OBJECTIVE: To investigate the effects and mechanisms of equol and its enantiomers on urethane-induced lung cancer in mice. METHODS: A total of 120 5-week-old male C57BL/6 mice were randomly divided into 8 groups: lung cancer tumor control group (CG), genistein control group (GCG), low dose racemic equol group (LEG), high dose racemic equol group (HEG), low dose R-equol group (LRE), high dose R-equol group (HRE), low dose S-equol group (LSE) and high dose S-equol group (HSE). Urethane was injected subcutaneously twice a week for 4 weeks to induce lung cancer and then the mice were fed for 4 months. The body weight and food intake of each group were measured and recorded weekly. After the mice were sacrificed, the blood, livers and lungs of the mice were collected. The incidence of lung cancer in each group was recorded. The concentration of serum superoxide dismutase (SOD), malondialdehyde (MDA) and 8-hydroxydeoxygunosine (8-OHdG) were detected by the corresponding kits. Western blotting was used to detect the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the livers. Between-group differences in body weight and food intake of the mice were compared using repeated measures ANOVA, and ANOVA for the differences between non-repeated measurements, with post hoc analysis using Tukey's method if there were between-group differences. Comparisons of categorical data were performed by chi-square test, and if there were differences between the groups, the Bonferroni method was used for pairwise comparison. RESULTS: A total of 49 in the 120 mice developed lung cancer. The overall incidence of lung cancer was 40.8%. Compared with the control group, the incidence of lung cancers in each experimental group was lower, and the difference was statistically significant. The incidence of lung cancer in the high-dose experimental group was significantly lower than that in the low-dose experimental group. However, the incidence of lung cancer was similar in the three equol groups and the genistein group at the same dose. Compared with the control group, the high-dose experimental group had higher serum SOD concentration, lower MDA and 8-OHdG concentrations, and the differences were statistically significant. Western blotting analysis showed that the expression levels of Nrf2 protein in the experimental groups were higher than those in the control group except the low-dose racemic equol group, and the Nrf2 protein expression level in the high-dose equol groups was higher than that in the low-dose equol groups. CONCLUSION Racemic equol and its enantiomers mayinhibit lung carcinogenesis through antioxidant effects.
Animals ; Body Weight ; Equol ; Genistein ; Lung Neoplasms/prevention & control* ; Male ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2 ; Superoxide Dismutase ; Urethane/toxicity*

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System

OBJECTIVE: To summarize and compare the clinical baseline characteristics of patients with monoclonal gammopathy of undetermined significance (MGUS), primary light chain amyloidosis (pAL), multiple myeloma (MM), or MM with concurrent amyloidosis, especially the differences in cytogenetic abnormalities. METHODS: The clinical data of 15 cases of MGUS, 34 cases of pAL, 842 cases of MM and 23 cases of MM with concurrent amyloidosis were analyzed and compared retrospectively. RESULTS: Cytogenetic statistics showed that the incidence of t (11; 14) in the four groups (MGUS vs pAL vs MM vs MM with concurrent amyloidosis) was 0%, 33.3%, 16.4%, and 15.8%, respectively (P=0.037); that of 13q deletion was 20.0%, 14.7%, 45.8% and 56.5%, respectively (P<0.001); gain of 1q21 was 50.0%, 12.5%, 47.4% and 40.9%, respectively (P=0.001). Proportion of pAL patients with 0, 1 and≥2 cytogenetic abnormalities (including 13q deletion, 17p deletion, 1q21 amplification and IgH translocation) accounted for 41.9%, 41.9% and 16.1%, respectively; while the proportion of the same category in MM was 17.6%, 27.3%, and 55.2% respectively; this ratio of MM with concurrent amyloidosis was more similar to MM. Subgroup analysis showed that genetic abnormalities (including 13q deletion, 17p deletion and 1q21 amplification) were comparable within t (11; 14) negative and positive groups. Compared with positive cases, t(11; 14) negative patients with MM or MGUS were more likely to have 13q deletions and multiple genetic abnormalities. CONCLUSION Clinical characteristics of pAL, especially cytogenetic abnormalities, are significantly different from MM with concurrent amyloidosis. It suggests that although the onset characteristics are similar, actually the two diseases belong to different disease subtypes which should be carefully predicted and identified.
Amyloidosis ; Humans ; In Situ Hybridization, Fluorescence ; Monoclonal Gammopathy of Undetermined Significance/complications* ; Multiple Myeloma ; Retrospective Studies

The pathogenesis of metabolic syndrome （MS） includes insulin resistance （IR）， central obesity， chronic low-grade inflammation， oxidative stress， endoplasmic reticulum stress， elevated free fatty acid levels， intestinal flora imbalance， renin angiotensin system abnormality， and autophagy activity deficiency， etc. Most researchers believe that IR plays a central role in the pathogenesis of MS， and abdominal obesity is an important initial factor of MS. According to the incidence and clinical characteristics， MS is classified as "obesity" "pidan" " abdominal fullness " and other diseases. It is said that the pathogenesis of MS is related to the deficiency of spleen and kidney， the formation of phlegm， turbidity， blood stasis and other pathological products， which damage the body's functions of qi， blood， yin and yang. Traditional Chinese medicine （TCM） has unique advantages in treating MS based on the holistic view and syndrome differentiation concept. It has multi-level， multi-target and multi-channel treatment characteristics. It can intervene insulin signal transduction， regulate adipocyte factor secretion level， relieve oxidative stress and endoplasmic reticulum stress response， regulate intestinal flora and renin angiotensin system， reduce free fatty acid level and regulation Autophagy and other ways to improve chronic low-grade inflammation and IR status， and then comprehensive prevention and treatment of MS and its complications. However， the following problems still exist：lack of high-quality randomized controlled clinical research and large sample real-world research， clinical unified diagnosis and treatment standard has not yet formed， lack of genetic animal model in basic research， relatively single signal pathway and target of experimental research， and difficulty in timely formation of clinical transformation of scientific research achievements. Therefore， we should make full use of modern scientific and technological means to carry out systematic and standardized multicenter， large sample， high-quality randomized controlled trials or real-world research， we should prepare perfect animal models， focus on the crosstalk relationship between multiple related cell signaling pathways， and actively explore the potential relationship between signaling pathways and prescription compatibility， so as to actively promote basic scientific research achievements Clinical practice may be the key research direction in the prevention and treatment of MS in TCM.

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).
Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B e Antigens ; immunology ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Male ; Medicine, Chinese Traditional ; Organophosphonates ; therapeutic use ; Young Adult

BACKGROUNDAlthough previous reports had reported the use of temporary internal distraction as an aid to correct severe scoliosis, two-stage surgery strategy (less invasive internal distraction followed by posterior correction and instrumentation) has never been reported in the treatment of patients with severe spinal deformity. This study aimed to report the results of the surgical treatment of severe scoliosis and kyphoscoliosis by two-stage and analyse the safety and efficacy of this surgical strategy in the treatment of severe spinal deformities.

METHODSA total of 15 patients with severe scoliosis, kyphoscoliosis or kyphosis who underwent two-stage surgeries (less invasive internal distraction followed by posterior correction and instrumentation) were studied based on hospital records. Pretreatment radiographs and radiographs taken after first surgery (internal distraction by two small incisions), before second surgery (posterior correction, instrumentation and fusion), one week after second surgery and final follow-up were measured. Subjects were analyzed by age, gender, major coronal curve magnitude, flexibility of major curve, major sagittal curve magnitude before first surgery, after first surgery, before second surgery, after second surgery and at final follow-up. Complications related to two-stage surgeries were noted in each case.

RESULTSThe average major curve magnitude was 129.4° (range, 95° to 175°), reduced 58.9° or 45.4% after first stage surgery and reduced 30.6° or 24.6% after second stage surgery. The loss of correction during the interval between two surgeries was 7.1%. The total major coronal curve correction was 81.4° or 62.9%. At the final follow up, the average loss of correction of major coronal curve was 3.9° and the final average correction rate was 59.7%. The average major sagittal curve magnitude was 80.3° (range, 30° to 170°), and the total major sagittal curve correction was 48.2°. Loss of correction averaged 4.0° for major sagittal curve and the final correction averaged 42.2°. Clinical complications were noted in the peri-operative and long-term periods.

CONCLUSIONSTwo-stage surgery was a safe and effective surgical strategy in this difficult population. Using two-small-incision technique, the first stage surgery was less invasive. No permanent neurologic deficit was noted in this series.

Adolescent ; Child ; Female ; Humans ; Kyphosis ; diagnostic imaging ; surgery ; Male ; Radiography ; Scoliosis ; diagnostic imaging ; surgery ; Treatment Outcome

To explore the reasonable procedures and strategies of diagnosis and treatment of congenital neutropenia (CN), clinical data and laboratory examination results of a boy suspected of CN were collected; gene ELA2, GFI1, HAX1, and WASp of whom were sequenced, granulocyte colony-stimulating factor receptor (G-CSFR) expression on neutrophil was analyzed, and cytoplasmic domain of G-CSFR was sequenced. The results showed that the diagnosis of non-syndromic variants of CN (NSVCN) was made on this patient according to the criteria; sequencing results revealed no mutation occurred in ELA2, GFI1, HAX1 and WASp; a normal expression level of G-CSFR on neutrophil from this patient was detected and no truncated mutation was found in the intracellular domain of G-CSFR. It is concluded that reasonable procedure of diagnosis and treatment of CN is established, and a sporadic NSVCN with no recognized pathogenic mutation is confirmed in this patient.
Child ; DNA Mutational Analysis ; Humans ; Male ; Neutropenia ; congenital ; diagnosis ; genetics ; therapy ; Receptors, Granulocyte Colony-Stimulating Factor ; metabolism

OBJECTIVEMannan-binding lectin (MBL) is a C-type serum lectin that plays a central role in the innate immune response. At present there is no a reference range of serum MBL levels for children in China. This study investigated serum MBL levels in preschool children from Shenzhen.

METHODSA total of 118 children (62 boys and 56 girls) at ages of 3-6 years and sampled randomly from three kindergartens of Shenzhen were enrolled in this study. Serum MBL concentrations were determined using enzyme-linked immunosorbent assay.

RESULTSThe mean serum MBL concentration in these children was 779.07+/-268.98 ng/mL. There were no significant differences in the value of serum MBL between boys and girls (783.89+/-252.30 ng/mL vs 773.65+/-288.29 ng/mL) (P>0.05). Sixteen children (13.6%) had MBL concentrations less than 500 ng/mL (the low limited value used abroad), including 14 cases with 50-500 ng/mL and 2 cases with less than 50 ng/mL.

CONCLUSIONSThis study provides a reference range of serum MBL concentration for preschool children. MBL may be a useful marker for the prevention of infection in children.

Child ; Child, Preschool ; Female ; Humans ; Immunity, Innate ; Male ; Mannose-Binding Lectin ; blood

Objecfive To establish a method for in vitro culture and identification of neural stem cells(NSCs)derived from the olfactory bulb(OB)of adult mice and test the possibility of the OB as a new source of seed cells of adult NSCs. Methads NSCs were isolated from the OB of adult mice and cultured in serum-free medium.Clonal culture and BrdU incorporation assay were performed to assess the self-renewal and proliferative activities of the NSCs.Fluorescence immunocytochemistry was carried out to examine the expression of the NSC markers nestin and SOX2,neuronal marker Tujl,astrocyte marker GFAP and oligodendroeyte marker 04. Results NSCs possessing self-renewal and proliferative capacities were obtained from the OB of adult mice,and the cells grew in the form of floating neurospheres in the medium.The neurospheres consisted of cells were positive for NSC markers nestin and SOX2,which Were able to differentiate into Tuj1-positive neurons,GFAP-positive astrocytes and 04-positive oligodendrocytes. Conclusion NSCs are present in the OB of adult mice,and the NSCs isolated from the OB can proliferate and differentiate in vitro with obvious stem cell properties.suggesting the feasibility of using OB as anew source of adult NSCs.

OBJECTIVETo transfect pcDNA3.1/hTM plasmids containing human thrombomodulin (hTM) gene into human umbilical vein endothelial cells (HUVECs), and investigate the expression of hTM and anticoagulating function of transfected HUVECs.

METHODSHUVECs were transfected with pcDNA3.1/hTM by lipofectin. Expression of hTM mRNA was determined by semi-quantitative RT-PCR, hTM antigen on HUVECs membrane by immunohistochemistry, and activated protein C (PC) in HUVECs by chronometry. By using a semiautomatic coagulator, the effect of the reacting liquid from transfected HUVECs mixed with PC from normal peripheral blood was assayed.

RESULTSAbout 10% HUVECs were transfected by pcDNA3.1/hTM with high-level hTM mRNA and protein expression. Activated PC produced by pcDNA3.1/hTM group, pcDNA3.1(+)/neo group and untransfected group was (2.80 +/- 0.43) microg/ml, (0.75 +/- 0.08) microg/ml and (0.85 +/- 0.11) microg/ml, respectively. APTT was (51.68 +/- 2.73) s, (38.38 +/- 2.44) s, (39.65 +/- 2.39) s, (33.93 +/- 1.73) s and (34.60 +/- 1.86) s and PT was (21.89 +/- 1.66) s, (20.56 +/- 1.74) s, (20.42 +/- 2.04) s, (19.57 +/- 1.36) s and (20.16 +/- 1.35) s in pcDNA3.1/hTM group, pcDNA3.1(+)/neo group, untransfected group, inactivating PC group and control, respectively.

CONCLUSIONSThe pcDNA3.1/hTM plasmid could be transfected into endothelial cells and expressed biologically functioning hTM protein on HUVECs membrane. Activated PC could inhibit intrinsic coagulation pathway obviously with slight effect on extrinsic pathway.

Cells, Cultured ; Endothelial Cells ; metabolism ; Endothelium, Vascular ; cytology ; Gene Expression Regulation ; Genes, Transgenic, Suicide ; Humans ; In Vitro Techniques ; Partial Thromboplastin Time ; Plasmids ; Protein C ; Prothrombin Time ; Thrombomodulin ; genetics ; Transfection ; Umbilical Veins ; cytology