In recent studies,obesity is a risk factor for a variety of cancers,including breast cancer and colorectal cancer.Obesity can regulate the tumorigenesis and development of cancer by some factors,such as insulin and insulin-like growth factor-1 (IGF-1),leptin,fat cytokines and hormones.Understanding the relationship between obesity and cancer can provide a new perspective for the prevention and treatment of cancer.

Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily. It is highly related to the formation of metabolic syndrome and the glucose homeostasis, and therefore represents an important drug target against metabolic diseases and diabetes. In recent years, great progress has been made in the agonists, antagonists, and crystal structures of FXR. The diverse FXR ligands and their structure-activity relationship are reviewed in this article. The advances in the crystal structures of FXR in complex with different ligands are also introduced.

A novel high performance liquid chromatographic method was developed for the determination of 4-O-methylhonokiol in rabbit plasma and was applied to its pharmacokinetic investigation.Plasma samples were treated by one-fold volume of methanol and acetonitrile to remove the interference proteins.A reverse phase column of SHIMPACK VP-ODS (150 mm× 4.6 mm,5.0 μm) was used to separate 4-O-methylhonokiol in the plasma samples.The detection limit of 4-O-methylhonokiol was 0.2 μg/L and the linear range was 0.012- 1.536 mg/L.The good extraction recoveries were obtained for the spiked samples (84.7％,89.3％ and 87.7％ for low,middle and high concentrations of added standards,respectively).The relative standard deviation of intra-day and inter-day precisions was in the range from 0.6％ to 13.5％.The pharmacokinetic study of 4-O-methylhonokiol was made and the results from the plasmaconcentration curve of 4-O-methylhonokiol showed a two-apartment open model.This work developed a sensitive,stable and rapid HPLC method for the determination of 4-O-methylhonokiol and the developed method has been successfully applied to a pharmacokinetic study of 4-O-methylhonokiol.

A novel high performance liquid chromatographic method was developed for the determination of 4-O- methylhonokiol in rabbit plasma and was applied to its pharmacokinetic investigation. Plasma samples were treated by one-fold volume of methanol and acetonitrile to remove the interference proteins. A reverse phase column of SHIM- PACK VP-ODS （150 mm ×4.6 mm, 5.0 μm） was used to separate 4-O-methylhonokiol in the plasma samples. The detection limit of 4-O-methylhonokiol was 0.2 μg/L and the linear range was 0. 012 - 1. 536 mg/L. The good extraction recoveries were obtained for the spiked samples （84.7%, 89.3% and 87.7% for low, middle and high concentrations of added standards, respectively）. The relative standard deviation of intra-day and inter-day precisions was in the range from 0.6% to 13.5%. The pharmacokinetic study of 4-O-methylhonokiol was made and the results from the plasmaconcentration curve of 4-0-methylhonokiol showed a two-apartment open model. This work developed a sensitive, stable and rapid HPLC method for the determination of 4-O-methylhonokiol and the developed method has been successfully applied to a pharmacokinetic study of 4-O-methylhonokiol.

The aim of this study was to observe whether necroptosis is involved in the process of cardiac hypertrophy induced by pressure overload. SD rats underwent transverse abdominal aortic constriction (TAC) operation for establishing cardiac hypertrophy model. The structure and function of the left ventricle of rats were evaluated via echocardiography, left ventricular mass index, the expression of markers of cardiac hypertrophy and histological detection. Real-time PCR and Western blot were used to measure the gene and protein expression of receptor interacting protein kinase 1 and 3 (RIPK1 and RIPK3, the necroptosis markers) respectively. Four weeks after TAC operation, rat model for cardiac hypertrophy was established. The experimental data showed that the gene and protein expressions of RIPK1 and RIPK3 in the rat heart hypertrophic tissues after TAC for 4 weeks were increased significantly compared with those in the sham group. HE staining showed cardiomyocytes injury and hypertrophy in the hearts of TAC rat models. By transmission electron microscope, we observed that mitochondria of cardiomyocytes were damaged seriously in the TAC models. Treatment with losartan used, the selective antagonist of angiotensin II type I receptor could improve the cardiac function of TAC rats. Moreover, losartan treatment decreased the expression of RIPK1 and RIPK3 in heart tissues of TAC rats. The results suggest that necroptosis occurrs in the process of cardiac hypertrophy with pressure overload, and losartan could alleviate the cardiac hypertrophy and inhibit necroptosis.
Animals ; Apoptosis ; Cardiomegaly ; pathology ; Disease Models, Animal ; Echocardiography ; Heart ; physiopathology ; Losartan ; pharmacology ; Myocytes, Cardiac ; Pressure ; Protein-Serine-Threonine Kinases ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Receptor-Interacting Protein Serine-Threonine Kinases ; metabolism

Objective To investigate the correlation between serum C1q/tumor necrosis factor related protein 9(CTRP9)and soluble CD146(sCD146)levels and coronary artery lesions(CAL)in children with Kawasaki disease(KD).Methods A total of 116 children with KD admitted to the People's Hospital of Kaizhou District,CQ from October 2020 to February 2023 were selected as the study subjects(KD group).According to the ultrasound diagnosis results,children with KD were grouped into CAL group(n=40)and non CAL group(n=76).According to the severity of CAL,children with KD in the CAL group were separated into mild group(n=14),moderate group(n=18)and severe group(n=8).Enzyme linked immunosorbent assay(ELISA)was applied to measure serum levels of CTRP9 and sCD146.The differences in serum levels of CTRP9 and sCD146 in control group,CAL group,non CAL,and children with different severity of CAL were compared.Multiple Logistic regression was applied to analyze the factors affecting the occurrence of CAL in children with KD.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum CTRP9 and sCD146 levels for the occurrence of CAL in KD children.Results Compared with the control group,the serum CTRP9 level in the KD group was decreased(3.27±0.27ng/ml vs 3.79±0.91ng/ml),while the sCD146 level was increased(191.28±50.39 ng/ml vs 143.97±38.29 ng/ml),with significant differences(t=5.900,8.051,all P＜0.05).The serum CTRP9 level in the CAL group was lower than that in the non CAL group(3.01±0.23ng/ml vs 3.41±0.29 ng/ml),but the sCD146 level was higher than that in the non CAL group(232.18±59.37 ng/ml vs 169.76±45.66 ng/ml),with significant differences(t=7.557,6.294,all P＜0.05).Compared with the mild group,the serum CTRP9 level in the moderate and severe groups was decreased(q=3.277,6.281),with sCD146 level increased(q=3.154,5.551),the serum CTRP9 level in the severe group was lower than that in the moderate group(q=3.845),with sCD146 level was higher than that in the moderate group(q=3.145),and the differences were statistically significant(all P＜0.05).The results of multivariate logistic regression analysis showed that white blood cell count(WBC),erythrocyte sedimentation rate(ESR),C reactive protein(CRP),CTRP9 and sCD146 were all influencing factors for the occurrence of CAL in children with KD(all P＜0.05).The results of ROC curve showed that the AUCs of CTRP9 and sCD146 separately predicted the occurrence of CAL in KD children were 0.781 and 0.782,with sensitivity of 82.5％and 67.5％,and specificity of 52.2％and 55.7％,respectively.The AUC for the combined diagnosis of CAL in children with KD was 0.889,with sensitivity and specificity of 97.5％and 65.9％,respectively.Conclusion Serum CTRP9 and sCD146 were influencing factors for the occurrence of CAL in children with KD,and the level of CTRP9 was decreased,while sCD146 was increased in the serum of children with CAL.The combination of the two can effectively predict the occurrence of CAL in children with KD.

Objective To explored the correlation between diabetic kidney disease(DKD)and MRI of cerebral small vessel disease(CSVD).Methods 476 type 2 diabetes mellitus(T2DM)patients who were hospitalized in Chengdu University of Traditional Chinese Medicine Affiliated Hospital from January to August 2022 were selected and divided into simple T2DM group(UACR＜30 mg/g,n=330)and DKD group(UACR≥30 mg/g,n=146).General data,biochemical indicators and head MRI images of the two groups were compared.The correlation between DKD and CSVD and the influencing factors of white matter hyperintensities(WMHs)severity were analyzed.Results Age,DM duration,TG,Scr,HbA1c,SUA,cystatin C(Cys C),fibrinogen(Fib)and the incidence of hypertension were higher(P<0.05),while the ALT was lower in DKD group than in T2DM group(P<0.05).Spearman correlation analysis showed tha the presence of DKD was positively correlated with WMHs,lacunar infarction(LI)and brain atrophy(P<0.05).eGFR was negatively correlated with WMHs,LI and brain atrophy(P<0.05).Logistic regression analysis showed that age and HbA1c were the influencing factors for the severity of WMHs.Conclusion Patients with DKD have a higher incidence of CSVD,which may be related to worsening renal function.HbA1c may have predictive value for the severity of WMHs.

Objective:To observe any effect of using the International Classification of Functioning, Disability and Health (ICF) rehabilitation set in rehabilitating the physical ability of hemiplegic stroke survivors.Methods:Ninety stroke survivors with hemiplegia were selected and randomly divided into an observation group ( n=45) and a control group ( n=45). The observation group was first assessed using the ICF and then given 60 minutes of individualized rehabilitation, 5 or 6 times a week for 4 weeks in addition to a weekly one-hour rehabilitation course. The control group were evaluated and treated traditionally. Before and after the intervention, both groups were evaluated using the Fugl-Meyer exercise assessment (FM) and functional independence assessment (FIM). Results:After the treatment the average upper and lower limb scores as well as the total FM scores had improved significantly. Those of the observation group were then significantly different from the control group′s averages.Conclusion:Basing rehabilitation on the ICF can more effectively improve the physical functioning of hemiplegic stroke survivors.

Objective:To explore the clinical efficacy and safety of the camrelizumab combined with apatinib and chemotherapy as second-line or later therapy in human epidermal growth factor receptor-2 (HER-2) negative advanced gastric cancer.Methods:A total of 66 patients with HER-2 negative advanced gastric cancer and first-line treatment failure in Shandong Cancer Hospital Affiliated to Shandong First Medical University from March 2018 to September 2021 were selected. They were divided into study group ( n=22) and control group ( n=44) according to the different treatment regimens. The patients in the study group were treated with camrelizumab combined with apatinib and chemotherapy, and the patients in the control group were treated with chemotherapy alone. The short-term efficacy, progression-free survival (PFS) , overall survival (OS) and the occurrence of adverse reactions were compared, and Cox regression analysis was used to analyze the influencing factors of prognosis. Results:After at least 2-4 cycles of treatment, the ORR in the study group and the control group were 9.1% (2/22) and 0 (0/44) respectively, with no statistically significant difference ( P=0.108) . DCR in the two groups were 77.3% (17/22) and 45.5% (20/44) respectively, with a statistically significant difference ( χ2=6.03, P=0.014) . The study group didn’t reach median OS and the median OS in the control group was 11.7 months, with no statistically significant difference ( χ2=1.59, P=0.207) . The study group didn’t reach median PFS and the median PFS in the control group was 3.2 months, with a statistically significant difference ( χ2=10.13, P=0.001) . Multivariate Cox regression analysis showed that treatment method was an independent influencing factor for PFS in patients with HER-2 negative advanced gastric cancer ( HR=0.33, 95% CI: 0.15-0.75, P=0.008) . In terms of adverse reactions, there was a statistically significant difference in the incidence of elevated alanine aminotransferase between the study group and the control group [31.8% (7/22) vs. 6.8% (3/44) , χ2=5.32, P=0.021]. There were no adverse-related deaths in both groups. Conclusion:Compared with chemotherapy alone, camrelizumab combined with apatinib and chemotherapy as a second-line or later therapy in HER-2 negative advanced gastric cancer can prolong PFS and improve DCR, but the incidence of elevated alanine aminotransferase increases significantly.