Low calf circumference is associated with frailty in diabetic adults aged over 80 years.

BACKGROUND: Frailty is now seen as a significant factor in older people with diabetes, whose mortality and disability increased. This study aims to investigate the association between calf circumference (CC) with frailty in diabetic adults aged over 80 years. METHODS: A cross-sectional analysis was performed on the data of 426 diabetic adults aged over 80 years. On admission, demographic data and laboratory parameters were recorded. CC was measured on the lower right leg at the point of the maximal circumference. All participants accepted frailty assessments. Frailty was mainly defined using the Fried frailty phenotype criteria. RESULTS: The CC levels were significantly lower in the frail than the non-frail (26.7 ± 4.0 vs. 31.2 ± 4.0, P < 0.001). CC was negatively correlated with the Fried frailty phenotype index (P < 0.001). Logistic regression analysis of frailty revealed that age (Odds Ratio (OR), 1.368; 95% Confidential Interval (CI) 1.002-1.869; P = 0.049), CC (OR, 0.756; 95%CI 0.598-0.956; P = 0.019) were independent impact factors of frailty after adjusting all the potential confounders. Participants with low CC tertile had a significantly higher Fried frailty phenotype index than those with high CC tertiles. The best CC cut-off value for predicting frailty was 29.3 cm, its sensitivity was 75.0%, and the specificity was 78.6%, and areas under the curve (AUC) was 0.786 (P < 0.001). CONCLUSIONS: CC was strongly related to frailty in diabetic adults aged over 80 years, suggesting that CC may be helpful for monitoring physical frailty in older adults in clinical and research settings.

Traditional Chinese medicine pharmacovigilance in signal detection: decision tree-based data classification.

BACKGROUND: Traditional Chinese Medicine (TCM) is a style of traditional medicine informed by modern medicine but built on a foundation of more than 2500 years of Chinese medical practice. According to statistics, TCM accounts for approximately 14% of total adverse drug reaction (ADR) spontaneous reporting data in China. Because of the complexity of the components in TCM formula, which makes it essentially different from Western medicine, it is critical to determine whether ADR reports of TCM should be analyzed independently. METHODS: Reports in the Chinese spontaneous reporting database between 2010 and 2011 were selected. The dataset was processed and divided into the total sample (all data) and the subsample (including TCM data only). Four different ADR signal detection methods-PRR, ROR, MHRA and IC- currently widely used in China, were applied for signal detection on the two samples. By comparison of experimental results, three of them-PRR, MHRA and IC-were chosen to do the experiment. We designed several indicators for performance evaluation such as R (recall ratio), P (precision ratio), and D (discrepancy ratio) based on the reference database and then constructed a decision tree for data classification based on such indicators. RESULTS: For PRR: R1-R2 = 0.72%, P1-P2 = 0.16% and D = 0.92%; For MHRA: R1-R2 = 0.97%, P1-P2 = 0.20% and D = 1.18%; For IC: R1-R2 = 1.44%, P2-P1 = 4.06% and D = 4.72%. The threshold of R,Pand Dis set as 2%, 2% and 3% respectively. Based on the decision tree, the results are "separation" for PRR, MHRA and IC. CONCLUSIONS: In order to improve the efficiency and accuracy of signal detection, we suggest that TCM data should be separated from the total sample when conducting analyses.

Early amplitude-integrated EEG monitoring 6 h after birth predicts long-term neurodevelopment of asphyxiated late preterm infants.

UNLABELLED: The present study aimed to assess the prognostic value of early amplitude-integrated electroencephalogram (aEEG) in late preterm infants who were born at a gestational age between 34 0/7 and 36 6/7 weeks for the prediction of neurobehavioral development. Late preterm infants (n = 170) with normal, mild, and severe asphyxia underwent continuous recording of aEEG for 4-6 h starting 6-8 h after delivery. The recordings were analyzed for background pattern, sleep-wake cycle (SWC), and seizures. Survivors were assessed at 18 months by neurological examination and Bayley Scales of Infant Development II. The incidence of adverse neurological outcome in the asphyxia group was significantly higher than in the normal group. For late preterm infants in the asphyxia group, abnormal aEEG pattern had a predictive potential of neurological outcomes with sensitivity of 78.57% (specificity, 87.80%; positive predictive value [PPV], 68.75%; negative predictive value [NPV], 92.31%; power, 85.45%). Non-SWC and intermediate SWC significantly were increased (25.45 and 52.73%, respectively) in the asphyxia group vs. the normal group. SWC pattern had neurological prognosis value in the asphyxia group with sensitivity of 64.29% (specificity, 87.80%; PPV, 64.29%; NPV, 87.80%; power, 81.82%). CONCLUSION: Early aEEG patterns are important determinants of long-term prognosis of neurodevelopmental outcome in asphyxiated late preterm infants.

Insufficient TRPM5 Mediates Lipotoxicity-induced Pancreatic ß-cell Dysfunction.

OBJECTIVE: While the reduction of transient receptor potential channel subfamily M member 5 (TRPM5) has been reported in islet cells from type 2 diabetic (T2D) mouse models, its role in lipotoxicity-induced pancreatic ß-cell dysfunction remains unclear. This study aims to study its role. METHODS: Pancreas slices were prepared from mice subjected to a high-fat-diet (HFD) at different time points, and TRPM5 expression in the pancreatic ß cells was examined using immunofluorescence staining. Glucose-stimulated insulin secretion (GSIS) defects caused by lipotoxicity were mimicked by saturated fatty acid palmitate (Palm). Primary mouse islets and mouse insulinoma MIN6 cells were treated with Palm, and the TRPM5 expression was detected using qRT-PCR and Western blotting. Palm-induced GSIS defects were measured following siRNA-based Trpm5 knockdown. The detrimental effects of Palm on primary mouse islets were also assessed after overexpressing Trpm5 via an adenovirus-derived Trpm5 (Ad-Trpm5). RESULTS: HFD feeding decreased the mRNA levels and protein expression of TRPM5 in mouse pancreatic islets. Palm reduced TRPM5 protein expression in a time- and dose-dependent manner in MIN6 cells. Palm also inhibited TRPM5 expression in primary mouse islets. Knockdown of Trpm5 inhibited insulin secretion upon high glucose stimulation but had little effect on insulin biosynthesis. Overexpression of Trpm5 reversed Palm-induced GSIS defects and the production of functional maturation molecules unique to ß cells. CONCLUSION: Our findings suggest that lipotoxicity inhibits TRPM5 expression in pancreatic ß cells both in vivo and in vitro and, in turn, drives ß-cell dysfunction.

Proteomics for early prenatal screening of gestational diabetes mellitus.

In this editorial, we comment on the article by Cao et al. Through applying isobaric tags for relative and absolute quantification technology coupled with liquid chromatography-tandem mass spectrometry, the researchers observed significant differential expression of 47 proteins when comparing serum samples from pregnant women with gestational diabetes mellitus (GDM) to the healthy ones. GDM symptoms may involve abnormalities in inflammatory response, complement system, coagulation cascade activation, and lipid metabolism. Retinol binding protein 4 and angiopoietin like 8 are potential early indicators of GDM. GDM stands out as one of the most prevalent metabolic complications during pregnancy and is linked to severe maternal and fetal outcomes like pre-eclampsia and stillbirth. Nevertheless, none of the biomarkers discovered so far have demonstrated effectiveness in predicting GDM. Our topic was designed to foster insights into advances in the application of proteomics for early prenatal screening of GDM.

Re-evaluating the necessity of routine laboratory monitoring during isotretinoin therapy for acne.

In this letter, we discuss the topic of necessity of routine laboratory monitoring during isotretinoin treatment for acne. According to Park and colleagues, it is advisable to monitor the levels of triglycerides, alanine aminotransferase, and aspartate aminotransferase every 5 to 6 months. Additionally, the levels of total cholesterol and low-density lipoprotein should be checked within the first two months of treatment. Isotretinoin is a commonly prescribed agent mainly used to treat acne. Despite its high effectiveness, it necessitates regular monitoring of laboratory parameters due to its side effect profile. Currently, there remains a lack of consensus on the appropriate frequency for monitoring these parameters during treatment with isotretinoin. This letter will provide insight into this complex and controversial topic. Based on existing literature, we concluded that the incidence of changes in lipid and liver aminotransferase levels during isotretinoin treatment for acne was low and likely clinically insignificant. For generally healthy people, we recommend testing lipid and liver profiles once at baseline and a second time at the peak dosage. However, frequent testing might still be beneficial in certain populations of patients.

[Inhibitory effect of silencing of HMGB1 gene expression on the invasive and metastatic abilities of MGC-803 gastric cancer cells].

OBJECTIVE: To investigate the effect of high mobility group box-1 (high mobility group box B 1, HMGB1) on the invasive and metastatic abilities of gastric cancer cell line MGC-803 and analyze the possible mechanisms. METHODS: HMGB1 gene targeting siRNA was designed and synthesized, and HMGB1 siRNA oligonucleotides were transfected into the MGC-803 cells with Lipofectamine 2000. The invasive and migratory abilities were detected by transwell assay and scratch assay. The Matrigel matrix glue adhesive ability of MGC-803 cells was evaluated by MTT assay. NF-κB activity was detected by electrophoretic mobility shift assay. The mRNA and protein levels of HMGB1 and MMP-9 were determined by RT-PCR and Western blot, respectively. RESULTS: The siRNA down-regulated the levels of HMGB1 mRNA and protein. Compared with that of the control group, the number of invasive (142.7 ± 3.4 /view vs. 303.5 ± 4.3/view) and migratory (293.7 ± 4.4/view vs. 445.5 ± 5.6/view) cells was significantly increased (P < 0.05) and the adhesive ability of MGC-803 cells to Matrigel was significantly elevated (33.4 ± 0.03% vs. 57.4 ± 4.2%, P < 0.05). In addition, silencing of HMGB1 gene significantly inhibited the activity of NF-κB and the relative expression folds of mRNA (0.2 ± 0.1 vs. 1.4 ± 0.4, P < 0.05)and protein (0.4 ± 0.1 vs. 2.3 ± 0.7, P < 0.05) of MMP-9. CONCLUSION: Silencing of HMGB1 can effectively inhibit the invasion and migration of gastric cancer cells and this effect of HMGB1 may be partly due to its regulation of NF-κB and MMP-9 expressions.

Metabolic disorders increase the risk to incident cardiovascular disease in middle-aged and elderly Chinese.

OBJECTIVE: The association of metabolic syndrome (MetS) with cardiovascular diseases (CVD) has not been adequately explored in middle-aged and elderly Chinese. This study aimed to investigate MetS' prevalence and its impact on the CVD incidence in this specific population group. METHODS: A data set of a community-based prospective cohort study was analyzed. A total of 2300 subjects aged 40-94 years were followed up for the CVD events. MetS defined according to the JCDCG criteria was assessed at baseline, and the middle-aged and elderly groups were classified by the WHO definition. RESULTS: As compared with the middle-aged group, the prevalence of MetS increased by 0.6 times (34.6% vs. 21.3%) and the incidence density of CVD increased by 4.9 times in the elderly group (52.3/1000 person-year vs. 8.9/1000 person-year). Furthermore, the multivariate Cox regression revealed that the risk to CVD incidence was independently related to increased waist circumference in the middle-aged group (HR=2.23, P<0.01) and to elevated blood glucose in the elderly group (HR=1.39, P<0.01). CONCLUSION: MetS was highly prevalent in middle-aged and elderly Chinese. MetS significantly increased the risk to CVD incidence in the elderly. All individuals with metabolic disorders should receive active clinical care to reduce the incidence of CVD.

Adverse pregnancy outcomes and mother-to-child transmission in patients with hepatitis B virus infection and intrahepatic cholestasis of pregnancy.

OBJECTIVES: The aim of this study was to investigate adverse pregnancy outcomes (APOs) and mother-to-child transmission (MTCT) of intrahepatic cholestasis in pregnancy (ICP) in hepatitis B virus infection (HBV) patients. MATERIAL AND METHODS: We performed a retrospective study at Beijing Youan Hospital in China from January 2010 through May 2017. A total of 232 patients were enrolled, including 106 HBV-infected ICP patients (Group H + C), 20 ICP patients (Group C) and 106 HBV-infected patients (Group H). Characteristics, APOs and MTCT rate of HBV were compared between groups. Group H + C was subdivided into 3 groups according to total bile acid (TBA) values and gestational age at diagnosis (GA). APOs were also compared within Group H + C according to TBA values and GA. RESULTS: There was no difference in live birth delivery mode and APOs between Groups H + C and C. Compared with Groups H, no difference was in live birth and MTCT rates of HBV. However, cesarean section delivery and APOs rates were higher in Group H+C (p < 0.05). Compared with Group H, adverse maternal outcomes such as postpartum hemorrhage and premature birth were more likely to occur in Group H + C (p < 0.001). Adverse fetal outcomes, the proportions of amniotic fluid reaching III degrees (AFIII), NICU admission, neonatal asphyxia and SGA were significantly higher among Group H + C than Group H (p < 0.05). Contamination of the AFIII rate increased with increasing TBA (p < 0.05). The rate of preterm birth and small for gestational age (SGA) was more common in GA 28-32 w compared with GA < 28 w and > 33 w (p < 0.01). CONCLUSIONS: H + C patients had more APOs than HBV patients, but the difference was not significant when compared with ICP patients. Although we did not find any difference in MTCT rate between H + C and HBV patients, active treatment to prevent neonatal asphyxia and HBV infection should be considered. Therefore, it is necessary to emphasize maternal and fetal monitoring during pregnancy and delivery.

Which Is Safer, Chinese Medicine or Western Medicine? Comparative Analysis Based on Chinese Spontaneous Reporting Database.

OBJECTIVE: To compare the safety differences between Chinese medicine (CM) and Western medicine (WM) based on Chinese Spontaneous Reporting Database (CSRD). METHODS: Reports of adverse events (AEs) caused by CM and WM in the CSRD between 2010 and 2011 were selected. The following assessment indicators were constructed: the proportion of serious AEs (PSE), the average number of AEs (ANA), and the coverage rate of AEs (CRA). Further comparisons were also conducted, including the drugs with the most reported serious AEs, the AEs with the biggest report number, and the 5 serious AEs of interest (including death, anaphylactic shock, coma, dyspnea and abnormal liver function). RESULTS: The PSE, ANA and CRA of WM were 1.09, 8.23 and 2.35 times higher than those of CM, respectively. The top 10 drugs with the most serious AEs were mainly injections for CM and antibiotics for WM. The AEs with the most reports were rash, pruritus, nausea, dizziness and vomiting for both CM and WM. The proportions of CM and WM in anaphylactic shock and coma were similar. For abnormal liver function and death, the proportions of WM were 5.47 and 3.00 times higher than those of CM, respectively. CONCLUSION: Based on CSRD, CM was safer than WM at the average level from the perspective of adverse drug reactions.

Non-alcoholic fatty liver disease's prevalence and impact on alanine aminotransferase associated with metabolic syndrome in the Chinese.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is becoming a major public health hazard in China. The present study aimed to estimate the prevalence of NAFLD, NAFLD with abnormal serum alanine aminotransferase (ALT) levels, and determine the potential associations of ALT levels with the components of metabolic syndrome (MetS) in the absence or presence of NAFLD in Chinese adults. METHODS: A population-based cross-sectional survey was conducted with 2226 participants. Physical examinations, laboratory tests and hepatic ultrasounds were performed. Individuals were further stratified into higher or lower ALT subgroups with the upper quartiles of ALT in this population. The MetS was identified according to the criteria of the Chinese Joint Committee for Developing Chinese Guidelines (JCDCG). RESULTS: The standardized prevalence of NAFLD was 23.3% (NAFLD with abnormal ALT levels, 3.1%), 26.5% (NAFLD with abnormal ALT levels, 5.1%) in males, and 19.7% (NAFLD with abnormal ALT levels, 0.9%) in females. Multivariate logistic analysis revealed that higher ALT was significantly associated with elevated triglyceride (TG) in the non-NAFLD participants, independent of age, smoking status, drinking status, and other MetS-related measures with odds ratios (95% confidence intervals) of 3.4 (1.6-7.1) and 2.3 (1.4-3.7) in males and females, respectively. On the other hand, the higher ALT was statistically associated with elevated TG and hyperglycemia in the NAFLD cases with odds ratios of 2.2 to 2.5 (P<0.05). CONCLUSIONS: The prevalence of NAFLD has become epidemic in Shanghai adults. NAFLD combined with ALT levels may be used to identify the individuals at the different risk levels of metabolic disorders.

Protocol for in vivo and ex vivo assessments of glucose-stimulated insulin secretion in mouse islet ß cells.

Pancreatic islet ß cells secrete insulin in a biphasic manner when sensing high blood glucose level. This protocol describes the evaluation of different phases of insulin secretion, as well as basal, glucose-stimulated and total insulin secretion abilities, thereby enabling precise assessment of ß cell function both in vivo and ex vivo. The in vivo assay consists of intravenous tube imbedding surgery and hyperglycemic clamp. The ex vivo assay consists of islet isolation, dynamic perfusion and static immersion. For complete details on the use and execution of this protocol, please refer to Sun et al. (2021).

Comparison of the efficacy of Nutritional Risk Screening 2002 and Mini Nutritional Assessment Short Form in recognizing sarcopenia and predicting its mortality.

OBJECTIVE: This study aimed to examine the efficacy of Nutritional Risk Screening 2002 (NRS2002) and Mini Nutritional Assessment Short Form (MNA-SF) in recognizing sarcopenia and predicting its mortality in Chinese geriatric hospitalized patients. METHODS: A prospective analysis was performed in 430 hospitalized geriatric patients. Nutrition status was assessed using the NRS2002 and MNA-SF scales. Anthropometric measures and biochemical parameters were carried out for each patient. Sarcopenia was defined according to the revised consensus definition of the European Working Group on Sarcopenia in Older People (EWGSOP2). Patients were follow-up for up to 26 months. RESULTS: The overall prevalence of sarcopenia was 35.3% in this population. In the sarcopenic patients, 53 (34.9%) were malnutrition/nutritional risk according to NRS2002 assessment and 101 (66.4%) patients were malnutrition/nutritional risk according to MNA-SF assessment. NRS2002 vs MNA-SF showed moderate agreement (κ = 0.460, P < 0.001). Receiver operating characteristic analysis showed that the area under the curve of MNA-SF was larger than NRS2002 in recognizing sarcopenia (0.763 vs 0.649, P = 0.001). During a median follow-up time of 20.22 months, 48 (31.6%) sarcopenic patients died. The Kaplan-Meier curve demonstrated that malnutrition/nutritional risk patients according to whether NRS2002 or MNA-SF assessment had a higher risk of death than the normal nutrition patients (χ2 = 15.728, P < 0.001; χ2 = 7.039, P = 0.008, respectively). Age, serum albumin levels, and NRS2002 score were independent factors influencing the mortality. CONCLUSION: MNA-SF score may be better than the NRS2002 score to recognize sarcopenia in Chinese geriatric population. Both NRS2002 and MNA-SF scores could predict mortality, but NRS2002 score was the independent predict factor.

Comparison of the value of malnutrition and sarcopenia for predicting mortality in hospitalized old adults over 80 years.

OBJECTIVE: This study aimed to compare the prognostic value of malnutrition and sarcopenia for mortality in old adults over 80 years. METHODS: A prospective analysis was performed in 427 hospitalized old adults. Anthropometric measures and biochemical parameters were carried out for each patient. Sarcopenia was defined according to the revised consensus definition of the European Working Group on Sarcopenia in Older People (EWGSOP2). Malnutrition was defined according to the European Society of Clinical Nutrition and Metabolism (ESPEN) criteria. Mortality data were available for up to 32 months of follow-up. RESULTS: The overall prevalence of sarcopenia and malnutrition was 35.1% and 19.4%, respectively. The percentage of coexistence of sarcopenia and malnutrition was 12.2%. Of the 427 participants, 83 deaths were reported during the mean follow-up periods of 24.9 months. Compared with non-sarcopenic subjects with well-nutrition, sarcopenic subjects with well-nutrition and non-sarcopenic subjects with well-nutrition had higher mortality risk (Hazard Ratio (HR), 2.36; 95% confidence interval (CI), 1.31-4.24, P < 0.001; HR, 4.33; 95% CI, 2.12-8.85, P = 0.004; respectively). The patients who coexisted with sarcopenia and malnutrition had the highest risk of mortality (HR, 7.31; 95% CI, 4.21-12.69, P < 0.001). Both sarcopenia and malnutrition could predict mortality separately. Still, from the components of the Cox regression multivariate models, the malnutrition was one of the independent factors influencing the death, sarcopenia was not. CONCLUSION: When malnutrition and sarcopenia were compared together in a longitude cohort, malnutrition was an independent risk factor for mortality, while sarcopenia was not. The coexistence of malnutrition and sarcopenia showed a synergistically accumulated risk for death.

Ets1-Mediated Acetylation of FoxO1 Is Critical for Gluconeogenesis Regulation during Feed-Fast Cycles.

The homeostatic balance of hepatic glucose uptake and production is exquisitely controlled by hormonal signals during feed-fast cycles. FoxO1, a transcription factor that functions in the regulation of glucose homeostasis, undergoes posttranslational modifications, such as acetylation, in response to hormonal signals, yet the mechanism remains poorly elucidated. Through expression profiling of 324 co-factors of CBP, a well-known acetyl-transferase of FoxO1, we identify Ets1 as a modulator of FoxO1 acetylation that is highly associated with feed-fast cycles. Mechanistic assays suggest that Ets1 enhances FoxO1 acetylation through the formation of a complex with CBP, which further promotes FoxO1 nuclear exclusion and inhibits its binding to gluconeogenic promoters. Functional studies further reveal that Ets1 inhibits gluconeogenesis under physiological and diabetes statuses, while the hyperinsulinemic-euglycemic clamp assay suggests hepatocyte Ets1 knockout mice have enhanced hepatic glucose production. Our study identifies Ets1 as an enhancer of FoxO1 acetylation and a repressor of hepatic gluconeogenesis in response to hormonal signals.

Low Calf Circumference Predicts Nutritional Risks in Hospitalized Patients Aged More Than 80 Years.

OBJECTIVE: The aim of this study was to determine whether low calf circumference (CC) could predict nutritional risk and the cutoff values of CC for predicting nutritional risk in hospitalized patients aged ⪖ 80 years. METHODS: A total of 1,234 consecutive patients aged ⪖ 80 years were enrolled in this study. On admission, demographic data, CC, and laboratory parameters were obtained. Patients with Nutritional Risk Screening 2002 (NRS-2002) total score ⪖ 3 were considered as having nutritional risk. RESULTS: CC values were significantly lower in patients with nutritional risk compared to those in patients without nutritional risk [27.00 (24.50-31.00) vs. 31.00 (29.00-33.50], P < 0.001]. CC was negatively correlated with age and nutritional risk scores. Logistic regression analysis of nutritional risk revealed that body mass index, albumin level, hemoglobin level, cerebral infarction, neoplasms, and CC (OR, 0.897; 95% confidence interval, 0.856-0.941; P < 0.001) were independent impact factors of nutritional risk. Nutritional risk scores increased with a decrease in CC. In men, the best CC cutoff value for predicting nutritional risk according to the NRS-2002 was 29.75 cm. In women, the cutoff value was 28.25 cm. CONCLUSION: CC is a simple, noninvasive, and valid anthropometric measure to predict nutritional risk for hospitalized patients aged ⪖ 80 years.

Modulation Effect of Peroxisome Proliferator-Activated Receptor Agonists on Lipid Droplet Proteins in Liver.

Peroxisome proliferator-activated receptor (PPAR) agonists are used for treating hyperglycemia and type 2 diabetes. However, the mechanism of action of these agonists is still under investigation. The lipid droplet-associated proteins FSP27/CIDEC and LSDP5, regulated directly by PPARγ and PPARα, are associated with hepatic steatosis and insulin sensitivity. Here, we evaluated the expression levels of FSP27/CIDEC and LSDP5 and the regulation of these proteins by consumption of a high-fat diet (HFD) or administration of PPAR agonists. Mice with diet-induced obesity were treated with the PPARγ or PPARα agonist, pioglitazone or fenofibrate, respectively. Liver tissues from db/db diabetic mice and human were also collected. Interestingly, FSP27/CIEDC was expressed in mouse and human livers and was upregulated in obese C57BL/6J mice. Fenofibrate treatment decreased hepatic triglyceride (TG) content and FSP27/CIDEC protein expression in mice fed an HFD diet. In mice, LSDP5 was not detected, even in the context of insulin resistance or treatment with PPAR agonists. However, LSDP5 was highly expressed in humans, with elevated expression observed in the fatty liver. We concluded that fenofibrate greatly decreased hepatic TG content and FSP27/CIDEC protein expression in mice fed an HFD, suggesting a potential regulatory role for fenofibrate in the amelioration of hepatic steatosis.

[Influence of TLR2- and TLR4-activated Mesenchymal Stem Cells on Migration of Cord Blood CD34+ Cells].

OBJECTIVE: This study was aimed to investigate the possible effect of Toll-like receptors 2 (TLR2) and Toll-like receptors 4 (TLR4) on the migration function of umbilical cord blood (UCB) CD34+ hematopoietic stem/progenitor cells induced by bone marrow-derived mesenchymal stem cells (MSCs) and to explore the underlying mechanism. METHODS: The expression of TLR2 and TLR4 on MSC was detected with flow cytometry. After the MSC were pretreated with TLR2 agonist (PAM3CSK4) and/or TLR4 agonist (LPS), the supernatants were collected. The effect of the supernatants on the migration of CD34+ cells was evaluated with chemotaxis assays. Alterations of chemokine (SDF-1) secreted by MSC in the supernatants were assayed by ELISA. RESULTS: The expression levels of TLR2 and TLR4 were (31.5±4.6)% and (85.6±6.7)% respectively. Compared with the blank group, the migration ability of CD34+ cells increased significantly in control, LPS and/or PAM3CSK4 groups (P<0.01). Further study found that LPS and/or PAM3CSK4 enhanced the chemotactic ability of CD34+ cells (P<0.05), but the concentration of SDF-1 was not changed significantly in all of LPS and/or PAM3CSK4 groups (P>0.05) in comparison with the control group. CONCLUSION: TLR2 and TLR4 signalings may indirectly increase the migration of CD34+ hematopoietic stem/progenitor cells by modulating BM-MSC functions, which may not significantly correlate with the production of chemokine SDF-1 by MSCs.

[Influence of TLR2 and TLR4 agonists on migration of human bone marrow mesenchymal stem cells].

This study was aimed to investigate the influence of TLR2 and TLR4 agonists on the migration and adhesion activity of human bone marrow-derived mesenchymal stem cells (MSC) and to clarify the underlying mechanisms. The expression of TLR2 and TLR4 on MSC was detected by flow cytometry. The effects of TLR2 agonist (PAM3CSK4) and TLR2 agonist (LPS) on MSC migration and adhesion ability were evaluated with chemotaxis and adhesion test. The results indicated that expressive levels of TLR2 and TLR4 on surface of human bone marrow MSC were (24.5 ± 3.2)% and (91.3 ± 5.2)% respectively. Compared with the control group, the migration activity of MSC toward SDF-1 was decreased significantly in PAM3CSK4 group, while the adhesion activity of MSC was promoted by PAM3CSK4 exposure. However, both the migration activity toward SDF-1 and the adhesion activity of MSC were not changed significantly in LPS-treated group. Further, it was found that PAM3CSK4 did not affect the expressive level of CXCR4 on MSC, however, it could inhibit the spontaneous migration of MSC in dose dependent manner. It is concluded that activation of TLR2 can decrease the migration ability of MSC, which may associate with the decreased spontaneous migration ability and the increased adhesion activity of MSC.

[The clinical value of F-18 FDG PET/CT in patients with secondary hemophagocytic syndrome].

The aim of this study was to investigate the role of F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) in diagnosis and prognostic evaluation of secondary hemophagocytic syndrome (HPS). A total of 11 secondary HPS patients examined with 18F-FDG-PET/CT were retrospectively analyzed. The diagnostic value of F-18 FDG PET/CT for malignancy detection was assessed. The values of maximum standardized uptake value (SUV(max)) in spleen (SUVS(p)) and in bone marrow (SUVBM) were measured to analyze their relationship with various laboratorial parameters and clinical outcome of secondary HPS patients. The results showed that 4 out of the 11 patients had malignancies, the sensitivity, specificity and diagnostic accuracy of F-18 FDG PET/CT for malignancy detection were 100%, 66.7% and 75% respectively, the SUV(max) of spleen and bone marrow showed no significant correlation with laboratorial parameters, a maximum SUVS(p) of 3.10 and a maximum SUVBM of 3.47 were the optimal cutoffs for predicting patients' outcome, the increased uptake of F-18 FDG in the BM and spleen were significantly associated with shorter survival time according to univariate analysis. It is concluded that 18F-FDG PET/CT may especially play an important role in diagnosis and predicting outcome of secondary HPS for the small sample size.