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 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.

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.

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 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.

The purpose of this study was to investigate the effect of low-magnitude vibration on osteogenesis of osteoblasts in ovariectomized rats with osteoporosis via estrogen receptor α(ERα). The mRNA expression of osteogenic markers were examined with qRT-PCR, based on which the optimal vibration parameter for promoting osteogenesis was determined (45 Hz × 0.9 g, g = 9.8 m/s
Animals ; Cell Differentiation ; Estrogen Receptor alpha/genetics* ; Female ; Osteoblasts ; Osteogenesis ; Osteoporosis ; Ovariectomy ; Rats ; Vibration

Objective To retrospectively analyze the epidemiological trend of children with lower gastrointestinal bleeding in recent 10 years,and investigate the change of their disease burden,so as to provide a theoretical basis for the accurate prevention and control of children's lower gastrointestinal bleeding. Methods A total of 671 children with "lower gastrointestinal bleeding" who were diagnosed in our hospital from 2012 to 2021 were collected as research subjects. To analyze the microscopic examination rate and common etiology of lower gastrointestinal bleeding in children in the past 10 years,as well as the epidemiological characteristics of different age groups, different regions and different basic diseases; Calculate and compare the rate of disability life lost (YLD), early death life lost (YLL) and disability adjusted life year (DALY) of children with lower gastrointestinal bleeding within 10 years, and calculate the annual change percentage (AAPC) to analyze the change trend of disease burden. Results The microscopic examination rate of children with lower gastrointestinal bleeding showed a trend of increasing in the past 10 years (P<0.001). Among them, the most common causes are Crohn's disease, ulcerative colitis and chronic colitis. The proportion of children with lower gastrointestinal bleeding was higher in boys, >18 years old, hypertension and gastroenteritis. The DALY rate, YLL rate and YLD rate caused by lower gastrointestinal bleeding in the past 10 years showed an upward trend (P<0.05). Conclusion The microscopic examination rate of lower gastrointestinal bleeding in children was graduallyincreasing,and the prevalence rate of basic diseases such as boys,hypertension and gastroenteritis was increasing;in addition,the disease burden caused by children's lower gastrointestinal bleeding was also increasing year by year and should be protected.