In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

In In recent years, small-molecule targeted protein degraders inducing protein degradation have been developing rapidly. These molecules are attracting substantial interest from researchers since they can overcome such limitations of traditional small-molecule inhibitors as their inapplicability to ‘undruggable’ targets and tendency to induce drug resistance. Compared with other targeted protein degraders, small-molecule hydrophobic tags (HyTs) may have a smaller number of hydrogen bond donors/acceptors, smaller molecular weights, and better pharmacokinetic profiles, thus attracting extensive attention from researchers. This review focuses on the possible mechanisms and popular types of HyTs, with special attention to the potential application value of adamantane, a typical hydrophobic tag, in the fields of cancer and neurodegeneration. In general, there are still some problems like fewer types of hydrophobic tags and insufficient research on degradation mechanisms, which still need to be further explored. This review is expected to provide researchers working in the fields of small-molecule targeted protein degraders with some valuable reference.

ObjectiveTo analyze the epidemiological trends and characteristics of brucellosis in humans (hereinafter referred to as brucellosis) in Tangshan City, Hebei Province from 2016 to 2023, and to provide a scientific basis for formulating brucellosis prevention and control strategies in the region. MethodsThe incidence data of human brucellosis in Tangshan City from 2016 to 2023 were collected from the China Disease Prevention and Control Information System. The diagnosis time, infection route, and clinical characteristics of the cases were obtained from the case investigation reports. Descriptive epidemiological methods were used to analyze the temporal, spatial, demographic distributions, and clinical characteristics of human brucellosis. Brucella species were identified using agglutination tests with bacterial suspension and A/M antigen-positive serum. ResultsA total of 2 193 cases of human brucellosis were confirmed and clinically diagnosed in Tangshan City from 2016 to 2023, with the peak incidence occured from March to August, and which exhibited distinct geographic distribution patterns. The highest incidence rate was found in people aged 60‒<70 years. The occupation of cases were primarily farmers. The incidence rate in males (528/100 000) was higher than that in females (184/100 000). All cases had confirmed exposure to infected animals or contaminated animal products. ConclusionThe epidemic of human brucellosis in Tangshan exhibited an overall steady downward trend from 2016 to 2023, except for a slight increase in 2016 and 2021, with the incidence rate controlled at 289/100 000‒335/100 000. The prevention and control situation of human brucellosis still remains severe, with the highest incidence rate in the eastern region of Tangshan, which are characterized by the breeding, slaughtering, and processing of cattle and sheep. Therefore, it it is necessary to enhance the prevention and control of human brucellosis among the personnel engaged in these industries in the eastern areas.

Humans ; Tranexamic Acid/therapeutic use* ; Arthroplasty, Replacement, Knee ; Antifibrinolytic Agents/therapeutic use* ; Blood Loss, Surgical ; Postoperative Hemorrhage

Methods: Patients with dry eye who were treated in the Ophthalmology Ward and Outpatient Department of the First Hospital of Hunan University of Chinese Medicine from October 1, 2020, to October 30, 2021 were enrolled as the research participants in the study. They were assigned to two groups based on traditional Chinese medicine (TCM) syndrome types: heat stagnation in liver meridian pattern group and Qi-Yin deficiency pattern group. Healthy volunteers who underwent health check-ups in the Health Management Department were included as healthy group following the random number table method. The tears of the patients and the healthy volunteer participants were tested by high-performance liquid chromatography-mass spectrometry (LC-MS). The differential metabolites were screened out by multivariate statistical analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was performed on the differential metabolites. Finally, the association analysis of differential proteins and metabolites was conducted to verify and supplement the metabolites. Results: A total of 32 dry eye patients were enrolled, including 16 cases with heat stagnation in liver meridian pattern and 16 cases with Qi-Yin deficiency pattern. Fourteen healthy volunteers were included as healthy group. There were no significant differences in baseline characteristics among the three groups (P > 0.05). A total of 412 biomarkers were determined in Qi-Yin deficiency pattern group, mainly including lipids, lipid-like molecules, organic acids and their derivatives, organic heterocyclic compounds, and nucleosides and their analogues. For heat stagnation in liver meridian pattern group, 112 metabolites were determined, mainly including organic acids and their derivatives, lipids, and lipid-like molecules. The KEGG enrichment results of pathways and the relative content analysis of differential markers demonstrate that purine metabolism and caffeine metabolism pathways are common metabolic characteristics of all dry eyes. Among them, deoxyinosine monophosphate (dIMP) and 2-(formamido)-N1-(5-phospha-D-ribosyl) acetamidine can serve as their biomarkers. The main characteristics of Qi-Yin deficiency syndrome pattern were the significant enhancement of metabolic pathways such as lysine degradation, ovarian steroidogenesis, cholesterol metabolism, pyrimidine metabolism, and bile secretion (P < 0.05). Dry eye associated with the heat stagnation in liver meridian pattern is mainly characterized by inhibition of the valine, leucine, and isoleucine biosynthesis pathways (P < 0.05). Conclusion Metabolomics can be used as an effective basis for TCM syndrome classification. Different patterns of dry eye syndrome exhibit typical characteristics in the types and concentrations of metabolites, which correspond to the syndrome classification in TCM. This study initially confirms the rationality of TCM syndrome classification and provides significant reference for the mechanism of dry eye and drug development.

Metal-organic frameworks (MOFs) are crystalline materials with a multidimensional porous network structure, formed through coordination bonds with metal ions as nodes and organic ligands as connecting bridges. Due to their excellent physicochemical properties, MOFs have extensive applications in the field of biomedicine, ranging from antibacterials, drug carriers, imaging to sensors. Nanoscale metal-organic frameworks (nMOFs), commonly utilized drug carriers, can gain enhanced safety, targeted delivery, and superior therapeutic effect through endocytosis. In this review, we comprehensively summarize the factors influencing the endocytosis of nMOFs, focusing on three key physicochemical properties, particle size, morphology and surface modification. Based on different illness models, the review succinctly summarizes the latest advancements in understanding the endocytosis pathways of nMOFs while critically reflecting on the inherent limitations of current research methods. Lastly, the review offers valuable insights into future research methodologies and objectives, aiming to lay the groundwork and provide meaningful guidance for the synthesis and development of nMOFs as promising versatile drug carriers.

Objective To investigate the detection rate,epidemiology and resistance mechanism of methicil-lin-resistant Staphylococcus aureus(MRSA)in a hospital in recent 5 years.Methods A total of 762 strains of non repetitive Staphylococcus aureus detected from 2016 to 2020 in a hospital were collected retrospectively.Methicillin-sensitive Staphylococcus aureus(MSSA)was 392 strains(MSSA group)and 370 strains caused by MRSA(MRSA group),and 95 strains of MRSA isolated in 2020 were further used for resistance mechanism.Staphylococcus aureus was identified and tested for drug sensitivity by Vitek 2 automatic microbial system.Molecular epidemiological typing was determined by multilocus sequence typing.The biofilm formation was performed by crystal violet staining.PCR amplification was used to detect drug resistance genes,virulence genes and biofilm related genes,and logistic regression analysis was used to investigate the independent risk factors of its occurrence.Results The detection rate of MRSA in past five years was 48.56％,mainly was from pus samples and secretion samples(38.38％,33.51％respectively).MRSA was found in the general sur-gery(18.65％)and otorhinolaryngology(12.70％).ST88 was the most common multilocus sequence typing(37.89％),and followed by ST951(24.21％).Moderate biofilm formation was the most common,accounting for 74.73％.Multivariate regression analysis showed that compared with MSSA group,hypoproteinemia,en-docrine system diseases,wound infection and history of antibiotic use within six months were the independent risk factors for infection in MRSA group.Compared with the control group,hospital transfer,wound infection and tumor were independent risk factors for infection in MRSA group(P＜0.05).Conclusion The detection rate of MRSA in a hospital is high,and the carrying rate of various drug-resistant genes is high.The hospital should pay attention to the prevalence of MRSA and related risk factors,so as to prevent it early.

Objective:To analyze the change characteristics of creatinine level in the early stage of patients with diquat (DQ) poisoning, and to explore the early risk factors and the value of prognosis.Methods:A retrospective analysis was carried out on patients with DQ admitted to the the first affiliated hospital of Zhengzhou University from January 2020 to June 2022. The DQ patients were divided into death group and the survival group according to the 28 days survival status after posioning. The basic data and serum indexes and blood gas analysis of the patients on day 1 (D1), day 3 (D3) and day 5 (D5) were collected. The difference of clinical features between the two groups was analyzed, the variables were screened by multiple logistic regression analysis, and the predictive value of the variables was evaluated by drawing receiver operating characteristic curve (ROC curve).Results:A total of 88 patients were included, including 40 patients in the survival group and 48 patients in the death group. The toxic dose in death group was significantly higher than that in survival group [100(40.00, 120.00) mL vs. 50.00(20.00, 90.00) mL, P=0.003]. The higher the toxic dose, the higher the fatality rate. All 4 patients with oral doses greater than 200 mL died. Compared with the survival group, the levels of alanine aminotransferase (ALT) (D3, D5), creatinine (CR) (D3, D5), blood amylase (AMY) (D5) and oxygen partial pressure (PaO 2) (D5) in the death group were significantly higher than those in the survival group (all P<0.05). Multiple Logistic regression analysis showed that CR (D3) and AMY(D5) were independent risk factors for death after poisoning, and PaO 2(D5) was independent protective factor. ROC curve showed that the areas under ROC curve of CR (D3), AMY (D5) and PaO 2 (D5) were 0.814, 0.741 and 0.702, respectively. Conclusion:The higher the oral dose, the higher the death rate. After admission, CR(D3), AMY (D5) and PaO 2 (D5) were independent factors influencing the prognosis of DQ poisoning. In particular, CR (D3) is more effective in predicting death after poisoning.

Objective:To explore the clinical application and triage management value of using blood circulating cell-free DNA (cfDNA) (cysteine dioxygenase type 1 gene, CDO1, and Homeobox protein A9 gene, HOXA9) hypermethylation level to detect and diagnose ovarian cancer.Methods:A case-control study was conducted on patients who went for surgery at Chengdu Womens and Childrens Central Hospital from November 2022 to October 2023. Blood samples were collected before surgery for evaluation of cancer antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA) score, and DNA methylation testing. The basic clinical information, biomarkers, and transvaginal ultrasound (TVS) information were collected simultaneously. Information from a total of 151 patients was collected, including 122 cases with benign pathology and 29 ovarian cancer cases. The pathologic diagnosis of ovarian tissue was defined as the gold standard. The multivariate logistic regression analysis was used to identify high-risk factors for ovarian cancer. The clinical efficacy of DNA methylation detection for ovarian cancer was analyzed using the area under curve (AUC).Results:The results showed that the age, menopausal status, CA125 and HE4 detection, ROMA score, positivity rate of CDO1 gene and HOXA9 gene single or combined testing in ovarian cancer patients were higher than those in the benign group and showed significant differences ( P<0.05). Among these detection protocols, the AUC of CDO1 and HOXA9 dual gene methylation testing for ovarian cancer was the highest at 0.936 (95% CI, 0.878-0.994), with 89.7% (95% CI 73.6%-96.4%) sensitivity and 97.5% (95% CI 93.0%-99.2%) specificity, respectively. The positive detection rate of CDO1 and HOXA9 dual gene methylation in early ovarian cancer FOGO I-II stage is 12/14 higher than other tests. Conclusion:Blood cfDNA methylation detection, a simple, non-invasive, and highly sensitive detection method, is superior to the current ovarian cancer testing in the risk assessment and early detection.

Objective To explore the antimicrobial resistance of carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from blood and the related risk factors for infection in patients.Methods Clinical data of 383 KP-infected patients from whose blood Klebsiella pneumoniae(KP)were isolated during hospitalization period in a hos-pital from January 2018 to December 2021 were retrospectively analyzed.Patients were divided into CRKP group(n=114)and non-CRKP group(n=269)based on antimicrobial resistance.According to the prognosis,114 patients in the CRKP group were subdivided into the death group(n=30)and the survival group(n=84).General informa-tion,underlying diseases,antimicrobial use,and infection outcomes of two groups of patients were compared,and risk factors for infection and death after infection were analyzed.Results The resistance rates of KP to tigecycline and compound sulfamethoxazole showed upward trends,with statistically significant differences(both P=0.008).The CRKP group had higher resistance rates to amikacin,aztreonam,compound sulfamethoxazole,ciprofloxacin,cefepime,cefoperazone/sulbactam,piperacillin/tazobactam,tigecycline,ceftazidime,tobramycin,and levofloxacin,as well as higher in-hospital mortality than the non-CRKP group,with statistically significant differences(all P＜0.05).Acute pancreatitis prior to infection(OR=16.564,P＜0.001),hypoalbuminemia(OR=8.588,P＜0.001),stay in in-tensive care unit prior to infection(OR=2.733,P=0.017),blood transfusion(OR=3.968,P=0.001),broncho-scopy(OR=5.194,P=0.014),surgery within 30 days prior to infection(OR=2.603,P=0.010),and treatment with carbapenems(OR=2.663,P=0.011)were independent risk factors for the development of CRKP blood-stream infection(BSI).Cardiac insufficiency before infection(OR=11.094,P=0.001),combined with pulmonary infection(OR=20.801,P=0.010),septic shock(OR=9.783,P=0.002),disturbance of consciousness(OR=11.648,P=0.001),and receiving glucocorticoid treatment(OR=5.333,P=0.018)were independent risk factors for mortality in patients with CRKP BSI.Conclusion The resistance rate of KP from BSI to tigecycline and com-pound sulfamethoxazole presents upward trend.Underlying diseases,invasive procedures,and carbapenem treat-ment are closely related to CRKP BSI.Cardiac insufficiency,pulmonary infection,septic shock,disturbance of con-sciousness,and glucocorticoid treatment can lead to death of patients with CRKP BSI.