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Hai-jian Xia,1,2 Zhen-hai Zhang,1 Xin Jin,1 Qin Hu,1 Xiao-yun Chen,1 Xiao-bin Jia11Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China; 2College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaAbstract: Mixed micelles are widely used to increase solubility and bioavailability of poorly soluble drugs. One promising antitumor drug candidate is 20(S)-protopanaxadiol (PPD), although its clinical application is limited by low water solubility and poor bioavailability after oral administration. In this study, we developed mixed micelles consisting of PPD–phospholipid complexes and Labrasol® and evaluated their potential for oral PPD absorption. Micelles were prepared using a solvent-evaporation method, and their physicochemical properties, including particle size, zeta potential, morphology, crystal type, drug loading, drug entrapment efficiency, and solubility, were characterized. Furthermore, in vitro release was investigated using the dialysis method, and transport and bioavailability of the mixed micelles were investigated through a Caco-2 cell monolayer and in vivo absorption studies performed in rats. Compared with the solubility of free PPD (3 µg/mL), the solubility of PPD in the prepared mixed micelles was 192.41 ± 1.13 µg/mL in water at room temperature. The in vitro release profiles showed a significant difference between the more rapid release of free PPD and the slower and more sustained release of the mixed micelles. At the end of a 4-hour transport study using Caco-2 cells, the apical-to-basolateral apparent permeability coefficients (Papp) increased from (1.12 ± 0.21) × 106 cm/s to (1.78 ± 0.16) × 106 cm/s, while the basolateral-to-apical Papp decreased from (2.42 ± 0.16) × 106 cm/s to (2.12 ± 0.32) × 106. In this pharmacokinetic study, compared with the bioavailability of free PPD (area under the curve [AUC]0–8), the bioavailability of PPD from the micelles (AUC0–8) increased by approximately 216.36%. These results suggest that novel mixed micelles can significantly increase solubility, enhance absorption, and improve bioavailability. Thus, these prepared micelles might be potential carriers for oral PPD delivery in antitumor therapies.Keywords: 20(S)-protopanaxadiol, phospholipid complex, Labrasol, mixed micelles, Caco-2 cell monolayer, bioavailability

4-cyanobenzoic acid serves as a crucial intermediate for the synthesis of various high-value organic compounds. The enzymatic hydrolysis of terephthalonitrile to produce 4-cyanobenzoic acid using nitrilase offers the advantages of a simple reaction pathway, environmental friendliness, and easy product separation. In order to efficiently develop nitrilases that meet industrial production requirements, the virtual screening method used in the study is established and mature. From a total of 371 amino acids in the nitrilase AfNIT, which exhibits activity in terephthalonitrile hydrolysis, three candidate sites (F168, S192, and T201) were identified, and a "small and accurate" mutant library was constructed. The triple mutant F168V/T201N/S192F was screened from this small mutant library with a specific activity of 227.3 U mg -1 , which was 3.8 times higher than that of the wild-type AfNIT. Using the whole-cell biocatalyst containing the mutant F168V/T201N/S192F, terephthalonitrile was successfully hydrolyzed at a concentration of 150 g L -1 to produce 4-cyanobenzoic acid with a final yield of 170.3 g L -1 and a conversion rate of 98.7%. The obtained nitrilase mutant F168V/T201N/S192F in this study can be effectively applied in the biomanufacturing of 4-cyanobenzoic acid using terephthalonitrile as a substrate. Furthermore, the results also demonstrate the significant improvement in predictive accuracy achieved through the latest AI-assisted computer simulation methods. This approach represents a promising and feasible new technological pathway for assisting enzyme engineering research, laying a theoretical foundation for other related studies., (© 2024 Wiley-VCH GmbH.)

Objective: Based on data from the National Health and Nutrition Examination Survey (NHANES), this study aimed to investigate the effect of high levels of systemic immune inflammation (SII) on hepatic steatosis by conducting a population-based cross-sectional survey of research subjects., Subjects and Methods: The population included 5,119 participants from the NHANES 2017-2020 cycle who were selected as the research subjects. We used (neutrophil count × platelet count)/lymphocyte count as the formula for calculating SII. The formula for calculating HSI levels was 8 × the ratio of [alanine aminotransferase (ALT) / aspartate aminotransferase (AST)] + body mass index (BMI) + 2 (with diabetes mellitus) + 2 (for women). HSI=36 was taken as the cut-off value for evaluating hepatic steatosis. Multivariate logistic regression analysis was used to evaluate the relationship between hepatic steatosis and SII in different models. Subgroup analysis was used to explore the relationship between different subgroups of SII and hepatic steatosis. Interaction analyses were used to assess the heterogeneity., Results: Out of a total of 5,119 participants, hepatic steatosis was observed in 2,742 individuals. Multivariate logistic regression showed that the independent risk factor for hepatic steatosis was a high SII level (OR=1.33, 95% CI: 1.11-1.49, p<0.05). After adjusting for differences in BMI and HSI using propensity score matching (PSM), bariatric surgery also reduced SII risk., Conclusions: There is a correlation between SII and hepatic steatosis, and bariatric surgery can effectively reduce SII risk in the hepatic steatosis population.

Objective: To investigate the association between disease location and segmental mucosal healing (SMH) following exclusive enteral nutrition (EEN) in children with Crohn's disease (CD)., Methods: Treatment-naive pediatric patients with endoscopically active CD treated with EEN alone as induction therapy were retrospectively enrolled from January 1, 2017 to June 30, 2022. The simple endoscopic score for CD (SES-CD) was employed to score disease activity in the upper gastrointestinal (GI) tract (esophagus, stomach, duodenum), rectum, left colon, transverse colon, right colon, and terminal ileum. While the Lewis score assessed that of the small bowel from the jejunum to the proximal ileum (except the terminal ileum). The variation in the total scores for each segment and SES-CD subscores for each ileocolonic segment from baseline to 1 year after EEN therapy and the segmental endoscopic outcomes and potential predictors associated with SMH for the segments scored by SES-CD were evaluated., Results: Overall, 82 children with CD were enrolled. Except for the upper GI segment, scores in other segments declined significantly from baseline to EEN completion (all P < 0.001). We analyzed 486 segments (79, 80, 81, 82, 82 and 82 from upper GI tract, terminal ileum, right colon, transverse colon, left colon, and rectum) and found that the segmental SES-CD at baseline (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.55-0.70, P < 0.001) and upper GI location (OR 0.25, 95% CI 0.11-0.55, P = 0.001) were associated with SMH at EEN completion., Conclusion: Disease location of the upper GI segment in pediatric CD was associated with SMH following EEN therapy., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objectives: Intestinal Behçet's disease (BD) predominantly affects the ileocecal region and is currently diagnosed based on endoscopic features and clinical manifestations. It is difficult to distinguish between intestinal BD and Crohn's disease (CD) due to similar patient populations, gastrointestinal involvement, extraintestinal manifestations, and long-term recurrent course. In this study we aimed to compare the clinicopathological and immunophenotypic features of intestinal BD to CD., Methods: The medical and pathological records of 29 cases of intestinal BD and 120 cases of CD diagnosed at Sir Run Run Shaw Hospital were retrospectively analyzed. Immunohistochemistry for CD3, CD20, FOXP3, myeloperoxidase, and quantitative analysis of the infiltrating inflammatory cells was conducted., Results: Intestinal BD with ileocecal ulcer had a higher incidence of abdominal pain and a higher erythrocyte sedimentation rate than CD, while chronic diarrhea was more common in CD. Excessive neutrophils in the mucosal lamina propria, neutrophilic exudate on the ulcer surface, and prominent lymphocytic infiltration in ulcer tissues were statistically more frequent in intestinal BD than in CD. The numbers of FOXP3 + T cells, CD3 + T cells, and CD20 + B cells in biopsy tissue from intestinal BD were significantly higher than CD, but the ratio of FOXP3 + T cells to CD3 + T cells was not statistically different., Conclusion: Besides the typical clinical and endoscopic findings, diagnostic biopsies from the ileocecal region in intestinal BD show some histological and immunophenotypic features that are different from CD, which may be useful in distinguishing these two entities., (© 2023 The Authors. Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Patients with lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) deficiency have a variety of clinical symptoms, but there is no apparent genotype-phenotype correlation, and patients carrying the same mutations may have different phenotypes. Therefore, it is not easy for doctors to make a decision regarding hematopoietic stem cell transplantation (HSCT) for LRBA-deficient patients. We hypothesized that there may be a protein-phenotype correlation to indicate HSCT for LRBA-deficient patients., Aim: To report on three Chinese LRBA-deficient patients and determine the correlation between residual protein expression and disease phenotypes ., Methods: Clinical data of three Chinese LRBA-deficient patients were collected, and protein levels were detected by Western blot analysis. In addition, LRBA mutation information of another 83 previously reported patients was summarized., Results: All the major clinical findings indicated enteropathy, but patients 1 and 3 presented with more severe symptoms than patient 2. Endoscopy and histology indicated nonspecific colitis for patients 1 and 3 but Crohn's disease-like colitis for patient 2. Compound heterozygous mutations in LRBA were found in patient 1, and homozygous mutations in LRBA were found in patient 2 and patient 3. Only patient 2 responded well to traditional immunosuppressive treatment. Residual expression of the LRBA protein in patients 1 and 3 was very low, but in patient 2, a more than 0.5-fold in expression of the LRBA protein was found compared to that in the control. After HSCT, patient 1 had increased LRBA protein expression. We summarized the genetic information of 86 patients, and the mutations in patients 1 and 3 were novel mutations., Conclusion: We described three Chinese LRBA-deficient patients, two of whom carried novel mutations. These patients had no genotype-phenotype correlations, but their residual LRBA protein expression might be associated with disease outcome and could be an indicator for HSCT., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aim: To analyze postoperative clinical results after implantation of trifocal intraocular lenses (IOLs) in highly myopic eyes with different axial lengths (ALs)., Methods: This retrospective study describes 61 eyes of 44 patients that were implanted with trifocal diffractive IOLs (AT LISA tri 839MP). Twenty-one eyes (15 patients) were included in the AL<26 mm group, 19 eyes (13 patients) in the AL≥26 mm and <28 mm group, and 21 eyes (16 patients) in the AL≥28 mm group. Postoperative outcomes, including corrected and uncorrected distance visual acuity (UDVA), intermediate and near visual acuity at 167 cd/m 2 luminance, depth of focus at 85 cd/m 2 luminance, and objective optical quality parameters assessed using the Optical Quality Analysis System (OQAS), were compared among the groups at 3mo., Results: There were no significant differences in the mean UDVA, uncorrected intermediate visual acuity, uncorrected near visual acuity, corrected distance visual acuity, distance-corrected intermediate visual acuity, and distance-corrected near visual acuity (DCNVA) among the three groups ( P >0.05). Better near and intermediate visual acuity (from -1.5 D to -3.0 D) were noted on the defocus curve of the AL<26 mm group ( P <0.01 vs AL≥28 mm group). Significantly higher objective scatter index (OSI) values and lower modulation transfer function (MTF) cut-off values, Strehl ratio (SR), and OQAS values (OVs) were observed in the AL≥28 mm group ( P <0.01 vs AL<26 mm group). All OQAS parameters had statistically significant correlations with DCNVA and visual acuity at the vergence of -2.5 D ( P <0.05 to P <0.01)., Conclusion: Implantation of trifocal IOLs provides good short-term visual and refractive outcomes in highly myopic eyes with different ALs. However, the near vision decreases in the extremely myopic eyes at lower luminance, which is associated with the lower objective optical quality in these eyes., (International Journal of Ophthalmology Press.)

Following oil extraction in the wetland of the Yellow River Delta, heavy metal contamination of coastal saline-alkaline soil, especially with cadmium (Cd), has become a serious environmental problem in some regions. Biochar application has been proposed to remedy Cd-contaminated soil, but the remediation effect is related to preparation conditions of biochar (e.g., pyrolysis temperature and raw material) and soil properties. The invasive plant, Spartina alterniflora, produces a high amount of biomass, making it suitable for biochar production in coastal China. We investigated the effect of S. alterniflora-derived biochar (SDB) pyrolyzed at four temperatures (350, 450, 550, and 650 °C) crossed with three addition ratios (1, 5, and 10%) and control on Cd contamination of coastal saline-alkaline soil. Pyrolysis temperature affected pH, surface area, and functional groups of SDB. SDB markedly improved soil pH and soil organic matter, but the degree of improvement was affected by pyrolysis temperature and addition ratio. SDB significantly altered available Cd content in soil, but reduced it only at low pyrolysis temperatures (350 and 450 °C). Available Cd content had a positive correlation with soil pH (R 2  = 0.298, P < 0.01), but was not related to salinity and soil organic matter content. Thus, SDB pyrolyzed at 350 °C with 5% addition was optimal for passivating Cd in coastal saline-alkaline soil, since available Cd content in soil decreased mostly (by 26.9%). These findings act as a reference for the development of an application strategy for SDB to ameliorate Cd-contaminated coastal saline-alkaline soil., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To explore the methods and appliaction value for self-constructing brainstem fiber bundles by neurosurgeon through 3D-Slicer software in neurosurgical preoperative planning. Methods: The DCIOM format imaging data of 31 patients with neurosurgical brainstem lesions were collected who admitted to Neurosurgery Department at the First Affiliated Hospital of Chongqing Medical University from June 2018 to May 2019 and imported into the 3D-Slicer software system. The neurosurgery specialists independently constructed the fiber bundles to generate two-dimensional Fraction Anisotropy maps, Directionally Encoded Color maps and three-dimensional fiber bundle tracing maps. Building a preopertive virtual pathological anatomical imaging system and understanding the three-dimensional pathological anatomical relationship between lesions and brain stem fiber bundles to develop an accurate surgical approach and simulate surgicalprocedures before surgery. Results: All cases were reconstructed by neurosurgeon, and the self-constructed 3D virtual images were used to develop the surgical plan. All the operations were successfully completed under the assistance of microsurgical techniques and neuroendoscopy while avoiding fiber bundles as much as possible, and the total or subtotal tumor was achieved without damage to the fiber bundle. After operation, the symptoms of new brainstem fiber bundle injury were mild. 31 patients were followed up 3 months after operation without obvious symptoms of brainstem fiber bundle injury, and 31 patients were followed up 6 months after operation without obvious symptoms of brainstem fiber bundle injury. Conclusions: Constructing brainstem fiber bundles by neurosurgeon can accurately and purposefully reconstruct the shape of brainstem fiber bundles, so that neurosurgeons can more accurately understand the three-dimensional pathological anatomical relationship between tumor and brain stem fiber bundles. In order to formulate the surgical plan in a more reasonable way, choose the optimal surgical approach, understand the location of the "relative safe area" , and be more confident to avoid damage to the brain stem fiber bundle while achieving subtotal or total resection of the tumor,also the nerve function of the patient is preserved as much as possible.

A number of studies have linked abnormalities in the function of the serotonergic and noradrenergic systems to the pathophysiology of depression. It has been reported that selective serotonin reuptake inhibitors promote the expression of tryptophan hydroxylase (TPH), which is involved in the synthesis of serotonin. However, limited evidence of TPH alteration has been found in selective serotonin and noradrenaline reuptake inhibitors (SNRIs), and more key enzymes need to be investigated. The aim of the present study was to determine whether venlafaxine (VLX; a classical SNRI) regulates TPH and other key enzymes responsible for the synthesis and metabolism of monoaminergic transmitters in rats with chronic unpredictable stress (CUS). The present results suggested that CUS‑exposed rats exhibited decreased locomotor activity in the open‑field test and increased immobility time in the forced swim test, as compared with the controls. Pretreatment with VLX (20 mg/kg) significantly increased locomotor activity and reduced immobility time in the CUS‑exposed rats. In addition, VLX (20 mg/kg) treatment prevented the CUS‑induced reduction in tyrosine hydroxylase and TPH expression in the cortex and hippocampus. Furthermore, VLX alleviated the CUS‑induced oxidative stress in the serum, cortex and hippocampus. However, VLX administration did not have an effect on indoleamine‑2,3‑dioxygenase overexpression in the hippocampus. It was therefore concluded that the regulation of abnormalities in the synthesis and metabolism of monoaminergic transmitters may be associated with the antidepressant effects of VLX, suggesting that multimodal pharmacological treatments can efficiently treat depression.

Biomechanical methods may provide a novel way to understand blood accumulation in intracerebral hemorrhage (ICH). The current study presents the results of a biomechanical analysis of blood accumulation in ICH using a finite element analysis, with an emphasis on the pressure exerted by the mass effect of blood in early ICH. A two-dimensional finite model of the human brain parenchyma and the human ventricular system was developed and analyzed under two preloading conditions. The material properties of the human parenchyma were derived from previous reports. Ogden's theory was applied to describe the stress-strain association in soft tissue. The results of the present study indicated that maximal stress was located at the two ends of the hemorrhage cavity, with the majority of stresses distributed on the zone surrounding the bleed. The two load environments demonstrated similar stress distributions. The loads put on the detached edges were not less than the intracranial pressure (ICP) when the stress threshold was reached. The results of the present study suggest that the direction of blood accumulation can be determined by the shape of the initial blood mass. Mechanical factors (blood pressure and ICP) did not serve a definitive role in preventing blood from accumulating in the early stages of ICH. The present study may aid in understanding the effects of mechanical factors in blood accumulation and hemostasis in patients with early ICH.

The dedifferentiation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of vascular remodeling-related disease. The present study aimed to investigate the effects of shexiangbaoxin (SXBX) pill, a traditional Chinese medicinal formula on VSMCs dedifferentiation and its potential mechanisms. High-fat diet (HFD) was introduced to lipoprotein receptor-deficient (LDLR -/- ) mice to generate hyperhomocysteinemia (HHcy), and plasma Hcy and lipid levels were analyzed. The phenotype of VSMCs was assessed in mice with the treatment of low (45 mg/kg/d) or high (90 mg/kg/d) SXBX pill by measuring the contractile protein α-SMA, SM22α and synthetic proteins OPN using RT-qPCR, western blotting and immunofluorescence assay. In vitro , the proliferation, migration and dedifferentiation of VSMCs were measured by MTT, Edu incorporation, wound healing and western blotting assay. Small interfering RNA technology was used to examine the role of NLRP3 in the effects of SXBX pill on dedifferentiation. The results indicated that although SXBX pill had no influence on HFD-induced HHcy and hyperlipidaemia, it reversed HHcy-induced dedifferentiation of VSMCs in vivo . SXBX pill significantly inhibited proliferation, migration and dedifferentiation of Hcy-treated VSMCs. In addition, we found that Hcy activated NLRP3 inflammasomes in VSMCs and SXBX pill could attenuate NLRP3 inflammasomes activation. Moreover, subsequent analysis suggested that SXBX pill inhibited NLRP3 inflammasomes activation through regulation of ERK1/2 and p38 MAPK pathway. Knockdown of NLRP3 reversed the inhibitory effects of SXBX pill in VSMCs. In conclusion, SXBX pill inhibited Hcy-induced proliferation, migration and dedifferentiation of VSMCs by suppressing NLRP3 inflammasomes activation via of ERK/p38 MAPK pathway., Competing Interests: None.

Objective: To study the value of neuroendoscopy assisted microneurosurgery technique in the treatment of posterior cranial fossa lesion. Methods: Clinical data of 36 patients with posterior fossa lesions who accepted neuroendoscopy assisted microneurosurgery (NEAM group) in the department of neurosurgery of the First Affiliated Hospital of Chongqing Medical University, from January 2014 to December 2016, were retrospectively enrolled. A total of 113 cases diagnosed with the same lesions and accepted conventional microneurosurgery (non-NEAM group) in the same period were analyzed as control group. The total tumor resection rate, postoperative leakage of cerebrospinal fluid, intracranial infection, operating time and the recovery of facial nerve function were compared between the two groups. Results: Ninety-three patients with acoustic neuroma were analyzed, which were divided into non-NEAM group 78 cases (removed posterior lip of internal auditory canal in different degrees) and NEAM group 15 cases (not removed posterior lip of internal auditory canal). The total tumor resection rate and postoperative facial nerve function had no significant statistical differences between two groups. The operating time of NEAM group was longer than that of non-NEAM group ( P =0.048, P <0.05), but the rate of leakage of cerebrospinal fluid and intracranial infection did not increase. Twenty-seven cases were diagnosed with cerebellopontine angle cholesteatoma. These cases were divided into two groups, 17 cases in non-NEAM group and 10 cases in NEAM group. NEAM group have higher total tumor resection rate ( P =0.014, P <0.05), better short-term postoperative facial nerve function ( P =0.039, P <0.05), and longer operating time ( P =0.015, P <0.05), compared with non-NEAM group. No significant statistical differences were observed on long-term postoperative facial nerve function and postoperative complications. Of the 16 cases diagnosed tentorial meningioma, 10 cases were in non-NEAM group and 6 cases in NEAM group. Six cases in non-NEAM group and 4 cases in NEAM group were total removal. For the mean operating time, non-NEAM group was (6.6±1.0) hours and NEAM group was (7.1±0.7) hours. Thirteen cases were with fourth ventricular cholesteatoma, which all were totally resected, and 8 cases were in non-NEAM group and 5 cases in NEAM group. For non-NEAM group, 5 cases dissected cerebellar vermis and the mean operating time is (6.0±0.7) hours. However, NEAM group all did not dissect cerebellar vermis and the mean operating time is (6.4±0.4) hours. Conclusions: Neuroendoscopy assisted microneurosurgery for cranial fossa lesions was benefit to totally resect tumor and reduce unnecessary injury. It needed longer operating time, but not increase postoperative intracranial infection.

Objective: To investigate the effectiveness and clinical significance of dynamic retraction microneurosurgery for the treatment of medial tentorial meningiomas. Methods: From January 2011 to December 2016, a cohort of 28 patients with medial tentorial meningiomas were treated by microneurosurgery at the First Affiliated Hospital of Chongqing Medical University. Patients who treated intraoperatively with dynamic retraction surgery from January 2014 to December 2016 were assigned into dynamic retraction group, and those with fixed retractors intraoperatively from January 2011 to December 2013 were assigned into retractor group. The surgical approaches tailored in our patients were based on predominant direction of tumor extension. The extent of tumor resection was scored according to the Simpson's classification scale. Comparisons of tumor size, operation time, hospitalization time, retraction-related injury, tumor Simpson resection grade and Karnofsky Performance Scale(KPS) score six months after surgery were also made between two groups. Results: A total of 12 patients(retractor group) were treated with the use of self-retaining brain retractors intraoperatively and dynamic retraction surgical procedure was performed intraoperatively in 16 patients(dynamic retraction group). The difference between two groups with regard to sex, age, tumor size, operation time and tumor Simpson resection grade was not statistically significant(all P >0.05). The mean duration of hospital time was shorter in the dynamic retraction group than that in the retractor group(18.3 d±1.8 d vs 20.2 d±1.3 d, P =0.004). The dynamic retraction group had lower incidence of retraction-related injury compared with the retractor group(1/16 vs 6/12), P =0.022]. The dynamic retraction group had better neurological recovery rate with KPS >80 evaluated six months after surgery compared with the retractor group(14/16 vs 5/12, P =0.017). Conclusions: Dynamic retraction microneurosurgery for the treatment of medial tentorial meningiomas is feasible, which can obviate or reduce the amount of brain retraction needed, and may be of help in lowering the risk of postoperative neurological deficits and complications and leading to reduced hospitalization cost and improved surgical outcomes.

Krüppel-like factors (KLFs) are a family of zinc finger transcription factors regulating embryonic development and diseases. The phylogenetics of KLFs has not been studied in tree shrews, an animal lineage with a closer relationship to primates than rodents. Here, we identified 17 KLFs from Chinese tree shrew (Tupaia belangeri chinensis). KLF proteins are highly conserved among humans, monkeys, rats, mice and tree shrews compared to zebrafish and chickens. The CtBP binding site, Sin3A binding site and nuclear localization signals are largely conserved between tree shrews and human beings. Tupaia belangeri (Tb) KLF5 contains several conserved post-transcriptional modification motifs. Moreover, the mRNA and protein expression patterns of multiple tbKLFs are tissue-specific . TbKLF5, like hKLF5, significantly promotes NIH3T3 cell proliferation in vitro. These results provide insight for future studies regarding the structure and function of the tbKLF gene family.

Human/simian immunodeficiency virus (HIV/SIV) infection can cause severe depletion of CD4(+) T cells in both plasma and mucosa; it also results in damage to the gut mucosa barrier, which makes the condition more conducive to microbial translocation. In this study, we used SIV-infected Chinese rhesus macaques to quantify the extent of microbial translocation and the function of immune cells in the entire gastrointestinal tract and to compare their differences between rapid and slow progressors. The results showed that in the slow progressors, microbial products translocated considerably and deeply into the lamina propria of the gut; the tissue macrophages had no significant differences compared with the rapid progressors, but there was a slightly higher percentage of mucosal CD8(+) T cells and a large amount of extracellular microbial products in the lamina propria of the intestinal mucosa of the slow progressors. The data suggested that although microbial translocation increased markedly, the mucosal macrophages and CD8(+) T cells were insufficient to clear the infiltrated microbes in the slow progressors. Also, therapies aimed at suppressing the translocation of microbial products in the mucosa could help to delay the progression of SIV disease., (© 2016 John Wiley & Sons Ltd.)

The tree shrew is becoming an attractive experimental animal model for human breast cancer owing to a closer relationship to primates/humans than rodents. Tree shrews are superior to classical primates because tree shrew are easier to manipulate, maintain and propagate. It is required to establish a high-efficiency tree shrew breast cancer model for etiological research and drug assessment. Our previous studies suggest that 7,12-dimethylbenz(a)anthracene (DMBA) and medroxyprogesterone acetate (MPA) induce breast tumors in tree shrews with a low frequency (<50%) and long latency (∼ 7-month), making these methods less than ideal. We induced mammary tumors in tree shrew (Tupaia belangeri chinensis) by injection of lentivirus expressing the PyMT oncogene into mammary ducts of 22 animals. Most tree shrews developed mammary tumors with a latency of about three weeks, and by 7 weeks all injected tree shrews had developed mammary tumors. Among these, papillary carcinoma is the predominant tumor type. One case showed lymph node and lung metastasis. Interestingly, the expression levels of phosphorylated AKT, ERK and STAT3 were elevated in 41-68% of PyMT-induced mammary tumors, but not all tumors. Finally, we observed that the growth of PyMT-induced tree shrew mammary tumors was significantly inhibited by Cisplatin and Epidoxorubicin. PyMT-induced tree shrew mammary tumor model may be suitable for further breast cancer research and drug development, due to its high efficiency and short latency., (© 2015 UICC.)

Objective. To observe the fellow eye in patients undergoing surgery on one eye for treating myopic traction maculopathy. Methods. 99 fellow eyes of consecutive patients who underwent unilateral surgery to treat MTM were retrospectively evaluated. All patients underwent thorough ophthalmologic examinations, including age, gender, duration of follow-up, refraction, axial length, intraocular pressure, lens status, presence/absence of a staphyloma, and best-corrected visual acuity (BCVA). Fundus photographs and SD-OCT images were obtained. When feasible, MP-1 microperimetry was performed to evaluate macular sensitivity and fixation stability. Results. At an average follow-up time of 24.7 months, 7% fellow eyes exhibited partial or complete MTM resolution, 68% stabilized, and 25% exhibited progression of MTM. Of the 38 eyes with "normal" macular structure on initial examination, 11% exhibited disease progression. The difference in progression rates in Groups 2, 3, and 4 was statistically significant. Refraction, axial length, the frequency of a posterior staphyloma, chorioretinal atrophy, initial BCVA, final BCVA, and retinal sensitivity all differed significantly among Groups 1-4. Conclusions. Long axial length, chorioretinal atrophy, a posterior staphyloma, and anterior traction contribute to MTM development. Patients with high myopia and unilateral MTM require regular OCT monitoring of the fellow eye to assess progression to myopic pre-MTM. For cases exhibiting one or more potential risk factors, early surgical intervention may maximize the visual outcomes.

We present a modified GPU (graphics processing unit) version of MrBayes, called ta(MC)(3) (GPU MrBayes V3.1), for Bayesian phylogenetic inference on protein data sets. Our main contributions are 1) utilizing 64-bit variables, thereby enabling ta(MC)(3) to process larger data sets than MrBayes; and 2) to use Kahan summation to improve accuracy, convergence rates, and consequently runtime. Versus the current fastest software, we achieve a speedup of up to around 2.5 (and up to around 90 vs. serial MrBayes), and more on multi-GPU hardware. GPU MrBayes V3.1 is available from http://sourceforge.net/projects/mrbayes-gpu/., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Resveratrol is a natural phenol, produced from red grapes, berries and peanuts. Previous studies have suggested that resveratrol exerts anticancer effects. Activation of the signal transducer and activator of transcription 3 (Stat3) is important in cancer. However, the mechanisms by which resveratrol suppresses the Stat3 signaling pathway remain to be elucidated. The aim of the present study was to investigate the effects of resveratrol on GRIM‑19‑Stat3 signaling in HeLa cells, derived from a cervical tumor. HeLa cells were divided into experimental groups and treated with resveratrol. Western blotting was used to analyze the expression levels of p‑Stat3, Stat3, GRIM‑19 and β‑actin. Cell viability was determined using an MTT assay. The results showed that 100 µM resveratrol suppressed the proliferation and Stat3 phosphorylation in HeLa cells, and induced the expression of the gene associated with retinoid‑IFN‑induced mortality 19 (GRIM‑19) protein. Overexpression of GRIM‑19 suppressed the Stat3 signaling pathway in HeLa cells. The Stat3 signaling pathway was activated following the downregulation of GRIM‑19 expression using short interfering RNAs (siRNAs). Resveratrol suppressed cell proliferation, however, this effect was decreased through the use of siRNAs. The suppression of Stat3 phosphorylation by resveratrol decreased following treatment with siRNAs. To the best of our knowledge, the present study is among the first to identify GRIM‑19‑Stat3 signaling as a target of resveratrol, and further elucidates the mechanisms underlying the antitumor activity of resveratrol.

The difference between three representative components of total salvianolic acids in pharmacodynamic activity were compared by three different pharmacological experiments: HUVECs oxidative damage experiment, 4 items of blood coagulation in vitro experiment in rabbits and experimental myocardial ischemia in rats. And the effects of contribution rate of each component were calculated by multi index comprehensive evaluation method based on CRITIC weights. The contribution rates of salvianolic acid B, rosmarinic acid and Danshensu were 28.85%, 30.11%, 41.04%. Apparent oil/water partition coefficient of each representative components of total salvianolic acids in n-octyl alcohol-buffer was tested and the total salvianolic acid components were characterized based on a combination of the approach of self-defined weighting coefficient with effects of contribution rate. Apparent oil/water partition coefficient of total salvianolic acids was 0.32, 1.06, 0.89, 0.98, 0.90, 0.13, 0.02, 0.20, 0.56 when in octanol-water/pH 1.2 dilute hydrochloric acid solution/ pH 2.0, 2.5, 5.0, 5.8, 6.8, 7.4, 7.8 phosphate buffer solution. It provides a certain reference for the characterization of components.

Tree shrew has increasingly become an attractive experimental animal model for human diseases, particularly for breast cancer due to spontaneous breast tumours and their close relationship to primates and by extension to humans. However, neither normal mammary glands nor breast tumours have been well characterised in the Chinese tree shrew (Tupaia belangeri chinensis). In this study, normal mammary glands from four different developmental stages and 18 spontaneous breast tumours were analysed. Haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) showed that normal mammary gland morphology and structures of tree shrews were quite similar to those found in humans. Spontaneous breast tumours of tree shrews were identified as being intraductal papilloma, papillary carcinoma, and invasive ductal carcinoma with or without lung metastasis. To further analyse breast cancer tumours among tree shrews, 40 3-4 month-old female tree shrews were orally administrated 20 mg 7,12-dimethylbenz(a)anthracene (DMBA) or peanut oil thrice, and then, 15 of these DMBA administrated tree shrews were implanted with medroxyprogesterone acetate (MPA) pellets. DMBA was shown to induce breast tumours (12%) while the addition of MPA increased the tumour incidence (50%). Of these, three induced breast tumours were intraductal papillary carcinomas and one was invasive ductal carcinoma (IDC). The PTEN/PIK3CA (phosphatase and tensin homologue/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), but not TP53 and GATA3, genes are frequently mutated in breast tumours, and the PTEN/PIK3CA gene mutation status correlated with the expression of pAKT in tree shrew breast tumours. These results suggest that tree shrews may be a promising animal model for a subset of human breast cancers with PTEN/PIK3CA gene mutations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The angiotensin (Ang) converting enzyme 2 (ACE2)/Ang-(1-7)/Mas receptor pathway is an important component of the renin-angiotensin system and has been suggested to exert beneficial effects in ischemic stroke., Aims: This study explored whether the ACE2/Ang-(1-7)/Mas pathway has a protective effect on cerebral ischemic injury and whether this effect is affected by age., Methods: We used three-month and eight-month transgenic mice with neural over-expression of ACE2 (SA) and their age-matched nontransgenic (NT) controls. Neurological deficits and ischemic stroke volume were determined following middle cerebral artery occlusion (MCAO). In oxygen and glucose deprivation (OGD) experiments on brain slices, the effects of the Mas receptor agonist (Ang1-7) or antagonist (A779) on tissue swelling, Nox2/Nox4 expression reactive oxygen species (ROS) production and cell death were measured., Results: (1) Middle cerebral artery occlusion -induced ischemic injury and neurological deficit were reduced in SA mice, especially in eight-month animals; (2) OGD-induced tissue swelling and cell death were decreased in SA mice with a greater reduction seen in eight-month mice; (3) Ang-(1-7) and A779 had opposite effects on OGD-induced responses, which correlated with changes in Nox2/Nox4 expression and ROS production., Conclusions: Angiotensin converting enzyme 2/Ang-(1-7)/Mas axis protects brain from ischemic injury via the Nox/ROS signaling pathway, with a greater effect in older animals., (© 2014 John Wiley & Sons Ltd.)

Histone acetylation has been linked to depression, the etiology of which involves many factors such as genetics, environments, and epigenetics. The aim of the present study was to investigate whether it was associated with epigenetic histone modification and gene expression of enzymes responsible for the biosynthesis of norepinephrine and serotonin in rat depression model induced by chronic unpredictable stress (CUS). Eight-week-old male Sprague-Dawley rats were exposed to CUS over 28 days. It was shown that the CUS-induced rats displayed remarked anxiety- and depression-like behavior with weakened locomotor activity in open field test and prolonged immobility in forced swimming test. Western blot revealed that CUS led to significant decrease in acetylation of H3 at Lysine 9 (K9) and H4 at Lysine 12 (K12) with obviously increasing histone deacetylases 5 (HDAC5) expression in hippocampus of CUS-induced rats. Meanwhile, there was an obviously decreased expression of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) both at protein and mRNA levels. Administration of sodium valproate (VPA), a histone deacetylase 5 (HDAC5) inhibitor, not only significantly relieved the anxiety- and depression-like behaviors of CUS-induced rats but also clearly blunted decrease of H3(K9) and H4(K12) acetylation and expression of TH and TPH, and prevented increase of HDAC5 expression. The results indicate that there exists possible interrelation between TH and TPH gene expression and epigenetic histone acetylation in CUS-induced depressive rats, which at least partly contributes to the etiology of depression.

Traditional Chinese medicines have a long history, with a large quantity of efficient traditional Chinese medicines and prescriptions. However, the vast majority of pharmaceutical dose forms remain common preparations, with very few efficient, long-lasting and low-dose preparations. The sustain-release preparation allows sustained drug release in a longer period of time, maintains blood drug concentration, reduces the toxic effect and medication frequency, and improves medication compliance. Unlike monomer drugs, the material base of traditional Chinese medicine and compounds is multi-component, instead of single or several active monomers. Therefore, under the guidance of the Chinese medicine theories, modern multi-component sustained-release preparations were developed for oral traditional Chinese medicines, with the aim of finally improving the clinical efficacy of traditional Chinese medicines.

Both chemical drugs and traditional Chinese medicines have the problem of low bioavailability. However, as traditional Chinese medicines are a multi-component complex, their dosage forms are required to be designed in line with their characteristics, in order to improve the bioavailability of traditional Chinese medicines. Traditional Chinese medicines are mostly prepared into pill, powder, paste, elixir and decoction, but with such drawbacks as high administration dose and poor efficacy. With the process of modernization of traditional Chinese medicines, new-type preparations have be developed and made outstanding achievements. However, they fail to make an organic integration between traditional Chinese medicine theories and modern preparation theories. Characteristics of traditional Chinese medicines are required to be taken into account during the development of traditional Chinese medicines. In the article, multi-component preparation technology was adopted to establish a multi-component drug release system of traditional Chinese medicines on the basis of multiple components of traditional Chinese medicines.

In this study, the biopharmaceutical properties of 20 (S)-protopanaxadiol (PPD) were studied. Firstly, the equilibrium solubility and apparent oil/water partition coefficient of PPD were used to predict the absorption in vivo. Meanwhile the membrane permeability and absorption window were studied by Caco-2 cell model and single-pass intestinal perfusion model. Furthermore, the bioavailability and metabolism were combined to study the absorption properties and metabolic properties in vivo. All of them were used to provide theoretical and practical foundation for designing PPD preparation. The results showed that PPD is poorly water-soluble, and the equilibrium solubility in water is only 35.24 mg x L(-1). The oil-water partition coefficient is 46.21 (logP = 1.66). By Caco-2 cell model, the results showed PPD uptake in general, and it also has efflux. By in situ intestinal perfusion model, the results showed that the absorption of PPD in the intestine is good, and the effective permeability coefficient were duodenum > jejunum > ileum > colon. The oral bioavailability of PPD was 29.39%. It was not well. Metabolic studies showed PPD in vivo presented a wide spread metabolism. So the main factors that restricted oral bioavailability of PPD were the poor solubility and first-pass effect.

Objective: To apply PVP-S630 in the preparation of tanshinone II(A) (TS II(A)) solid dispersion, in order to improve its dissolution in vitro and reduce the moisture absorption of the solid dispersion., Method: Tanshinone II(A) solid dispersion was prepared by spray drying method. Such analytical methods as SEM, DSC, XRD were used to characterize their phases and detect their dissolution, moisture absorption and stability., Result: In the solid dispersion prepared with tanshinone II(A) and copovidone with proportion of 1:10, tanshinone II(A) was scattered on the surface of the carrier in the amorphous form, with a dissolution in vitro up to 100% at 0.5 h and a lower moisture absorption than PVP-K30 solid dispersion prepared with the same proportion. After a three-month accelerated stability test, it showed no significant change in drug dissolution and content., Conclusion: The solid dispersion prepared with copovidone as the carrier can significantly improve the dissolution of tanshinone II(A), with a relatively low moisture absorption and high stability, thereby having a good prospect of application.

It is currently widely accepted that immune activation in HIV-infected individuals leads to a severe loss of CD4⁺ T cells and the progression to AIDS. However, the underlying mechanism of this immune activation remains unclear. Experimental data suggest that the activation of plasmacytoid dendritic cells (pDCs) by plasma viremia may play a critical role in HIV-induced immune activation. In this study, we found that the level of immune activation was higher in the late phase of SIVmac239 infection compared with chronic infection, which suggests that immune activation might be related to disease progression in SIVmac239-infected non-human primate models. Our work also showed that chloroquine could effectively inhibit the activation of pDCs in vitro and in vivo. However, chloroquine treatment of SIVmac239-infected macaques had no significant influence on the Cellular composition of peripheral blood in these animals.

CD4(+)CD25(high) regulatory T cells (Treg), which are a specialized subset of T cells, play an important role in the prevention of autoimmune diseases, maintenance of immune system homeostasis and tolerance to self-antigens. Chinese rhesus macaques (CRMs) are widely used in preclinical research on potential therapeutic drugs, vaccines and mechanisms of human diseases. However, the basic immunological characterization of Treg cells of CRMs has not been well established. To characterize Treg cells, peripheral blood of 43 adult CRMs was analyzed for CD4+ T lymphocytes by flow cytometry. It was found that Treg cells ranged from 1.52% to 11.1% of CD4+ T cells, and the average value was 5.7%. With our SIV-infected CRM model, through further studies, it was found that Treg cells in peripheral blood increased both in relative and absolute quantities. Moreover, Treg cells maintained their functions by suppressing Th1 cytokine secretion of their target cells. The results show that Treg cells might render cellular immunity against SIV viruses dysfunctional during the early stage after infection.

The MHC class I (MHC I) molecules play a pivotal role in the regulation of immune responses by presenting antigenic peptides to CTLs and by regulating cytolytic activities of NK cells. In this article, we show that MHC I A in rhesus macaques can be alternatively spliced, generating a novel MHC I A isoform (termed "MHC I A-sv1") devoid of α(3) domain. Despite the absence of β2-microglobulin (β2m), the MHC I A-sv1 proteins reached the cell surface of K562-transfected cells as endoglycosidase H-sensitive glycoproteins that could form disulfide-bonded homodimers. Cycloheximide-based protein chase experiments showed that the MHC I A-sv1 proteins were more stable than the full-length MHC I A in transiently or stably transfected cell lines. Of particular interest, our studies demonstrated that MHC I A-sv1 could form β2m-free heterodimers with its full-length protein in mammalian cells. The formation of heterodimers was accompanied by a reduction in full-length MHC I A ubiquitination and consequent stabilization of the protein. Taken together, these results demonstrated that MHC I A-sv1 and MHC I A can form a novel heterodimeric complex as a result of the displacement of β2m and illustrated the relevance of regulated MHC I A protein degradation in the β2m-free heterodimerization-dependent control, which may have some implications for the MHC I A splice variant in the fine tuning of classical MHC I A/TCR and MHC I A/killer cell Ig-like receptor interactions.

Breast cancer is a common malignant tumor. It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches. Tree shrews (Tupaia belangeri chinensis) have a closer evolutionary relationship with humans than do rodents, which have been widely used in laboratory research. Spontaneous breast tumors were identified in tree shrews in 1960s; however, no detailed studies about tree shrew breast tumors have been conducted to date. Here, we characterized a spontaneous breast tumor from tree shrews by Haematoxylin Eosin (H&E) staining. This tumor was identified as a papillary tumor. Immunohistochemical staining (IHC) for progesterone receptor (PR), Ki-67 and cleaved caspase-3 showed that tumor cells were positive for PR, highly proliferative, and less apoptotic compared to normal breast epithelial cells. Thus, the spontaneous tumor of tree shrew is very close to human papillary tumors in terms of morphology and pathology and we concluded that tree shrew may be a suitable animal model for breast cancer research.

Objective: To compare three techniques of the transarticular screw placement in the lower cervical spine., Methods: The techniques of transarticular screw placements used by Takayasu (group A), Dalcanto (group B) and Klekamp (group C) were applied in twenty-four cervical specimens, among which 14 specimens were male and 10 specimens were female, ranging in age from 55 to 80 years, with an average of 68 years. The entry point of Takayasu technique was between the superior and median third of the vertical medial line of the lateral mass with 60 to 80 degrees caudal tilt and 0 degrees lateral tilt. Dalcanto technique started 2 mm caudal to the midpoint of lateral mass with 40 degrees caudal tilt and 20 degrees lateral tilt. Klekamp technique inserted the screws with the starting point being 1 mm medial and 1 mm inferior to the midpoint of the lateral mass with 40 degrees caudal tilt and 20 degrees lateral tilt. The splits of facets, the encroachment of the cervical nerve roots and vertebral arteries, and no-involving facets screws were observed and analyzed., Results: One hundred and ninety-two transarticular screws were implanted on both sides in twenty-four cervical cadavers, sixty-four for each group. There were twenty-five splits of inferior facets in group B, 2 splits in group C and none in group A. No superior facets were found to be broken in all cases. The difference of splits between group B and the other two groups was significant (Chi2AB = 31.07, P < .001; Chi2BC = 24.83, P < 0.01), while there was no statistical difference between group A and C (Chi2AC = 2.03, P > 0.05). Thirty-six screws encroached the vertebral arteries in group A, none in group B and C. There was significant statistical difference between group A and the other two groups (Chi2AB = 50.09, P < 0.01; Chi2AC = 50.09, P < 0.01). Forty anterior branches of lower cervical nerve roots were involved in group A, five in group B and three in group C. There were statistical differences between group A and the other two groups (Chi2AB = 41.98, P < 0.01; Chi2AC = 47-94, P < 0.01), and there was no statistical difference between group B and C. Sixteen posterior branches of lower cervical nerve roots were encroached in group A, 18 in group B and 14 in group C. There was statistical difference among the three groups (Chi2AB = 0.16, P > 0.05; Chi2AC = 0.17, 0.05; Chi2 = BC = 0.67, P >0.0 ). Although all screws went through facets in the study except for 5 in group A, there were no statistical differences between each groups Chi2AB k =3.33, P >0.05; X2A C =3.33, P> 0.05)., Conclusion: There are high risk of injury of anterior branch of cervical nerve root and vertebral artery if the screws are too long and the Takayasu's technique is used. However, the rate of facet split is high if the Dalcanto's technique is applied. Klekamp's technique is value to be applied.

Cancer is the second leading disease causing human death. Pre-clinical in vivo studies are essential for translating in vitro laboratory research results into the clinic. Rodents, including the mouse and rat, have been widely used for pre-clinical studies due to their small size, clear genetic backgrounds, rapid propagation, and mature transgenic technologies. However, because rodents are evolutionarily distinct from humans, many pre-clinical research results using rodent models cannot be reproduced in the clinic. Non-human primates (NHPs) may be better animal models than rodents for human cancer research because NHPs and humans share greater similarity in regards to their genetic evolution, immune system, physiology and metabolism. This article reviews the latest progress of cancer research in NHPs by focusing on the carcinogenesis of different NHPs induced by chemical and biological carcinogens. Finally, future research directions for the use of NHPs in cancer research are discussed.

Non-human primates such as Chinese rhesus macaques (Ch Rhs) provide good animal models for research on human infectious diseases. Similar to humans, there are two principal subsets of dendritic cells (DCs) in the peripheral blood of Ch Rhs: myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). In this study, two-color fluorescence-activated cell sorting (FACS) analyses were used to identify the main DC subsets, namely CD1c(+) mDCs and pDCs from Ch Rhs. Then, the apoptosis and immunophenotype changes of DCs subsets were first described during the acute phase of SIVmac239 infection. Both the DCs subsets showed decreased CD4 expression and enhanced CCR5 expression; in particular, those of pDCs significantly changed at most time points. Interestingly, the plasma viral loads were negatively correlated with CD4 expression, but were positively correlated with CCR5 expression of pDCs. During this period, both CD1c(+) mDCs and pDCs were activated by enhancing expressions of co-stimulatory molecules, accompanied with increase in CCR7. Either CD80 or CD86 expressed on CD1c(+) mDCs and pDCs was positively correlated with the plasma viral loads. Our analysis demonstrates that the pDCs were more prone to apoptosis after infection during the acute phase of SIVmac239 infection, which may be due to their high expressions of CD4 and CCR5. Both DCs subsets activated through elevating the expression of co-stimulatory molecules, which was beneficial in controlling the replication of SIV. However, a mere broad immune activation initiated by activated DCs may lead to tragic AIDS progression.

Background: Several studies have demonstrated that SIV infection progresses more slowly to experimental AIDS in Chinese rhesus macaques (Ch Rhs) than in Indian rhesus macaques (Ind Rhs). Here we investigated the dynamic and functional changes in dendritic cell (DC) subsets in SIVmac239-infected Ch Rhs., Results: The numbers of both mDC and pDC strongly fluctuated but were not significantly changed during the acute and chronic phases of infection. However, the concentration of both poly (I:C)-induced IL-12 and HSV-1-induced IFN-α significantly increased in the acute phase of infection but returned to normal levels at the chronic phase of infection. The peak of IFN-α emerged earlier than that of IL-12, and it had a significantly positive correlation with IL-12, which indicated that IFN-α may initiate the immune activation. We also found that only the concentration of IFN-α was positively correlated with CD4+ T-cell counts, but it was negatively correlated with viral load., Conclusion: High levels of IFN-α in the early stage of infection may contribute to effective control of virus replication, and normal levels of IFN-α during chronic infection may help Ch Rhs resist the disease progression. The change in DC subsets dynamics and cytokine production may help further our understanding of why Ch Rhs are able to live longer without progressing to an AIDS-like illness.

Cerebral vasospasm (CV) is the main complication of spontaneous subarachnoid hemorrhage (SAH), affecting clinical outcome of patients with SAH. Accumulating evidence indicates that apolipoprotein E (apoE protein, APOE gene) gene polymorphism is associated with prognosis of patients with SAH. The current study aimed to investigate the association of promoter polymorphism of APOE with CV in patients with SAH. One hundred and one patients with spontaneous SAH were involved in this study. Venous blood samples were collected to identify the promoter genotype of APOE by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CV was judged by transcranial Doppler sonography (TCD) combined with patients' condition. Associations of APOE promoter polymorphism with CV after SAH were analyzed by χ(2) test, uni- and multivariate logistic regression analyses. In 101 patients, 42 of 87 patients (48.3%) with promoter -219T allele showed CV, which was significantly different from those with -219G allele (23/61, 37.7%, P=0.04). Uni- and multivariate logistic regression analyses also showed that promoter -219T was a risk factor to predispose CV after SAH. However, there was no significant association between promoter -491A/T (rs#449647) or -427C/T (rs#769446) polymorphisms and SAH induced CV (P>0.05). Our finding suggests that patients with APOE -219T promoter are apt to CV after spontaneous SAH., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Non-human primate models are widely used in research of AIDS mechanism, transmission, vaccine and drugs. Dendritic cells (DC), as antigen presenting cells linking the innate immunity and acquired immunity, play a pivotal role in AIDS progression. Studies on the change of DC subsets number, phenotype and function in AIDS non-human primate models are important for revealing some mechanism of AIDS progression. This article reviews the progress in DC subsets of non-human primate AIDS models, which will provide an avenue for further study in AIDS.

Non-human primates such as Chinese rhesus macaques are the favorable models for preclinical study of potential therapeutic drugs, vaccines and mechanisms of human diseases. Little is known about the normal levels of leukocyte subpopulations of Chinese rhesus macaques. To obtain these data, 100 blood samples from Chinese rhesus macaques were collected. The normal range of major leukocyte subpopulations, such as T lymphocytes, B lymphocytes, monocytes, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), were quantitatively analyzed by flow cytometry through BD trucount tubes. The influence of age and sex on the cell counts of leukocyte subpopulations was analyzed. The counts of CD3(+) T cells, CD3(+)CD4(+) T cells, CD3(+)CD8(+) T cells and B cells decreased with age, but those of monocytes, mDCs and pDCs had no significant correlation with age. Significant differences existed in the cell counts of most leukocyte subpopulations between the male and female groups except pDCs. And the values of the females were higher than those of the males. The study provided basic information about the leukocyte subpopulations of Chinese rhesus macaques, and it may be valuable for immunobiological study of Chinese rhesus macaques.

Objective: To compare two techniques of the transarticular screw placement in the lower cervical spine, and to suggest and confirm a new technique of the placement., Methods: The techniques of transarticular screw placements used by Takayasu (group A) and Dalcanto (group B) were applied in eight cervical specimens. The splits of facets,the encroachment of the cervical nerve roots and transverse foramens were observed and analyzed. The numbers of transarticular screws which not gone through the facets were counted in both group A and B, respectively., Results: Sixty-four transarticular screws were implanted,thirty-two for group A, the same for group B. Although no splits of the facets were seen in group A, two transarticular screws did not go through the facets. There were ten splits of facets in group B, in which seven involved the inferior border of the inferior facets and three for the lateral border. No superior facets were found to be broken both in group A and B. Eight screws encroached the transverse foramens in group A and none in group B. Eleven of anterior branch and eight of posterior branch of lower cervical nerve roots were involved in group A, two and nine respectively in group B., Conclusion: There are high risk of injury of anterior branch of cervical nerve root and vertebral artery if the screws are too long and the Takayasu's technique is used. However, the rate of facet split is high if the Dalcanto's technique is applied.

Objective: To study the percutaneous lag screw internal fixation of LX technique for sacroiliac joint diseases or injuries., Methods: There were 38 patients (25 male and 13 female) with an average age of 35.6 years ranged from 18 to 59 years. Among them, thirty-one cases with trauma of Tile B type, five cases with sacroiliitis and two cases with sacral cystis degeneration. There were 11, 15, 5 cases of Tile B1, B2, B3 type respectively. Pelvic anterior-posterior radiography and spiral computed tomography (CT) were undertaken for all patients. Axis planar, coronal planar, sagittal planar and curve planar of sacral reconstruction of spiral CT images were obtained for every patient. There were 28 cases with delitescence posterior ring injury. All these patients were performed percutaneous lag screw fixation procedures of LX technique under epidural anesthesia. Localization with spiral CT guidance was performed by the radiologist using spiral CT followed by the orthopaedic surgeon. Percutaneous fusion of sacroiliac joint was performed for seven patients who suffered from sacroiliac joint diseases., Results: The blood loss were from 25 to 70 ml (means 36 ml) during operation. All patients were followed up for 3 to 39 months (means 15.6 months). There were no postoperative complications such as infection, fracture nonunion, iatrogenic injuries of nerve and blood vessel, breakage and slippage of fixtors. According to the evaluation of pelvic injuries, the results of imageology were excellent in 34 cases and good in 4, the results of clinical were excellent in 32 and good in 6., Conclusion: Percutaneous lag screw internal fixation of LX technique minimizes operation injury during a short procedure with few subsequent complications and allows early mobilization of the patients. That is an ideally safe and effetive operation technique for the sacroiliac joint diseases and injuries.

Objective: To explore the location of the anterior border of facets and the posterior border of vertebral bodies in lower cervical spine,and to provide a quantitative data to evaluate the correct length of transarticual screws in lower cervical spine during procedure., Methods: One hundred standard lateral X-ray films and fifty CT films on cervical spine were used to measure the distance of the anterior border of facets and the posterior border of vertebral bodies in lower cervical spine. HS, HM and HI were defined as parameters, which means the distance between the anterior border of the superior (HS), median (HM) and inferior (HI) part of facets and the posterior border of corresponding vertebral bodies. The value will be negative if the anterior border of the facet located before the vertebral body., Results: 'HS > HM > HI' was found in all facets in lower cervical spine. The anterior border of the facet in C(3,4) located before the posterior border of the vertebral body of C3. The anterior border of C(4,5) and C(5,6) was inclined to posterior. The anterior border of C(6,7) located after the posterior border of the vertebral body of C6. The pattern of HS increased from C(3,4) to C(6,7), the minimal (0 +/- 0.25) mm and the maximal (2.91 +/- 1.05) mm. The tendency of HM raised from C(3,4) to C(6,7), the minimal (-1.57 +/- 0.53) mm and the maximal (1.54 +/- 0.39) mm. The pattern HI added from C(3,4) to C(6,7), the minimal (-2.03 +/- 0.40) mm and the maximal (1.08 +/- 0.70) mm., Conclusion: During the implantation of the transarticular screws, the tip of the screws should be 0-2 mm before the posterior border of the vertebral body of C3 at C(3,4), 0-2 mm after that of C4 at C(4,5), 0.5-2.5 mm at C(5,6) and 1-3 mm at C(6,7). The quantitative location between the anterior border of facets and the posterior border of the corresponding vertebral bodies can offer an indirect method to evaluate the correct length of transarticual screws in lower cervical spine during procedure.

Downregulation of the transcription factor AtMYB103 using transgenic technology results in early tapetal degeneration and pollen aberration during anther development in Arabidopsis thaliana. This paper describes the functional analysis of the AtMYB103 gene in three knock-out mutants. Two male sterile mutants, ms188-1 and ms188-2, were generated by ethyl-methane sulfonate (EMS) mutagenesis. A map-based cloning approach was used, and ms188 was mapped to a 95.8-kb region on chromosome 5 containing an AtMYB103 transcription factor. Sequence analysis revealed that ms188-1 had a pre-mature stop codon in the AtMYB103 coding region, whereas ms188-2 had a CCT-->CTT base-pair change in the first exon of AtMYB103, which resulted in the replacement of a proline by a leucine residue in the R2R3 domain. The third mutant, an AtMYB103 transposon-tagging line, also showed a male sterile phenotype. Allelism tests indicated that MS188 and AtMYB103 belong to the same locus. Cytological observation revealed defective tapetum development and altered callose dissolution in ms188 plants. Additionally, most of the microspores in mature anthers were degraded and surviving microspores lacked exine. AtMYB103 encoded an R2R3 MYB protein that is predominantly located in the nucleus. Real-time RT-PCR analysis indicated that the callase-related gene A6 was regulated by AtMYB103. Expression of the exine formation gene MS2 was not detected in mutant anthers. These results implicate that AtMYB103 plays an important role in tapetum development, callose dissolution and exine formation in A. thaliana anthers.

The Arabidopsis (Arabidopsis thaliana) inositol polyphosphate 6-/3-kinase gene (AtIpk2beta) is known to participate in inositol phosphate metabolism. However, little is known about its physiological functions in higher plants. Here, we report that AtIpk2beta regulates Arabidopsis axillary shoot branching. By overexpressing AtIpk2beta in the wild type and mutants, we found that overexpression of AtIpk2beta leads to more axillary shoot branches. Further analysis of AtIpk2beta overexpression lines showed that axillary meristem forms earlier and the bud outgrowth rate is also accelerated, resulting in more axillary shoot branches. The AtIpk2beta promoter/beta-glucuronidase (GUS) fusion (AtIpk2betaGUS) expression pattern is similar to that of the auxin reporter DR5GUS. Moreover, AtIpk2beta can be induced in response to exogenous indole-3-acetic acid (IAA) treatments. In addition, AtIpk2beta overexpression plants exhibit IAA-related phenotypes and are more resistant to exogenous IAA treatments. Further analysis employing reverse transcription-polymerase chain reaction shows that some genes, including auxin-biosynthesis (CYP83B1), auxin-transport (PIN4), and auxin-mediated branching genes (MAX4 and SPS), are regulated by AtIpk2beta. Taken together, our data provide insights into a role for AtIpk2beta in axillary shoot branching through the auxin signaling pathway.

The exaggerated cardiac arrhythmias in cardiomyopathy induced by L-thyroxine treatment are related to ion channelopathies and to an abnormal endothelin (ET) pathway. It was hypothesized that an increased incidence of ventricular fibrillation (VF) could be mediated by inflammatory factors including the ET pathway, nuclear factor kappa B (NFkappaB), tumor necrosis factor-alpha (TNFalpha) and inducible nitric oxide synthase (iNOS). Abnormal expression of NFkappaB, TNFalpha, iNOS and enhanced VF are linked with the activated ET pathway and a significant reversion could be achieved by the selective endothelin A receptor antagonist darusentan. Cardiomyopathy in rats was produced by L-thyroxine treatment (0.3 mg kg(-1) d(-1), sc) for 10 days. The mRNA expression of the ET pathway, NFkappaB, TNFalpha, iNOS and the activity of the redox system were assayed in association with the incidence of VF produced by coronary ligation/reperfusion. Darusentan was administered on days 6-10 of L-thyroxine treatment. The VF incidence, which was higher in the l-thyroxine cardiomyopathy group, was suppressed by darusentan. The mRNA levels of preproET-1, endothelin converting enzyme, endothelin receptor A (ET(A)R), endothelin receptor B (ET(B)R), NFkappaB, TNFalpha and iNOS in left ventricle were up-regulated in the cardiomyopathic heart. There was significant oxidative stress in this cardiomyopathy model. Darusentan suppressed the up-regulated mRNA levels of ET(A)R, ET(B)R, NFkappaB, TNFalpha, and iNOS. These results indicate that the high incidence of VF which is related to up-regulation of inflammatory factors in the cardiomyopathic myocardium is significantly suppressed by selective ET(A)R blockade.

The depressed sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) and Ca2+-release channels (ryanodine receptor RyR2) are involved in the diabetic cardiomyopathy. However, an implication of a down-regulation of FK506-binding protein or calstabin-2 (FKBP12.6) is undefined. It was hypothesized that the down-regulation of FKBP12.6 and SERCA2a of the intracellular calcium handling system is closely related to an up-regulated endothelin (ET) system. An ET receptor antagonist CPU0213 is newly discovered and expected to ameliorate cardiac insufficiency which is mediated by the depressed FKBP12.6 and SERCA2a in diabetic rat heart. Diabetes was developed in male Sprague-Dawley rats 8 weeks after an injection of streptozotocin (60 mg/kg IP), and CPU0213 was instituted 30 mg/kg, SC in the last 4 weeks. The assessment of the cardiac function, cardiac calcium handling proteins, endothelin system, and redox enzyme system were conducted. The compromised cardiac function in diabetic rats was accompanied by a significant down-regulation of expression of FKBP12.6 as well as SERCA2a and phospholamban. These were closely linked with an increased ET-1 and up-regulation of endothelin converting enzyme, PropreET1, and inducible nitric oxide synthase mRNA in diabetic cardiomyopathy. After 4-week treatment, CPU0213 was capable to attenuate completely the down-regulated FKBP12.6 and SERCA2a, and up-regulated ET system in association with a recovery of the cardiac insufficiency of diabetic cardiomyopathy.

Inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase/IP(3)K) plays an important role in signal transduction in animal cells by phosphorylating inositol 1,4,5-trisphosphate (IP3) to inositol 1,3,4,5-tetrakisphosphate (IP(4)). Both IP(3) and IP(4) are critical second messengers which regulate calcium (Ca(2+)) homeostasis. Mammalian IP3Ks are involved in many biological processes, including brain development, memory, learning and so on. It is widely reported that Ca(2+) is a canonical second messenger in higher plants. Therefore, plant IP3K should also play a crucial role in plant development. Recently, we reported the identification of plant IP3K gene (AtIpk2beta/AtIP3K) from Arabidopsis thaliana and its characterization. Here, we summarize the molecular cloning, biochemical properties and biological functions of IP3Ks from animal, yeast and plant. This review also discusses potential functions of IP3Ks in signaling crosstalk, inositol phosphate metabolism, gene transcriptional control and so on.