Objective To observe the relationship between vitamin D3 and the severity as well as prognosis in patients with sepsis, and to explore whether exogenous vitamin D3 can improve the prognosis in patients with sepsis.Methods A prospective randomized double-blind placebo study was conducted. Fifty-seven patients with sepsis admitted to intensive care unit (ICU) of Shengjing Hospital Affiliated to China Medical University from March to November in 2015 were enrolled. Twenty patients with systemic inflammatory response syndrome (SIRS) and 20 healthy volunteers with normal physical examination as control were enrolled during the same time. Patients with sepsis were divided into general sepsis group and severe sepsis group (including septic shock) according to the criteria for the diagnosis of severe sepsis and septic shock in 2012. According to the diagnostic criteria established by the American Endocrine Society, and on the basis of 25-hydroxy vitamin D3 [25(OH)D3], the sepsis patients with deficiency [25(OH)D320-30μg/L] or insufficiency [25(OH)D3 < 20μg/L] of vitamin D were divided into D3 treatment group (supplemented 300 kU vitamin D3) and placebo group (injected 1 mL physiological saline). 28th day was set as the end point, and the patients with sepsis were divided into survival group and death group. The levels of serum 25(OH)D3 in each group were measured by electrochemical luminescence method, and the difference in 25(OH)D3 levels among patients with different severity, gender, and age were recorded. Procalcitonin (PCT), C-reactive protein (CRP), blood routine, liver and kidney function, electrolytes and arterial blood gas analysis, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure score (SOFA), duration of mechanical ventilation, and length of ICU stay of patients with sepsis were observed. Multivariate Cox proportional hazard regression analysis was used to analyze the risk factors of prognosis in patients with sepsis.Results ① In 57 patients with sepsis, there were 15 patients in general sepsis group, and 42 in severe sepsis group; 29 in D3 treatment group, and 28 in the placebo group; 8 patients died within 28 days with mortality rate of 14.04%. ② The levels of serum 25(OH)D3 in sepsis group and SIRS group were significantly lower than those in healthy control group [μg/L: 3.92 (< 3.00, 11.22), 6.99 (3.51, 9.77) vs. 17.25 (13.48, 22.50), both P < 0.01], but there was no significant difference in the serum 25(OH)D3 level between sepsis group and SIRS group as well as patients with different degrees of sepsis. The serum 25(OH)D3 level in female patients with sepsis (n = 24) was significantly lower than that in male (n = 33), and the difference was statistically significant [μg/L: <3.00 (<3.00, 3.87) vs. 11.96 (5.14, 17.29),Z = -4.020,P = 0.000]. There was no significant difference in serum 25(OH)D3 level between the young (age <60 years old,n = 30) and the old (age ≥ 60 years old,n = 27) patients with sepsis [μg/L: 4.54 (<3.00, 9.88) vs. 3.00 (<3.00, 15.08),Z = -0.601,P = 0.548]. ③ In patients with sepsis, there was no significant difference in the duration of mechanical ventilation [hours: 41.00 (7.50, 82.50) vs. 67.00 (4.75, 127.75)], length of ICU stay (days: 5.48±4.08 vs. 6.68±4.87) and 28-day mortality (10.34% vs. 17.86%) between D3 treatment group and placebo group (allP > 0.05). It was shown by Kaplan-Meier survival curve analysis that there was no significance in 28-day accumulated survived rate between the two groups [log-rank test: χ2 = 0.222,P = 0.638]. It was shown by multivariate Cox regression analysis that APACHE Ⅱ score [relative risk (RR) = 8.487, 95% confidence interval (95%CI) = 1.506-47.835, P = 0.015] and 25(OH)D3 < 20μg/L (RR = 0.088, 95%CI = 0.013-0.592,P = 0.012) were the risk factors of prognosis in patients with sepsis.Conclusions The serum 25(OH)D3 level in ICU patients with sepsis was lower than that in healthy people, but there was no significant difference between patients with sepsis and SIRS. The serum 25(OH)D3 level in sepsis patients was related with gender, and the level of the female was lower than that of the male, but was not related with age. Exogenous vitamin D3 supplementation cannot improve the prognosis of ICU patients with sepsis. APACHE Ⅱ score and 25(OH)D3 < 20μg/L were risk factors for the prognosis in ICU patients with sepsis.

Objective To investigate the factors associated with awareness of dyslipidemia among residents in Beijing.Methods Cross-sectional data of 3 373 patients with dyslipidemia from CCEIP were analyzed.The patients were seleted from 10 054 residents from Daxing,Chaoyang,Haidian,and Xicheng Districts of Beijing during June-August,2007.The socioeconomic status and awareness of dyslipidemia were surveyed by questionnaires.The risk factors for cardiovascular diseases(CVDs),such as hypertension,obesity and diabetes,were assessed by physical examination and fasting blood analysis.Results (1)Awareness of dyslipidemia was improved with the increase of patients' age (P

Objective To investigate the effects of preconditioning and postconditioning with isoflurane on pro-inflammatory cytokines and lipid peroxidation in focal cerebral ischemic/reperfusion (I/R) injury in rats.Methods Thirty-two Sprague-Dawley (SD) rats were randomly divided into four groups:control group,model group,isoflurane preconditioning group and isoflurane postconditioning group,with 8 rats in each group.Rats in control group did not receive any challenge.In rats of model group right middle cerebral artery occlusion (MCAO) was conducted for 90 minutes.Rats in isoflurane preconditioning group received 2％ isoflurane exposure for 30 minutes 24 hours before MCAO for 90 minutes.Rats in isoflurane postconditioning group were given 60-minute 2％ isoflurane exposure after reperfusion of right MCAO.Twenty-four hours after the procedure,all rats were anesthetized with isoflurane,and blood sample taken from the heart was centrifuged,and the pro-inflammatory cytokines,including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α),and lipid peroxidation products such as malonaldehyde (MDA) and superoxide dismutase (SOD) were determined.The mRNA and protein expression levels of matrix metalloproteinase (MMP-2,MMP-9),tight junction protein Calaudin-5 and Occludin were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot.Results Compared with control group,serum levels of IL-1 β (ng/L),TNF-α (ng/L) and MDA (μmol/L) were elevated and activity of SOD (U/L) decreased in rats of model group (IL-1β:76.81 ± 11.14 vs.52.43 ± 8.86,TNF-α:64.93 ± 10.81 vs.33.64 ± 7.94,MDA:8.63 ± 1.42 vs.4.14 ± 0.98,SOD:0.95 ± 0.21 vs.2.36 ± 0.80,all P＜0.05).After isoflurane preconditioning and postconditioning,compared with model group,the levels of IL-1 β,TNF-α and MDA were lowered,while activity of SOD was increased (IL-1 β:54.37 ± 9.06,56.82 ± 8.67 vs.76.81 ± 1 1.14,TNF-α:43.72 ± 6.16,39.49 ± 9.34 vs.64.93 ± 10.81,MDA:5.65 ± 0.83,5.82 ± 0.78 vs.8.63 ± 1.42,SOD:1.64 ± 0.47,1.71 ± 0.52 vs.0.95 ± 0.21,all P＜0.05).Focal cerebral I/R injury could lead to an increased expression of MMP accompanied with a decreased expression of tight junction protein.Compared with model group,after isoflurane preconditioning and postconditioning,it was found that there were decreased mRNA and protein expression of MMP-2 and MMP-9 (MMP-2 mRNA:1.25 ± 0.08,1.32 ± 0.12 vs.2.48 ± 0.26,MMP-2 protein:1.56 ± 0.09,1.50 ± 0.08 vs.2.12 ± 0.11 ; MMP-9 mRNA:1.26 ± 0.13,1.20 ± 0.12 vs.2.74 ± 0.28,MMP-9 protein:1.53 ± 0.04,1.51 ± 0.05 vs.2.23 ± 0.09,all P＜0.05) and increased levels of Calaudin-5 and Occludin (Claudin-5 mRNA:0.40 ± 0.08,0.38 ± 0.06 vs.0.28 ± 0.03,Claudin-5 protein:0.80 ± 0.06,0.81 ± 0.07 vs.0.39 ± 0.02; Occludin mRNA:0.54 ± 0.07,0.50 ± 0.08 vs.0.26 ± 0.06,Occludin protein:0.64 ± 0.06,0.69 ± 0.05 vs.0.49 ± 0.02,all P＜0.05).Conclusion Preconditioning and postconditioning with isoflurane can lower the levels of pro-inflammatory cytokines and the degree of lipid peroxidation,and lower the hydrolytic activity of MMP to the tight junction protein in cerebral tissue,thereby decrease the loss of tight junction protein and alleviate I/R injury.

Objective To investigate the prediction of maternal HBV transmission by breast milk of postpartum women with chronic HBV infection.Methods HBV DNA levels in serum and breast milk weredetected by fluorescent quantitative polymerase chain reaction in 64 postpartum women with chronic HBV infection.HBV DNA≥1.0×103copies/ml was defined as positive,and correlation analysis was conducted.Results HBV DNA positive rate was 78.1%and 62.5%in serum and breast milk respectively,with a HBV DNA range of 1.05×103～3.87 ×104copies/ml in breast milk.When HBV DNA in serum was 1.0×105～1.0×107copies/ml,the HBV DNA positive rate in breast milk reached to 94.9%;however,when HBV DNA in serum was 1.0×103～1.0×104copies/ml,the positive rate in breast milk was only 18.2%.Conclusion The HBV DNA positive rate of breast milk in postpartum women with chronic HBV infection is correlated with the HBV DNA levels in serum;and breast-feeding should be avoided for postpartum women with HBV DNA≥1.0×105copies/ml in the serum.So serum HBV DNA detection is necessary in antenatal care for women with chronic HBV infection.

ObjectiveTo demonstrate the efficacy and safety of Hangzhou tacrolimus capsule (Saishi Tac capsule,Hangzhou Zbongmei Huadong Pharmaceutical Co.Ltd,China) in Chinese liver transplant recipients.MethodsMulticenter,randomized open-labeled,prospective controlled clinical trial was performed in de novo Chinese liver transplant recipients.According to inclusive and exclusive criterion,83 liver recipients from 11transplant centers were enrolled.The recipients accepted Saishi Tac capsule,mycopheolate and steroid 48 h post-operation.The initial dose of Tac was 0.1-0.15 mg kg-1day-1and C0 was 8-12 ng/ml in the first 60 days,followed by 5-10 ng/ml until the terminal observation time poiut (12 weeks after transplantation).The efficacy and safety were estimated during the period.The primary efficacy endpoint of the study was the incidence of biopsy-confirmed acute rejection.Graft survival was the secondary endpoint.Safety was assessed by monitoring laboratory parameters and adverse events reported over the course of the study,such as infection,renal damage,hypertension,hyperlipema and diabetes mellitus and other adverse affairs.ResultsThe dose of Tac at 1st,2nd,4th and 8th week post-operation was (4.1±1.9),(4.5±2.1),(4.5±2.1),(4.4±1.8) and (4.1±2.1) mg,and correspondjng values to the C0 were (8.1±4.5),(8.9±4.5),(8.8±4.3),(8.8±4.1) and (8.0±2.8) ng/ml.During 12 weeks of follow-up,the incidence of biopsy-confirmed acute rejection was 4.8％ (4/83),and all of cases were reversed by implosive therapy.The survival rate of graft hver was 100％.The incidence of lung infection and diabetes mellitus was both 6.02％.ConclusionSaishi Tac capsule was safe and effective to Chinese liver transplant recipients.

Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC.
Animals ; Apoptosis ; Cause of Death ; Cell Proliferation ; Colon ; Colorectal Neoplasms* ; Fluorouracil ; Heterografts ; Humans ; In Vitro Techniques ; Mice ; Repression, Psychology ; RNA, Small Interfering

The negative effects of low temperature can readily induce a variety of diseases. We sought to understand the reasons why cold stress induces disease by studying the mechanisms of fine-tuning in macrophages following cold exposure. We found that cold stress triggers increased macrophage activation accompanied by metabolic reprogramming of aerobic glycolysis. The discovery, by genome-wide RNA sequencing, of defective mitochondria in mice macrophages following cold exposure indicated that mitochondrial defects may contribute to this process. In addition, changes in metabolism drive the differentiation of macrophages by affecting histone modifications. Finally, we showed that histone acetylation and lactylation are modulators of macrophage differentiation following cold exposure. Collectively, metabolism-related epigenetic modifications are essential for the differentiation of macrophages in cold-stressed mice, and the regulation of metabolism may be crucial for alleviating the harm induced by cold stress.
Acetylation ; Animals ; Cold-Shock Response ; Epigenesis, Genetic ; Macrophages/metabolism* ; Mice ; Mitochondria/metabolism*