ObjectiveTo study the anti-inflammatory effects of Blumea balsamifera （L.） DC oil （BBO） based on nuclear factor kappa-B （NF-κB） nonclassical and arachidonic acid （AA） pathway. MethodsEffects of BBO on the production of slow reacting substance of anaphylaxis （SRS-A） were detected by the ileal smooth muscle method. The contents of prostaglandin E₂ （PGE₂） and leukotriene B₄ （LTB₄） in lipopolysaccharides （LPS） -induced macrophages were detected by ELISA kit. The expression of COX-2， 5-LOX， FLAP and RelB were detected by qRT-PCR. Western blot was performed to detect the effects of BBO on the level of NF-κB nonclassical pathway proteins TNF receptor associated factor 3 （TRAF3）， TNF receptor associated factor 2 （TRAF2）， NF-κB-inducing kinase （NIK）， p100 and RelB. ResultsThe contractile tension of guinea pig ileum was reduced （P<0.001）， and the SRS-A production inhibition rate reached 65.34% at 1mg·mL^-1 BBO concentration. Compared with LPS group， BBO reduced the concentrations of PGE₂ （P<0.05） and LTB₄ （P<0.05）_， and decreased the expressions of COX-2 （P<0.05）， 5-LOX （P<0.05） and FLAP （P<0.05） in AA pathway at concentrations of 40-80 μg·mL^-1. Moreover， 40-80 μg·mL^-1 BBO decreased the concentrations of TRAF3 （P<0.05）， TRAF2 （P<0.05）， and NIK （P<0.05）， and further inhibited the phosphorylation of p100 （P<0.05）， as well as the level of the transcription factor RelB in genes （P<0.05） and proteins （P<0.05） in nonclassical NF-κB pathway， whereas BBO did not cause such changes. ConclusionBBO may potentially exert its anti-inflammatory effects by suppressing the regulatory proteins TRAF3 and TRAF2 and the transcription factor RelB in NF-κB nonclassical pathway. The inhibitory action extending to the induction kinase function of NIK， further hindering the phosphorylation of p100 and its binding with the transcription factor RelB. Consequently， downstream elements in the AA pathway， including the pivotal rate-limiting enzymes COX-2， 5-LOX and FLAP， were altered. This modulation influences the levels of inflammatory mediators such as PGE₂ and LTB₄.

Objective To investigate the influencing factors of adverse pregnancy outcomes in patients with preeclampsia and the predictive value of serum trace elements in the second trimester.Methods A total of 98 patients with preeclampsia admitted to Qujing First People's Hospital from January 2019 to June 2022 were enrolled in the study.Patients were divided into poor outcome group and good outcome group according to whether they had adverse pregnancy outcomes.The clinical data of all patients enrolled in the study were col-lected and the serum levels of trace elements calcium,copper,zinc and iron were detected in the second trimes-ter.Univariate analysis and multivariate Logistic regression were used to analyze the influencing factors of ad-verse pregnancy outcomes in patients with preeclampsia.The levels of serum trace elements in the second tri-mester of pregnancy were compared between the poor outcome group and the good outcome group.The re-ceiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum trace elements calcium,copper,zinc and iron for adverse pregnancy outcomes in patients with preeclampsia.Results Univari-ate analysis showed that compared with the good outcome group,the poor outcome group had significantly higher systolic blood pressure,24 h urinary protein quantitation,and D-dimer level(P＜0.05)and significantly less gestational age and platelet count at admission(P＜0.05).Multivariate Logistic regression analysis showed that 24 h urinary protein quantification,D-dimer and platelet count were the influencing factors of ad-verse pregnancy outcomes in patients with preeclampsia(P＜0.05).The levels of serum trace elements calci-um,copper,and zinc in the poor outcome group were significantly lower than those in the good outcome group(P＜0.05),and the level of iron was significantly higher than that in the good outcome group(P＜0.05).ROC curve analysis showed that the areas under the curves(AUCs)of serum calcium,copper,zinc,and iron in the second trimester of pregnancy for predicting adverse pregnancy outcomes in preeclampsia patients were 0.830(95％CI:0.780-0.880),0.855(95％CI:0.805-0.905),0.847(0.797-0.897)and 0.861(95％CI:0.811-0.911),respectively.Conclusion Adverse pregnancy outcomes in patients with preeclampsia are re-lated to 24 h urine protein,D-dimer and platelet count.The levels of serum trace elements calcium,copper,zinc and iron in the second trimester of pregnancy change significantly in patients with adverse pregnancy out-comes,which may become predictive markers of adverse pregnancy outcomes.

Glioma is the most common primary tumor of the brain,accounting for 81%of central nervous system(CNS)malignant tumors.The degree of malignancy is high,and the current treatment methods are limited.In recent years,with the in-depth study of intestinal flora and brain-gut axis,it has been found that the diversity of gut microbiota plays an important role in the regulation of glioma.The mechanism is that the intestinal flora affects the development of glioma through the role of immune regulation and metabolites.In addition,it has been con-firmed that there is a certain correlation between some probiotics and glioma,which provides a new application prospect for the treatment of glioma.This paper discusses the main intestinal bacteria that regulate gliomas as well as the role and regulatory mechanisms of intestinal flora in the development of gliomas,and provides ideas for the discovery of new targets for glioma treatment and further improvement of treatment options.

The Pituitary Society released the 2023 International Consensus on the Diagnosis and Treatment of Prolactin-Secreting Adenomas, marking another update following the guidelines from the Endocrine Society in 2006 and 2011. Published in Nature Reviews Endocrinology, this consensus is based on the latest research evidence in recent years, covering topics such as the efficacy, long-term adverse effects, and withdrawal protocols of dopamine receptor agonists, as well as indications for surgery, preoperative medical therapy, and radiation therapy. It comprehensively discusses the treatment of prolactin-secreting adenomas in special periods and conditions. This article provides a detailed interpretation of the core recommended points in the consensus, focusing on four major aspects: diagnosis, treatment, special populations, and rare conditions of prolactinoma, aiming to help clinicians gain a comprehensive understanding of the consensus and provide assistance in clinical management.

Hepatic stellate cell(HSC)activation is a key link in the development of liver fibrosis.The metabolic reprogramming of activated HSC has become a hot topic in current research,especially the change of glycolysis is an important factor in regulating HSC activation.Based on the metabolic reprogramming in the process of HSC activation,this paper expounds the mechanism of regulating HSC activation and liver fibrosis through glycolysis,and reviews the research progress of traditional Chinese medicine and its active ingredients in regulating HSC glycolysis to prevent and treat liver fibrosis.Liver fibrosis is a complex pathological process involving multiple factors and pathways.From the perspective of regulating the glycolysis of activated HSC,it can provide a new idea for the development of anti-liver fibrosis drugs.

Purpose To investigate the clinicopathological and histological features of non-small cell lung cancer(NSCLC)patients with high expression of PD-L1 and positive driver muta-tion.Methods The clinical data of 141 patients with PD-L1 high expression and driver mutation-positive NSCLC were col-lected.Immunohistochemical methods,ARMS-PCR,and next-generation sequencing(NGS)were used to detect PD-L1 ex-pression and driver gene mutations.The clinicopathological fea-tures were analyzed and the related literatures were reviewed.Results There were 141 cases NSCLC patients with high ex-pression of PD-L1 in tumor cells,of which 57 cases were≥50％,＜60％;≥60％,＜70％in 18 cases;≥70％,＜80％in 35 cases;≥80％in 31 cases.Among 141 cases NSCLC patients with high PD-L1 expression,53 cases(37.6％)had driver gene mutations,including 4 cases BRAF 15 exon mutations,9 cases MET-associated mutations,17 cases EGFR-associated mutations,16 cases KRAS 2 exon mutations,4 cases EML4-ALK fusion mutations,and 3 cases other rare mu-tations.The high expression of PD-L1 and the occurrence of driver gene mutation were related to the gender,smoking history and pathological type of patients(P＜0.05).MET-related mu-tations and KRAS 2 exon mutations were more common in males than in females.All BRAF 15 exon mutations were female.The mean percentage of PD-L1 expression was highest in patients with MET mutation,KRAS 2 exon mutation,and 3 cases rare mutations.In 33 cases with BRAF 15 exon mutation,MET am-plification or mutation,EGFR-related mutation,and 3 cases oth-er rare mutations,PD-L1 was highly expressed in solid,glandu-lar,and micropapillary tumor cells.In 20 cases with KRAS 2 exon mutation and EML4-ALK fusion mutation,PD-L1 was highly expressed in solid nested tumor cells.Conclusion In NSCLC,high expression of PD-L1 and positive driver gene mu-tation are negatively correlated with the degree of tumor differen-tiation.In the poorly differentiated surgical specimens of lung adenocarcinoma,solid,micropapillary,or glandular tubular tumor tissues should be selected as far as possible for PD-L1 ex-pression and driver gene mutation detection.

Objective:To explore the feasibility of rapid identification of methicillin-resistant Staphylococcus aureus using different algorithms of the matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometer. Methods:Totally 314 clinical isolates of Staphylococcus aureus were selected from the bacterial bank at Beijing Tongren Hospital from January 2017 to June 2019. The samples were identified by MALDI-TOF MS, and screened by cefoxitin disk method (inhibition ring diameter ￡21 mm) and PCR mecA gene. The strains were divided into a methicillin-resistant Staphylococcus aureus (MRSA) group (130 strains) and a methicillin-susceptible Staphylococcus aureus (MSSA) group (184 strains). Then, after collecting the spectrograms of these samples using formic acid extraction, the MRSA group and MSSA group were divided into three subgroups each, namely MRSA-1 (43 strains), MRSA-2 (42 strains), MRSA-3 (45 strains) and MSSA-1 (60 strains), MSSA-2 (61 strains) and MSSA-3 (63 strains). The groups were studied using genetic algorithm (GA), fast classification algorithm (QC) and supervised neural network algorithm (SNN) in the ClinProTools software on the Bruker MALDI-TOF mass spectrometer, and the convolutional neural network algorithm (CNN) in the Ex-SmartSpec software on the Zhongyuan Hui-Ji mass spectrometer. These studies were repeated for 3 rounds. The first round with MRSA-1 and MRSA-2, MSSA-1 and MSSA-2 being model groups, MRSA-3 and MSSA-3 being validation groups. The validation groups were rotated for each round. The areas under the receiver operating characteristic (ROC) curve expansions of the four algorithms were used to confirm each program′s performance. Then, 38 MRSA strains and 40 MSSA clinical strains were selected from the bacterial bank of the Laboratory of Beijing Tongren Hospital from July 2019 to December 2019, and were put through the formic acid extraction method to collect their spectra. These samples were tested independently with their convolutional neural network models. Results:After three rounds of modeling and verification, the areas under the ROC curves of the three Bruker ClinProTools programs were as follows: for genetic algorithm, the areas were 0.89, 0.74, and 0.64 respectively; for fast classification algorithm, the areas were 0.77, 0.95, and 0.94 respectively; and for supervised neural network algorithm, the areas were 0.90, 0.98, and 0.98 respectively. The areas under the ROC curves of the convolutional neural network algorithm with Zhongyuan Huiji mass spectrometer′s Ex-SmartSpec software were 0.95, 0.99, and 0.99 respectively. The independent test results of convolutional neural network algorithm showed that these results have an accuracy, specificity, sensitivity and AUC of 88.82% (810/912), 81.15% (779/960), 84.88% (1 589/1 872) and 0.92 respectively.Conclusions:The supervised neural network algorithm of Bruker′s ClinProTools and the convolutional neural network algorithm of Zhongyuan Hui-Ji mass spectrometer′s EX-Smartspec is clinically acceptable for rapid identification of MRSA performance indicators. Using convolutional neural network algorithm and MALDI-TOF mass spectrometry, MRSA strains can be identified quickly, providing timely advice for clinical medications.

OBJECTIVE To optimize the extraction process of blumeatin from Blumea balsamifera and to evaluate its antibacterial and anti-inflammatory activity. METHODS The content of blumeatin in the extract of B. balsamifera was determined by HPLC. On the basis of the single factor experiment， the extraction technology of blumeatin was optimized by the Box-Behnken response surface method with the volume fraction of ethanol， liquid-solid ratio and extraction time as the factors， using the yield of blumeatin as index. Microdilution method was used to determine the antibacterial activity of blumeatin against Streptococcus pyogenes， Staphylococcus aureus， Streptococcus agalactiae， Streptococcus mutans， Bacillus subtilis and Micrococcus luteus. The anti-inflammatory activity of blumeatin was evaluated by ear swelling test and capillary permeability test in mice. RESULTS The optimal extraction technology was as follows： ethanol concentration of 90%， liquid-material ratio of 15∶1， extraction time of 2 h at 80 ℃； the yield of blumeatin using this extraction process was 1.97 mg/g. The minimum inhibitory concentrations of blumeatin for S. pyogenes， S. aureus， S. agalactiae， S. mutans， B. subtilis and M. luteus were 50.00， 200.00， 400.00， 400.00， 800.00 and 1 600.00 μg/mL， respectively； the minimum bactericidal concentrations of blumeatin for S. pyogenes and S. aureus were 400.00 and 1 600.00 μg/mL， respectively. Blumeatin could significantly inhibit the ear swelling induced by xylene and capillary permeability induced by acetic acid in mice（P＜0.05 or P＜0.01）. CONCLUSIONS The optimized extraction technology of blumeatin is stable and feasible. The extracted blumeatin has a certain antibacterial effect against S. pyogenes and a good anti-inflammatory activity.

Objective:To characterize the geriatric osteoporotic pelvic fractures using 3-D computed tomography (CT) fracture mapping.Methods:Retrospectively analyzed were the 79 elderly patients with pelvic fracture who had been admitted to Department of Orthopaedics, The 7th Medical Center of PLA General Hospital between January 2017 and December 2021. There were 24 men and 55 women, aged from 60 to 98 years (average, 74.3 years). The CT scan data of the pelvis from all patients were imported into the software (Mimics Medical 18.0, Geomagic Studio 2014, Rhinoceros 6.0, and Matlab) to create a 3-D pelvic fracture model. The fracture pieces were imported into a standard pelvic template to obtain the morphology of the fracture lines after fitting. A map of fracture line distribution frequency and a fracture heat map were created by fitting the fracture lines of all patients into a common pelvic template.Results:Of the 79 elderly patients with pelvic fracture, 69 (87.3%) had fractures of both the anterior and the posterior rings. The fracture map and heat map of geriatric pelvic fractures showed the following: the fracture lines of the anterior ring were concentrated in the junction of the cancellous bone and cortical bone of the superior and inferior pubic rami; the fracture lines of the posterior ring were concentrated in the middle and posterior 1/3 of the ilium and in the sacral wing; the fracture frequencies incurred by the pubic bone, sacrum, and ilium were from the highest to the lowest.Conclusions:Fracture mapping can visually characterize the distribution of fracture lines of the geriatric pelvic fractures. Simultaneous fractures of the anterior and posterior rings of the pelvis are the most typical kind of pelvic fractures in the elderly. The junction of the cancellous and cortical bones of the superior and inferior pubic rami and the area surrounding the sacroiliac joint are the most frequent locations for the fractures.

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*