[Percutaneous pedicle screw fixation combined expandable tubular retractor in the treatment of spinal metastases].

OBJECTIVE: To investigate the effectiveness of percutaneous pedicle screw fixation combined expandable tubular retractor in the treatment of patients with spinal metastases. METHODS: In the study, 12 patients of spinal metastases treated with percutaneous pedicle screw fixation combined expandable tubular retractor in our hospital were retrospectively reviewed between June 2017 and October 2019. Among the 12 patients, 9 were males and 3 were females; the median age was 62.5 years [(65.1±2.9) years]. The decompression segment of 7 patients was located at the lower thoracic spine (including 1 patient with incomplete paraplegia) and the decompression segment of 5 patients was located at the lumbar spine; Tomita score was 6.0±0.6. Perioperative data of the patients were reviewed. Visual analog scale (VAS score), Karnofsky score, and Eastern Cooperative Oncology Group (ECOG) score were compared before and after surgery. The patient's survival, adjuvant treatment, and internal fixation failure were observed in the follow-up period. RESULTS: All the 12 patients had a successful operation with percuta-neous pedicle screw fixation combined expandable tubular retractor. The average operative time, blood loss, and blood transfused of the patients were (247.0±14.6) min, (804.2±222.3) mL and (500.0±100.0) mL, respectively. The average amount of drainage was (240.8±79.3) mL. Drainage tubes were pulled out early postoperative [(3.2±0.3) d], allowing early mobilization. The patients discharged (7.8±0.8) d postoperative. All the patients were followed up for 6-30 months, and the average overall survival time was (13.6±2.4) months. During the follow-up period, 2 patients experienced screw displacement, the internal fixation was stable after conservative treatment and no revision surgery was performed. The VAS of the patients was 7.1±0.2 before surgery, which decreased to 2.3±0.1 and 2.8±0.4 at 3 and 6 months after surgery (P < 0.05). The Karnofsky score of the patients was 59.2±1.9 before surgery, which increased to 75.0±1.9 and 74.2±3.1 at 3 and 6 months after surgery (P < 0.05). The ECOG of the patients was 2.3±0.2 before surgery, which decreased to 1.7±0.1 and 1.7±0.2 at 3 and 6 months after surgery (P < 0.05). CONCLUSION: For selected patients with spinal metastases, minimally invasive surgical treatment of spinal metastases (percutaneous pedicle screw internal fixation combined with expandable tubular retractor) can effectively relieve the clinical symptoms and improve the quality of life, with satisfactory clinical outcome.

[Surgical treatment for perihilar cholangiocarcinoma:a single-center experience].

Objective: To investigate surgical strategies and the corresponding benefits for patients with perihilar cholangiocarcinoma(pCCA). Methods: A total of 81 patients with pCCA who underwent radical excision in the Department of Biliary and Pancreatic Surgery of Sun Yat-Sen Memorial Hospital between January 2014 and December 2021 were retrospectively collected.The cohort consisted of 50 male and 31 female patients,with an age of (62.5±11.5)years(range:26 to 83 years).Seventy-five cases were diagnosed with jaundice,60 of whom received preoperative biliary drainage,while 20 patients received portal vein embolization.Their serum bilirubin level within one week before the operation(M(IQR)) was 44.3 (41.9) µmol/L(range:8.0 to 344.2 µmol/L).Preoperative imaging examinations were performed to evaluate the Bismuth-Corlette type of pCCA,showing 3,6,21,27,and 24 cases of Bismuth-Corlette type Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ,respectively.The primary outcome was overall survival (OS),and the secondary outcomes were relapse-free survival (RFS),90-day postoperative morbidity and 90-day postoperative mortality.OS and RFS were estimated using the Kaplan-Meier method and compared by the Log-rank test.Significant prognostic factors were determined using univariate and multivariable Cox proportional hazard regression analyses. Results: In the cohort of 81 pCCA patients,67 cases(82.7%) underwent major hepatectomy while 3 cases received major hepatectomy combined with pancreaticoduodenectomy.Thirty-four patients underwent hepatectomy combined with vascular resection and reconstruction(18 cases of portal vein resection and reconstruction alone;9 cases of hepatic artery resection and reconstruction alone;7 cases of combination of portal vein and hepatic artery resection and reconstruction).Margin negative(R0 excision) were achieved in 53.1%(43/81) of these patients.The operation duration was (627±136)minutes(range:565 to 940 minutes),and the intraoperative blood loss was 400(455)ml(range:200 to 2 800 ml).The 90-day postoperative mortality was 3.7%(3/81).Grade 3-4 postoperative morbidity was 23.4% (19/81) according to the Clavien-Dindo classification of surgical complications.Up to the last follow-up at September 2022,the follow-up time was 34.0(24.2)months (range:0.4 to 103.6 months).Three patients who died within 90 days after surgery were excluded from the survival analysis.The median OS was 36.10 months (95%CI:18.23 to 42.97 months) and the 1-,3-and 5-year OS rates were 85.3%,46.8% and 27.3%,respectively.The median OS of 41 patients with negative margins was 47.83 months(95%CI:36.90 to 58.80 months) and that of 37 patients with positive margins was 20.47 months(95%CI:10.52 to 30.58 months).The median RFS of 70 patients with R0 and R1 resection was 24.50 months(95%CI:12.15 to 31.85 months)and the 1-,3-and 5-year RFS rates were 65.2%,45.7% and 29.9%,respectively.The median RFS of 41 patients with R0 resection was 38.57 months(95%CI:21.50 to 55.63 months) and that of 29 patients with R1 resection was 10.83 months(95%CI:2.82 to 19.86 months). Conclusions: The primary therapy for pCCA is radical surgical resection.A precise preoperative evaluation and sufficient preparation can reduce postoperative morbidity.Surgical treatment can achieve a better survival outcome by increasing the radical resection rate.

[Protective effect and mechanism of AKAP1 on myocardial injury induced by highland hypobaric hypoxia].

Objective: To investigate the protective effect and its possible mechanism of A-kinase anchored protein 1 (AKAP1) on the myocardial injury induced by highland hypobaric hypoxia. Methods: From January 2021 to May 2022, male C57BL/6 SPF grade mice were divided into wild type control (WT) group and highland hypobaric hypoxia (HH) group with 6 mice in each group. HH group simulated 6000 m altitude with low pressure oxygen chamber for 4 weeks to build the model. Primary myocardial cells of SD rats were divided into normoxia control group and hypoxia experimental group (n=3). Cell models were constructed in a three-gas hypoxia incubator with 1% oxygen concentration for 24 h. AKAP1 protein and mRNA expression in myocardial tissue and cells were detected by western blotting, immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). After myocardial point injection of the AKAP1 or the control adenovirus, the mice were divided into 3 groups (n=6) : WT group, highland hypobaric hypoxia overexpression control group (HH+Ad-Ctrl group) and highland hypobaric hypoxia overexpression experimental group (HH+Ad-AKAP1 group). The cardiac function of mice was detected by noninvasive M-type ultrasonic cardiomotive, myocardial fibrosis was detected by Masson and Sirius Red staining, and cardiomyocyte hypertrophy was detected by wheat germ agglutinin. After the expression of AKAP1 in primary cardiomyocytes was downregulated by siRNA and upregulated by adenovirus, the cells were divided into three groups (n=3) : normoxia control group, hypoxia interference control group (hypoxia+siCtrl group), hypoxia AKAP1 knockdown group (hypoxia+siAKAP1 group) ; normoxia control group, hypoxia overexpression control group (hypoxia+Ad-Ctrl group), hypoxia AKAP1 overexpression group (hypoxia+Ad-AKAP1 group). Apoptosis was detected by flow cytometry, AKAP1, apoptosis-related protein and mRNA expression levels were detected by western blotting and qPCR, mitochondrial membrane potential was detected by JC-1 staining, and mitochondrial reactive oxygen specie (ROS) level was detected by MitoSOX. Results: The expression of AKAP1 in cardiac muscle of HH group was lower than that in the WT group, and the expression of AKAP1 in hypoxia experimental group was lower than that in normoxia control group (P<0.01). Compared with WT group, the left ventricular ejection fraction and fraction shortening of left ventricle in HH+Ad-Ctrl group were decreased (P<0.01), myocardial fibrosis and hypertrophy were aggravated (P<0.01), and the expression of B-cell lymphoma-2 (BCL-2) was decreased, the expressions of BCL-2-associated X protein (BAX), Caspase 3 and Caspase 9 were increased (P<0.01). After AKAP1 overexpression, compared with HH+Ad-Ctrl group, the left ventricular ejection fraction and left ventricular fraction shortening were increased in HH+Ad-AKAP1 group (P<0.01), myocardial fibrosis and hypertrophy were reduced (P<0.01), and the expression of BCL-2 was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased (P<0.01). Compared with normoxia control group, the expression of BCL-2 in hypoxia+siCtrl group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased (P<0.01), the mitochondrial membrane potential was decreased and the production of ROS was increased (P<0.01). After AKAP1 knockdown, compared with hypoxia+siCtrl group, the expression of BCL-2 in hypoxia+siAKAP1 group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased (P<0.01), mitochondrial membrane potential was decreased, and the production of ROS was increased (P<0.01). After AKAP1 overexpression, compared with hypoxia+Ad-Ctrl group, the expression of BCL-2 in hypoxia+Ad-AKAP1 group was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased (P<0.05), the apoptosis level was decreased (P<0.01), and the mitochondrial membrane potential was enhanced, and the production of ROS was decreased (P<0.01) . Conclusion: The downregulation of AKAP1 in cardiomyocytes under highland hypobaric hypoxia may lead to the decrease of mitochondrial membrane potential and the increase of ROS generation, leading to the apoptosis of cardiomyocytes, and thus aggravating the myocardial injury at highland hypobaric hypoxia.

[Progress in study on intervention of silica-induced pulmonary fibrosis with the exosomes released from mesenchymal stem cells].

Pneumoconiosis is an occupational disease which seriously endangers the health of workers exposed to dust. Silica is regarded as the most serious cause of pneumoconiosis because it can cause diffuse pulmonary fibrosis in workers' lung tissue. Mesenchymal stem cells (MSCs) are adult stem cells with multiple differentiation potential. As member of extracellular vesicles family, exosomes can be secreted from MSCs to regulate and intervene tumorigenesis, cardiovascular disease, immune system disorder and tissue damage disease. This article reviews the experimental results in the field of intervention of MSCs and its exosomes in silicosis research in recent years, which plays an important role in indicating direction in the future research on the mechanism and function of MSCs exosomes in the therapy of silica-induced pulmonary fibrosis.

[Analysis of influencing factors for pathogen culture result in patients with pyogenic spondylitis].

OBJECTIVE: To investigate the effect of clinical factors on the pathogen culture results in the patients with pyogenic spondylitis, and to find out clinical controllable factors which could increase the positive rate of the pathogen culture. METHODS: A retrospective study reviewed 40 patients who were diagnosed with pyogenic spondylitis in Peking University First Hospital from January 2011 to July 2017. The patients were divided into two groups depending on the culture results, culture negative or culture positive. The influence of clinical uncontrollable factors [the patient's age, gender, predisposing factors, infection site except spine, visual analogue score (VAS), course of disease, spinal segment, white blood cell (WBC), (neutrophilic granulocyte)% (NE%), the incidence of systemic inflammatory response syndrome (SIRS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the incidence of paravertebral abscess] and controllable factors (prior antibiotics exposure within 2 weeks, tissue homogenate, surgical approach) on pathogen culture results were analyzed. RESULTS: Of the 40 patients, 18 patients were female and 22 patients were male. Causative germ was identified in 24/40 patients (60.00%) and dominant by gram positive cocci (68.00%). For clinical uncontrollable factors, there was no significant difference between the two groups in the patient's age, gender, predisposing factors, infection site except spine, VAS, course of disease, spinal segment, WBC, NE% and the incidence of SIRS. ESR [(94.38±6.91) mm/h, P=0.023)], CRP [(64.74±13.51) mg/L, P=0.040], and the incidence of paravertebral abscess (75%, P=0.018) in culture negative group were lower in contrast to culture positive group. For clinical controllable factors, prior antibiotics exposure within 2 weeks (P=0.058, OR=4.030, 95%CI: 0.956-16.993) and tissue homogenate (P=0.014, OR=0.171, 95%CI: 0.042-0.695) were significantly associated with the pathogen culture result. Surgical approach was not significantly associated with pathogen culture result. CONCLUSION: Patients with high level of ESR, CRP, and paravertebral abscess, would have high positive rate of pathogenic culture. Prior antibiotics exposure was associated with lower positive pathogen culture rate. Culture with tissue homogenate was more likely to find the causative germ, especially for patients without paravertebral abscess who had low level of ESR, CRP and prior antibiotics exposure.

[Perioperative clinical characteristics of patients with pathological fracture of proximal femur].

OBJECTIVE: To investigate the perioperative clinical characteristics of patients with pathological fracture of proximal femur. METHODS: A retrospective study reviewed 28 patients who received proximal resection and tumor hemiarthroplasty for malignant proximal femoral tumor in Peking University First Hospital from January 2011 to February 2017. According to the fracture, the patients were divided into two groups: pathological fracture group and non-pathological fracture group. We investigated the clinical characteristics during perioperative period between the two groups. RESULTS: Of the 28 patients, 14 (50.0%) patients suffered pathological fracture, and there was no significant difference between the two groups in the patient's age, gender, limb involvement, and tumor source (P>0.05). There was no significant difference between the two groups in hemoglobin (HGB), hematocrit (Hct), and lower extremity thrombosis. The albumin (ALB) of pathological fracture group were lower in contrast to non-pathological fracture group (P=0.031). There was no significant difference between the two groups in decline of HGB and Hct on postoperation day 1, operative time, bleeding during operation, time for walking with help of ambulation aid postoperative, and postoperative hospital stay (P>0.05). On post-operation day 7, HGB (P=0.025) and Hct (P=0.039) of pathological fracture group were significant lower in contrast to non-pathological fracture group. Whereas, the total blood loss calculated by Gross equation of pathological fracture group was significant higher in contrast to non-pathological fracture group [(2 066.3±419.8) mL vs. (786.0±152.6) mL, P=0.039]. The patient needed blood transfusion during operation (7/14 vs. 1/14, P=0.033) and postoperative (8/14 vs. 1/14, P=0.013) in pathological fracture group were more than in non-pathological fracture group. At last, Barthel daily life ability score (P=0.009) of pathological fracture group was lower in contrast to non-pathological fracture group, and visual analogue scale (VAS) score was higher (P<0.001). They were almost equal when the patients were discharged (P>0.05). CONCLUSION: Patients with pathological fracture had lower ALB during perioperative period. Pathological fracture had no effect on operative time, bleeding during operation and function outcomes. However, the patients with pathological fracture had more total blood loss and lower HGB, Hct in contrast to the patients without pathological fracture. Blood transfusion was more needed in pathological fracture patients.

miR-146a rs2910164 polymorphism might be associated with coronary artery disease risk in Asians.

Recently, several studies reported the association between miR-146a rs2910164 polymorphism and coronary artery disease (CAD) risk. However, the results were inconclusive. We therefore did a meta-analysis to investigate this association. Electronic databases, including PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) databases, were searched. The strength of association was assessed by calculating odds ratios (OR) and 95% confidence interval (CI). Five eligible studies included in this meta-analysis. The total sample size of this meta-analysis was 1565 cases and 1541 controls. We found that miR-146a rs2910164 polymorphism was significantly associated with an increased CAD risk (OR = 1.19; 95% CI 1.07 - 1.32; P = 0.002). In the subgroup analysis by race, miR-146a rs2910164 polymorphism was significantly associated with an increased CAD risk in Asians (OR = 1.18; 95% CI 1.04 - 1.33; P = 0.008). However, we did not find significant result in Caucasians (OR = 1.22; 95% CI 0.86 - 1.74; P = 0.25). In the subgroup analysis by age, we found that miR-146a rs2910164 polymorphism increased CAD risk in old population (OR = 1.22; 95% CI 1.09 - 1.38; P = 0.0008). In conclusion, this meta-analysis found that miR-146a rs2910164 polymorphism was significantly associated with CAD risk.

[Clinical characteristics and prognosis of cultured negative pyogenic spondylitis].

OBJECTIVE: There are limited data describing the clinical characteristics and prognosis of culture negative pyogenic spondylitis. The aim of this study was to investigate the treatment, prognosis and clinical characteristics of culture negative pyogenic spondylitis. METHODS: A retrospective study reviewed 74 patients who were diagnosed with spondylitis in Peking University First Hospital from January 2010 to December 2015. A total of 27 patients suffered from pyogenic spondylitis. According to the pathogenic culture results, the patients were divided into two groups: culture negative group and culture positive group. The clinical characteristics and treatment outcomes between the two groups were compared. RESULTS: The elder were more vulnerable to pyogenic spondylitis, and of the 27 patients, 12 patients were female and 15 male. All patients had no history of administration of antibiotics prior to obtaining culture samples. A causative germ was identified in 14/27 patients (51.9%) with Staphylococcus aureus being the most common pathogen. There was no significant difference between the two groups in the patient's age, gender, visual analogue score (VAS), predisposing factor, clinical symptom, sign and spinal segment (P>0.05). Erythrocyte sedimentation rate (ESR) (P=0.056) and C-reactive protein (CRP) (P=0.040) of culture negative group were lower in contrast to culture positive group. The incidence of vertebral abscess in culture negative group was higher than in culture positive group (P=0.046). After treatment, ESR dropped almost equally in both groups, and CRP dropped faster in the culture positive group (P=0.192). At last, there was no significant difference between the two groups in hospital stay, pain relief, open debridement operation rate, and recurrence rate of infection. CONCLUSION: ESR and CRP of the culture negative patient were lower than those of the culture positive patient, and the incidence rate of paravertebral abscess was higher than that of the culture positive patient. After administration of antibiotics, there was no significant difference between the two groups in duration of antibiotics, open debridement operation rate and recurrence rate of infection. So, culture negative may not necessarily be a negative prognostic factor for pyogenic spondylitis. However, we should watch out for the drug resistant bacteria or double infection, due to the long term use of wide-spectrum antibiotic in culture negative patients.

[Genetic characteristics and survival analysis of 27 cases of juvenile myelomonocytic leukemia].

Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ2=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ2=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ2=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.

A cascade of structure in a drop falling from a faucet.

A drop falling from a faucet is a common example of a mass fissioning into two or more pieces. The shape of the liquid in this situation has been investigated by both experiment and computer simulation. As the viscosity of the liquid is varied, the shape of the drop changes dramatically. Near the point of breakup, viscous drops develop long necks that then spawn a series of smaller necks with ever thinner diameters. Simulations indicate that this repeated formation of necks can proceed ad infinitum whenever a small but finite amount of noise is present in the experiment. In this situation, the dynamical singularity occurring when a drop fissions is characterized by a rough interface.

[LIG4 syndrome: a report of four cases and literature review].

Objective: To analyze clinical, immunological and genetic characteristics of 4 cases of LIG4 syndrome. Methods: We retrospectively analyzed the clinical data of 4 patients from 3 families with LIG4 syndrome who were admitted to Children's Hospital of the Capital Institute of Pediatrics from June 2017 to May 2018, and reviewed related articles, the clinical, immunological and genetic characteristics of LIG4 syndrome were summarized and analyzed. Results: Those 4 cases (P1 to P4), including 2 males and 2 females, had an average age of 1.5 years. All of them presented with special facial features, such as microcephaly, beak-like-nose, and receding forehead. Three of them presented with delayed physical development. P3 suffered from mental retardation and P4 had feeding difficulty. BCG scars were repeatedly ruptured in 3 cases, 4 cases had pneumonia, 1 case had EB virus infection, 2 cases had cytomegalovirus infection, 1 case had fungal infection, and 1 case had chronic diarrhea. Blood routine tests showed decreased neutrophil and lymphocyte counts. Immunoassay showed decreased absolute count of CD4(+)T lymphocyte and B lymphocyte, with normal CD8(+)T cells. P1, P2 presented with decreased immunoglobulin. All of those patients had LIG4 gene complex heterozygous mutations, of whom one had missense mutation had mild clinical phenotype and another three cases had frameshift mutation presented with severe clinical phenotype. One patient underwent hematopoietic stem cell transplantation, and has established normal immune function. He did not have recurrent infection during one year follow-up period. The other 3 patients had preventive anti-infection treatment and received regular human immunoglobulin infusion, but they still had recurrent infection. In literature review, 67 articles were retrieved, totally 37 case were reported, showing special faces and recurrent infection as characteristic presentation of this disease. Conclusions: The typical manifestations of LIG4 syndrome are microcephaly, special facial features and repeated infection. The average age at diagnosis of LIG4 syndrome was more than one year old. If a patient presented with microcephaly, BCG scar infection and leukopenia, LIG4 syndrome should be considered. Immunoglobulin is decreased at different degrees, and CD4(+) and CD19(+) lymphocyte counts always decrease, Naive T and B cells decrease more prominently, and CD8(+)T cells were normal in patients with typical LIG4 syndrome. It is effective to reconstruction of immune system with bone marrow transplantation in LIG4 syndrome patients.

Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells.

Adult hepatic progenitor cells (HPCs) are involved in a wide range of human liver diseases, including hepatocellular carcinoma (HCC). Bmi1 has been reported to have vital roles in stem cell self-renewal and carcinogenesis. We have previously demonstrated that Bmi1 is upregulated in HCC with bile duct tumor thrombi, a subtype of HCC characterized by profuse expression of hepatic stem cell markers. However, the function of Bmi1 in HPCs has not yet been well elucidated. The current study was designed to investigate the effects of Bmi1 on the biological properties of rat HPCs. To accomplish this, Bmi1 was silenced or enhanced in two HPC cell lines (WB-F344 and OC3) by, respectively, using either small interfering RNA against Bmi1 or a forced Bmi1 expression retroviral vector. The biological functions of Bmi1 in HPCs were investigated through cell proliferation assays, colony-formation assays, cell cycle analysis and invasion assays, as well as through xenograft-formation assays. In this study, genetic depletion of Bmi1 repressed cell proliferation, colony formation and invasion in both assessed HPC cell lines relative to controls. Conversely, forced expression of Bmi1 in two HPCs cell lines promoted cell proliferation, colony formation and invasion in vitro. Aldehyde dehydrogenase (ALDH) assay revealed a significant increase in the number of ALDH-positive cells following the forced expression of Bmi1 in HPCs. Most importantly, transplantation of forced Bmi1 expression HPCs into nude mice resulted in the formation of tumors with histological features of poorly differentiated HCC. Taken together, our findings indicate that forced expression of Bmi1 promotes the malignant transformation of HPCs, suggesting Bmi1 might be a potential molecular target for the treatment of HCC.

L-Stepholidine rescues memory deficit and synaptic plasticity in models of Alzheimer's disease via activating dopamine D1 receptor/PKA signaling pathway.

It is accepted that amyloid ß-derived diffusible ligands (ADDLs) have a prominent role in triggering the early cognitive deficits that constitute Alzheimer's disease (AD). However, there is still no effective treatment for preventing or reversing the progression of the disease. Targeting α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor trafficking and its regulation is a new strategy for AD early treatment. Here we investigate the effect and mechanism of L-Stepholidine (L-SPD), which elicits dopamine D1-type receptor agonistic activity, while acting as D2-type receptor antagonist on cognition and synaptic plasticity in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice, and hippocampal cultures or slices treated with ADDLs. L-SPD could improve the hippocampus-dependent memory, surface expression of glutamate receptor A (GluA1)-containing AMPA receptors and spine density in hippocampus of APP/PS1 transgenic mice. L-SPD not only rescued decreased phosphorylation and surface expression of GluA1 in hippocampal cultures but also protected the long-term potentiation in hippocampal slices induced by ADDLs. Protein kinase A (PKA) agonist Sp-cAMPS or D1-type receptor agonist SKF81297 had similar effects, whereas PKA antagonist Rp-cAMPS or D1-type receptor antagonist SCH23390 abolished the effect of L-SPD on GluA1 trafficking. This was mediated mainly by PKA, which could phosphorylate serine residue at 845 of the GluA1. L-SPD may be explored as a potential therapeutic drug for AD through a mechanism that improves AMPA receptor trafficking and synaptic plasticity via activating D1/PKA signaling pathway.

Entropy-driven phase transition in binary mixtures.

Based on the principle of entropy maximum, a transparent method to study the phase separation is proposed. The excluded volume effects of binary mixtures of hard spheres with two different diameters are analyzed and the role of entropy is emphasized. As a result of the entropy variation caused by the packing of large spheres, there is a critical volume fraction to denote the phase boundary. It is shown that the variation of free volume fraction is influenced by the ratio alpha=d(L)/d(S) of large to small sphere diameters and the ratio x=eta(L)/(eta(L)+eta(S)) of large-sphere volume fraction to the total volume fraction of large- and small-spheres. We introduce a modification factor beta to describe the overlap degree of two large spheres excluded volumes when they pack together. The critical volume fractions for large-sphere packing with different values of alpha and x are calculated, and the corresponding phase boundaries are determined. Our results are in quite good agreement with previous experimental measurements.

[Regulation of Chinese medicine bailong and hexamethylene bisacetamide on cyclin dependent kinase inhibitor P16 genes in human cancer cell].

OBJECTIVE: To study the regulation of bailong, a Chinese herbal anticancer preparation and hexamethylene bisacetamide (HMBA) on cyclin dependent kinase inhibitor P16 (CKI-P16) genes in human cancer cells. METHODS: The expression of CKI-P16 in different human cancer cells treated by Bailong or HMBA under different condition, was examined using Northern hybridization, Western blotting assay, etc. RESULTS: After being treated by Bailong or HMBA, the P16 expression increased. This effect was closely related to co-regulation of cAMP-PKA and DAC-PKC signal pathway. When PKA pathway was blocked with PKA inhibitor, the P16 expression decreased, while PKC pathway was blocked, it enhanced. CONCLUSION: (1) The low P16 expression in G1 phase of cancer cell, as compared with that in S, G2 and M phases, might be an important factor responsible to the incompetence of P16 in inhibiting effectively the malignant change of cancer cell. (2) Mechanism of Bailong and HMBA on cancer cell proliferation inhibition might be correlated with the enhancement of P16 expression in G1 phase of cancer cells. (3) Regulation and expression of Bailong and HMBA on P16 showed the common character of Chinese and western medicine in regulating cancer cells. (4) This study elucidated that upstream of P16 was related to cAMP/PKC signal pathway closely.

Prevalence of obesity and associated risk factors in Northeastern China.

AIM: To investigate the prevalence of obesity and associated risk factors in the Northeastern Chinese city of Dehui. METHODS: A cross-sectional study involving random sampling methods generated 3598 completed questionnaires by permanent residents of Dehui. Binary multivariate logistic regression analysis was used to identify factors that were significantly associated with obesity. RESULTS: Based on the 2000 WHO diagnostic criterion regarding populations in the Asia-Pacific region, the prevalence of obesity was 37.71% (34.77% of females; 41.11% of males). Elevated body mass index (BMI) was significantly associated with cardiovascular disease (CVD)-associated conditions (P<0.05), and increased prevalence of abnormally high transaminase levels (P<0.05). Binary logistic regression analysis demonstrated the following variables were associated with obesity: increased age (odds ratio [OR]: 1.01, 95% confidence interval [CI]: 1.0-1.02), high total cholesterol (TC) (OR: 1.26, 95% CI: 1.03-1.54), high triglycerides (TG) (OR: 1.38, 95% CI: 1.16-1.64), hypertension (OR: 1.62, 95% CI: 1.39-1.90), fatty liver (OR: 2.91, 95% CI: 2.41-3.49), living in an urban setting (OR: 2.84, 95% CI: 2.39-3.38), and advanced education (OR: 1.22, 95% CI: 1.06-1.40). CONCLUSIONS: Obesity is prevalent among the adult population in Northeastern China and is significantly associated with CVD risk factors such as hypertension, dyslipidemia, as well as transaminase abnormalities.

Resistance of helicobacter pylori to metronidazole, tetracycline and amoxycillin.

Resistance to metronidazole, tetracycline and amoxycillin, and beta-lactamase production were determined for 153 clinical isolates of Helicobacter pylori. Of these isolates, 77.8% were resistant to metronidazole (MIC > 8 mg/L), 58.8% to tetracycline (MIC > 16 mg/L) and 71.9% to amoxycillin (MIC > 0.5 mg/L); 39.2% were multiresistant. Resistance to metronidazole was more common in isolates from females than in those from males (P < 0.05). None of the isolates produced beta-lactamase, so the mechanism of amoxycillin resistance was not linked to production of beta-lactamase.