Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Objective: To explore the feasibility of remotely obtaining complex information on traditional Chinese medicine (TCM) pulse conditions through voice signals. Methods: We used multi-label pulse conditions as the entry point and modeled and analyzed TCM pulse diagnosis by combining voice analysis and machine learning. Audio features were extracted from voice recordings in the TCM pulse condition dataset. The obtained features were combined with information from tongue and facial diagnoses. A multi-label pulse condition voice classification DNN model was built using 10-fold cross-validation, and the modeling methods were validated using publicly available datasets. Results: The analysis showed that the proposed method achieved an accuracy of 92.59% on the public dataset. The accuracies of the three single-label pulse manifestation models in the test set were 94.27%, 96.35%, and 95.39%. The absolute accuracy of the multi-label model was 92.74%. Conclusion Voice data analysis may serve as a remote adjunct to the TCM diagnostic method for pulse condition assessment.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*

The laccase (PpLAC) gene family members in peach fruit were identified and the relationship between their expression pattern and chilling induced browning were investigated. The study was performed using two varieties of peaches with different chilling tolerance, treated with or without exogenous γ-aminobutyric acid (GABA) during cold storage. Twenty-six genes were screened from the peach fruit genome. These genes were distributed on 6 chromosomes and each contained 5-7 exons. The PpLAC gene family members shared relatively similar gene structure and conserved motifs, and they were classified into 7 subgroups based on the cluster analysis. Transcriptome sequencing revealed that the expression levels of PpLAC7 and PpLAC9 exhibited an increasing pattern under low temperature storage, and displayed a similar trend with the browning index of peach fruit. Notably, GABA treatment reduced the degree of browning and inhibited the expression of PpLAC7 and PpLAC9. These results suggested that PpLAC7 and PpLAC9 might be involved in the browning of peach fruit during cold storage.
Food Storage ; Fruit/genetics* ; Laccase/genetics* ; Prunus persica/genetics*

Objective To investigate the status of nutritional risk and nutritional support in general surgery patients, and to explore their association with postoperative complications and length of hospital stay.Methods From January 2014 to February 2015, 853 inpatients in general surgical wards in the Second Hospital of Hebei Medical University were enrolled.Nutritional Risk Screening 2002 (NRS 2002) was used to estimate nutritional status of patients.The patients were divided into 2 groups based on whether they received nutritional support.The length of hospital stay in days and postoperative complications were recorded.The association of nutritional risk and nutritional support with complications and length of hospital stay were analyzed.Results In the 853 surgery patients, the prevalence of nutritional risk was 31.1％ (265/853) and that of malnutrition was 5.4％ (46/853).The incidence of postoperative complications was 14.2％ (121/853).The patients with nutritional risk had a significantly higher incidence of postoperative complications compared to those without nutritional risk [29.8％ (79/265) vs.7.1％ (42/588) , P ＜ 0.000] , and a longer hospital stay [(12.5 ±6.4) days vs.(4.2 ±3.9) days, P ＜0.001].In the 853 patients, 27.3％ (233/853) received nutrition support.In the patients with nutritional risk, those on nutritional support had a significantly lower incidence of complications compared with those not on nutritional support [16.7％ (32/192) vs.64.4％ (47/73), P＜0.05] and shorter hospital stay [(7.5±4.6) days vs.(16.3±8.5)days, P ＜ 0.05].Conclusions According to NRS 2002 result, a fairly high percentage of general surgery patients may have nutritional risk.Patients with decreased body mass, less dietary intake, and at higher age may be more likely to have nutritional risk.Nutritional risk may be associated with a higher incidence of postoperative complications and longer hospital stay.Patients at nutritional risk appear to be more likely to benefit from nutritional support.

Objective To investigate the antimicrobial resistance of main clinical isolates from ICU during 2012 .Methods Auto-matic microbiology analysis system and the disk diffusion method were performed to determine the antimicrobial susceptibility .All the data were analyzed by WHONET5 .6 software according to the breakpoints of The American Association of Clinical Laboratory Standardization Institute (CLSI) 2012 .Results A total of non-repeated 1 374 clinical isolates were collected in ICU during 2012 , including 1 089 strains (79 .3% ) of Gram-negative bacilli and 285 strains (20 .7% )of Gram-positive cocci ;The top five pathogens were Acinetobacter baumannii ,Pseudomonas aeruginosa ,Escherichia coli ,Klebsiella pneumoniae and Staphylococcus aureus ;Some Enterobacteriaceae strains were resistant to imipenem or ertapenem .2 strains of Enterococcus faecium were found resistant to van-comycin .Conclusion Non-fermenting bacteria ,Enterobacteriaceae and Staphylococci remain the predominant pathogens isolated from the patients in ICU ,their drug resistance is serious ,it is important to use antibacterial agents rationally and strengthen the sur-veillance of bacterial drug resistance .

Objeetive To construct the cell DNA damage models for the human CML K562 cell line before or after imarlnib mesylate treatment and observe the repairing process dynamically for investigating the iniluence of imatinib mesylate on the repair function of K562 cells after cell DNA danlage.Methods The MTT assay was used to estimate the optimal pretreatment concentration of imatinib mesylate in K562 cells and Western blot was employed to evaluate the phosphorylation status in K562 cells after imatinib mesylate treatment to estimate BCR/ABL tyrosine kinase inhibition by imatinib mesylate.The comet assay was used to detect the DNA damage induced by hydrogen peroxide at various concentrations in K562 cells with or without the pretreatment of imatinib mesylate.A dynamic observation on the repairing process after cell DNA damage was made by the comet assay.Results The pretreatment by imatinib mesylate for K562 cells was optimized to be at a final concentration of 1 μmol/L for 24 h as revealed by the MTT assay additionly imatinib mesylate treatment at this concentration could effectively inhibit the phosphorylation of the BCR-ABL fusion protein at Tyr177(Deusityrate 0.100±0.018).When compared with the control group(Deusityrate 0.425±0.039),the BCR/ABL phosphorylation at Tyr177 was significantly decreased by (77. 11±5.59) % (t=4. 57,P＜0. 05). The cell DNA damage models for both imatinib mesylate-nontreated and imatinib mesylate-pretreated K562 cell groups were constructed with hydrogen peroxide treatment at a final concentration of 10 μmol/L for 10 min at 4℃ as confirmed by the comet assay. When compared with the control imatinib mesylatenontreatod K562 cell group,the time duration required for the DNA repair in imatinib mesylate-pretreated K562 cell group was significantly prolonged (F= 97.79,P＜0. 05 ). Conclusions The cell DNA damage models for the leukemic K562 cell groups before or after imatinib mesylate treatment were successfully constructed and the tyrosine kinase inhibitor imatinib mesylate for BCR/ABL fusion protein was revealed to attenuate the DNA repair capacity of the K562 cells after DNA damage.

Objective To characterize the localization and expression of cyclooxygenase (COX) in thoracic spinal cord before and after acute contusion. Methods 48 Sprague Dawley rats, 250 to 300 g in weight, were used for the study. The injuries of spinal cord were induced at the T8,9 level by dropping a weight of 10.24 g form a height of 50 mm (Allen’ s model). All the animals with spinal cord injury were sacrificed at time points ranging from 2 to 48 hours (2, 4, 8, 16, 24, and 48 hours) after management. Expressions of COX- 1 and COX- 2 in the thoracic spinal cords, normal and injured, were studied with immunohistochemistry. Results COX- 1 immunoreactivity was found to constitutively express in cytoplasmof glial cells and neuropils in white matter. Tiny COX- 1 immunoreactivity was found in glial cells, neuropils and neurons in the gray substance. It was found that COX- 2 immuno- labeling expressed constitutively in cytoplasm and closely surrounding the nucleus of neurons in both ventral and dorsal horns. Contusion to the spinal cord did not result in changes of COX- 1 protein localization and expression according to evaluation of immunohistochemistry. COX- 2 immunoreactivity improved only in neurons 4 hours following contusion. The positive COX- 2 protein reactivity reached the peak 24 hours after contusion. Conclusions In contrast to their expression in the majority of peripheral tissues, both COX isoforms express constitutively in the normal rat thoracic spinal cord. The major isoform of COX involved in the secondary spinal cord injury is COX- 2 after the spinal cord is mechanically injured.

Objective To construct the transformed mouse BaF3-P210 cell line stably expressing BCR/ABL and to initially investigate the influence of BCR/ABL on the cell biological characteristics of BaF3 cell line. Methods The retroviral vector with bcr/abl gene was transfected into the packaging cell line. The BaF3 cells were infected with the collected viral supernatant. The transgenic BaF3-P210 cell line stably expressing BCR/ABL were screened and subcloned. The integration of the bcr/abl gene in the genome of the target cell was determined by PCR and DNA sequencing,trypan blue staining assay,flow cytometry and MTT assay. Results The bcr/abl gene was integrated into the BaF3 cell genome; RT-PCR and Western blot verified the stable expression of the bcr/abl gene and protein in the screened subclone cell line BaF3-P210. Compared with the control group,the cell proliferation rate was promoted (P

Objective Our purpose was to improve the konwlege and diagnosis level of esophageal intramural pseudodiverticulosis(EIPD).Methods All 3 cases were underwent single and double contrast esophagograms.Analyze the findings on esophagography in 3 cases.Results Multiple small tiny cyst like outpouchings with a narrow neck extending outward esophageal wall were found in all of the 3 cases, the length range of outpouchings diameter was 1-4 mm,and the length range of neck was 1-2 mm,the pseudodiverticula had a diffuse distribution in 2 cases,and segmental distribution on the middle and the lower esophagus in the other case.Some necks of pseudodiverticula incline to stomach with 30?-45? in 2 cases;and intramural tracking was found in 1 case,the length range of tracking was 5-10 mm;esophageal stenosis in esophagogastic junction and reflux esophagitis was found only in 1 case;1 case underwent endoscopy and ostiums of pseudodiverticula were found;biopsy showed submucosal chronic inflammation surrounding the neck of pseudodiverticula,squamous metaplasia of the epithelium in both the neck and outpouchings.Conclusion EIPD is a rare benign disorder characterized by dilation of the submucosal glands.The value of esophagography is to distinguish sublimes ulcer caused by esophagitis and esophageal fenestrate from EIPD.The characteristic radiographic appearance is numerous intramural esophageal contrast-filled cystiform outpouchings,and some necks incline in the direction of stomach.When the typical appearance found on barium studies,the diagnosis of EIPD can be made.