Health-related quality-of-life among patients with premature ovarian insufficiency: a systematic review and meta-analysis.

PURPOSE: To systematically review studies investigating health-related quality-of-life (HrQoL) in patients with premature ovarian insufficiency (POI), to examine questionnaires used and to conduct a meta-analysis of control studies with normal ovarian function. METHODS: Data sources: PubMed, Embase, Web of science, CNKI, and CQVIP, searched from inception until June 2018. The search strategy was a combination of medical (e.g. POI), subjective (e.g. well-being) and methodological (e.g. questionnaires) keywords. PRISMA guidelines were used to assess outcome data quality/validity by one reviewer, verified by a second reviewer. Risk of bias within studies was evaluated. A meta-analysis compared HrQoL in patients and non-patients. Due to measurement differences in the studies, the effect size was calculated as standard mean difference. RESULTS: We identified 6869 HrQoL studies. Nineteen geographically diverse studies met inclusion criteria, dated from 2006, using 23 questionnaires. The meta-analysis included six studies with 645 POI participants (age 33.3 ± 5.47) and 492 normal-ovarian control subjects (age 32.87 ± 5.61). Medium effect sizes were found for lower overall HrQoL (pooled SMD = - 0.73, 95% CI - 0.94, - 0.51; I2 = 54%) and physical function (pooled SMD = - 0.54, 95% CI - 0.69, - 0.39; I2 = 55%). Heterogeneity was investigated. Effect sizes varied for sexual function depending on the measure (SMD = - 0.27 to - 0.74), overall HrQoL (SF-36) had the largest effect size (- 0.93) in one study. The effect sizes for psychological and social HrQoL were small. CONCLUSION: POI is associated with low-to-medium effect size on HrQoL compared to normal ovarian controls. The greatest effects are found in general HrQoL and most sexual function areas. Condition-specific questionnaires and RCTs are recommended for further investigation.

[Feasibility and value of index of microcirculatory resistance in patients with acute myocardial infarction after primary percutaneous coronary intervention].

Objective: To evaluate the feasibility of detecting index of microcirculatory resistance (IMR) and the relationship between IMR and left ventricular (LV) systolic function after acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The patients with first AMI received primary PCI in Peking University Third Hospital were enrolled from January 2014 to March 2016. IMR were measured immediately after PCI by using pressure/temperature wire. The relationship between IMR and left ventricular ejection fraction (LVEF) assessed by echocardiography at first day and 6 months after admission was evaluated. Results: Twenty-eight patients with anterior wall AMI were enrolled, with an average age (56±13) years. The success rate of IMR detection was 100%. The mean IMR was (33±18 )mmHg·s. There was no complication related to intravenous adenosine triphosphate (ATP) (140 µg· kg(-1)· min(-1)). The IMR was negatively correlated with TIMI blood flow grade after primary PCI (r=-0.386, P=0.043), and positively correlated with female gender, CK peak value and TnT peak value (r=0.430, P=0.022; r=0.431, P=0.025; r=0.434, P=0.024). After 6 months of follow-up, no adverse cardiovascular events (including cardiac death, nonfatal myocardial infarction, malignant arrhythmia, unplanned revascularization, hospitalization for unstable angina pectoris and severe heart failure requiring hospitalization) occurred. LVEF increased significantly compared with the first day after PCI (0.54±0.08 vs 0.47±0.06, P=0.001), and IMR was negatively correlated with LVEF after 6 months (r=-0.477, P=0.014). Multivariable linear regression analysis showed that CK peak and IMR were predictors of LVEF after six months ( ß=-0.595, t=-3.814, P=0.01; ß=-0.352, t=-2.26, P=0.036). Conclusions: Immediate detection of IMR in patients with anterior wall AMI after PCI is safe and feasible. The immediate IMR after PCI reflects the extent of myocardial necrosis and myocardial perfusion, and is a predictor of LVEF at 6 months after PCI.

[Application value of corneal hysteresis in diagnosis and treatment of glaucoma].

Glaucoma is the first leading cause of irreversible blindness world widely, but the pathogenesis was still unclear. The collagen fibers from cornea and sclera connect to each other and both of them have similar extracellular matrix components. The biomechanical characteristics of optic nerve lamina cribrosa may associated with the biomechanical properties of the cornea. Therefore, the study of corneal physiological can indirectly reflex the compression and damage in optic nerve lamina cribrosa. The technical developments in corneal hysteresis examination had been updated these years constantly. Many researches implicated that low corneal hysteresis involved in pathogenesis and progression of glaucoma which refresh our recognition of the relationship between cornea and glaucoma. This review summarized the characteristics of corneal hysteresis, the examination and the connection with glaucoma to provide the reference for clinical work. (Chin J Ophthalmol, 2017, 53: 140-143).

729G/C polymorphism in Toll-like receptor 4 results in increased susceptibility to bladder cancer.

In this study, the association between the 729G/C polymorphism in Toll-like receptor 4 (TLR4) and the risk of bladder cancer was investigated. A total of 376 patients with bladder cancer and 380 healthy volunteers from the Third Xiangya Hospital of Central South University (China) were enrolled in this study between January 2008 and February 2014. The TLR4-729G/C polymorphism was detected by the polymerase chain reaction-restriction fragment length polymorphism assay. There was a significant difference in the distribution of the TLR4-729G/C genotype between bladder cancer patients and healthy controls (P < 0.001). Our analysis showed that the GC genotype (OR = 2.99; 95%CI = 1.01-4.81, P = 0.046) and CC genotype (OR = 3.67; 95%CI = 2.11-7.27, P = 0.017) were significantly associated with increased bladder cancer risk when the GG genotype served as a reference. Furthermore, carriers of the C allele had a significantly increased risk of developing bladder cancer (OR = 3.89; 95%CI = 2.88-8.53; P = 0.009). Our results suggest a correlation between the TLR4-729G/C polymorphism and the risk of developing bladder cancer in this Chinese population.

A double-blind comparative study of Chinese herbal medicine Jinlianqingre Effervescent Tablets in combination with conventional therapy for the treatment of uncomplicated hand, foot, and mouth disease.

Chinese herbal medicine Jinlianqingre Effervescent Tablets (JET) are the recommended control measure for uncomplicated hand, foot, and mouth disease (HFMD) by the Ministry of Health of China. However, high-quality evidence to support this recommendation is limited. A total of 288 patients ranging in age from 1 to 13 years were randomly assigned to JET in combination with conventional therapy (mainly including the reduction of temperature by applying physical cooling paste or warm bathing), or conventional therapy with placebo group for 7 days. The objective was to test the hypothesis that JET combination therapy is more effective than conventional therapy for uncomplicated HFMD. A randomized, double-blind, placebo-controlled trial was designed. Our study showed that, compared with conventional therapy, the median time to fever resolution was significantly shorter in the JET combination therapy (8 vs. 80 h; p < 0.0001); the risk of fever resolution increased in the JET combination therapy [hazard ratio, 19.8; 95% confidence interval (CI), 12.8 to 30.7]; the median healing time of rash or oral ulcer was significantly shorter in the JET combination therapy (14 vs. 74 h; p < 0.0001); and the median symptom score for skin or oral mucosa lesions improved more rapidly in the JET combination therapy during the follow-up period. The median duration of hospital stay was 6 days in the JET combination therapy and 7 days in the conventional therapy (p < 0.0001). No significant adverse events and complications were found in both groups. The addition of JET to conventional therapy reduced fever clearance time, healing time of skin or oral mucosa lesions, and duration of hospital stay in children with uncomplicated HFMD.

Active screening and patient-placement and cohort-placement strategies to decrease carbapenem-resistant gram-negative bacilli colonization and infection in pediatric patients: A 5-year retrospective observational study in China.

Carbapenem-resistant gram-negative bacilli (CR-GNB) colonization screening was initiated across high-risk departments (PICU, NICU, neonatal wards, and hematology departments) in January 2017, and several CR-GNB cohort and patient-placement strategies were introduced throughout the hospital in January 2018. The colonization and infection rates decreased to varying degrees from 2017 to 2021.

The role of bacterial colonization of ventilator circuit in development of ventilator-associated pneumonia: a prospective observational cohort study.

OBJECTIVES: Ventilator-associated pneumonia (VAP) is a significant cause of prolonged hospital stay and increased mortality in mechanically ventilated children. Studies of the relationship between bacterial colonization of ventilator circuits (VCs) and VAP are lacking. This study aimed to investigate the role of bacterial colonization of VCs in the development of VAP, and to provide evidence for preventing VAP. METHODS: Mechanically ventilated patients admitted to the paediatric intensive care unit of a teaching hospital in China from October 2018 to November 2019 were enrolled. Specimens were collected from the VC and the patient's lower respiratory tract (LRT) for bacterial culture. Paired bacteria isolated from the VC and the patient's LRT, where colonization of the VC preceded that of the LRT, were evaluated for relatedness using pulsed field gel electrophoresis (PFGE). RESULTS: A total of 114 patients were included; the incidence rate of VAP was 28.1% (32/114). A total of 1368 samples were collected from VCs; 16% had positive bacterial culture. There was no significant difference in bacterial colonization of VCs between VAP and non-VAP. In 13 patients, the LRT and VC were concurrently colonized with the same bacteria, where colonization of the VC occurred before colonization of the patient's LRT. PFGE results demonstrated high correlation between bacteria from the LRT and VC in 11 patients. Among 114 mechanically ventilated children, VAP caused by bacteria from the VC occurred in six patients, accounting for 18.8% (6/32) of the overall VAP rate in this study. DISCUSSION: Bacterial colonization of the VC is a significant cause of VAP development in mechanically ventilated children. Preventive strategies for early identification and decontamination measures for contaminated VC may play a key role in preventing VAP.

[A multicentric study on clinical characteristics and antibiotic sensitivity in children with methicillin-resistant Staphylococcus aureus infection].

Objective: To investigate the clinical characteristics of pediatric methicillin-resistant Staphylococcus aureus (MRSA) infection and the antibiotic sensitivity of the isolates. Methods: The clinical data of children with MRSA infection and antibiotic sensitivity of the isolates from 11 children's hospitals in Infectious Diseases Surveillance of Paediatrics (ISPED) group of China between January 1, 2018 and December 31, 2018 were collected retrospectively. The children's general condition, high-risk factors, antimicrobial therapy and prognosis, differences in clinical disease and laboratory test results between different age groups, and differences of antibiotic sensitivity between community-acquired (CA)-MRSA and hospital-acquired (HA)-MRSA were analyzed. The t test and Wilcoxon rank sum test were used for statistical analysis of the quantitative data and Chi-square test were used for comparison of rates. Results: Among the 452 patients, 264 were males and 188 were females, aged from 2 days to 17 years. There were 233 cases (51.5%) in the ≤1 year old group, 79 cases (17.5%) in the>1-3 years old group, 29 cases (6.4%) in the >3-5 years old group, 65 cases (14.4%) in the >5-10 years old group, and 46 cases (10.2%) in the>10 years old group. The main distributions of onset seasons were 55 cases (12.2%) in December, 47 cases (10.4%) in February, 46 cases (10.2%) in November, 45 cases (10.0%) in January, 40 cases (8.8%) in March. There were 335 cases (74.1%) CA-MRSA and 117 (25.9%) cases HA-MRSA. Among all cases, 174 cases (38.5%) had basic diseases or long-term use of hormone and immunosuppressive drugs. During the period of hospitalization, 209 cases (46.2%) received medical interventions. There were 182 patients (40.3%) had used antibiotics (ß-lactams, glycopeptides, macrolides, carbapenems, oxazolones, sulfonamides etc) 3 months before admission. The most common clinical disease was pneumonia (203 cases), followed by skin soft-tissue infection (133 cases), sepsis (92 cases), deep tissue abscess (42 cases), osteomyelitis (40 cases), and septic arthritis (26 cases), suppurative meningitis (10 cases). The proportion of pneumonia in the ≤1 year old group was higher than the >1-3 years old group,>3-5 years old group,>5-10 years old group,>10 years old group (57.5% (134/233) vs. 30.4% (24/79), 31.0% (9/29), 38.5% (25/65), 23.9% (11/46), χ(2)=17.374, 7.293, 7.410, 17.373, all P<0.01) The proportion of skin and soft tissue infections caused by CA-MRSA infection was higher than HA-MRSA (33.4% (112/335) vs. 17.9% (21/117), χ(2)=10.010, P=0.002), and the proportion of pneumonia caused by HA-MRSA infection was higher than CA-MRSA (53.0% (62/117) vs. 42.1% (141/335), χ(2)=4.166, P=0.041). The first white blood cell count of the ≤1 year old group was higher than that children > 1 year old ((15±8)×10(9)/L vs. (13±7)×10(9)/L, t=2.697, P=0.007), while the C-reactive protein of the ≤1 year old group was lower than the 1-3 years old group,>5-10 years old group,>10 years old group (8.00 (0.04-194.00) vs.17.00 (0.50-316.00), 15.20 (0.23-312.00), 21.79(0.13-219.00) mg/L, Z=3.207, 2.044, 2.513, all P<0.05), there were no significant differences in procalcitonin (PCT) between different age groups (all P>0.05). After the treatment, 131 cases were cured, 278 cases were improved, 21 cases were not cured, 12 cases died, and 10 cases were abandoned. The 452 MRSA isolates were all sensitive to vancomycin (100.0%), linezolid (100.0%), 100.0% resistant to penicillin, highly resistant to erythromycin (85.0%, 375/441), clindamycin (67.7%, 294/434), less resistant to sulfonamides (5.9%, 23/391), levofloxacin (4.5%, 19/423), gentamicin (3.2%, 14/438), rifampicin (1.8%, 8/440), minocycline (1.1%, 1/91). The antimicrobial resistance rates were not significantly different between the CA-MRSA and HA-MRSA groups (all P>0.05). Conclusions: The infection of MRSA is mainly found in infants under 3 years old. The prevalent seasons are winter and spring, and MRSA is mainly acquired in the community. The main clinical diseases are pneumonia, skin soft-tissue infection and sepsis. No MRSA isolate is resistant to vancomycin, linezolid. MRSA isolates are generally sensitive to sulfonamides, levofloxacin, gentamicin, rifampicin, minocycline, and were highly resistant to erythromycin and clindamycin. To achieve better prognosis. clinicians should initiate anti-infective treatment for children with MRSA infection according to the clinical characteristics of patients and drug sensitivity of the isolates timely and effectively.

Characterization of Microbacterium sp. F10a and its role in polycyclic aromatic hydrocarbon removal in low-temperature soil.

A polycyclic aromatic hydrocarbon degrading bacterium isolated from oil-polluted soil was identified as Microbacterium sp. F10a based on 16S rDNA gene sequence analysis. Plant growth promoting characteristics of the strain, degradation rate of phenanthrene and pyrene, and cell surface hydrophobicity characteristics of the strain were further characterized. The strain was also evaluated for promoting the growth of wheat and phenanthrene and pyrene removal from soil artificially contaminated with a mixture of phenanthrene (200 mg.kg-1) and pyrene (150 mg.kg-1) in pot experiments. The strain had the plant growth promoting characteristics of producing indole acetic acid, siderophore, and 1-aminocyclopropane-1-carboxylate deaminase activity and solubilizing inorganic phosphate. The strain also has a cell surface hydrophobicity that could increase the aqueous polycyclic aromatic hydrocarbon solubility. High-performance liquid chromatographic analysis showed that the degradation rates of phenanthrene (50 mg.L-1) and pyrene (20 mg.L-1) were 98% and 65%, respectively, under 28 degrees C after 7 days. Inoculation with the strain was found to significantly increase (p < 0.05) the growth of wheat and phenanthrene and pyrene removal in the unplanted or planted soils in a low-temperature environment. There were no significant differences in culturable bacterial numbers between live bacterial inoculation and dead bacterial inoculation controls in the unplanted and planted soils. However, the numbers of polycyclic aromatic hydrocarbon degrading bacteria were significantly greater in the inoculated planted or unplanted soils compared with the dead bacterial inoculation controls.

SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival.

Sperm-associated antigen 5 (SPAG5) is involved in various biological processes. However, the roles of SPAG5 in bladder urothelial carcinoma (BUC) are unknown. This study showed that upregulation of SPAG5 was detected frequently in primary BUC tissues, and was associated with significantly worse survival among the 112 patients that underwent radical cystectomy (RC). Up and downregulating the expression of SPAG5 enhanced or inhibited, respectively, the proliferation of BUC cells in vitro and in vivo, and suppressed or enhanced, respectively, apoptosis in vitro and in vivo. Moreover, SPAG5 increased the resistance of BUC cells to chemotherapy-induced apoptosis. Mechanistic investigations showed that SPAG5 promotes proliferation and suppresses apoptosis in BUC at least partially via upregulating Wnt3 through activating the AKT/mTOR signaling pathway. The importance of the SPAG5/AKT-mTOR/Wnt3 axis identified in BUC cell models was confirmed via immunohistochemical analysis of a cohort of human BUC specimens that underwent RC. Collectively, our data suggested that in patients with BUC who underwent RC, high SPAG5 expression is associated with poor survival. In addition, targeting SPAG5 might represent a novel therapeutic strategy to improve the survival of patients with BUC.

Solute carrier family 12 member 5 promotes tumor invasion/metastasis of bladder urothelial carcinoma by enhancing NF-κB/MMP-7 signaling pathway.

Solute carrier family 12 member 5 (SLC12A5), an integral membrane KCl cotransporter, which maintains chloride homeostasis in neurons, is aberrantly expressed and involved in the tumorigenesis of certain cancers. However, the clinical significance and biological role of SLC12A5 in human bladder urothelial carcinoma (BUC) remains unclear. In this study, the expression of SLC12A5 was examined in clinical specimens of primary BUC and in BUC cell lines using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC). The prognostic value of SLC12A5 expression and its correlation with the clinicopathological features of patients with BUC were analyzed statistically. A series of in vitro and in vivo assays were performed to elucidate the effect of SLC12A5 in BUC and its underlying mechanisms. The present results showed that SLC12A5 expression was significantly increased in BUC tissues. SLC12A5 expression significantly correlated with the tumor node metastasis (TNM) stage. Kaplan-Meier survival curves showed that high SLC12A5 expression was associated with poor survival in patients with BUC. Multivariate analysis indicated that SLC12A5 expression was an independent prognostic marker for the survival of patients. Downregulation of SLC12A5 inhibited the migratory and invasive abilities of BUC cells in vitro, and knocking down SLC12A5 diminished BUC metastasis in vivo. Moreover, we identified that SLC12A5 promoted the migration and invasion of BUC by enhancing MMP-7 expression via NF-κB-dependent transcription. Taken together, our findings indicated that SLC12A5 might function as a tumor metastasis promoting factor in the development and progression of BUC by regulating the NF-κB/MMP-7 signaling pathway. Thus, SLC12A5 might be a prognostic marker as well as a therapeutic target for BUC.

Diagnostic and prognostic significance of E-cadherin and Ki-67 expression in non-small cell lung cancer patients.

OBJECTIVE: To elucidate the relationship between E-cadherin (E-cad) and Ki-67, and to determine their clinical significance in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 68 NSCLC paraffin embedded tissue specimens and tumor-adjacent normal tissue specimens were collected. The expression of E-cad and Ki-67 was examined by immunohistochemistry and the relationships between the expression of these two markers were evaluated. The clinicopathological features were correlated with the expression of E-cad and Ki-67 to check whether these proteins have any association and if exist an association whether E-cad and Ki-67 can be used in diagnosis and prognosis of NSCLSC. RESULTS: E-cad was expressed in all the normal tissues but Ki-67 expressed in only 5.8% of normal tissues. Ki-67 and E-cad expression were observed in 61.8% and 25% of NSCLC tissues respectively. Correlation analysis revealed an inverse association between the expression of E-cad and Ki-67 (r = 0.524, p = 0.000). The clinicopathological features such as tumor differentiation, TNM stage, lymph node metastasis and pleural invasion were all significantly associated with E-cad and Ki-67 expression (p < 0.05). CONCLUSIONS: E-cad and Ki-67 together play a key role in the development, invasion and metastasis of NSCLC and combined detection of them serve as a potential marker for clinical diagnosis in addition to exploiting them as a therapeutic target.

Effect of magnesium ion on human osteoblast activity.

Magnesium, a promising biodegradable metal, has been reported in several studies to increase bone formation. Although there is some information regarding the concentrations of magnesium ions that affect bone remodeling at a cellular level, little is known about the effect of magnesium ions on cell gap junctions. Therefore, this study aimed to systematically investigate the effects of different concentrations of magnesium on bone cells, and further evaluate its effect on gap junctions of osteoblasts. Cultures of normal human osteoblasts were treated with magnesium ions at concentrations of 1, 2 and 3 mM, for 24, 48 and 72 h. The effects of magnesium ions on viability and function of normal human osteoblasts and on gap junction intercellular communication (GJIC) in osteoblasts were investigated. Magnesium ions induced significant (P<0.05) increases in cell viability, alkaline phosphate activity and osteocalcin levels of human osteoblasts. These stimulatory actions were positively associated with the concentration of magnesium and the time of exposure. Furthermore, the GJIC of osteoblasts was significantly promoted by magnesium ions. In conclusion, this study demonstrated that magnesium ions induced the activity of osteoblasts by enhancing GJIC between cells, and influenced bone formation. These findings may contribute to a better understanding of the influence of magnesium on bone remodeling and to the advance of its application in clinical practice.

1,25-Dihydroxyvitamin D3 regulates expression of LRP1 and RAGE in vitro and in vivo, enhancing Aß1-40 brain-to-blood efflux and peripheral uptake transport.

Alzheimer's disease (AD) is characterized by the accumulation and deposition of plaques of amyloid-ß (Aß) peptide in the brain. Growing epidemiological and experimental studies have shown that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) exerts neuroprotection against AD. However, the underlying mechanisms of the action remain unclear. Since Aß clearance plays a crucial role in Aß balance in the brain, the aim of the present study was to investigate potential effects of 1,25(OH)2D3 on Aß1-40, the major soluble oligomeric form of Aß, clearance via transport across blood-brain barrier (BBB) mediated by low-density lipoprotein receptor-related protein 1 (LRP1) (efflux) and receptor for advanced glycation end products (RAGE) (influx) and peripheral uptake by liver mediated by LRP1. We identified colocalization of LRP1 and RAGE at BBB of mice, established an in vitro BBB model by culturing monolayer mouse brain microvascular endothelial cell line (bEnd.3) cells under hypoxia and observed that 1,25(OH)2D3 treatment enhanced Aß1-40 efflux across the BBB model and uptake by HepG2 cells. After 1,25(OH)2D3 exposure, LRP1 expression was increased significantly both in vivo and in vitro, and RAGE expression was reduced in the in vitro BBB model but not in microvascular endothelial cells of mice hippocampus. Additionally, we explored the correlation between the corresponding effects of 1,25(OH)2D3 and its nuclear hormone receptor vitamin D receptor (VDR) level. We found that VDR expression was upregulated after 1,25(OH)2D3 treatment both in vivo and in vitro. Collectively, our finding that 1,25(OH)2D3 reduces cerebral Aß1-40 level by increasing Aß1-40 brain-to-blood efflux and peripheral uptake through regulating LRP1 and RAGE could shed light on the mechanism of 1,25(OH)2D3 neuroprotection against AD. And the action of 1,25(OH)2D3 might be associated with the VDR pathway.

Relationship between CD4+CD25+ Treg and expression of HIF-1α and Ki-67 in NSCLC patients.

OBJECTIVE: To investigate the relationship between the CD4+CD25+ Treg cell proportion in the peripheral blood and the clinicopathologic features of non-small cell lung cancer (NSCLC) patients and hypoxia-inducible factor-1α (HIF-1α), Ki-67 expression. PATIENTS AND METHODS: Flow cytometry was used to measure the CD4+CD25+ Treg cell level in peripheral blood and immunohistochemical staining used to detect the expression of HIF-1α and Ki-67 protein in cancer tissue of each of 50 NSCLC patients. RESULTS: The level of CD4+CD25+ Treg cell in peripheral blood was related to pathologic grades (t = 3.265, p = 0.006) and clinical stage (t = 4.417, p = 0. 001) of NSCLC instead of to patient's gender and pathologic type of tumor (p > 0.05). The level of CD4+CD25+ Treg cell was positively correlated with the expression of HIF-1α (r = 0.711, p = 0.003) and Ki-67 (r = 0.517, p = 0.04), respectively. CONCLUSIONS: CD4+CD25+ Treg cell can be used as a predictor of immune status and prognosis of NSCLC patients and the levels of HIF-1α and Ki-67 protein expression may relate to inhibition of immune cells.

Genotoxicity of complex PAH mixtures recovered from contaminated lake sediments as assessed by three different methods.

Although human exposure generally occurs to mixtures of chemicals, limited toxicological information is available to characterize the potential interactions of the components of environmental mixtures. This study was conducted to compare the genotoxicity of chemically characterized polycyclic aromatic hydrocarbon (PAH) mixtures using in vitro and in vivo techniques. A total of three extracts (E1-E3) were selected from sediment samples collected from a lake adjacent to an abandoned coal gasification site. Sediments were collected on a grid moving downstream and away from the most likely source of PAH contamination, with E1 collected closest to the shore, E2 at an intermediate distance, and E3 furthest from the shore. The sediment samples were extracted in methylene chloride and methanol, dried, and redissolved in an appropriate solvent for evaluation in a battery of genotoxicity assays. Samples were evaluated for their ability to produce point mutations in bacteria and DNA adducts in vitro without metabolic activation or in vivo. Samples were also analyzed using GC/MS. Sample E1 had both the highest concentration of benzo(a)pyrene (BP) (46.5 ppm) and carcinogenic PAHs and, using 32P-postlabeling, induced the highest adduct levels overall in vitro and in vivo. Sample E2, which had a BP concentration of 14 ppm, induced the greatest number of revertants in the bacterial mutagenicity assay. Sample E3, which had the lowest level of carcinogenic PAHs and BP, induced the lowest adduct levels. However, E3 was capable of inducing a positive genotoxic response in bacteria (with S9), although the slope of the response at lower doses was less than that of E2. The in vivo data showed that the major adduct formed by E1 and E2 was a BP adduct. This information could not have been obtained with the Salmonella or in vitro postlabeling tests. Among internal organs, the extracts of all three samples induced the greatest adduct levels in the lung, similarly to previous complex PAH mixtures studied. These data demonstrate the limitations of predicting genotoxic or carcinogenic potential based on chemical analysis or a single biological test. The results suggest that mixture interactions, cytotoxicity and metabolism are likely to have an influence on the potential of a complex mixture of chemicals to produce a carcinogenic effect. In addition, the concentration of genotoxic PAHs and both in vitro and in vivo DNA adduct formations were decreased with increasing distance from the shoreline.

Effects of hemin on erythropoiesis.

It is clear that in vitro hemin increases the number of blood BFU-E derived colonies from normal donors. This occurs with sickle donors as well, despite the increased levels of hemin in vivo in these patients. The effect of hemin on relative gamma globin synthesis is inconsistent, however. In a few cases, delayed addition of hemin led to increased gamma globin synthesis. In time course studies of cultures from normal donors, hemin added on day 0 shifted the day of peak colony number from 13-14 to 16-20 days. The temporal decline in gamma globin synthesis was not altered. In cultures from sickle donors we found that the time for maximal colony number was later than in normals, occurring at 16-20 days even without hemin, and was not further delayed by hemin. The relative proportion of gamma globin synthesis was higher on day 14 in the sickle than the normal cultures, and the temporal decline was somewhat slowed in the sickle cultures by hemin. The elevated gamma synthesis and the later time for peak colony growth in the sickle cultures suggest that the erythroid progenitors in the blood of the sickle patients are less mature than those from normal individuals. There are several possible explanations for the detection of increased numbers of colonies in cultures containing hemin. Hemin may delay the final maturation of erythroblasts within erythroid colonies, thus shifting the time of maximal growth. It may also increase the extent of final maturation, leading to more complete hemoglobinization of the erythroblasts within the colonies, and thus increasing the number of colonies that are eventually recognized as erythroid.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethnopharmacologic investigation on tropane-containing drugs in Chinese solanaceous plants.

The role of tropane-containing drugs derived from Solanaceae has long been recognized. This report deals with Chinese solanaceous plants, including historic, botanical, phytochemical, pharmacological and clinical aspects. Our investigation revealed that this kind of drug is constantly being confirmed to be of true therapeutic value; however, further studies are in order.

[HPTLC separation and fluorodensitometric determination of isoquinoline alkaloids in Chelidonine majus L].

The quantitative analysis of isoquinoline alkaloids in Chelidonine majus L. was investigated and a HPTLC method has been established. Using this method, we separated and determined eight isoquinoline alkaloids, i.e. chelidonine, protopine, berberine, coptisine, tetrahydrocoptisine, 6-methoxydihydrochelerythrine, 6-methoxydihydrosanguinarine and dihydrosanguinarine. The HPTLC method developed used one developing system on high performance silica gel plate (10 x 10 cm). After separation of these eight alkaloids, fluorescence derivatization was carried out in situ. The content was determined by fluorescence scanning. TLC fluorescence derivatization, fluorescence enhancement and fluorescence stability have been studied. Experiments showed that this method is simple, fast, highly sensitive and highly selective.