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.

Phytochemical investigation on the ethanol extract of a well-known medicinal herb Leonurus japonicus, led to the separation of 18 labdane type diterpenoids (1-18). Through comprehensive spectroscopic analyses and quantum chemical calculations, these compounds were structurally characterized as six new interesting 5,5,5-di-spirocyclic ones (1-6), two new (7 and 8) and six known (13-18) interesting 6,5,5-di-spirocyclic ones, a new rare 14,15-dinor derivative (9), and three new ones incorporating a γ-lactone unit (10-12). An in vitro neuroprotective assay in RSC96 cells revealed that compounds 7 and 12 exhibited neuroprotective activity in a concentration-dependent way, comparable to the reference drug N-acetylcysteine.
Magnetic Resonance Spectroscopy ; Leonurus/chemistry* ; Plants, Medicinal ; Diterpenes/chemistry* ; Plant Components, Aerial ; Molecular Structure

Objective To investigate the therapeutic effect of different combination regimens on patients with high-frequency sudden sensorineural hearing loss(SSNHL). Methods 82 patients with high-frequency SSNHL from December 2013 to May 2017 were enrolled. The control group was treated with hormone,lidocaine, and genetein combination therapy,while the observation group received systemic hormones,and local hormones combined with hyperbaric oxygen therapy,the average frequency of pure tone valve improvement,complications and adverse reactions in two groups were compared.Results After the treatment,the average pure tone of the two groups was significantly improved than pretherapy(tcontrol group = 10.28,P = 0.00;tobservation group = 11.06, P=0.00),but there was no significant difference in hearing improvement between the two groups(t=0.680,P=0.698),the total effective rate in the control group was 63.41%,in which the observation group was 68.29%,the difference was not statistically significant(χ2=0.230,P=0.816),but the cure rate was 26.83% in the observa-tion group which was higher than that in the control group(7.32%)(χ2=2.05,P=0.040).There was no signifi-cant difference in improvement of complication(tinnitus and ear nausea)between the two groups(χ2Tinnitus =0.000,P=1.000;χ2Aurussion=0.000,P=1.000),and there was no obvious adverse reaction in both groups. Conclusions Treatment of high-frequency SSNHL,hormone and hyperbaric oxygen therapy is good and safe, which can effectively improve the patient′s complication(tinnitus and ear nausea).

Objective To observe the clinical efficacy of acupuncture at Shixuan (EX-UE11) plus rehabilitation in improving the upper-limb spasticity and hand function after cerebral stroke. Method Sixty patients with upper-limb spasm due to cerebral stroke were randomized into two groups. The observation group was intervened by conventional acupuncture plus needling Shixuan and rehabilitation training, while the control group was by conventional acupuncture plus rehabilitation training. The Modified Ashworth Scale (MAS) and Modified Barthel Index (MBI) were evaluated before and after the intervention. The effects of the two methods in improving the upper-limb spastic intensity, hand function, and activities of daily living after cerebral stroke were evaluated based on the scores before and after the intervention. Result After treatment, the upper-limb spastic intensity and muscle tension decreased in both groups, and there was a significant difference in comparing the MAS score between the two groups (P<0.05); the improvement of MBI in the treatment group was more significant than that in the control group (P<0.05). Conclusion Acupuncture at Shixuan plus rehabilitation can produce a more significant efficacy in treating upper-limb spasm, improving hand function and activities of daily living after cerebral stroke, compared to the conventional acupuncture plus rehabilitation.

Objective To study the changes in interleukin-32 (IL-32) in rats with Klebsiella bacillus pneumonia and approach its significance. Methods Seventy-two Sprague-Dawley(SD)rats were divide into control group,model group and experimental group by the method of random digits table,then the experimental group was subdivided into 4 hours and 1,3 and 5 days experimental subgroups(each n=6). The rat model of Klebsiella bacillus pneumonia was established by injection of 0.3 mL Klebsiella bacterial suspension into the trachea. Before the establishment of the model in the experimental group,IL-32 inhibitory agent,protease activated receptor-2(PAR2) was injected into the abdominal cavity. After model establishment,at different time points,blood was collected via tail vein to observe the changes in serum levels of IL-32,tumor necrosis factor-α(TNF-α),IL-6 and IL-8 in all the groups. The lungs were removed and stained with hematoxylin-eosin(HE)method to investigate the histopathological changes of the lung tissues under the light microscope. Results Compared to the control group, with the prolongation of time the levels of IL-32,TNF-α,IL-8 and IL-6 were increased gradually in the model group,and reached their peaks at 3 days〔IL-32(ng/L):84.40±28.24 vs. 18.57±3.86,t=5.544,P=0.002;TNF-α(ng/L):79.27±14.64 vs. 17.82±3.86, t=9.994, P=0.000;IL-8(ng/L):55.85±10.90 vs. 16.66±3.76,t=8.544, P=0.000;IL-6(ng/L):56.65±2.57 vs. 28.48±2.11,t=19.693,P=0.000〕;PAR2 could inhibit above indexes significantly,there was statistical difference at 3 days compared with the model group〔IL-32(ng/L):54.13±6.68 vs. 84.40±28.24,t=2.560,P=0.046;TNF-α(ng/L):49.12±3.56 vs. 79.27±14.64,t=4.901,P=0.003;IL-8 (ng/L):22.95±2.52 vs. 55.85±10.90,t=7.204,P=0.000;IL-6(ng/L):36.49±2.63 vs. 56.65±2.57,t=13.443, P=0.000〕. Under the light microscope,the inflammatory changes in the lung tissue in experimental group were milder than those in the model group. Conclusion As a pro-inflammatory cytokine,IL-32 can induce the production of TNF-α,IL-6 and IL-8,and the inhibition of IL-32 production may play a role in suppression of the development of Klebsiella bacillus pneumonia.

Objective:To investigate the variation of the drug resistance of Escherichia coli(Eco)against antibacterial in clinical specimens in the hospital, and to evaluate the simultaneous use of antibacterial, to explore to provide the reference for the reasonable clinical use of antibacterial. Method:Eco was separated from all kinds of clinical specimens of out-patients and in-patients in the hospital from August of 2005 to April of 2006,and ESBLs was detected with Kirby-Bauer (K-B) disk diffusion method. It was also counted that the antibacterial drugs ranked the first 30 in sales per month and their use frequencies in the same period in the hospital. Result:The detectable rate of producing ESBLs Eco was 58.6%. Eco was completely sensitive to imipenem. It had lower resistance rates, only 2% and 4% , against piperacillin/tazobactam and cefoperazone/sulbactam; and had 59% and 55% resistance rates respectively against cefotaxime claforan and ceftazidime pentahydrate in the third generation cephalosporin. The third generation cephalosporin and quinolones kept high in sales and their use frequencies ranked the first three. The use of the third generation cephalosporin with anhydrase inhibitors also had an uptrend. Conclusion:There is a direct relation between the use of a great deal of antibacterial and the imitative drug resistance of Eco. It is necessary to strengthen its clinical management and to raise the level of drug use.