baseline(correlation coefficient and P value were r=-0.40,P＜0.05;r=-0.42,P＜0.05,respectively).The ACC GABA+/W difference resulted of treatment in patient group was positively associated with the difference of working memory score and the difference of reasoning and problem-solving score(correlation coefficient and P value were r=0.58,P＜0.05;r=0.66,P＜0.05,respec-tively).Conclusion:The cognitive dysfunction of patients with major depression disorder may not be related to the degree of depression and anxiety.And improvement of cognitive function may be associated with increase of ACC GABA concentrations.

Objective:To assess the efficacy and toxicities of carboplatin+etoposide(CE)regimens combined with abiraterone+prednisone(AAP)in patients with metastatic castration-resistant prostate cancer(mCRPC)after progression with docetaxel+prednisone(DP)regimens chemotherapy and novel hormone therapy(NHT).Methods:Retrospective analysis of mCRPC treated with DP regimens chemotherapy and/or NHT after progression,received CE regimens with AAP every 3 weeks for one cycle×6 cycles.The outcome were prostate specific an-tigen(PSA)response rate,time to PSA progression(TTPP),radiographic progression-free survival(rPFS),30%reduction in PSA,90%reduc-tion in PSA,the objective response remission rate and overall survival(OS).Results:From March 2019 to February 2024,37 eligible mCRPC patients were admitted to Cancer Hospital of Huanxing Chaoyang District Beijing and National Cancer Center/National Cancer Clinical Re-search Center/Cancer Hospital.After progression,CE regimens combined with AAP regimens was used for treatment.The median follow-up was 12.0(3.0-57.0)months.The median treatment cycle was 4 cycles.The PSA response rate was 42.1%.The median TTPP was 4.0 months;the median rPFS was 8.9 months and the median OS was 15.0 months.The objective remission rate was 24.3%,the proportion of 30%de-crease in PSA was 59.5%,and the proportion of 90%decrease in PSA was 16.2%.As for treatment side effects,10 cases had grade 3 or higher adverse reactions.Conclusions:CE regimens combined with AAP for mCRPC patients who failed DP regimens chemotherapy and/or NHT initially showed good clinical efficacy and tolerability.Additional sample size and follow-up time are needed to further validate the effic-acy.

Objective This article aimed to explore the inhibitory effect of β-ionone(BI)on the proliferation of breast canc-er cells through the nuclear factor kappa-B(NF-κB)pathway and its possible mechanism.Methods The methylene blue assay and MTT assay were used to determine the viability of breast cancer cells.The malachite green phosphate assay was used to detect the ac-tivity of protein phosphatase 2A(PP2A).Western blot was used to detect the levels of phosphorylated P65(s534 and s311)(p-P65),PP2A(A,B and C),and phosphorylated ataxia telangiectasia mutant(p-ATM)(s1981)protein.Results BI could significant-ly inhibit the proliferation of human breast cancer BT549 cells and MCF-7 cells in a time-and dose-dependent manner,and the difference was statistically significant(P<0.01).After treated with BI,NF-κB activity was significantly inhibited in MCF-7 cells,as shown by a significant decrease in the level of phosphorylated P65(s311 and s534)protein and an increase in the level of PP2A pro-tein,and the difference was statistically significant(P<0.05).In addition,BI also significantly reduced the phosphorylation of P65 protein and ATM protein in MCF-7 cells by the PP2A inhibitor-okada acid(OA).Conclusion This study shows that BI inhibits the proliferation of breast cancer cells by inhibiting NF-κB activity,and its mechanism may be achieved by increasing PP2A activity to regulate the NF-κB pathway.

Objective:To investigate the current situation and influence factors of prehospital thrombolysis treatment for ST segment elevation myocardial infarction (STEMI) in China, to analyze the main factors affecting prehospital thrombolysis implementation, and optimize the pre-hospital thrombolysis strategy for STEMI to reduce mortality.Methods:A multicenter cross-sectional survey was conducted. 21 cities from six major geographical regions in China were selected by using convenient sampling method. An anonymous online electronic questionnaire was used to investigate the current situation and influence factors of prehospital emergency physicians and grassroots physicians implementing prehospital thrombolysis treatment for STEMI patients. Chi-square test was used to analyze the differences in count data between groups, and multivariate logistic regression was used to analyze the factors affecting prehospital thrombolysis in STEMI.Results:A total of 5 163 prehospital emergency physicians and physicians from grassroots township health centers/community health service centers or village clinics participated in this survey. Among them, 3208 (62.13%) have never implemtent thrombolysis, and 1 955 (37.87%) have did it before. The results of the multivariate logistic regression analysis indicated that physicians with 5-10 years of experience ( OR=1.41, 95% CI: 1.18-1.69, P<0.01), 11-20 years of experience ( OR=1.25, 95% CI: 1.03-1.52, P=0.02), those working in village clinics ( OR=1.30, 95% CI: 1.05-1.61, P=0.02), those in pre-hospital emergency medical institutions/departments ( OR=3.19, 95% CI: 2.80-3.64, P<0.01), those whose units are equipped with remote ECG transmission capabilities ( OR=1.72, 95% CI: 1.50-1.96, P<0.01), or ECG AI-assisted diagnostic tools ( OR=1.31, 95% CI: 1.15-1.49, P<0.01), and those who believe that thrombolysis is highly effective and should be widely adopted ( OR=2.55, 95% CI: 2.09-3.12, P<0.01) or consider it somewhat effective but warranting caution ( OR=2.11, 95% CI: 1.73-2.59, P<0.001), were more likely to make pre-hospital thrombolysis decisions for STEMI patients. To improve the current situation of pre-hospital thrombolysis for STEMI, the top four measures prioritized by pre-hospital emergency and grassroots physicians were enhancing the rescue capabilities of primary care doctors (92.22%), strengthening guidance from higherlevel hospitals (84.99%), increasing support for information technology (83.37%), and improving public health education (74.75%). Conclusions:The implementation rate of prehospital thrombolysis for STEMI in China still needs to be improved. Optimizing the prehospital thrombolysis strategy for STEMI, strengthening the allocation of basic medical resources and information technology support, and improving the referral mechanism are conducive to the implementation of prehospital thrombolysis for STEMI.