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Background/aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH., Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients., Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH., Conclusions: Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Phage therapy offers a promising approach to combat the growing threat of antimicrobial resistance. Yet, key questions remain regarding dosage, administration routes, combination therapy, and the causes of therapeutic failure. In this study, we focused on a novel lytic phage, ФAb4B, which specifically targeted the Acinetobacter baumannii strains with KL160 capsular polysaccharide, including the pan-drug resistant A. baumannii YQ4. ФAb4B exhibited the ability to effectively inhibit biofilm formation and eradicate mature biofilms independently of dosage. Additionally, it demonstrated a wide spectrum of antibiotic-phage synergy and did not show any cytotoxic or haemolytic effects. Continuous phage injections, both intraperitoneally and intravenously over 7 d, showed no acute toxicity in vivo. Importantly, phage therapy significantly improved neutrophil counts, outperforming ciprofloxacin. However, excessive phage injections suppressed neutrophil levels. The combinatorial treatment of phage-ciprofloxacin rescued 91% of the mice, a superior outcome compared to phage alone (67%). The efficacy of the combinatorial treatment was independent of phage dosage. Notably, prophylactic administration of the combinatorial regimen provided no protection, but even when combined with a delayed therapeutic regimen, it saved all the mice. Bacterial resistance to the phage was not a contributing factor to treatment failure. Our preclinical study systematically describes the lytic phage's effectiveness in both in vitro and in vivo settings, filling in crucial details about phage treatment against bacteriemia caused by A. baumannii, which will provide a robust foundation for the future of phage therapy., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Introduction: This study examined the prevalence of tobacco exposure and drinking and ascertained the relationships between tobacco exposure, alcohol drinking, concurrent smoking and drinking, and hypertension in rural southwestern China., Methods: Data were collected from a cross-sectional health interview and examination survey, which included 7572 adults aged ≥35 years, in rural China. Participant demographic characteristics, smoking habits, exposure to secondhand smoke (SHS), and alcohol drinking habits were obtained using a standard questionnaire. Blood pressure (BP), height, weight, and waist circumference were measured for each participant., Results: The overall prevalence of smoking, SHS exposure, drinking, concurrent smoking and drinking, concurrent exposure to SHS and drinking, and hypertension was 37.7%, 27.4%, 16.2%, 12.6%, 1.6%, and 41.3%, respectively. Males had a significantly higher prevalence of smoking (74.1% vs 2.2%, p<0.01), drinking (31.1% vs 1.7%, p<0.01), and concurrent smoking and drinking than females (25.3% vs 0.3%, p<0.01). However, females had a higher prevalence of SHS exposure than males (30.2% vs 20.6%, p<0.01). Ethnic minorities had a higher prevalence of SHS exposure, drinking, and concurrent smoking and drinking, than Han participants (p<0.01). Participants with a higher education level had a higher prevalence of smoking, drinking, and concurrent smoking and drinking than their counterparts (p<0.01). In contrast, participants with a lower education level had a higher prevalence of SHS exposure than their counterparts (p<0.01). Multivariate logistic regression analysis found that smokers (AOR=1.31; 95% CI: 1.13-1.51), individuals exposed to SHS (AOR=1.24; 95% CI: 1.11-1.43), drinkers (AOR=1.31; 95%: CI: 1.15-1.50), and concurrent smokers and drinkers (AOR=1.45; 95% CI: 1.25-1.67) all had a higher probability of having hypertension (p<0.01). Additionally, concurrent smoking and drinking had the strongest association with the prevalence of hypertension (AOR=1.45; 95% CI: 1.25-1.67; p<0.01)., Conclusions: Socioeconomic factors play an important role in influencing the prevalence of smoking, exposure to SHS, and drinking in rural southwest China. Interventions to prevent and reduce hypertension should, in particular, focus on smokers, individuals exposed to SHS, drinkers, and, in particular, concurrent smokers and drinkers., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Li G. et al.)

Background/Aims: Recent studies revealed that patients with persistent aminotransferase elevations after antiviral treatment had higher risk of hepatic events; yet its underlying causes remain unclear. Our study aimed to investigate the etiologies of persistent aminotransferase elevations in patients treated with nucleos(t)ide analogs (NAs). Materials and Methods: A retrospective study was conducted on chronic hepatitis B (CHB) patients who had been receiving NA treatment for over a year and had an aminotransferase level greater than 40 IU/mL (more than twice, with a 3-month interval) and subsequently underwent a liver biopsy. Results: The study group included 46 patients (34 males) with a mean age of 44.8 ± 20.3 years (range: 24-71 years).The average dura- tion of NA therapy was 3.7 years (1.1-10.6 years). The etiologies of persistant transaminase elevation were categorized into 4 groups: patients with low hepatitis B virus (HBV) viral load (LVL, n = 11); concurrent non-alcoholic fatty liver disease (NAFLD, n = 12); concurrent other liver diseases (OLD, n = 12); and unknown liver dysfunction (ULD, n = 11). The proportion of G ≥ 2 inflammation was significantly higher in the LVL group (90.9%) compared to NAFLD (33.3%), OLD (50%), and ULD (27.2%) groups (P = .012). The hepatitis B e-antigen (HBeAg)-positive group exhibited a younger age (34.5 ± 10.2 vs. 48.1 ± 9.4 years, P < .001), a lower proportion of fibrosis F ≥ 2 (36.3% vs. 77.1%, P = .012), and a higher prevalence of detectable HBV DNA (54.5% vs.14.2%, P = .00632) compared to the HBeAg-negative group. Conclusion: The etiology of persistent aminotransferase elevations in CHB patients undergoing NAs treatment warrants investigation. Besides the commonly observed NAFLD and low HBV viral load, concurrent presence of other liver diseases requires elucidation.The proportion of G≥2 inflammation was higher in the LVL group.

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1223/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: Currently, numerous treatment measures exist for postpartum stress urinary incontinence (PSUI); however, the study results are inconsistent., Method: Computer searches of PubMed, Embase, Web of Science, CKNI, and Wanfang databases were conducted to search the literature on 13 different intervention modalities for PSUI from the date of establishment to January 2023 for analysis. The literature was independently screened, and the information was extracted by 2 researchers. A reticulated meta-analysis was conducted using Stata software., Results: The findings of the reticulated meta-analysis revealed that, in terms of the effectiveness of the 13 interventions for treating PSUI from highest to lowest, the most effective was acupressure + pelvic floor muscle training (94.6%). Following this, the interventions ranked from best to worst were electroacupuncture + trans moxibustion (79.1%), pelvic floor muscle training + acupuncture (64.3%), pelvic floor muscle training + pelvic floor electrical stimulation (60.3%), biofeedback electrical stimulation + acupuncture (60.0%), pelvic floor muscle training + biofeedback electrical stimulation (59.8%), biofeedback electrical stimulation + acupuncture + herbal hot compresses (56.6%), moxibustion + pelvic floor muscle training (56.6%), pelvic floor muscle training + pelvic floor electrical stimulation + acupuncture (53.1%), biofeedback electrical stimulation + moxibustion (52.1%), pelvic floor muscle training (17.6%), biofeedback electrical stimulation (16.1%), and health coaching (0.2%). The evidence indicates that acupressure + pelvic floor muscle training may be the most effective intervention for treating PSUI occurrence., Conclusion: Improvement in 13 clinical indicators was observed in patients with PSUI, and significant enhancement was achieved through acupressure + pelvic floor muscle training., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Coal structure is one of the key geological factors that affects the effect of coal reservoir stimulation. Based on the geological spatial combination characteristics, thickness, and proportion of different coal structures, the coal reservoir is divided into different coal structure combination types. The hydraulic fracturing device is used to carry out indoor fracturing experiments and dissect the crack initiation and expansion characteristics with different coal structure combinations. The results show that the coal structure combination is of the binary type (undeformed coal + granulated coal or cataclastic coal + granulated coal), and the undeformed coal (cataclastic coal) can overcome the tensile strength and minimum principal stress when it is driven by the high-pressure fluid. The undeformed coal (cataclastic coal) ruptures and forms longitudinal cracks. The increasing proportion of granulated coal inhibits crack expansion and promotes the transverse deformation of coal. The interface contact point between the undeformed coal (cataclastic coal) and granulated coal easily fractures along the cross section of the specimen. When the coal structure combination is the triplex type (undeformed coal + granulated coal + cataclastic coal or cataclastic coal + granulated coal + cataclastic coal), the undeformed coal or cataclastic coal is transformed. The forming fractures in the undeformed coal (cataclastic coal) can cut through the soft coal when the thickness of the undeformed coal (cataclastic coal) is large and the thickness of granulated coal is thin. On the contrary, it is not easy to cut through. When the coal structure combination is granulated coal + cataclastic coal + granulated coal, the cataclastic coal fails under shear stress and forms the crack along the cross section of the coal sample. The granulated coal inhibits the crack expansion at both ends. The research results have an important indicative significance for further understanding the fracture initiation and propagation mechanism of hydraulic fracturing with complex coal structures in coal reservoirs., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The evaluation of radiation resistance of the treated radioactive contaminated soil is crucial. The irradiation behavior of simulated radioactive soil waste irradiated with 1.5 MeV Xe 20+ ions at fluences of 1 × 10 12 -1 × 10 15 ions/cm 2 was studied. Before the irradiation experiment, all the samples were sintered by microwave. The results showed that microwave sintering may be used to treat radioactive contaminated soil. In addition, the irradiation experiment results show that when the Nd 2 O 3 content was low (<20 wt.%), the irradiation has little effect on the sample. When the Nd 2 O 3 content was higher, the Vickers hardness of the sample (25 wt.%) decreased by 7 % at a fluence of 1 × 10 15 ions/cm 2 , which may be due to the high Nd 2 O 3 content that destroyed the overall stability of the glass waste form. The low normalized leaching rate of the irradiated sample (LR Nd , ∼10 -6  g·m -2 ·d -1 ) also proved that it had good aqueous durability. Moreover, the radiation resistance of the sample was illustrated by studying the influence mechanism of 1.5 MeV Xe 20+ irradiation on radioactive contaminated soil. This work can help to study the environmental pollution problems of radioactive contaminated soil containing various contents of actinide nuclear waste., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Complications and diagnostic efficiency for liver biopsy are main concerns for clinicians. This study aimed to assess the safety and efficacy of transjugular liver biopsy (TJLB) compared with percutaneous liver biopsy (PLB) when patients had equal level of liver function and number of passes, using propensity score matching (PSM)., Methods: The clinical and pathological data of patients who received TJLB or PLB between January 2012 and October 2022 were collected. Matching factors included age, gender, cirrhosis, portal hypertension, liver function, creatinine, number of passes, hemodialysis, history of anti-coagulation and anti-platelet, and comorbidities. Coagulation indexes were not considered as matching factors due to different indications of the two techniques., Results: 2711 PLBs and 30 TJLBs were evaluated. By PSM, 75 patients (50 PLBs, 25 TJLBs) were matched. The complication rates for TJLB and PLB were 4.0% (1/25) and 10.0% (5/50) (P > 0.05). Two PLBs had hepatic hemorrhage, one of which required only close monitoring (Grade 1) and the other needed hemostasis and rehydration therapy (Grade 2). The other 3 cases presented with mild abdominal pain (Grade 1). And only one TJLB presented with mild pain. The median number of complete portal tracts were 6.0 and 10.0 for TJLBs and PLBs (P < 0.05). Moreover, the median length of sample for TJLBs and PLBs were 10.0 and 16.5 mm (P < 0.05). The diagnostic efficiency of hepatopathy of unknown etiology of TJLB versus PLB groups before and after matching were 96.4% vs. 94.1% and 95.7% vs. 93.2%, respectively (P > 0.05)., Conclusion: TJLB is an effective invasive diagnostic procedure that expands indications for liver biopsy with reliable diagnostic quality., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The application of novel bioorganic fertilizer (BIO) has been established as a weed biocontrol strategy, and reduce herbicides pollution and negatively effects on agricultural ecosystems. However, its long-term influences on soil bacterial communities are unknown. Here, 16 S rRNA sequencing to identify the changes that occur in soil bacterial community and enzyme under BIO treatments after five years in a field experiment. BIO application effectively controlled weeds, however no obvious differences between treatments were observed under BIO-50, BIO-100, BIO-200 and BIO-400 treatment. Anaeromyxobacter and Clostridium&#95; sensu&#95; stricto&#95;1 were the two dominant genera among BIO-treated soil samples. The BIO-800 treatment had a slight influence on the species diversity index, which was more remarkable after five years. The seven significantly-different genera between BIO-800 treatment and untreated soils included C.&#95;sensu&#95;stricto&#95;1, Syntrophorhabdus, Candidatus&#95;Koribacter, Rhodanobacter, Bryobacter, Haliangium, Anaeromyxobacter. In addition, BIO application had different effects on soil enzymatic activities and chemical properties. The extractable P and pH saliency correlated with Haliangium and C.&#95;Koribacter, and C.&#95;sensu&#95;stricto&#95;1 observably correlated with exchangeable K, hydrolytic N and organic matter. Taken together, our data suggest that BIO application effectively controlled weeds and a slight influence on soil bacterial communities and enzymes. These findings expand our knowledge of the application of BIO as widely used as a sustainable weed control in rice paddy., (© 2023. The Author(s).)

Through field investigation, UPLC-MS/MS technology and MaxEnt model were performed to predict the suitable distribution area for red huajiao ( Zanthoxylum bungeanum maxim.) in China from 2021 s to 2060 s, and evaluate the effects of climate factors on the quality of red huajiao. The results demonstrated that mean temperature of the coldest quarter and min temperature of the coldest month were the most important environmental variables influencing red huajiao distribution. Suitable habitats for red huajiao were located mainly in dry and hot valley zone in the Qinba Mountains and the semi-humid and semi-arid areas of the Loess Plateau. The amides contents were higher in high suitability areas, while it was decreased in medium and low suitability areas, and temperature, wind speed and precipitation played a key role in their accumulation. This investigation was of great significance for the planting area optimization, quality control, benefit improvement and industrial development of red huajiao., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Aberrant cytokeratin 7 expression by hepatocytes (CK7 + Hs) is the hallmark characteristic of cholestasis diseases, especially in ductopenia diseases such as primary biliary cholangitis (PBC). This study attempted to evaluate the differences and relationships between the clinical and histological features of aberrant cytokeratin 7 (CK7) expression by hepatocytes in PBC patients., Methods: The clinicopathological data of patients diagnosed with PBC at the Second Hospital of Nanjing between January 2016 and September 2018 were analysed with SPSS 20.0., Results: Eighty-nine PBC patients who underwent liver biopsy were enrolled in this study, and 15, 29 and 45 patients had aberrant CK7 expression by hepatocytes (CK7 + Hs (2 +), CK7 + Hs (1 +), and CK7 - Hs, respectively). There were significant differences in TB, DB, ALP, TA, IgM, interface activity, and ductopenia grade between patients with CK7 - Hs and CK7 + Hs (2 +) (P < 0.05). The ductopenia grade was also significantly different between patients with CK7 + Hs (2 +) and CK7 + Hs (1 +) according to sex (P < 0.05). Upon merging the data of CK7 + Hs (2 +) and CK7 + Hs (1 +) into CK7 + Hs, we found significant differences in AMA, AMA-M2, anti-gp210, TB, DB, ALP, TA, IgM, fibrosis, and ductopenia grade between CK7 + Hs and CK7 - Hs (P < 0.05). The odds ratios (ORs) (and 95% confidence intervals (CIs)) of CK7 + Hs according to anti-gp210, ductopenia grade, and interface activity were 6.413 (95% CI 1.363-30.162), 4.145 (95% CI 1.898-9.052) and 3.247 (95% CI 1.556-6.775), respectively (P < 0.05). Spearman's rank correlation according to interface activity and ductopenia grade in patients with CK7 + Hs (2 + , 1 + , 0) was r = 0.359 (P = 0.001) and r = 0.396 (P < 0.001), respectively., Conclusion: CK7 + Hs serves as a cholestasis index of PBC and are associated with the ductopenia grade and interface activity. Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis., (© 2022. The Author(s).)

Six sets of brake systems were tested using a brake dynamometer, and the brake wear particles (BWPs) and volatile organic compounds (VOCs) were collected during the braking process. In total, 39 elements, 12 water-soluble ions, 7 carbon components, and 18 polycyclic aromatic hydrocarbons (PAHs) in BWPs were extracted and detected, and 74 VOCs in gas samples were analyzed. The average mass fractions of 12 inorganic elements (i.e., Sb, Mg, Cu, Zn, Ti, Ca, Si, Zr, K, Ba, Al, and Fe) with higher contents in PM 2.5 and PM 10 were 43.4% and 40.3%, respectively, and the average mass fraction of Fe was the highest, accounting for 16.6% and 13.1% of PM 2.5 and PM 10 , respectively. The average mass fractions of the 12 water-soluble ions in PM 2.5 and PM 10 were 16.5% and 12.6%, respectively, and NO 3 - , SO 4 2- , and Ca 2+ were the ions with high contents. The average mass fraction of total carbon (TC) in PM 2.5 and PM 10 were 21.9% and 18.1%, respectively, and the average mass fraction of organic carbon (OC) was approximately five times that of elemental carbon (EC). There were six types of PAHs with a detection rate greater than 50%, among which naphthalene (Nap) was the most abundant. The average mass concentration of 74 VOCs was 316.04 μg·m -3 , of which the aromatic hydrocarbon had the highest mass concentration. The compositions of BWPs and VOCs emitted by the six sets of brake systems were quite different, which was mainly determined by the brand and raw materials of the brake pads.

The Shank family proteins are enriched at the postsynaptic density (PSD) of excitatory glutamatergic synapses. They serve as synaptic scaffolding proteins and appear to play a critical role in the formation, maintenance and functioning of synapse. Increasing evidence from genetic association and animal model studies indicates a connection of SHANK genes defects with the development of neuropsychiatric disorders. In this review, we first update the current understanding of the SHANK family genes and their encoded protein products. We then denote the literature relating their alterations to the risk of neuropsychiatric diseases. We further review evidence from animal models that provided molecular insights into the biological as well as pathogenic roles of Shank proteins in synapses, and the potential relationship to the development of abnormal neurobehavioral phenotypes., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Liver cancer (LC) is one of the most common malignant tumors worldwide. Since the mechanism of LC pathogenesis and metastasis cannot be carried out directly on the human body, it is particularly important to establish human liver cancer cell lines for research in vitro . In this study, tissue block adherence method combined with cell clumps digestion method was used to establish primary human hepatocytes (PHHs) with a successful rate of 60% (45/75). Short tandem repeat (STR) analysis proved the cells were derived from its paired tissues. These cells from hepatocellular carcinoma (HCC) expressed NTCP and secreted ALB and AAT as detected by western blot, and expressed hepatocyte-specific membrane protein ASGR1 as detected by flow cytometry. Liver cancer biomarkers like CK7 in ICC (intrahepatic cholangiocarcinoma), AFP, and GPC3 in HCC expressed of different degree as detected by immunohistochemical analysis. These cells displayed typical liver cancer cell morphological characteristics and can passage stably. In conclusion, we developed an effective method to establish PHHs. Further studies are necessary to study if these cells maintaining other liver function and reproduce the physiology of the tumors and how these cells behavior in the drug development.

The microscopic pores in shales can be characterized based on different features, including pore morphology, pore size distribution and pore origin. In this work, shale samples from the Lower Permian Shanxi Formation and Upper Carboniferous Taiyuan Formation in the Linxing Block of the Ordos Basin were examined via experiments including X-ray diffraction (XRD), total organic carbon (TOC) analysis, field emission scanning electron microscopy (FE-SEM), automatic acquisition of large-image technology (MAPS), and low-temperature gas (CO₂ and N₂) adsorption/desorption experiments. The results show that clay minerals (average value of 53.9 wt.%) and quartz (average value of 39.0 wt.%) dominate the sample composition, with some K-feldspar, plagioclase, siderite, etc. The TOC values are between 1.15% and 8.46%, and all the shales are of middle-high maturity (the vitrinite reflectance ( R o ) ranges from 1.23% to 1.75%). Based on FE-SEM images, the observed pore types include interparticle (interP) pores, intraparticle (intraP) pores, and organicmatter (OM) pores, and the pores and fractures at different scales are examined by MAPS. The distributions of micro- and mesopores and the proportions of the different pore sizes were determined from the N₂ and CO₂ adsorption results. The pore size distribution results suggest that N₂ mainly penetratesmesopores (2-50 nm), while CO₂ mainly penetrates large micropores (0.7-2 nm). Micropores are the largest contributors to the total pores. The mesopores were further classified as small, medium and large mesopores, and the proportion of mesopores decreased with increasing pore size.

Synaptic protein shanks (SH3 and multiple ankyrin repeat domains protein, Shank) have emerged as an important mediator of synaptic remodeling. Synaptic remodeling is a common pathogenic process in various neurological disorders including epilepsy. However, the expression and function of shanks gene in epileptogenesis has not been investigated to date. Herein, we investigated the expression of shanks (shank1/2/3) mRNA expression in both epileptic rats and epilepsy patients. Furthermore, methyl target sequencing was applied to explore the relationship between shank mRNA expression and DNA methylation in both rats and human patients. In general rat model, shank1/2/3 mRNA was downregulated at acute stage, upregulated at latent stage, and returned to the basal level at chronic stage. Ten CpG sites of shank1 was found differentially methylated, out of which 6 were hypermethylated. Seventeen CpG sites of shank3 were differentially methylated, out of which 8 were hypermethylated. In human epilepsy patients, decreased shank2 mRNA was detected from the brain tissue, with DNA hypermethylation dominant from both brain (18 out of 30) and blood tissue (58 out of 80), indicating the regulation role of DNA methylation on shank2 expression. In conclusion, our finding suggests the participation of the shanks gene in the pathophysiology of seizure, out of which 2 shank3 CpG sites (Chr7: 130473419, and Chr7: 130473405) may play an important role in shank3 expression at both the acute and latent stages in the SE rat model.

Fractional-pel accurate motion is widely used in video coding. For subband coding, fractional-pel accuracy is challenging since it is difficult to handle the complex motion field with temporal transforms. In our previous work, we designed integer accurate motion-adaptive transforms (MAT) which can transform integer accurate motion-connected coefficients. In this paper, we extend the integer MAT to fractional-pel accuracy. The integer MAT allows only one reference coefficient to be the lowband coefficient. In this paper, we design the transform such that it permits multiple references and generates multiple lowband coefficients. In addition, our fractional-pel MAT can incorporate a general interpolation filter into the basis vector, such that the highband coefficient produced by the transform is the same as the prediction error from the interpolation filter. The fractional-pel MAT is always orthonormal. Thus, the energy is preserved by the transform. We compare the proposed fractionalpel MAT, the integer MAT, and the half-pel motion-compensated orthogonal transform (MCOT), while HEVC intra coding is used to encode the temporal subbands. The experimental results show that the proposed fractional-pel MAT outperforms the integer MAT and the half-pel MCOT. The gain achieved by the proposed MAT over the integer MAT can reach up to 1dB in PSNR.

Point cloud registration plays a key role in three-dimensional scene reconstruction, and determines the effect of reconstruction. The iterative closest point algorithm is widely used for point cloud registration. To improve the accuracy of point cloud registration and the convergence speed of registration error, point pairs with smaller Euclidean distances are used as the points to be registered, and the depth measurement error model and weight function are analyzed. The measurement error is taken into account in the registration process. The experimental results of different indoor scenes demonstrate that the proposed method effectively improves the registration accuracy and the convergence speed of registration error.

Objective: To explore the treatment skill and clinical effect of bone setting manipulation in treating proximal humeral fracture with shoulder dislocation., Methods: From January 2015 to December 2015, 118 cases of proximal humeral fractures with shoulder joint dislocation were treated by bone setting reduction and fixation with adhesive tape or Kirschner wire after reduction, including 56 males and 62 females with an average age of 61 years old ranging from 48 to 88 years old. The time from injury to treatment was 1 to 31 days with an average of 3 days. All fractures were closed, according to Neer standard classification, there were 27 cases of type II, 55 cases of type III and 36 cases of type IV. There were 85 cases of shoulder subglenoid dislocation, 33 cases of subcoracoid dislocation. All the patients were accompanied by obvious shoulder joint deformity, dysfunction and other symptoms. All cases were diagnosed by X-ray examination, and the bone setting manipulation was performed under the brachial plexus anesthesia. According to the type of fracture and fixation method, the patients were encouraged to exercise the limb rehabilitation, and the curative effect was determined by Constant-Murley shoulder score system., Results: All cases were followed up for 6 to 12 months with an average of 9 months. There were 1 case of humeral head necrosis, 2 cases of traumatic frozen shoulder. The score of shoulder joint function Constant-Murley was 84.5±4.5; among them, 78 cases were excellent, 28 cases were good, 9 cases were fair, 3 cases were poor, the excellent and the good rate was 89.8%. X-ray showed bony union of all cases., Conclusions: The treatment of proximal humeral fracture with dislocation of shoulder joint by bone setting manipulation is a skillful method, with simple operation, small trauma and satisfactory curative effect., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

A cross-sectional analysis of prevalence of hepatitis B virus infection (HBV) among rural couples was conducted between 2010 and 2014. Serologic HBV markers, including hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), were tested. Primary outcome of interest comprised HBsAg positivity in couples (both positive: F+M+, only wife positive: F+M-, only husband positive: F-M+), and secondary outcome consisted of prevalence and risk factors of HBsAg positivity among husbands or wives. Of 14,816,300 couples included, 0.7% were F+M+; 6.3% were F-M+; 4.4% were F+M-, resulting in the overall seroprevalence of 11.4%. Individually, 6.1% were HBsAg positive with a higher rate seen in husbands (7.0%) than in wives (5.2%). Wife's HBeAg(+)/HBsAg (+) (AOR = 2.61), HBeAg(-)/HBsAg (+) (AOR = 2.23), positivity of syphilis (AOR = 1.50), living in a high-risk region (AOR = 1.46) were significantly predictors of HBsAg positivity in husbands. Prevalence and predictors of HBsAg positivity in wives had similar results. Our data show a high burden and discordant pattern of HBV infection in rural couples, and partner's double positivity of HBeAg and HBsAg was the most significant factor of HBV infection in couples. A comprehensive strategy that emphasizes vaccination and education is needed.

Gait phase is widely used for gait trajectory generation, gait control and gait evaluation on lower-limb exoskeletons. So far, a variety of methods have been developed to identify the gait phase for lower-limb exoskeletons. Angular sensors on lower-limb exoskeletons are essential for joint closed-loop controlling; however, other types of sensors, such as plantar pressure, attitude or inertial measurement unit, are not indispensable.Therefore, to make full use of existing sensors, we propose a novel gait phase recognition method for lower-limb exoskeletons using only joint angular sensors. The method consists of two procedures. Firstly, the gait deviation distances during walking are calculated and classified by Fisher's linear discriminant method, and one gait cycle is divided into eight gait phases. The validity of the classification results is also verified based on large gait samples. Secondly, we build a gait phase recognition model based on multilayer perceptron and train it with the phase-labeled gait data. The experimental result of cross-validation shows that the model has a 94.45% average correct rate of set (CRS) and an 87.22% average correct rate of phase (CRP) on the testing set, and it can predict the gait phase accurately. The novel method avoids installing additional sensors on the exoskeleton or human body and simplifies the sensory system of the lower-limb exoskeleton., Competing Interests: The authors declare no conflict of interest.

Background: The ras genes play an important role in the development and progression of human tumours. Neutralizing Ras proteins in the cytoplasm could be an effective approach to blocking ras signalling. In this study, we prepared anti-p21Ras single chain fragment variable antibody (scFv) and investigated its immunoreactivity with human tumours., Methods: The coding sequences of H-ras, K-ras, and N-ras were separately ligated into the vector pET-28a(+). Then, recombinant expressing plasmids were induced by IPTG for p21Ras expression in E. coli. Hybridoma cell lines producing anti-p21Ras monoclonal antibodies were isolated using wildtype p21Ras proteins as immunogens. Anti-p21Ras scFv antibody was prepared from the hybridoma by the phage scFv display method. The immunoreactivity of the anti-p21Ras monoclonal antibody and the scFv antibody was identified by ELISA and immunocytochemistry., Results: We prokaryotically expressed wildtype H-p21Ras, K-p21Ras and N-p21Ras and generated the hybridoma cell line KGH-R1, producing anti-p21Ras monoclonal antibodies. It was demonstrated that KGH-R1 monoclonal antibody could recognize wildtype and mutated H-p21Ras, K-p21Ras and N-p21Ras in human tumour cell lines. In all 14 types of primary human cancer tissues tested, the monoclonal antibody presented strong immunoreactivity but showed weak or negative immunoreactivity in the corresponding normal tissues. Subsequently, we prepared anti-p21Ras scFv from hybridoma KGH-R1, which showed the same immunoreactivity as the original monoclonal antibody. Sequence analysis demonstrated that the nucleotides and amino acids of the scFv exhibited an approximately 50 % difference from the anti-p21Ras scFv reported previously., Conclusions: This study presents a novel anti-p21Ras scFv antibody. Our data suggest that the scFv may be useful for ras signalling blockage and may be a potential therapeutic antibody for ras-derived tumours.

Different enantiomers exhibit large differences in their biological activity and/or toxicity, but they rarely involve the relationship of the agents for molecular and cellular imaging with the chiral structure of ruthenium complexes. Here, we report that an enantiomer of a polypyridyl ruthenium complex can selectively accumulate in the nucleus of HepG2 cells. Confocal laser scanning microscopy studies show that this phenomenon occurs via a non-endocytotic, but temperature-dependent, mechanism of cellular uptake in HepG2 cells. DNA oligonucleotides with repetitive tracts of guanine bases that can form G-quadruplex structures have aroused interest as therapeutic agents and as targets for anticancer drug design. Various biophysical techniques show that the Λ-enantiomer of ruthenium complexes can selectively stabilize human telomeric G-quadruplex DNA and has a strong preference for G-quadruplex over duplex DNA. Judged from the NMR results, we speculate that at higher 4:1 ligand/G-quadruplex stoichiometry, complex Λ-Ru is likely to bind with each groove of the tetraplex in a dimeric form or intercalate with the G-tetrad in the 3' terminal face and coexist with other modes. The molecular modeling analysis is in agreement with the NMR titrations performed in this investigation indicating that ruthenium complexes are actually characterized by a mixed binding mode. The results provide many opportunities for the development of novel agents for living cell-related studies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Decreased Na(+) /K(+) -ATPase activity, and both sirtuin 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) have been reported to be involved in the development of diabetic cardiomyopathy (DCM). The present study aimed to investigate the advanced glycation end-products (AGE) that impair Na(+) /K(+) -ATPase stability by regulating the AMPK/SIRT1 pathway during progression of DCM. To study type 1 diabetic mellitus (T1DM), a disease model in rats was established by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg), and neonatal rat cardiomyocytes were also cultured. Heart function was detected by Doppler, and SIRT1 and AMPK protein expression were detected by immunohistochemistry and western blotting. Na(+) /K(+) -ATPase activity was also monitored. Using in vivo rat models of DCM, we showed that Na(+) /K(+) -ATPase activity decreased when both AMPK and SIRT1 expression were downregulated. In vitro, AGE impaired Na(+) /K(+) -ATPase activity and decreased the AMPK and SIRT1 expression. Sirtuin 1 overexpression increased Na(+) /K(+) -ATPase activity. 5-aminoimidazole-4-carboxamide-3-ribonucleoside (AICAR) upregulated SIRT1 expression and increased Na(+) /K(+) -ATPase activity, which could be partially abolished by splitomicin. Our results suggest that the dysfunction of DCM is related to AGE-induced Na(+) /K(+) -ATPase activity impairment through a mechanism involving the AMPK/SIRT1 pathway., (© 2014 Wiley Publishing Asia Pty Ltd.)

Two ruthenium(ii) polypyridyl complexes [Ru(phen)2(4idip)](ClO4)2 () and [Ru(bpy)2(4idip)](ClO4)2 () (phen = 1,10-phenanthroline, bpy = 2,2'-bipyridine, 4idip = 4-indoleimidazo[4,5-f][1,10]phenanthroline) designed as telomeric G-quadruplex ligands have been synthesized and characterized. The interaction of human telomeric G-quadruplex DNA (HTG21) with the designed ligands was explored by fluorescence analysis, absorption spectroscopy, continuous variation, circular dichroism spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay, telomerase repeat amplification protocol (TRAP), and visual studies. The results showed that both complexes could induce and stabilize different G-quadruplex structures by using a 1 : 1 [quadruplex]/[complex] binding mode ratio. Complex exhibited higher interaction ability and better G-quadruplex selectivity than duplex DNA. Furthermore, both ruthenium complexes led to the inhibition of the enzyme telomerase, and complex was the significantly better inhibitor.

Objective: To investigate the effect of oxygenation index (PaO(2)/FiO(2)) on patients' prognosis through comparative analyzing the monitoring indicators of acute respiratory failure patients treated by invasive mechanical ventilation., Methods: Data from 91 acute respiratory failure patients treated by invasive mechanical ventilation in respiration intensive care unit (ICU) of the General Hospital of PLA of Lanzhou from November 2006 to August 2011 were retrospectively analyzed. Patients were divided into survival group (n=55) and death group (n=36) by the outcome, the critical severity scores of the diseases and changes in blood gas analysis during ventilation were compared, and their correlation with prognosis were analyzed., Results: There were no significant differences in acute physiology and chronic health evaluationIII (APACHEIII) score, multiple organ dysfunction syndrome (MODS) score, acute lung injury (ALI) score between survival and death group before ventilation (62.77±22.92 vs. 74.62±25.77, 6.46±2.45 vs. 6.62±3.03, 1.90±0.57 vs. 2.10±0.73, all P>0.05). There was no significant difference in PaO(2)/FiO(2) between survival and death group on the first day of mechanical ventilation (132.18±67.29 mm Hg vs. 139.24±78.36 mm Hg, P>0.05). PaO(2)/FiO(2) in survival group were significantly higher than that in death group on the 3 days and 7 days of mechanical ventilation (3 days: 205.47±74.71 mm Hg vs. 149.76±70.38 mm Hg, 7 days: 225.37±67.20 mm Hg vs. 120.94±85.58 mm Hg, P<0.05 and P<0.01)., Conclusions: The present study demonstrated that the level of PaO(2)/FiO(2) is related with the prognosis of acute respiratory failure patients treated by invasive mechanical ventilation. Continuously monitoring the changes in PaO(2)/FiO(2) can be used as an important reference index to evaluate the prognosis of critical patients.

Telomerase inhibition is an attractive strategy for cancer chemotherapy. In the current study, we have synthesized and characterized two chiral ruthenium(II) complexes, namely, Λ-[Ru(phen)(2)(p-MOPIP)](2+) and Δ-[Ru(phen)(2)(p-MOPIP)](2+), where phen is 1,10-phenanthroline and p-MOPIP is 2-(4-methoxyphenyl)-imidazo[4,5f][1,10]phenanthroline. The chiral selectivity of the compounds and their ability to discriminate quadruplex DNA were investigated by using UV/Vis, fluorescence spectroscopy, circular dichroism spectroscopy, fluorescence resonance energy transfer melting assay, polymerase chain reaction stop assay and telomerase repeat amplification protocol. The results indicate that the two chiral compounds could induce and stabilize the formation of antiparallel G-quadruplexes of telomeric DNA in the presence or absence of metal cations. We report the remarkable ability of the two complexes Λ-[Ru(phen)(2)(p-MOPIP)](2+) and Δ-[Ru(phen)(2)(p-MOPIP)](2+) to stabilize selectively G-quadruplex DNA; the former is a better G-quadruplex binder than the latter. The anticancer activities of these complexes were evaluated by using the MTT assay. Interestingly, the antiproliferative activity of Λ-[Ru(phen)(2)(p-MOPIP)](2+) was higher than that of Δ-[Ru(phen)(2)(p-MOPIP)](2+), and Λ-[Ru(phen)(2)(p-MOPIP)](2+) showed a significant antitumor activity in HepG2 cells. The status of the nuclei in Λ/Δ-[Ru(phen)(2) (p-MOPIP)](2+)-treated HepG2 cells was investigated by using real-time living cell microscopy to determine the effects of Λ/Δ-[Ru(phen)(2)(p-MOPIP)](2+) on intracellular accumulation. The results show that Λ/Δ-[Ru(phen)(2)(p-MOPIP)](2+) can be taken up by HepG2 cells and can enter into the cytoplasm as well as accumulate in the nuclei; this suggests that the nuclei were the cellular targets of Λ/Δ-[Ru(phen)(2)(p-MOPIP)](2+)., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two arene ruthenium complexes [Ru(η(6)-C(6)H(6))(p-MOPIP)Cl](+)1 and [Ru(η(6)-C(6)H(6))(p-CFPIP)Cl](+)2, where p-MOPIP = 2-(4-methoxyphenyl)-imidazo[4,5f][1,10] phenanthroline and p-CFPIP = 2-(4-trifluoromethylphenyl)-imidazo[4,5f][1,10] phenanthroline, were prepared and the interactions of these compounds with DNA oligomers 5'-G3(T2AG3)3-3'(HTG21) have been studied by UV-vis and circular dichroism (CD) spectroscopy, gel mobility shift assay, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay and telomeric repeat amplification protocol (TRAP) assay. The results show that both complexes can induce the stabilization of quadruplex DNA but complex 1 is a better G-quadruplex binder than complex 2. The two ruthenium complexes tested led to an inhibition of the enzyme telomerase and complex 1 was the significantly better inhibitor. A novel visual method has been developed for making a distinction between G-quadruplex DNA and double DNA by our Ru complexes binding hemin to form the hemin-G-quadruplex DNAzyme. Furthermore, in vitro cytotoxicity studies showed complex 1 exhibited quite potent antitumor activities and the greatest inhibitory selectivity against cancer cell lines.

The plant hormone auxin transcriptionally activates Aux/IAA genes. Auxin plays an important role in regulating fruit growth and ripening of strawberry and Aux/IAA genes have been extensively studied in Arabidopsis, rice and tomato, but little information is available on strawberry fruit. In the present work, two full-length of early auxin-responsive Aux/IAA genes, termed FaAux/IAA1 and FaAux/IAA2 respectively, were isolated and characterized from strawberry fruit. Moreover, the expression profiles of two FaAux/IAA genes during fruit development, and the effect of naphthalene acetic acid (NAA) on their expressions of fruits at two different developmental stages were also investigated. The results showed that the levels of FaAux/IAA1 and FaAux/IAA2 transcripts were very high at early stage of fruit development, and decreased sharply at ripening stage (after white stage). In addition, NAA applied at the stage of large green and white fruit obviously increased the accumulations of FaAux/IAA1 and FaAux/IAA2 transcripts. These data suggested that the expressions of both FaAux/IAA1 and FaAux/IAA2 genes were likely to be involved in early fruit development, and the enhancement of FaAux/IAAs transcripts might be attributed at least or partially to auxin-induced fruit growth and delayed fruit ripening of strawberry.

Background: ABA-, stress- and ripening-induced (ASR) proteins have been reported to act as a downstream component involved in ABA signal transduction. Although much attention has been paid to the roles of ASR in plant development and stress responses, the mechanisms by which ABA regulate fruit ripening at the molecular level are not fully understood. In the present work, a strawberry ASR gene was isolated and characterized (FaASR), and a polyclonal antibody against FaASR protein was prepared. Furthermore, the effects of ABA, applied to two different developmental stages of strawberry, on fruit ripening and the expression of FaASR at transcriptional and translational levels were investigated., Methodology/principal Findings: FaASR, localized in the cytoplasm and nucleus, contained 193 amino acids and shared common features with other plant ASRs. It also functioned as a transcriptional activator in yeast with trans-activation activity in the N-terminus. During strawberry fruit development, endogenous ABA content, levels of FaASR mRNA and protein increased significantly at the initiation of ripening at a white (W) fruit developmental stage. More importantly, application of exogenous ABA to large green (LG) fruit and W fruit markedly increased endogenous ABA content, accelerated fruit ripening, and greatly enhanced the expression of FaASR transcripts and the accumulation of FaASR protein simultaneously., Conclusions: These results indicate that FaASR may be involved in strawberry fruit ripening. The observed increase in endogenous ABA content, and enhanced FaASR expression at transcriptional and translational levels in response to ABA treatment might partially contribute to the acceleration of strawberry fruit ripening.

Aim: To investigate the immunoreactivity of monoclonal anti-p21ras antibody KGH-R1 in colorectal benign and malignant lesions., Methods: Immunohistochemical staining was performed using monoclonal anti-p21ras antibody KGH-R1 prepared in our laboratory, in formalin-fixed, paraffin-embedded colorectal samples including normal colorectal tissues, colorectal inflammatory polyps, colorectal low-grade intraepithelial neoplasia, colorectal high-grade intraepithelial neoplasia, invasive colorectal carcinomas and corresponding adjacent tissues. Immunoreactivity of monoclonal antibody KGH-R1 was evaluated by percentage of positive cells and histological score (HSCORE)., Results: Immunostaining was found in 64.89% (61/94) of invasive colorectal adenocarcinomas with an average of 97.28% of carcinoma cells positive and average of 178.98 of HSCOREs. 60.24% (50/83) of colorectal high-grade intraepithelial neoplasia demonstrated immunostaining with KGH-R1, the average percentage of positive cells was 95.08%, the average HSCOREs was 156.38. 64.58% (31/48) of colorectal low-grade intraepithelial neoplasia demonstrated immunoreactivity with KGH-R1, the average percentage of positive cells was 82.52%, the average HSCOREs was 103.03. 39.97% (29/73) of colorectal inflammatory polyps showed immunoreactivity with KGH-R1, the average percentage of positive cells was 17.78%, the average HSCOREs was 18.66. 46.67% (21/45) of normal colorectal tissues showed immunostaining, but the immunoreactivity was very weak, the average percentage of positive cells was 2.64%, the average HSCOREs was 2.64. The the average percentage of positive cells and the average HSCOREs in invasive colorectal carcinomas had no statistical significance with adjacent high-grade intraepithelial neoplasia, but were higher than that in adjacent low-grade intraepithelial neoplasia. Weak immunostaining was found in 23.53% (20/85) of adjacent normal colorectal tissues., Conclusion: Suggested in this study that monoclonal anti-p21ras antibody KGH-R1 has a high immunoreactivity with invasive colorectal carcinomas and may be a potential therapeutic antibody in the future.

Objective: To investigate the relationship between the successful results with different methods and time of initiation of respiratory support in critically ill patients., Methods: The clinical data of 458 critical care patients were reviewed and analyzed. Among the patients, there were 47 cases of cardio-pulmonary resuscitation, 105 cases of acute airway obstruction, 156 cases of acute respiratory failure, and 150 cases of chronic respiratory failure. Intubation, or tracheostomy, or non-invasive positive pressure ventilation (NPPV) at different times and occasions were performed in the patients., Results: One hundred and seventeen cases (25.5%) died during the respiratory support treatment, 49 cases gave up the treatment, and 292 patients (63.8%) were cured after mechanical ventilation. As the success rate was the lowest in patients who survived cardio-pulmonary resuscitation (21.3%, 10/47), it was higher in acute respiratory failure (55.1%, 86/156), and the best result (82.8%, 87/105) was obtained in the acute airway obstruction group and patients with chronic respiratory failure (72.7%, 109/150). In the group of patients undergoing early respiratory support, the cure rate was 95.0% (57/60) in patients with invasive method, and 95.5% (21/22) in the NPPV group. The result was significantly different compared with that of later treatment group [81.7% (68/82) in invasive group, and 60.9% (2/29) in NPPV group, both P<0.01]. It demonstrated that the earlier the respiratory support was given the better results. If the respiratory support was delayed, cure rate was significantly reduced [65.6% (63/96) in invasive group and 48.1% (13/27) in NPPV group, both P<0.01]. The cure rate was no difference between different modes of respiratory support between early treatment groups, however, invasive respiratory support was much better than NPPV [44.4% (40/90) and 0 (0/5)] when instituted in the late stages (all P<0.01)., Conclusion: It is of prime importance to ensure optimal ventilation in the early stage of diseases, the difficulty and risk of establishment of a patent airway are main problems in the treatment of critically ill patients.

Aim: To investigate the role of histone deacetylases (HDACs) inhibitor FK228 in the IL-3 mediated proliferation and differentiation of human erythroid progenitor cells., Methods: CD34(+) cells were separated from the granulocyte colony-stimulating factor(G-CSF)-mobilized peripheral blood of cancer patients and cultured for 7 days with FK228 of different concentrations, stem cell factor(SCF) and interleukin 3 (IL-3) in serum-free medium. Flow cytometry was performed to analyze the expression of CD14, GPA, CD15 and CD36 on the cells and the colony assay of erythroid cells was conducted. Then the CD36(+)GPA(-) cells were enriched and cultured with with IL-3 and 0.5 microg/L FK228 supplemented serum-free semisolid cultures and the formation test of erythroid colony was conducted., Results: FK228 enhanced the generation of CD36(+) cells in a dose-dependent manner, in spite of that it displayed no influence on the generation of CD14(+) and CD15(+) cells. 0.5 g/L FK228 induced a remarkable increase in the cell number of CD36(+) cells cultured with IL-3; FK228 also significantly increased the number and size of CD36(+) cells colony cultured with IL-3 containing semisolid cultures. Moreover, FK228 augmented the formation of CD36(+) cells colony from CD36(+)GPA(-) cells cultured with IL-3., Conclusion: FK228 can promote the IL-3 mediated proliferation and differentiation of human erythroid progenitor cells.

Objective: To assess the clinical usefulness, accuracy, and safety of tele-manipulation for frameless stereotactic surgery using the CAS-R-5 robot system., Methods: We prospectively evaluated 32 patients underwent tele-manipulation of frameless stereotactic operations from Sep. 2005 to Sep. 2006. Tele-manipulations were performed via a digital data network by a neurosurgeon in Beijing while the patients were located in Yan'an. The distance is 1300 kilometers away. The accuracy of location and improvement of symptom were observed after operation. The period of follow-up was from 3 to 14 months (the average was 12 months)., Results: The surgical operations in 32 cases were successful. Remote fiducial registration was performed with a mean accuracy of 1. 50 mm and the standard difference were 0.32 mm between the planned and actual target. There were no complications., Conclusions: Diagnosis and treatment for intracranial disease by tele-manipulation frameless stereotactic surgeries are reliable and safe.

Objective: To explore the biological effect of Notch ligand Delta-1 (Notch L delta-1) on the sIL-6R during the differentiation of erythroid hematopoiesis., Methods: Mononuclear cells (MNCs) was isolated from the normal cord blood using Ficoll graduation solution. MNCs were enriched for CD34(+) CD38(-) cells by CD34 immunomagnetic beads and a FACS Vantage. CD34(+) CD38(-) cells was cultured for 7 days in the presence of SCF, Flt3L, TPO and IL-3 (4GFs). The cultured cells was detected for the expression of IL-6R and GPA. The subsequently enriched CD36(+) erythroid progenitors were sorted for cells with IL-6R(+) and IL-6R(-) using FACS Vantage. The CD36(+) GPA(-) IL-6R(-) cells were respectively cultured in the 4GFs, 4GFs + IL-6 or 4GFs + FP6 containing medium in the presence or absence of Notch L delta-1 for 14 days and CD36(+) GPA high red cells were counted., Results: IL-6R cells accounted for 95% of CD36(+) GPA(+) cells. The CD36(+) GPA(-) cells was clearly divided into IL-6R(+) (46%) and IL-6R(-) (54%) subpopulations, the IL-6R(+) cell subpopulation formed only a few GM colonies (2.1 +/- 1.8) and a greater number of BFU-E colonies were generated from the IL-6R(-) subpopulation (58.2 +/- 18.1) (P < 0.05). The number of CD36(+) GPA high cell was (1.400 +/- 0.180) x 10(6) in the presence of FP6, lower than that [(2.460 +/- 0.190) x 10(6)] in the presence of FP6 + Notch L delta-1 (P < 0.05)., Conclusion: Notch L delta-1 enhances the sIL-6R-mediated effects of IL-6 on the generation of erythroid cells.

Aim: To compare the effect, adverse events, cost-effectiveness and dose intensity (DI) of oral Xeloda vs calcium folinate (CF)/5-FU combination chemotherapy in patients with advanced gastrointestinal malignancies, both combined with bi-platinu two-way chemotherapy., Methods: A total of 131 patients were enrolled and randomly selected to receive either oral Xeloda (X group) or CF/5-FU (control group). Oral Xeloda 1,000 mg/m2 was administered twice daily from d 1 to 14 in X group, while CF 200 mg/m2 was taken as a 2-h intravenous infusion followed by 5-FU 600 mg/m2 intravenously for 4-6 h on d 1-5 in control group. Cisplatin and oxaliplatin were administered in the same way to both the groups: cisplatin 60-80 mg/m2 by hyperthermic intraperitoneal administration, and oxaliplatin 130 mg/m2 intravenously for 2 h on d 1. All the drugs were recycled every 21 d, with at least two cycles. Pyridoxine 50 mg was given t.i.d. orally for prophylaxis of the hand-foot syndrome (HFS). Then the effect, adverse events, cost-effectiveness and DI of the two groups were evaluated., Results: Hundred and fourteen cases (87.0%) finished more than two chemotherapy cycles. The overall response rate of them was 52.5% (X group) and 42.4% (control group) respectively. Tumor progression time (TTP) was 7.35 mo vs 5.95 mo, and 1-year survival rate was 53.1% vs 44.5%. There was a remarkable statistical significance of TTP and 1-year survival between the two groups. The main Xeloda-related adverse events were myelosuppression, gastrointestinal toxicity, neurotoxicity and HFS, which were mild and well tolerable. Therefore, no patients withdrew from the study due to side effects before two chemotherapy cycles were finished. Both groups finished pre-arranged DI and the relative DI was nearly 1.0. The average cost for 1 patient in one cycle was RMB9 137.35 (X group) and RMB8 961.72 (control group), or USD1 100.89 in X group and USD1 079.73 in control group. To add 1% to the response rate costs RMB161.44 vs RMB210.37 respectively (USD19.45 vs USD25.35). One-month prolongation of TTP costs RMB1 243.18 vs RMB1 506.17 (USD149.78 vs USD181.47). Escalation of 1% of 1-year survival costs RMB172.74 vs RMB201.64 (USD20.75 vs USD24.29)., Conclusion: Oral Xeloda combined with bi-platinu two-way combination chemotherapy is efficient and tolerable for patients with advanced gastrointestinal malignancies; meanwhile the expenditure is similar to that of CF/5-FU combined with bi-platinu chemotherapy, and will be cheaper if we are concerned about the increase of the response rate, TTP or 1-year-survival rate pharmacoeconomically.

To observe the effects of blood serum from rats with radiation injury, thermal injury and combined radiation-thermal lesions on growth of hematopoietic progenitor cells and the change of their serum cytokine levels, total body irradiation of rats was performed with 12 Gy gamma ray from a (60)Co source, and 30% total body surface area III degree thermal lesion on the back was inflicted with a 5 kW bromotungsten lamp. The blood serum from these animals was collected at 3, 12, 24, 48, 72 and 96 hours after injury. Then the blood serum was added to the culture medium of erythrocyte progenitor cells (CFU-E, BFU-E) or granulocyte-macrophage progenitor cells (CFU-GM) at final concentration of 10 microg/ml. The results showed that the colony number of CFU-E, BFU-E and CFU-GM formed after addition of the blood serum from rats with thermal or combined radiation-thermal injury was significantly higher than that from normal rats at 3, 12, 24, 48, 72 and 96 hours after injury and reached its peak value at 24 hours after injury (342.8, 261.6 and 228.4% respectively from burned rats, 252.4, 205.1 and 174.2% respectively from rats with combined radiation-thermal injury as compared with that of normal rats). However, a few CFU-E, BFU-E or CFU-GM formation was found after addition of the blood serum from irradiated rats. At the same time, the level of TNF alpha and IL-6 in serum of burn group and combined radiation-thermal injury group was markedly higher than that of normal group, even more higher than that of irradiation injury group (P < 0.01). It is concluded that the blood serum from rats with thermal lesion or combined radiation-thermal injury improves the growth of erythrocyte and granulocyte progenitor cells. On the contrary, the blood serum from the irradiated rats shows the inhibiting effects, definitely related to their serum cytokines changes.

Background & Objective: Up to now, there is no efficient immunotherapy for hepatocellular carcinoma (HCC). Dendritic cell (DC) vaccine could be a potential tool for HCC immunotherapy. This study was to evaluate the effect of dendritic cells (DCs) transfected with recombinant plasmid bearing hepatitis B virus surface antigen (HBsAg) gene, and the capability of generating specific cytotoxic T lymphocytes (CTL) response against HepG2.2.15 in vitro, which were induced by genetically modified DCs., Methods: After cultured for 5 days, the DCs were transfected with pCR3.1-S by liposome. The HBsAg gene expression on pCR3.1-transfected DCs was identified by Western blot analysis, and immunofluorescence methods. The cytotoxicity against HepG2.2.15, which were induced by DCs, was tested by MTT assay., Results: DCs up-regulated the expression of CD1a (55.0%), CD11c (98.6%), CD86 (86.1%), CD80 (66.1%), and HLA-DR (88.9%) after cultured for 5 days. Indirect immunofluorescence, and Western blot analysis showed that HBsAg gene was expressed on transfected DCs. The death rates of HepG2.2.15 cells induced by DCs transfected with pCR3.1-S were (52.3+/-2.8)% (E:T=5:1), (64.6+/-2.4)% (10:1), (78.8+/-2.6) (20:1), (82.1+/-2.4)% (40:1), while the pCR3.1- transfected and non-transfected DCs only induced relatively lower cytotoxicity (P< 0.05, n=4)., Conclusion: DCs transfected with recombined plasmid expressed HBsAg efficiently, and the genetically modified DCs evoke a higher CTL response in vitro.

Objective: To determine whether the expression level of beta-catenin correlates with the invasion and metastasis of human esophageal cancers., Methods: Using immunohistochemical staining technique, we investigated the expression of beta-catenin in different tissues from the specimens of the primary tumor and the nearby non-tumorous esophageal mucosa., Results: Strong expression of beta-catenin in the nearby non-tumorous esophageal mucosa was observed. However, in the primary esophageal cancers, the expression of beta-catenin was frequently reduced and disorderly distributed. The level of beta-catenin expression was closely related with the growth pattern, cellular differentiation, depth of invasion, and lymphatic metastasis., Conclusion: The down-regulation of beta-catenin expression might be a predictor indicating the metastatic potential of esophageal cancers.

Objective. To improve the quality of ultrasonic therapeutical treatment by improving the accuracy of temperature control. Method. Adaptive canceling methods were used to reduce the noise of temperature signal gained, and enhance signal-to-noise ratio. Result. The test's result corresponds basically to the theoretical curve. Conclusion. Adaptive canceling methods can be applied to clinic treatment.

Preliminary experiments indicated that target cells were resistant to glucocorticoid (GC) after pathological stress. This study was designed to investigate the alterations in plasma corticosterone level and GC receptor (GR) of liver cytosols, to assess the relative inflammatory cytokines contribution to GC resistant, and to observe the action of alpha-melanocyte-stimulating hormone (alpha-MSH) on the potential implications of glucocorticord regulatory effects in burned rats. Male Wistar rats (weight range, 180-200g) received a 35% total body surface area immersion scald and were randomly divided to receive either tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), polyclonal antibody (pAb), alpha-MSH, Ac-D-Lys-L-Pro-D-Val (KPV peptide), or saline (control). The binding capacity (Rt) of the steroid-binding sites was measured by radioligand binding assay, using [3H]dexamethasone as the ligand. We examined plasma levels of IL-1beta, TNFalpha, IL-10, and corticosterone following scald challenge in rats. The Rt of GR (208.45+/-30.78fmol/mg of protein) in hepatic cytosol in rats, 12h later the scald was significantly lower than that (306.71+/-27.96fmol/mg of protein) of the control group (P<0.01). The injections of anti-rat TNFalpha (257.80+/-12.82fmol/mg of protein), IL-1beta antibody (254.46+/-21.21fmol/mg of protein), alpha-melanocyte-stimulating hormone (278.32+/-7.76fmol/mg of protein) and KPV peptide (263.46+/-17.46fmol/mg of protein) might prevent the Rt of GR from decreasing in hepatic cytosols of rats with scald, respectively (all of P<0.05) in vivo. Scald-induced robust increases in plasma IL-1beta (214.08+/-27.25pg/ml), TNFalpha (111.18+/-23.97pg/ml), IL-10 (177.50+/-15.79pg/ml) and corticosterone (2680+/-443.23ng/ml) levels after 12h. The administration of TNFalpha, IL-1beta pAb, alpha-MSH and KPV might attenuate these increases. These studies suggest that pro-inflammatory cytokines are involved in downregulation of GRs and thus alpha-MSH and KPV might increase the level of GR in rats with immersion scald.

Objective: As effectors, glucocorticoid and mineralocorticoid receptors play an important role in pathologic stress. This study was designed to observe the changes in glucocorticoid receptor of liver cytosols and mineralocorticoid receptor of kidney cytosols after pathologic stress in rats., Design: Controlled laboratory study., Setting: Medical university., Subjects: Male Wistar rats (weight range, 180-200 g)., Interventions: Rats received a low-degree or heavy-degree immersion scald that covered 10% or 35% total body surface area and were randomly divided to receive either tumor necrosis factor-alpha, interleukin-1beta polyclonal neutralizing antibody, alpha-melanocyte-stimulating hormone, KPV peptide (Ac-D-Lys-L-Pro-D-Val), or saline (control). The binding capacity and the apparent dissociation constant of the steroid-binding sites of normal, low-degree, and heavy-degree scalded rats were measured by radioligand-binding assay, with [3H]dexamethasone and aldosterone as the ligand, respectively., Measurements and Main Results: The binding capacity of glucocorticoid receptor in hepatic cytosols in rats 12 hrs after heavy-degree scald (208.45 +/- 30.78 fmol/mg of protein) was lower than that of the control group (306.71 +/- 27.96 fmol/mg of protein; p < .01). The binding capacity of glucocorticoid receptor in hepatic cytosols in rats 12 hrs after low-degree scald (296.64 +/- 16.06 fmol/mg of protein) was not significantly different compared with the control group (p > .05). There were two types of mineralocorticoid receptor in kidney cytosols in rats, and their binding capacity and apparent dissociation constant were not identical. The binding capacity of mineralocorticoid receptor in rats 12 hrs after heavy-degree scald (binding capacity 1, 22.40 +/- 5.40 fmol/mg of protein; binding capacity 2, 196.30 +/- 32.50 fmol/mg of protein) was lower than that of the control group (binding capacity 1, 41.60 +/- 7.20 fmol/mg of protein; binding capacity 2, 317.60 +/- 70.00 fmol/mg of protein; p < .01). The binding capacity of mineralocorticoid receptor in kidney cytosols in rats 12 hrs after low-degree scald (binding capacity 1, 41.40 +/- 5.00 fmol/mg of protein; binding capacity 2, 314.80 +/- 45.70 fmol/mg of protein) was not significantly different compared with the control group (p > .05). The injections of anti-rat tumor necrosis factor-alpha, interleukin-1beta polyclonal neutralizing antibody, alpha-melanocyte-stimulating hormone, and KPV peptide (Ac-D-Lys-L-Pro-D-Val) might prevent a reduction in the binding capacity of glucocorticoid receptor in hepatic cytosols and mineralocorticoid receptor in kidney cytosols in rats with heavy-degree scald in vivo., Conclusions: These studies suggest that the glucocorticoid receptor of hepatic cytosols and the mineralocorticoid receptor of renal cytosols decreased in rats with heavy-degree immersion scald and that the injections of anti-rat tumor necrosis factor-alpha, interleukin-1beta polyclonal neutralizing antibody, alpha-melanocyte-stimulating hormone, and KPV peptide might increase the level of glucocorticoid receptor and mineralocorticoid receptor in vivo.

The binding of [3H]5-hydroxytryptamine (5-HT, serotonin) to cerebellar membranes was examined after preincubation of [3H]5-HT in the presence or absence of ascorbate. The tissue preparation was identical in all experiments and consisted of rat cerebellar homogenates in Tris-HCl buffer with 0.1% ascorbate. Cerebellar membranes were used because of their low density of 5-HT1 binding sites. In the presence of ascorbate during a 4-h preincubation period, minimal specific binding of 2 nM [3H]5-HT is detected. Similar results are obtained with equimolar concentrations of other antioxidants (butylated hydroxytoluene, sodium dithionite, and sodium metabisulfite). Apparent specific binding increases 14-fold following a 4-h preincubation of [3H]5-HT in the absence of ascorbate. The increase in apparent specific [3H]5-HT binding is time-dependent and plateaus after 4-6 h of preincubation. When ascorbate is present during the 4-h preincubation, Scatchard analysis of [3H]5-HT binding reveals a KD value of 3.0 +/- 0.3 nM and a Bmax value of 1.9 +/- 0.2 pmol/g tissue. When ascorbate is absent during the preincubation, the KD is essentially unchanged at 3.6 +/- 0.1 nM but the Bmax is significantly increased to 36.5 +/- 7 pmol/g tissue. Drug competition studies reveal that the apparent specific "[3H]5-HT binding" in the absence of ascorbate appears to be displaced by nanomolar concentrations of hydroxylated tryptamines (5-HT, bufotenine) but not by nonhydroxylated tryptamines (5-methoxytryptamine, tryptamine). HPLC analysis demonstrates that [3H]5-HT is essentially destroyed by a 4-h incubation at 22 degrees C in the absence of ascorbate.(ABSTRACT TRUNCATED AT 250 WORDS)