OBJECTIVETo investigate the protective effects of Chinese medicine formulation Chaihu Shugan San (, CHSGS) on nonalcoholic fatty liver disease (NAFLD) in rats with insulin resistance (IR) and its molecular mechanisms.

METHODSMale Sprague-Dawley rats were randomly divided into six groups: the control group, the model group, Dongbao Gantai group (, DBGT, 0.09 g methionine/kg), CHSGS high-dose group (CHSG-H, 12.6 g crude drug/kg), CHSGS medium-dose group (CHSG-M, 6.3 g crude drug/kg), and CHSGS low-dose group (CHSG-L, 3.15 g crude drug/kg). After establishing the NAFLD rat model and treatment for 8 weeks, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), fasting blood glucose (FBG), fasting insulin (FINS) contents in blood serum, and TC, TG contents in the hepatic homogenate were measured by an automatic biochemical analyzer, and a homeostasis model assessment was applied to assess the status of IR, insulin sensitivity index (ISI), and homeostasis model assessment for insulin secretion (HOMA-IS). The expression levels of adiponectin and leptin mRNA in liver tissue were analyzed by reverse transcription polymerase chain reaction. Pathological changes of livers were observed by hematoxylin-eosin staining of paraffin section.

RESULTSCompared with the model group, the serum levels of TC, TG, FFA, FBG, FINS, IRI, ISI, and the liver levels of TC and TG in CHSG-H, CHSG-M, CHSG-L groups showed significant declines (P<0.01 or P<0.05); the serum levels of HDL-C, HOMA-IS were significantly increased (P<0.01 or P<0.05); the expression of leptin mRNA was dramatically decreased and the expression of adiponectin mRNA was increased in the hepatic tissue (P<0.01 or P<0.05). The fatty deposition of liver cells could also be alleviated.

CONCLUSIONCHSGS could up-regulate the expression of adiponectin mRNA and down-regulate the expression of leptin mRNA on the liver, suggesting the CHSGS had positive therapeutic effect on NAFLD in rats with IR.

OBJECTIVETo evaluate the manipulation technique and clinical outcome of Tri-Lock bone preservation stem for acetabular protrusion combined with shorten defect of femoral head and neck.

METHODSFrom January 2013 to December 2015, 10 patients(12 hips) with acetabular protrusion combined with shorten defect of femoral head and neck were treated with total hip arthroplasty(THA) including 5 males and 5 female with an average age of(51.6±3.0) years old ranging from 42.5 to 67.5 years old. The acetabular prostheses were all biological prosthesis with the ceramic lining, the whole ceramic femoral head was used in all the cases. The posterior-lateral hip incision was adopted in the surgery. The follow-up was carried out in 12 months after the surgery, and later once a year. The Harris score system in growth of femoral side described was used to assess the joint function of the patients before and after the surgery.

RESULTSTen patients were followed up for 8 to 48 months with an average of 33.0±3.5. All the incisions healed well and there were no complications such as femoral fracture, infection, dislocation and neurovascular injuries. The biological compression of the acetabulum and the stem of the femur was realized immediately after operation in 10 patients(12 hips). X-ray at 3 months after the operation showed bone growth were extended in a wide range, which could achieve bone fixation, no loosening and re-invagination. The range of hip movement increased from (45.8±7.5)° to (90.0±6.5)° at the final follow-up, with flexion increased to (89.0±6.0)°, abduction increased to (35.5±7.3)° and internal rotation increased to(31.8±6.6)°, the outer rotation increased to(32.6±5.2)°. The mean Harris scores had improved from 45.7±7.5 pre-operatively to 93.5±8.0 post-operatively, there was statistically significant difference between before and after surgery (=144.832,<0.05).

CONCLUSIONSCombined with acetabular treatment, Tri-Lock bone retention of the femoral stem in the treatment of femoral head and neck with shortening of the acetabular retraction and severe hip joint soft tissue contracture in patients, could be well pressed and retained more bone. The reconstruction of the acetabulum and the delamination of soft tissue are required during the operation. The results were safe and satisfactory in the middle and short term follow-up.

OBJECTIVETo study the burden of pediatric cancer in Jiangxi, China, in 2010 and 2015 and its changes from 2010 to 2015.

METHODSThe data of pediatric cancer in Jiangxi in 2010 and 2015 were collected from the Global Burden of Disease Study 2015 in China, including number of cases, number of deaths, years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY). The standardized incidence rate, mortality rate, and DALY rate were calculated with the national census data in 2010 as the standard population, in order to evaluate the changes in incidence, mortality, and disease burden of pediatric cancer in Jiangxi.

RESULTSIn both 2010 and 2015, boys had higher numbers of cases, deaths, and DALY than girls, and the 5-14 years group had higher numbers than the 0-4 years group; boys had higher incidence rate, mortality rate, and DALY rate than girls, and the 0-4 years group had higher rates than the 5-14 years group. In 2015, the standardized incidence rate of pediatric cancer was reduced by 6.66% in the 0-4 years group and 17.56% in the 5-14 years group; the standardized mortality rate was reduced by 11.34% in the 0-4 years group and 21.78% in the 5-14 years group; the standardized DALY rate was reduced by 11.27% in the 0-4 years group and 21.67% in the 5-14 years group. Among the different types of pediatric cancer, leukemia had the highest standardized DALY rate in 2010 and 2015, followed by brain cancer and non-Hodgkin's lymphoma.

CONCLUSIONSThere was a certain reduction in the burden of pediatric cancer in Jiangxi from 2010 to 2015. Leukemia, brain cancer, and non-Hodgkin's lymphoma are the focus of prevention and treatment, and children aged less than 5 years and boys should be closely monitored.

BackgroundChronic kidney disease (CKD) is closely related to the cardiovascular events in vascular calcification (VC). However, little has known about the characteristics of kidney injury caused by VC. Fibroblast growth factor 21 (FGF21) is an endocrine factor, which takes part in various metabolic actions with the potential to alleviate metabolic disorder diseases. Even FGF21 has been regarded as a biomarker in CKD, the role of FGF21 in CKD remains unclear. Therefore, in this study, we evaluate the FGF21 on the kidney injury in VC rats.

MethodsThe male Sprague-Dawley rats were divided into three groups: (1) control group, (2) Vitamin D3 plus nicotine (VDN)-induced VC group, (3) FGF21-treated VDN group. After 4 weeks, the rats were killed and the blood was collected for serum creatinine, urea nitrogen, calcium, and phosphate measurement. Moreover, the renal tissues were homogenized for alkaline phosphatases (ALPs) activity and calcium content. The levels of FGF21 protein were measured by radioimmunoassay. The levels of β-Klotho and FGF receptor 1 (FGFR1) protein were measured by enzyme-linked immunosorbent assay (ELISA). The structural damage and calcifications in aortas were stained by Alizarin-red S. Moreover, the structure of kidney was observed by hematoxylin and eosin staining.

ResultsThe renal function impairment caused by VDN modeling was ameliorated by FGF21 treatment, inhibited the elevated serum creatinine and urea level by 20.5% (34.750 ± 4.334 μmol/L vs. 27.630 ± 2.387 μmol/L) and 4.0% (7.038 ± 0.590 mmol/L vs. 6.763 ± 0.374 mmol/L; P < 0.01), respectively, together with the structural damages of glomerular atrophy and renal interstitial fibrosis. FGF21 treatment downregulated the ALP activity, calcium content in the kidney of VC rats by 42.1% (P < 0.01) and 11.7% (P < 0.05) as well as ameliorated the aortic injury and calcification as compared with VDN treatment alone group, indicating an ameliorative effect on VC. ELISA assays showed that the expression of β-Klotho, a component of FGF21 receptor system, was increased in VDN-treated VC rats by 37.4% (6.588 ± 0.957 pg/mg vs. 9.054 ± 0.963 pg/mg; P < 0.01), indicating an FGF21-resistant state. Moreover, FGF21 treatment downregulated the level of β-Klotho in renal tissue by 16.7% (9.054 ± 0.963 pg/mg vs. 7.544 ± 1.362 pg/mg; P < 0.05). However, the level of FGFR1, the receptor of FGF21, kept unchanged under VDN and VDN plus FGF21 administration (0.191 ± 0.0376 ng/mg vs. 0.189 ± 0.032 ng/mg vs. 0.181 ± 0.034 ng/mg; P > 0.05).

ConclusionsIn the present study, FGF21 was observed to ameliorate the kidney injury in VDN-induced VC rats. FGF21 might be a potential therapeutic factor in CKD by cutting off the vicious circle between VC and kidney injury.

To investigate the characteristic methylation genes of pyretic arthralgia model in hot and dampness environment and the regulation effect of Baihu Guizhi decoction on this characteristic methylation genes. Plantar injection of CFA was used in hot and dampness environment to induce the pyretic arthralgia rat models. From 15th day after modeling, Baihu Guizhi decoction was given for 30 days. Foot volume was detected every 4 days after modeling, and HE staining was used to detect the histopathology of all rats' ankle joint at day 45.MeDIP-Seq sequencing method was used to detect the methylation level of knee joint synovial, and the method of difference sets was used to screen the characteristic methylation genesinpyretic arthralgia models.The contents of IL-1β, IL-17, TNF-α, EGF, IL-12p70, IL-4, IL-6 and IFN-γ in serum were measured by using suspension chips. The mRNA expression level of characteristic methylation genes was measured by qRT-PCR. The results suggested that as compared with adjuvant arthritis rat models(AA), the foot swelling and histopathology inpyretic arthralgia models (PA) were only slightly increased. As compared with normal group (NG), the wholegenome CpG island in both AA and PA groups was kept in a lower methylation state, furthermore, the methylation level was lowest in PA group; with 705 difference methylation genes in AA group and 2 418 difference methylation genes in PA group. As compared with AA, there were 1 287 difference methylation genes, including 974 down-regulated methylation genesand 313 up-regulated methylation genes. This difference methylation genes were mostly enriched in 32 KEGG pathways. Moreover, there were 52 characteristic methylation genes of PA models in promoter region, including 36 down-regulatedmethylation genes and 16 up-regulatedmethylation genes. After drug intervention, Baihu Guizhi decoction improved the foot swelling and pathological injury in PA models, significantly decreased the levels of IL-1β, TNF-α, EGF, VEGF, IL-17, IL-12p70, inhibited the mRNA expression levels of down-regulated methylation genes AHCY and RPL3, and promoted the mRNA expression levels of up-regulated methylation gene Agxt. In conclusion, unique methylation changes of synovial genes were present in PA models, and Baihu Guizhi decoction may adjust the methylation level of PA's characteristic methylation genes to achieve the therapeutic effect of pyretic arthralgia.

Changium smyrnioides is an endangered and endemic medicinal herb in China which contains rich furanocoumarins. Bergaptol, bergapten and xanthotoxin are natural furanocoumarins in Ch. smyrnioides, among which bergaptol is mainly contained in in vitro cultures while the latter ones distribute in all organs and cultures of the plant. In this study, methyl jasmonate was used to elicit furanocoumarins in both cultivated plant and suspension cells. The accumulations of biomass and 3 furanocoumarins as well as the activity of cell, phenylalanine ammonia-lyase and antioxidase were detected. The results showed that methyl jasmonate induced the biosynthesis of furanocoumarins markedly and suspension cells from petiole produced more furanocoumarins than those from leaf. In the case of suspension cells, the concentration at 100 μmol•L⁻¹ triggered the highest yield of furanocoumarins and the 10th day of the culture period was the proper time for treatment. After 4 days the yields of bergaptol, bergapten and xanthotoxin in suspension cells from petiole were enhanced to 2.83,14.04,0.62 mg•L⁻¹ respectively. The biomass and viability of treated suspension cells decreased. At the same time, the activity of antioxidase increased, which indicated that methyl jasmonate induced cell defense. In both in vivo and in vitro conditions, cells from petiole seemed to be more sensitive to methyl jasmonate treatment compared to those from leaf. Bergaptol and xanthotoxin mainly accumulated in medium and cell respectively. Bergapten was detected in both cell and medium. The elicitation treatment only enormously affected the yields but did not significantly involve the distributions of 3 furanocoumarins. This is the first systematic study focusing on the elicitation effects of methyl jasmonate and a series of changes which lead to the increase of furanocoumarins in Ch. smyrnioides cell suspension cultures. Methyl jasmonate appears to be an effective elicitor in the research and further efforts should be made to reveal the mechanism in detail.

OBJECTIVETo observe the effects of recombinant fusion protein interleukin (IL)-18 on the expression of immune-inflammatory factors in the mice infected with Staphylococcus aureus (SA), and to investigate the mechanism of action of IL-18 in defense of SA infection in vivo.

METHODSA total of 40 specific pathogen-free female BLAB/c mice were randomly divided into four groups: control, SA infection, immunized, and intervention. A mouse model of SA infection was established by nasal inoculation with SA liquid. The immunized group and the intervention group were intranasally given IL-18 before SA modeling, and then the SA infection group and the intervention group received the nasal inoculation with SA liquid; the control group was treated with phosphate buffered saline instead. The levels of IL-4, interferon (IFN)-γ, tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), IgM in the serum and bronchoalveolar lavage fluid (BALF) of mice were measured by enzyme-linked immunosorbent assay. The expression of macrophage inflammatory protein (MIP)-1α mRNA and MIP-2β mRNA in the lung tissue of mice were determined by real-time fluorescent quantitative PCR.

RESULTSCompared with the control group, the SA infection group and the immunized group had significantly higher levels of IL-4, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA and MIP-2β mRNA in the lung tissue (P<0.05); the SA infection group had a significantly lower level of IFN-γ and a significantly higher level of TNF in the serum and BALF (P<0.05); the immunized group had a significantly higher level of IFN-γ in the serum and BALF (P<0.05). Compared with the SA infection group, the intervention group had significantly higher levels of IL-4, IFN-γ, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA in the lung tissue. In contrast, the intervention group showed a significantly lower level of TNF in the serum and BALF and expression of MIP-2β mRNA in the lung tissue (P<0.05). All the above indicators in the intervention group were significantly higher than those in the control group (P<0.05), except the serum level of IFN-γ.

CONCLUSIONSIn the mice infected with SA, the recombinant fusion protein IL-18 by mucosal immunity can affect inflammatory factors in the serum and BALF and the expression of MIP-1α mRNA and MIP-2β mRNA in the lung tissue to promote the anti-infective immune response and enhance the ability to clear pathogens.

Animals ; Chemokine CCL3 ; analysis ; Female ; Granulocyte Colony-Stimulating Factor ; blood ; Interferon-gamma ; blood ; Interleukin-18 ; therapeutic use ; Interleukin-4 ; blood ; Mice ; Mice, Inbred BALB C ; Recombinant Fusion Proteins ; pharmacology ; therapeutic use ; Staphylococcal Infections ; drug therapy ; immunology

OBJECTIVETo investigate the fat emulsion tolerance in preterm infants of different gestational ages in the early stage after birth.

METHODSA total of 98 preterm infants were enrolled and divided into extremely preterm infant group (n=17), early preterm infant group (n=48), and moderate-to-late preterm infant group (n=33). According to the dose of fat emulsion, they were further divided into low- and high-dose subgroups. The umbilical cord blood and dried blood filter papers within 3 days after birth were collected. Tandem mass spectrometry was used to measure the content of short-, medium-, and long-chain acylcarnitines.

RESULTSThe extremely preterm infant and early preterm infant groups had a significantly lower content of long-chain acylcarnitines in the umbilical cord blood and dried blood filter papers within 3 days after birth than the moderate-to-late preterm infant group (P<0.05), and the content was positively correlated with gestational age (P<0.01). On the second day after birth, the low-dose fat emulsion subgroup had a significantly higher content of short-, medium-, and long-chain acylcarnitines than the high-dose fat emulsion subgroup among the extremely preterm infants (P<0.05). In the early preterm infant and moderate-to-late preterm infant groups, there were no significant differences in the content of short-, medium-, and long-chain acylcarnitines between the low- and high-dose fat emulsion subgroups within 3 days after birth.

CONCLUSIONSCompared with moderate-to-late preterm infants, extremely preterm infants and early preterm infants have a lower capacity to metabolize long-chain fatty acids within 3 days after birth. Early preterm infants and moderate-to-late preterm infants may tolerate high-dose fat emulsion in the early stage after birth, but extremely preterm infants may have an insufficient capacity to metabolize high-dose fat emulsion.

Carnitine ; analogs & derivatives ; blood ; Fat Emulsions, Intravenous ; analysis ; metabolism ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; metabolism

Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity. The expression levels of global immune-related genes were determined by comparing undifferentiated and differentiated stem cells and three types of human somatic cells: dermal papilla cells, ovarian granulosa cells and foreskin fibroblast cells. We identified the differentially expressed genes CD24, GATA3, PROM1, THBS2, LY96, IFIT3, CXCR4, IL1R1, FGFR3, IDO1 and KDR, which overlapped with selected immune-related gene lists. In further analyses, mammalian target of rapamycin complex (mTOR) signaling was investigated in the differentiated stem cells following treatment with rapamycin and lentiviral transduction with specific short-hairpin RNAs. We found that the inhibition of mTOR signal pathways significantly downregulated the immunogenicity of differentiated stem cells. We also tested the immune responses induced in differentiated stem cells by mixed lymphocyte reactions. We found that CD24- and GATA3-deficient differentiated stem cells including neural lineage cells had limited abilities to activate human lymphocytes. By analyzing the transcriptome signature of immune-related genes, we observed a tendency of the hPSCs to differentiate toward an immune cell phenotype. Taken together, these data identify candidate immune-related genes that might constitute valuable targets for clinical applications.
Embryonic Stem Cells ; Female ; Fibroblasts ; Foreskin ; Granulosa Cells ; Humans* ; Induced Pluripotent Stem Cells ; Lymphocyte Culture Test, Mixed ; Lymphocytes* ; Major Histocompatibility Complex ; Phenotype ; Pluripotent Stem Cells* ; RNA ; Signal Transduction ; Sirolimus ; Stem Cells ; Transcriptome

Rheumatoid arthritis (RA) is a most common inflammatory joint disease with direct invasion of joint synovial membrane, cartilage and bone. Currently, although the RA mitigation drugs are being improved continously, but these drugs only can delay the development of joint dysfunction. Total hip arthroplasty or total knee arthroplasty(THA or TKA) has become the only choices for patients with advanced RA, and the joint function and deformity of the patients after surgical treatment can be improved to some extent. However, the progression of RA has a direct effect on the long-term clinical effect of the surgery, and how to improve perioperative management, and combine the joint replacement surgery and drug therapy effectively, have become the focus of attention in clinical doctors. This article intends to summarize the current situation of domestic and foreign management of usage of pre-operative drugs, operation skills, prosthesis selection, postoperative treatment, rehabilitation and complications, so as to improve the long-term efficacy of joint replacement.