[Risk factors for progression to chronic kidney disease in patients with cardiac valve replacement surgery-associated acute kidney injury].

Objective: To explore the risk factors for progression to chronic kidney disease (CKD) in patients with cardiac valve replacement surgery-associated acute kidney injury (AKI). Methods: A retrospective, nested case-control study was conducted at Fuwai Central China Cardiovascular Hospital. The study subjects were patients who underwent cardiac valve replacement surgery from January 1, 2018 to December 31, 2020, with a baseline estimated glomerular filtration rate (eGFR)>60 ml·min-1·(1.73 m2)-1 and postoperative complication of AKI. The patients were followed up for 90 days after discharge from hospital. The endpoint event was defined as progression to CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. The patients were divided into CKD group and non-CKD group based on whether they experienced endpoint event. The baseline clinical data were compared between the two groups. The measurement data with non-normal distribution was represented as M (Q1,Q3). Logistic regression model was used to analyze the risk factors of endpoint event. The receiver-operating characteristic (ROC) curve was drawn to evaluate the performance for predicting CKD in cardiac valve replacement surgery-associated AKI patients. Results: A total of 149 cardiac valve replacement surgery-associated AKI patients (86 males and 63 females) were included in the study, aged (59.0±10.2) years. There were 27 patients (18.1%) who progressed to new-onset CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. Compared with non-CKD group, patients in CKD group had older age [66 (58, 70) vs 59 (53, 64) years], lower baseline eGFR [76.3 (65.8, 98.5) vs 92.7 (78.5, 101.6) ml·min-1·(1.73 m2)-1], higher proportion of preoperative hypertension [51.9% (14/27) vs 27.9% (34/122)] and serum creatinine at discharge [136 (101, 165) vs 86 (65, 104) µmol/L], and the differences were statistically significant (all P<0.05). The multivariate logistic regression analysis results revealed that older age (OR=1.063, 95%CI: 1.001-1.129, P=0.047), preoperative hypertension (OR=3.070, 95%CI: 1.105-8.532, P=0.031) and higher serum creatinine at discharge (OR=1.026, 95%CI:1.013-1.038, P<0.001) were risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI. The clinical risk model including age, preoperative hypertension, preoperative baseline eGFR, and serum creatinine at discharge produced a moderate performance for predicting progression to CKD in patients with cardiac valve replacement surgery-associated AKI [the area under the curve (AUC)=0.865, 95%CI: 0.790-0.940, P<0.001]. Conclusion: Older age, preoperative hypertension and higher serum creatinine at discharge are risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI.

The potential pigmentation-related genes in spider mites revealed by comparative transcriptomes of the red form of Tetranychus urticae.

Colouration in spider mites is due to the presence of carotenoids with diverse colours, including yellows, oranges and reds. Tetranychus urticae has two main colour forms, red and green. Although a ketolase has been implicated in determining the colour, the underlying genetic basis of body colour divergence between the two forms has remained unclear. Based on a combination of comparative transcriptomes and RNA interference, we found that a gene encoding a cytochrome P450 enzyme of the CYP4 clan (CYP389B1) had remarkably high expression in adult females of the red T. urticae, as well as in hybrids obtained by crossing the red and green forms. Down-regulation of this gene by RNA interference resulted in decreased accumulation of red pigment. Up-regulation of the expressions of a scavenger receptor gene (SCARB1) and a mitochondrial glycine transporter (SLC25A38) also strongly contributed to red colour development in adult females. Suppressing the mRNA levels of these genes also resulted in reduced accumulation of red pigment in the three other spider mites with red body colour. Our results provide evidence that the body colour divergence between the two forms is caused by different expressions of pigmentation-related genes, and point to a possible role of a novel cytochrome P450 gene (CYP389B1) in regulating red-orange body colour. These findings expand the number of candidate cytochrome P450 genes involved in endogenous pigmentation and will help to understand their roles in determining colour patterns in mites and other species.

[Effect of actin-related protein 2-3 complex on phagocytosis defect of alveolar macrophages in a mouse model of chronic obstructive pulmonary disease].

Objective: To investigate the role of actin-related protein 2-3 complex (Arp2/3) complex on phagocytosis of alveolar macrophages (AMs) in a mouse model of chronic obstructive pulmonary (COPD). Methods: Forty mice were randomly divided into healthy control group, healthy Arp2/3 complex inhibitor (CK666) group, COPD group and COPD CK666 group with 10 mice in each group. COPD group and COPD CK666 group were established by cigarette smoke exposure, and the control group had no smoke exposure. After 90 days of molding, AMs were isolated from lung tissue of mice in each group. Mean fluorescence intensity (MFI) and the positive percent of AMs engulfing fluorescein isothiocyanate-labeled Escherchina coli (FITC-E.coli) (AM%) were detected by flow cytometry. Western blot was applied to detect protein. Laser scanning confocal microscopy was used to measure the mean optical density of Arp2, F-actin and engulfed FITC-E. coli and quantify the colocalization of Arp2 and F-actin by a Manders' overlap coefficient. Scanning electron microscopy was used to observe the ultrastructure of AM phagocytizing FITC-E.coli. Results: Phagocytosis of AM: MFI and AM% in the COPD group were significantly decreased than those in the healthy control group[(4 702±243), (8 684±234) and (32.21±1.66)%, (65.88±1.77)%, all P<0.01]. MFI and AM% in the COPD CK666 group [(3 597±307), (22.09±1.89)%] and in the healthy CK666 group [(7 446±236), (50.09±1.64)%] were decreased compared to those in their respective control groups (all P<0.01). The expressions of protein of Arp2 and F-actin in the COPD group were significantly decreased than those in the healthy control group (0.508±0.025, 0.813±0.040 and 0.462±0.029, 0.720±0.039) (all P<0.01). The F-actin in the COPD CK666 group (0.265±0.014) and in the healthy CK666 group (0.637±0.032) were significantly decreased compared to those in their respective control groups (all P<0.01). The mean optical density of Arp2, F-actin and FITC-E.coli in the COPD group were significantly decreased compared to those in the healthy group (34.43±0.56, 142.83±1.90 and 61.59±0.70, 145.93±3.05 and 41.49±0.33, 189.17±2.60) (all P<0.01); the mean optical density of F-actin, FITC-E. coli in the COPD CK666 group (37.73±1.04, 28.84±2.95) and in the healthy CK666 group (137.07±1.35, 157.46±1.00) were significantly decreased compared to those in their respective control groups (all P<0.01). The Manders' overlap coefficient of Arp2 and phalloidin' coefficient in the COPD group (0.395±0.014) were significantly decreased than the healthy control group (0.395±0.014 and 0.880±0.002, P<0.01). The Manders' overlap coefficient of Arp2 and phalloidin' coefficient in the COPD CK666 group (0.297±0.006) and in the healthy CK666 group (0.737±0.031) were significantly decreased compared to those in their respective control groups (all P<0.01). Shape of AM: Long filopodia protruding and plentiful dorsal ruffle can be seen in AM from the healthy control group; AM pseudopods extension and dorsal ruffle reduced in the health CK666 group; there were pseudopods and dorsal ruffle defects in the COPD group and the COPD CK666 group. Positive correlations existed between the proteins of Arp2, F-actin with MFI. Positive correlations also existed between the Manders' overlap coefficient of Arp2 and phalloidin' coefficient with MFI. Conclusion: Decreased activity of Arp2/3 complex leads to low phagocytosis of AM in COPD mice, and AM in COPD mice is more sensitive to Arp2/3 complex inhibitor.

[The effect of fine particles on the phagocytosis of alveolar macrophages potentially by Arp2/3 complex in a mouse model of chronic obstructive pulmonary disease].

Objective: To investigate the mechanism of fine particulate matter (PM2.5) on the phagocytosis of alveolar macrophages (AM) in mice with chronic obstructive pulmonary disease (COPD) through actin-related protein (Arp) 2/3 complex. Methods: Forty mice were divided into healthy control(A) group, healthy PM2.5 (B) group, COPD(C) group, and COPD PM2.5(D) group according to the random number table method. A mouse model of COPD was established by cigarette smoke exposure method. PM2.5 (662 µg/m(3)) model was established by continuously inhalation for 90 days in healthy PM2.5 group and COPD PM2.5 group. Flow cytometry was used to detect the ability of AM to phagocytose fluorescein isothiocyanate-labeled E.coli (FITC-E.coli), expressed as mean fluorescence intensity (MFI) and percentage of phagocytic positive cells (phagocytosis percentage); Western blotting was used to detect AM Arp2 and F-actin content, and laser confocal microscopy for AM Arp2 and F-actin and phagocytic FITC-E.coli average optical density and colocalization of Arp2 and F-actin, while scanning electron microscopy was used to observes the morphology of AM after phagocytizing FITC-E.coli. Results: AM phagocytosis: MFI and phagocytosis percentage in the COPD group [4 656±251, (31.9±1.7)%] were lower than the healthy control group [8 657±247, (65.7±1.9)%] (both P<0.01); and healthy PM2.5 group and COPD PM2.5 group [7 653±228, (47.9±1.6)% and 3 660±237, (19.2±1.2)%] were lower than the respective control groups (all P<0.01), and the decrease in the COPD group was more pronounced. AM Arp2, F-actin content: the COPD group (0.51±0.02, 0.46±0.03) were lower than the healthy control group (0.81±0.04, 0.71±0.04, both P<0.01); the healthy PM2.5 group and the COPD PM2.5 group [(0.64±0.03, 0.56±0.04) and (0.29±0.02, 0.26±0.02)] were lower than the respective control groups (all P<0.01), and the decrease in COPD group was more significant. Arp2, F-actin, and phagocytic FITC-E.coli mean optical density values: the COPD group (33.0±2.3, 62.0±0.7, 41.0±0.4) were lower than the healthy control group (141.0±4.2, 145.0±2.9, 189.0±2.6, both P<0.01); the healthy PM2.5 group and the COPD PM2.5 group (127.0±2.8, 124.0±0.7, 154.0±0.9, and 24.0±2.4, 37.0±0.4, 29.0±0.8) were lower than the respective control groups (all P<0.01), and the decrease in the COPD group was more significant. Colocalization of AM Arp2 and F-actin: Montessori colocalization coefficient (MOC) (0.38±0.03) in the COPD group was lower than the healthy control group (0.88±0.03, P<0.01); healthy PM2.5 group and COPD PM2.5 group [(0.58±0.03) and (0.14±0.02)] were lower than the respective control groups (both P<0.01), and the decrease in COPD group was more significant. Morphology of AM phagocytosis of FITC-E.coli: AM in the healthy control group was obviously deformed, and the surface of the cell membrane was slightly wrinkled and high, and the free edge of the micro-pleated fold had a long and dense filamentous pseudopodia extension. The changes of morphology of AM in the COPD group was not obvious, the micro-wrinkles on the surface of the cell membrane were rare, and the filopodia poorly extended or even absent. The AM form of the healthy PM2.5 group changed slightly, mostly irregular circular or elliptical. The micro-wrinkles on the surface of the cell membrane were less and flat, and the filopodia protrudes short and less; the AM form of the COPD PM2.5 group was stiff, and the micro-wrinkles on the surface of the cell membrane were few and flat, no obvious filopodia or protrusions. Correlation analysis: After basal state and PM2.5 intervention, AM Arp2, F-actin content and MOC values of Arp2 and F-actin were positively correlated with MFI. Conclusions: The phagocytic function of AM in COPD mice was low, which was related to the abnormal rearrangement of cytoskeleton involved in Arp2/3 complex and F-actin. It was speculated that PM2.5 might inhibit Arp2/3 complex and F-actin. The cytoskeletal rearrangement of proteins was involved in the aggravation of AM phagocytosis in mice with COPD.

Reflectance difference microscopy for nanometre thickness microstructure measurements.

The discontinuity of medium at the boundary produces optically anisotropic response which makes reflectance difference microscopy (RDM) a potential method for nanometre-thickness microstructure measurements. Here, we present the methodology of RDM for the edge measurement of ultrathin microstructure. The RD signal of microstructure's boundary is mathematically deduced according to boundary condition and polarization optics theory. A normal-incidence RDM setup was built simply with one linear polarizer, one liquid crystal variable retarder and one 5 × objective. Then, the performance of the developed setup was identified using homogenous reflection mirror and high quality linear polarizer. For demonstration, microstructures array with 100 nm step height was measured. The results show that the RD signal is sensitive to the edge and its sign reflects the change direction of the edge. Furthermore, a height sensitivity of better than 10 nm and a spatial resolution of ∼3 µm offer this technique a good candidate for characterizing ultrathin microstructures.

Protein and mRNA expression of follicle-stimulating hormone receptor and luteinizing hormone receptor during the oestrus in the yak (Bos grunniens).

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) have a central role in follicle growth, maturation and oestrus, but no clear pathway in the seasonal oestrus of yak (Bos grunniens) has been found. To better understand the role of FSH and LH in seasonal oestrus in the yak, six yaks were slaughtered while in oestrus, and the pineal gland, hypothalamus, pituitary gland, and gonads were collected. Using real-time PCR and immunohistochemical assays, we determined the mRNA and protein expression of the FSH and LH receptors (FSHR and LHR) in these organs. The analysis showed that the FSHR mRNA expression level was higher in the pituitary gland tissue compared with LHR (p < .01) during oestrus. By contrast, there was low expression of FSHR and LHR mRNA in the pineal gland and hypothalamus. FSHR mRNA expression was higher than that of LHR (p < .05) in the ovary, whereas LHR mRNA expression was higher than that of FSHR (p < .01) in the uterus. FSHR and LHR proteins were located in the pinealocyte, synaptic ribbon and synaptic spherules of the pineal gland and that FSH and LH interact via nerve fibres. In the hypothalamus, FSHR and LHR proteins were located in the magnocellular neurons and parvocellular neurons. FSHR and LHR proteins were localized in acidophilic cells and basophilic cells in the pituitary gland, and in surface epithelium, stromal cell and gland epithelium in the uterus. In the ovary, FSHR and LHR protein were present in the ovarian follicle. Thus, we concluded that FSHR and LHR are located in the pineal gland, hypothalamus, pituitary and gonad during oestrus in the yak. However, FSHR was mainly expressed in the pituitary gland and ovaries, whereas LHR was mainly expressed in the pituitary gland and uterus.

[Effects of preconditioning with hypertonic saline solution on postoperative delirium in the aged].

Objective: To evaluate and explore the mechanism of the effect of hypertonic pre-injection on postoperative delirium in the aged. Methods: From June 2016 to February 2017, participants scheduled hip arthroplasty surgery were randomly divided into four groups: Group 1 (H1) 30 patients pre-injected 4 ml/kg hypertonic solution were proceeded general anesthesia; Group 2 (H2) 30 patients pre-injected 4 ml/kg hypertonic solution were proceeded spinal canal anesthesia; Group 3 (C1) 30 patients pre-injected 4 ml/kg isotonic saline were proceeded general anesthesia; Group 4 (C2) 30 patients pre-injected 4 ml/kg isotonic saline were proceeded spinal canal anesthesia in Department of Anesthesiology, Third Hospital of Hebei Medical University.All these patients were operated after anesthesia.To avoid electrolyte disorder, the level of Na(+) , Ca(2+) , K(+) in the artery blood was analyzed.Peripheral venous blood was extracted to detect the concentration of inflammatory factors IL-1ß, IL-6, IL-10, TNF-α and nerve injury factor S100ß.In order to evaluate the relationship of these inflammatory fators with monocyte, we used flow cytometry to detect the number of mononuclear in peripheral venous blood.After operation 1 to 3 days, all these patients were assessed cognitive function by Nu-DESC. Results: Electrolytes fluctuationed in the normal range in four groups at different time points.Compared with before infusion, IL-6, IL-1ß and TNF-α of four groups were significantly increased in postoperative.Compared with group H(H1 or H2), IL-1ß, IL-6 and TNF-α were increased and IL-10 was decreased in group C(C1 or C2) after the surgery.S100ß of group C(C1 and C2) was higher than before infusion.No significant changes were found in the cotykines mentioned above between group H1 and H2. The expression of monocytes CD14(+) CD16(+) /CD14(+ +) was decreased and the incidence of postoperative delirium was lower in group H than group C(13.3%, 10.0% vs 33.3%, 36.7%, P<0.05). Conclusion: Hypertonic saline can improve postoperative delirium of the aged and the mechanism may be related to the inhibition of monocyte cells secreting inflammatory factors.

Mechanisms of cytotoxicity induced by the anesthetic isoflurane: the role of inositol 1,4,5-trisphosphate receptors.

Isoflurane can induce widespread cytotoxicity. We hypothesized that isoflurane induces apoptosis partly by causing excessive calcium release from the endoplasmic reticulum (ER) via direct activation of inositol 1,4,5-trisphosphate receptors (IP3R). Rat pheochromocytoma cells cultured for seven days with nerve growth factor were divided into four groups: control group (C), IP3R antagonist group (X), isoflurane group (I) and isoflurane + IP3R antagonist group (I+X). Groups I and I+X were treated with 1 MAC isoflurane for 12 h. Groups X and I+X were pretreated with IP3R antagonist. Annexin V/PI apoptosis and TUNEL assays were performed to evaluate cell apoptosis. TEM was used to observe changes in cell ultrastructure. Changes in calcium concentration ([Ca(2+)]i) in the cytoplasm were measured by flow cytometry. RT-PCR was performed to evaluate IP3R mRNA expression. TEM showed that isoflurane treatment altered cell ultrastructure. Compared to group C, cell apoptosis rate and [Ca(2+)]i increased in groups I and I+X (P < 0.05). Compared to group C, IP3R mRNA expression was lower in group X and higher in group I (P < 0.05). Compared to group X, cell apoptosis rate, [Ca(2+)]i and IP3R mRNA expression increased in groups I and I+X (P < 0.05). Compared to group I, cell apoptosis rate, [Ca(2+)]i and IP3R mRNA expression decreased in group I+X (P < 0.05). These results suggest that exposure to 1 MAC isoflurane for 12 h causes excessive calcium release partly by direct activation of IP3R on the ER membrane and triggers cell apoptosis.

A survey of the frequency of aminoglycoside antibiotic-resistant genotypes and phenotypes in Escherichia coli in broilers with septicaemia in Hebei, China.

1. The aim of this study was to investigate the occurrence of aminoglycoside resistance and the prevalence of 6 important modifying enzyme genes, i.e. (strA, strB, aph(3')-IIa, aac(3)-IIa, aac(6')-Ib and ant(3")-Ia), in Escherichia coli strains in broilers with septicaemia in Hebei, China. 2. A total of 111 clinical isolates of E. coli were collected from 46 large-scale farms. Antimicrobial susceptibility tests, using the Kirby-Bauer disc diffusion method, were performed on all 111 isolates. In addition, all were screened for the presence of modifying enzyme genes using the polymerase chain reaction (PCR). 3. The results show that the rates of resistance were as follows: streptomycin: 97.3%, kanamycin: 97.0%, gentamicin: 95.5%, neomycin: 50.5%, amikacin: 46.0%, spectinomycin: 22.5%. Of the genes examined, strB (73.9%) was the most frequently identified gene in the phenotypic resistant isolates, followed in order by: ant(3")-Ia, aac(3)-IIa, aac(6')-Ib, aph(3')-IIa and strA. 4. It is concluded that aminoglycoside resistance in E. coli from broilers with septicaemia remains a serious problem in Hebei, China. This emphasises the need to ban the non-therapeutic use of antibiotics, discourage their misuse and to be continually vigilant by providing appropriate scientific and technological support for the poultry industry.

Report of 457 sporotrichosis cases from Jilin province, northeast China, a serious endemic region.

BACKGROUND: Most reported sporotrichosis cases came from South American countries, the USA, India and Japan. This mycosis is also endemic in Northeast China. However, the situation is not clear for international researchers due to lack of large series reported in English. OBJECTIVES: To report and analyse 457 sporotrichosis cases. METHODS: Retrospective study of 457 cases of sporotrichosis diagnosed by fungal culture at the First Hospital of Jilin University from 1 January 2007 to 31 December 2009. RESULTS: In this series, the male: female ratio was 1:1.42. Mean age was 41.2 years. Cases from age group 51-60 years accounted for most of the cases (22.54%). A total of 434 patients lived in rural areas (94.97%). The onset of symptoms in 67.61% cases happened in cold seasons (winter and spring). History of trauma presented in 133 cases (29.1%). The mean duration of the symptoms before the presentation was 6.41 months. A total of 190 (41.58%) showed lymphocutaneous form, 252 patients (55.14%) showed fixed form, 8 patients (1.75%) showed disseminated cutaneous sporotrichosis and the clinical form of 7 patients (1.53%) could not be defined. Extremities and nodules were the most frequently involved sites and founded manifestation. Main histopathology findings were suppurative granuloma, tuberculoid granuloma and mixed inflammatory granuloma. A total of 75 cases (19.74%) had fungal elements revealed by Periodic Acid-Schiff staining. Patients responded well to potassium iodide (KI), itraconazole, terbinafine and combinations of these agents with a mean course of 2.17 months to resolve. CONCLUSION: As the first report of a large series of sporotrichosis cases from China to be published in English literature, our study indicated a serious sporotrichosis endemic situation in Jilin province, Northeast China, with epidemiological and clinical characteristics similar to those of previous Chinese reports, but different from those in other countries. KI, itraconazole and terbinafine are effective for the treatment.

[Effect of information-knowledge-attitude-practice theory-based health education on clonorchiasis control among community residents and primary school students in Zhongshan City].

OBJECTIVE: To evaluate the effect of information-knowledge-attitude-practice (IKAP) theory-based health education interventions on clonorchiasis control among community residents and primary school students in Torch High-tech Development Zone of Zhongshan City, so as to provide insights into formulation of clonorchiasis control strategies among different types of populations. METHODS: Residents were randomly sampled from two communities and students from two primary schools using a random cluster sampling method in Torch High-tech Development Zone, Zhongshan City from 2019 to 2021, and health education pertaining to clonorchiasis control was performed based on the IKAP theory. The changes in the awareness of basic clonorchiasis control knowledge and belief, self-reported risk of Clonorchis sinensis infections and dietary behaviors were compared among community residents and primary school students before and after health education interventions. RESULTS: The participants included 146 male and 151 female community residents and 158 male and 153 female primary school students, with no significant difference detected in gender distribution (χ2 = 0.16, P > 0.05). The mean awareness of basic clonorchiasis control knowledge increased by 44.71% and 43.28% among primary school students and community residents 6 months following health education, and there were significant differences in the awareness of each item of basic clonorchiasis control knowledge before and after health education (χ2 = 41.53 to 284.44, all P values < 0.05). The proportions of primary school students and community residents thinking very high and high risks of C. sinensis infections increased from 9.35% and 6.71% before health education to 22.15% and 37.75% after health education, but only the difference of the attitudes in community residents achieve statistical significance (χ2 = 92.18, P < 0.05). The frequency of separation of raw and cooked foods with chopping board and knife significantly increased among community residents and primary school students following health education (χ2 = 16.04 to 62.65, all P values < 0.05). The frequency of eating raw freshwater fish (χ2 = 32.85, P < 0.05), fish congee (χ2 = 7.02, P < 0.05) and fish fillet hot pot (χ2 = 4.88, P < 0.05) significantly reduced among primary school students following health education, while only the frequency and proportions of eating raw freshwater fish have significantly reduced in community residents (χ2 = 11.77, P < 0.05). CONCLUSIONS: Health education interventions based on the IKAP theory are effective to increase the awareness of clonorchiasis control knowledge and improve dietary behaviors associated with C. sinensis infections among community residents and primary school students in Zhongshan City.

Efficacy and safety of itraconazole pulses vs. continuous regimen in cutaneous sporotrichosis.

BACKGROUND: Primary observation of using itraconazole pulse regimen (commonly used for onychomycosis) in five sporotrichosis patients produced satisfactory effect, but there are no randomized controlled trials to assess this regimen and to compare with routine continuous regimen. OBJECTIVES: The aim of this study was to compare the efficacy and safety of itraconazole pulse regimen, as a new treatment option for cutaneous sporotrichosis, with continuous regimen. METHODS: A prospective, randomized, evaluator-blind, controlled study was performed. A total of 50 cutaneous sporotrichosis patients were divided randomly into two groups: Pulsed Rx (npulse=25), treated with itraconazole 200 mg b.i.d. for 1 week and off for 3 weeks; Daily Rx (ncont=25), treated with itraconazole 100 mg bid continuously. In total, 46 patients (npulse=22, ncont=24) were assessable at the end of the study. Cure rates at weeks 12, 24 and 48 along with the course of treatment and the rate of side effects were evaluated. RESULTS: In Pulsed Rx, the cure rates at weeks 12, 24 and 48 were 77.3%, 81.8%, 81.8% respectively. The mean course of treatment was 2.65±0.81 pulses and the rate of side effects was 4.5%; In Daily Rx, the corresponding cure rates were 79.2%, 91.7% and 95.8% respectively. The mean course of treatment was 2.80±2.33 months and the rate of side effects was 16.7%. These parameters had no significant difference between the two groups (P>0.05). CONCLUSION: The efficacy and safety of Itraconazole pulse regimen for cutaneous sporotrichosis were similar to the continuous regimen. It is an effective and safe alternative treatment for cutaneous sporotrichosis, which can also lower the cost by decreasing the number of capsules.

Bone remodeling analysis for a swine skull at continuous scale based on the smoothed finite element method.

In order to study bone response during chewing, bone remodeling analysis at a continuous scale is performed to a swine skull obtained using µCT. The smoothed finite element method (S-FEM) is utilized to replace the finite element method (FEM) in bone remodeling as it is solving the "overly-stiff" problem in FEM by introducing strain smoothing technology to soften the stiffness matrix. Three S-FEM models with different levels of softening effects are developed, including node-based, edge-based, and face-based, which leads to various bone remodeling results for a better understanding of the remodeling process. During the remodeling process, the strain energy density is used as the mechanical stimulus, and the surface elements or smoothing domains are regarded as cortical bone. Under the action of mechanical stimuli, cortical bone and cancellous bone have been remodeled. In remodeling progress, ES-FEM shows close results as compared with the experimental µCT in nodal bone density distribution, FEM and FS-FEM are close to the µCT experimental model in average nodal density. In summary, the combined use of several methods provides more angles for the description of bone remodeling.

A high-fidelity 3D S-FEM stress analysis of a highly heterogeneous swine skull.

Fracture healing and growth of the bones are highly related to the stress level. Numerical analysis of stresses is the most effective means to determine the stress level, but it usually requires sufficient resolution to ensure an accurate description of geometry features of bones. In this paper, high-fidelity smoothed finite element method (S-FEM) skull models are created using computed tomography (CT) and micro-computed tomography (µCT) images of a juvenile pig skull. The material properties of the heterogeneous bone are modeled by a varying distribution of Young's modulus mapped to each element and smoothing domain to accurately capture the high heterogeneity. Different types of S-FEM models, including node-based, edge-based, and face-based, are developed for this high-fidelity modeling work. It is found that S-FEM has higher accuracy, in terms of displacements, stresses, and strain energy, compared to the traditional finite element method (FEM). Graphical abstract.

4-dehydroxyepisarcovagine A, a new steroidal alkaloid from Sarcococca pruniformis Lindl.

A new steroidal alkaloid, 4-dehydroxyepisarcovagine A (1), along with seven known alkaloids, sarcovagine D (2), sarcovagenine C (3), epoxysarcovagenine D (4), Pachysamine L (5), Pachysamine E (6), sarcovagine A (7) and sarcovagine B (8), was isolated from the roots and stems of Sarcococca pruniformis Lindl. The structure of compound 1 was elucidated by means of spectroscopic analysis.

The influence of drug solubility and sampling frequency on metformin and glibenclamide release from double-layered particles: experimental analysis and mathematical modelling.

Co-axial electrohydrodynamic atomization was used to prepare core/shell polymethylsilsesquioxane particles for co-delivery of metformin and glibenclamide in a sustained release manner. The drug-loaded microparticles were mostly spherical and uniformly distributed in size, with average diameters between 3 and 5 µm across various batches. FTIR was used to confirm the presence of drugs within the particles while X-ray diffraction studies revealed drugs encapsulated existed predominantly in the amorphous state. Intended as systems that potentially can act as depot formulations for long-term release of antidiabetics, a detailed analysis of drug release from these particles was necessary. Drugs of different solubilities were selected in order to study the effects of drug solubility from a core/shell particle system. Further analyses to determine how conditions such as release into a limited volume of media, sampling rate and partitioning of drug between the core and shell layers influenced drug release were conducted by comparing experimental and mathematically modelled outcomes. It was found that while the solubility of drug may affect release from such systems, rate of removal of drug (sampling frequency) which upsets local equilibrium at the particle/solution interface prompting a rapid release to redress the equilibrium influenced release more.

Pharmacokinetics, Biodistribution, Excretion and Plasma Protein Binding Studies of Acteoside in Rats.

Acteoside is a representative phenylethanoid glycoside, exhibiting great potency in neurodegenerative diseases treatment, such as Alzheimer's disease. This study was aimed to explore the pharmacokinetic characteristics, tissue distribution, excretion and plasma protein binding of acteoside in Sprague-Dawley rats after oral administration at 20, 40 and 80 mg/kg by a validated LC-MS/MS method. Acteoside was absorbed quickly after oral administration at 3 dose levels. Acteoside reached the peak concentration at 0.29±0.17 h, exhibiting a maximum concentration (Cmax) of 312.54±44.43 ng/mL after oral administration at 40 mg/kg, and the elimination half-life was 1.05±0.23 h. Both the Cmax and AUC showed a linear increase with the oral doses administered. The absolute bioavailability of acteoside was only around 1%. After oral administration, acteoside was extensively and rapidly distributed in most tissues including brain, but little amount of acteoside was excreted in urine, bile or feces. And the rat plasma protein binding ratio with equilibrium dialysis was about 60%. The pharmacokinetic characteristics of the fast gastro-intestinal absorption, the noteworthy distribution in most tissues including brain, the absence of acteoside in urine, bile and feces and valuable plasma protein binding ratio in rats will provide important reference for further research.

A convenient and asymmetric protocol for the synthesis of natural products containing chiral alkyl chains via Zr-catalyzed asymmetric carboalumination of alkenes. Synthesis of phytol and vitamins E and K.

[reaction: see text]. A convenient and asymmetric protocol for the synthesis of chiral oligoisoprenoids is described. Typically, a C14 vitamin E side chain 5 was synthesized in 47% yield over four steps. Isomeric purity of 5 was upgraded to >99% R at C-2 and 97% R at C-6 by the statistical formation of stereoisomeric p-phenylenebisurethanes and their diastereomeric separation. In addition, phytol and vitamin K were synthesized in 21% and 28% overall yields, respectively, over five steps from 1.

Heat stress induces apoptosis through transcription-independent p53-mediated mitochondrial pathways in human umbilical vein endothelial cell.

Cells apoptosis induced by intense heat stress is the prominent feature of heat-related illness. However, little is known about the biological effects of heat stress on cells apoptosis. Herein, we presented evidence that intense heat stress could induce early apoptosis of HUVEC cells through activating mitochondrial pathway with changes in mitochondrial membrane potential(ΔΨm), release of cytochrome c, and activation of caspase-9 and -3. We further revealed that p53 played a crucial role in heat stress-induced early apoptosis, with p53 protein rapidly translocated into mitochondria. Using pifithrin-α(PFT), a p53's mitochondrial translocation inhibitor, we found that pretreated with PFT, heat stress induced mitochondrial p53 translocation was significantly suppressed, accompanied by a significant alleviation in the loss of ΔΨm, cytochrome c release and caspase-9 activation. Furthermore, we also found that generation of reactive oxygen species (ROS) was a critical mediator in heat stress-induced apoptosis. In addition, the antioxidant MnTMPyP significantly decreased the heat stress-induced p53's mitochondrial translocation, followed by the loss of ΔΨm, cytochrome c release, caspase-9 activation and heat stress-mediated apoptosis. Conclusively, these findings indicate the contribution of the transcription-independent mitochondrial p53 pathway to early apoptosis in HUVEC cells induced by oxidative stress in response to intense heat stress.