Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

Objective:To explore the deubiquitination modification of the deubiquitinase BRCC3 in rats with neuropathic pain (NPP) treated with meridian tuina of Zhuang medicine and its analgesic molecular mechanism.Methods:Rats were divided into normal group, sham-operation group, model group, sham-tuina group, and meridian tuina of Zhuang medicine group using a random number table method, with 9 rats in each group. Except for the normal and sham operation groups, spinal nerve ligation models were prepared in all other groups. On the first day after surgery, intervention was carried out on the meridian tuina of Zhuang medicine and sham-tuina groups for 14 days, while the other three groups were not intervened; the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) of each group of rats were measured at 0 days before operation, 1, 7, and 14 days after operation. Western blot was used to detect the expressions of BRCC3 and NLRP3 proteins in spinal cord tissue, and ELISA was used to detect the level of IL-1β in serum.Results:On postoperative 7 and 14 d, compared with the model group, the meridian tuina of Zhuang medicine group showed an increase in PWMT and PWTL, a decrease in NLPR3 and BRCC3 expression in spinal cord tissue, and a decrease in serum IL-1β levels ( P<0.05). Compared with the sham-tuina group, the meridian tuina of Zhuang medicine group showed an increase in PWMT and PWTL, a decrease in NLRP3 protein expression in spinal cord tissue, and a decrease in IL-1β levels in serum ( P<0.05). Conclusion:Meridian tuina of Zhuang medicine can alleviate pain sensitivity in SNL model rats, and its mechanism is related to the inhibition of the expression of deubiquitinase BRCC3 by meridian massage of Zhuang medicine, which increases the ubiquitination level of NLRP3 and hinders its activation, thereby blocking the immune inflammatory response mediated by inflammatory factors.

As a highly heterogeneous disease, breast cancer ranks first in new cases and deaths of female malignant tumors. In recent years, the incidence of breast cancer increases and tends to be younger. Early-onset breast cancer (<40 years old) is mostly associated with adverse biological characteristics and poor prognosis. Although immunotherapy and targeted therapy have advances in the treatment of breast cancer, a major challenge of neoplastic resistance to systemic therapy remains. Therefore, early diagnostic markers and potential therapeutic targets with high specificity and sensitivity must be identified. miR-21 affects the occurrence and development of breast cancer by targeting related genes and regulating related signaling pathways (PTEN/PI3K/Akt and NF-κB/ miR-21-5p/PDCD4 signaling pathways). This paper reviews the mechanism and progress of miR-21 in breast cancer.

Objective To investigate the-75 G/A single-nucleotide polymorphism in the promoter region of apolipoprotein A1 gene(apoA1)and its association with gestational diabetes mellitus(GDM)in pregnant women and to provide references for the exploration in the molecular genetic basis of GDM.Methods A total of 626 GDM patients and 1022 normal pregnant women,ie,the controls,were included in the study.The genotyping of apoA1-75 G/A polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP)analysis.Total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),and glucose(Glu)were measured by enzymatic methods.Plasma insulin(INS)was measured by chemiluminescence immunoassay.The protein levels of apoA1 and apoB were measured by the turbidimetric immunoassay.Results Allele frequencies of G and A were 0.718 and 0.282 in the GDM group and 0.713 and 0.287 in the control group,respectively.Distribution of the genotype frequencies was found to be in Hardy-Weinberg equilibrium in both the GDM and control groups.There was no significant difference in the frequencies of alleles G and A and the genotypes of apoA1-75 G/A polymorphism between the GDM and the control group(P>0.05).In the GDM group,the carriers with the genotype AA were associated with significantly higher levels of TC,HDL-C,and apoA1 than those with genotypes GG and GA did(all P<0.05).After the GDM patients were divided into obese and non-obese subgroups,the genotype-related apoA1 variation was observed only in obese patients,while the genotype-related TC and HDL-C variations were evident in non-obese patients(P<0.05).In the control group,carriers of genotypes AA and GA had higher systolic blood pressure(SBP)and HDL-C than the carriers of genotype GG did(all P<0.05).Carriers of genotypes AA had significantly lower Glu levels than carriers of genotypes GG and GA did(P<0.05).The control subjects were further divided into subgroups according to their body mass index(BMI).Analysis of the subgroups showed that AA carriers were associated with higher SBP levels in the obese control women only,while lower Glu levels were evident in both obese and non-obese control women.Conclusion These results suggest that-75 G/A polymorphism in the apoA1 gene is not associated with GDM.However,the genetic variation is closed associated with the plasma apoA1,HDL-C,and TC levels in GDM patients and plasma HDL-C,Glu,and SBP levels in the control subjects.The apoA1 variant-associated lipids and SBP variation is BMI dependent in both groups.

Ferroptosis is a novel iron-dependent mode of programmed cell death characterized by iron deposition and accumulation of lipid peroxidation. More and more studies have found that ferroptosis is closely related to the pathogenesis of type 2 diabetes mellitus （T2DM）. The yin-fire theory is an important part of LI Gao's spleen-stomach theory， and it is believed that qi-fire imblance and yin-fire internal generation is the main pathogenesis of T2DM. Abnormal iron metabolism may be an important prerequisite for T2DM yin-fire internal generation， while oxidative stress is the specific manifestation of T2DM qi-fire imbalance. Reactive oxygen species （ROS） is the end product of qi-fire imbalance， and lipid peroxide is the pathological products of T2DM yin-fire internal generation. This study intends to explore the pathological mechanism of qi-fire imbalance and yin-fire internal generation from the perspectives of iron metabolism， oxidative stress and lipid peroxidation， enriching the modern connotation of yin-fire theory， and benefiting traditional Chinese medicine to target against ferroptosis， and prevent and treat T2DM precisely.

Objective To investigate the role of cell adhesion molecule L1 like (CALL) in the genesis and development of esophageal squamous cell carcinoma (ESCC).Methods From July 2007 to December 2010,a total of 100 patients with ESCC who received radical resection of esophageal cancer were enrolled.The ESCC tissues and corresponding tumor-adjacent normal tissues were obtained.The expression of CALl was determined by tissue microarray technology and immunohistochemical staining.The CALL over-expressed esophageal cancer cell line was established.The effects of CALL on cell migration and invasion were detected by wound-healing assay and Transwell assay,respectively.The effects of CALL on actin microfilament was analyzed by filamentous actin (F-actin) staining.Chi square test,Fisher's exact test,multivariate analysis and t test were performed for statistical analysis.Results The positive expression rate of CALL in ESCC tissues was 56 ％ (56/100),which was lower than that of tumor-adjacent normal tissues (95％,95/100),and the difference was statistically significant (x2=41.114,P＜0.01).There were statistically significant differences in CALL expression at protein level among patients with ESCC of different differentiation degree,different pathological T stage,lymph node metastasis and different TNM stage (x2=13.702,5.317,21.453,Fisher's exact test;all P＜ 0.05).The five year disease related survival rate of ESCC patients with down-regulated expression of CALL was 0(0/49),which was lower than those with normal CALL expression (25.5％,13/51),and the difference was statistically significant (x2 =43.338,P＜0.01).The median survival time of CALL expression down-regulated group was 17 months,and that of normal expressed group was 38 months.CALL expression was an independent risk factor of disease special survival rate (hazard ratio (HR) 0.353,95％ confidence interval (CI) 0.188 to 0.666,P=0.001).The results of wound-healing assay showed that the migration ability of CALL overexpressed CALL-k30 cells was lower than that of Vec-k30 cells in control group on 24 hours after wound.The results of Transwell invasion test showed the number of migrating cells penetrating CALL k30 cells attached to the inferior surface of the membrane was 44.000±13.748,which was less than that of the Vec k30 cells (154.333±25.007),and the difference was statistically significant (t=5.136,P=0.036).The results of F-actin staining demonstrated that actin filaments of CALL-k30 cells was 234.667 ± 65.118,which was lower than that of Vec-k30 cells (597.000± 119.929),and the difference was statistically significant (t=4.707,P=0.042).Conclusions CALL lowers the migration and invasion abilities of esophageal cancer cells by inhibiting F-actin microfilaments.Its abnormal expression may play an important role in the genesis,development and prognosis of ESCC.

Objective To evaluate the relationship between the perfusion mode of neovascularization of carotid plaque in CEUS and the ischemic stroke in transient ischemic attack (TIA) patient.Methods A total of 73 TIA patients according to the inclusive criteria were enrolled.All the patients underwent routine carotid ultrasonic examination.And 61 patients with plaque thicker than 2.5 mm in carotid bifurcation underwent CEUS and follow-up for at least 18 months.All the patients were divided into recurrent and non-recurrent groups.Logistic regression analysis were performed to detect the risk factors for incurrence of ischemic stroke or recurrence of TIA in 18 months.Results There were statistical differences between 2 groups in hypertension,diabetes,hyperlipemia,smoking history,family history of stroke,medication compliance,two-dimensional ultrasound and CEUS characteristics (all P＜0.05).Multivariate Logistic regression analysis showed that all the factors correlated with the recurrency,from big to small order were the CEUS characteristics of carotid plaque,hypertension,medication compliance,diabetes,two-dimensional ultrasound characteristics of carotid plaque.Conclusion CEUS could evaluate the perfusion mode of neovascularization in carotid plaques.For TIA patients,CEUS could predict the incurrence of ischemic stroke or recurrence of TIA,which can guide TIA patients targeted prophylaxis of them.

Objective To assess the treatment of splenic artery aneurysms(SAA) and curative effect evaluation.Methods Twelve SAA patients treated in our hospital from January 2012 to May 2014 were clinical analyzed.The male in Twelve patients was 4 man and others were female.The vagus splenic artery aneurysms are originated from the superior mesenteric artery,tumors are single,from 1.5cm to 2.8cm in diameter,an average of 2.1cm.Twelve cases were performed surgery,4 patients underwent elective surgery,interventional embolization of the splenic aneurysm in 3 patient,The others were performed interventional embolization + superior mesenteric artery covered stents.Results Technical success was achieved in all twelve patients,2 patients had adverse effects such as abdominal pain,fever,etc.There revealed no aneurysm recurrence was found.Twelve patients were followed for 6-24 months,the follow-up by examinations with electronic computer X-ray tomography or color Doppler ultrasonic as well as angiography every 3 months.One patient died of severe abdominal bleeding 1 year later after the operation and the other eleven patients remained in good condition with no occurrence of re-canalization of the lesions.Conclusions For the vagus splenic aneurysm with suitable for anatornic conditions,cavity therapy is safe and effective,for the vagus splenic aneurysm involving hepatic artery,need to open surgery for vascular remodeling.

Hypofractionated three-dimensional confornul radiotherapy (3DCRT) makes it possible to further improve loeal control,overall survival and the quality of life for the patients with non-small-cell lung cancer (NSCLC).But the dose-fractionation and total dose are not yet clear,which need further study.Hypofractionated stereotactic body radiotherapy (SBRT) for early-stage NSCLC patients is well tolerated and results in excellent local control and overall survival.SBRT is expected to become a new standard treatment in patients with early stage NSCLC.