[Trends in the prevalence of schistosomiasis in Anhui Province from 2004 to 2020 based on Joinpoint regression analysis].

OBJECTIVE: To investigate the changing trends in the prevalence of schistosomiasis in Anhui Province from 2004 to 2020, so as to provide the evidence for formulating the schistosomiasis elimination strategy in the province. METHODS: The epidemiological data of schistosomiasis in Anhui Province from 2004 to 2020 were collected, and the trends in the endemic status of schistosomiasis were analyzed using a Joinpoint regression model. The trends in the prevalence of Schistosoma japonicum infections in humans, bovines and Oncomelania hupensis were measured in Anhui Province from 2004 to 2020 using average annual percent change (AAPC), and the correlations among the changing trends in the prevalence of S. japonicum infections in humans, bovines and O. hupensis snail status were evaluated using Pearson correlation analysis. RESULTS: The prevalence of S.japonicum human infections continued to decline in Anhui Province from 2004 to 2020, with an annual mean decline of 14.8% [AAPC = -14.8%, 95% confidential interval (CI): (-18.9%, -10.5%), P < 0.01]. The prevalence of S. japonicum infections continued to decline in bovines in Anhui Province from 2004 to 2015 [AAPC = -31.3%, 95%CI: (-35.1%, -27.2%), P < 0.01], and was 0 for 5 successive years from 2016 to 2020. During the period from 2004 to 2020, there was an annual mean decline of 0.7% in areas of snail habitats [AAPC = -0.7%, 95%CI: (-1.2%, 0.3%), P < 0.05] and an annual mean decline of 9.2% in the density of living snails [AAPC = -9.2%, 95%CI: (-18.3%, 1.0%), P = 0.08] in Anhui Province from 2004 to 2020, and an annual mean decline of 35.6% was found in the density of S. japonicum-infected snails [AAPC = -35.6%, 95%CI: (-49.2%, -18.3%), P < 0.01] from 2004 to 2012, with no infected snails detected in Anhui Province from 2013 to 2020. There were significant correlations in the prevalence of S. japonicum infections between humans and bovines (r = 0.959, P < 0.01), between the prevalence of S. japonicum human infections and the density of S. japonicum-infected snails (r = 0.823, P < 0.01) and between the prevalence of S. japonicum infections in bovines and the density of S. japonicum-infected snails (r = 0.902, P < 0.01). CONCLUSIONS: The prevalence of S. japonicum infections appeared a decline in humans, bovines and O. hupensis in Anhui Province from 2004 to 2020, and significant correlations were found among the changing trends in the prevalence of S. japonicum human infections, the prevalence of S. japonicum bovine infections and the density of S. japonicum-infected O. hupensis snails. Because of a minor decline in the area of snail habitats and widespread distribution of O. hupensis, however, there is still a risk of schistosomiasis transmission, and precision control for schistosomiasis remains to be reinforced in Anhui Province.

[Investigation on prevalence of Schistosoma japonicum infections in wild mice in Shitai County, Anhui Province, 2018].

OBJECTIVE: To investigate the prevalence of Schistosoma japonicum infection in wild mice in Shitai County, Anhui Province, so as to provide insights into precise control of the source of S. japonicum infections. METHODS: Wild mice were captured using the trapping method for three successive nights at snail-infested settings from Jitan Village of Jitan Township, and Shiquan Village and Xibai Village of Dingxiang Township, Shitai County, Anhui Province in June and October, 2018. All trapped wild mice were sacrificed and liver and mesenteric vein specimens were collected for detection of S. japonicum eggs using microscopy, while the fecal samples in mouse intestines were collected for identification of S. japonicum infections using Kato-Katz technique. In addition, the population density of trapped wild mice was estimated and the prevalence of S. japonicum infection was calculated in trapped wild mice. RESULTS: A total of 376 wild mice were trapped from three villages in Shitai County. The population density of trapped wild mice was 9.1% (376/4 124), and the prevalence of S. japonicum infection was 24.2% (91/376) in trapped wild mice. The highest prevalence of S. japonicum infection was detected in Shiquan Village of Dingxiang Township (30.1%), and the lowest prevalence was seen in Xibai Village of Dingxiang Township; however, there was no significant difference in the prevalence of S. japonicum infection in trapped wild mice among three villages (χ2= 4.111, P > 0.05). In addition, there was no significant difference in the prevalence of S. japonicum infection in wild mice captured between on June (26.8%, 34/127) and October (22.9%, 57/249) (χ2 = 0.690, P = 0.406). The trapped wild mice included 6 species, including Rattus norvegicus, Niviventer niviventer, R. losea, Apodemus agrarius, Mus musculus and N. coning, and the two highest prevalence of S. japonicum infection was detected in R. losea (34.9%, 22/63) and R. norvegicus (31.2%, 44/141). CONCLUSIONS: The prevalence of S. japonicum infections is high in wild mice in Shitai County, and there is a natural focus of schistosomiasis transmission in Shitai County.

[Effect analysis on endoscopic transnasal resection of epidural cholesteatoma at paracentral skull base].

Objective: To indicate the clinical features of endoscopic transnasal resection of epidural cholesteatoma at paracentral skull base and to analyze its efficacy. Methods: The total excision rate, postoperative complications and postoperative curative effect of 7 patients (4 males and 3 females, aging from 32 to 63 years old) who underwent middle skull base surgery for epidural cholesteatoma resection under transnasal endoscope at Tianjin Huanhu Hospital between August 2017 and August 2020 were retrospectively reviewed. All patients were followed up for 6 to 36 months. The postoperative MRI, clinical symptoms and recurrence were reviewed. Descriptive statistical methods were used for analysis. Results: Among the 7 patients, there were total resection (complete resection of cyst contents and capsule) in 4 patients, near-total resection (complete resection of cyst contents, incomplete resection of cyst capsule) in 1 patient, and subtotal resection (incomplete resection of cyst contents and capsule) in 2 patients. The clinical symptoms of all patients were improved postoperatively with 1 patient who had no clinical symptoms. One case had postoperative cerebrospinal fluid rhinorrhea, which was cured after lumbar drainage and nasal iodoform gauge packing. Up to now, 7 patients (including patients with partial resection) had no recurrence. Conclusion: Endoscopic transnasal approaches may be effectively used for resection of epidural cholesteatoma in the paracentral skull base in carefully selected cases.

[Neuroprotective effect of ginsenoside Rb-1 on a rat model of Alzheimer's disease].

Objective: To investigate the protective mechanism of ginsenoside Rb-1 on the brain in a rat model of Alzheimer's disease. Methods: Fifty-six male Sprague-Dawley rats were randomly divided into control group, model group, low-dose Rb-1 group (Rb-1: 25 mg•kg(-1)•d(-1)) and high-dose Rb-1 group (Rb-1:50 mg•kg(-1)•d(-1)). Morris water maze was designed to observe the changes of learning and memory ability in rats. Flow cytometry was used to detect the apoptosis of hippocampal neurons. Immunohistochemistry and Western blot were employed to detect the expression levels of apoptosis-related genes (p53, Bax, cytochrome C (Cyto C), Caspase-3 and caspase-9) and anti-oxidative stress-associated genes (nuclear Factor-E2-related factor 2 (Nrf2), kelch-like ECH-associated protein 1 (keap-1), heme oxygenase 1(HO-1) and NADPH quinone dehydrogenase 1 (NQO1)).The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were detected by relevant kits. ANOVA and Tukey-Kramer test were used for statistical analysis. Results: The learning and memory ability of rats in the model group was lower than that of the control group (P<0.01).The learning and memory ability of rats in the high-dose Rb-1 treatment group was significantly higher than that of the model group [(80±8) s vs (100±11) s, t=5.390, P<0.01]. The expression levels of apoptosis-related genes (p53, Bax, Cyto C, caspase-3 and caspase-9) in the model group were significantly higher than those in the control group (P<0.01), while the expression levels of these genes in low-dose and high-dose Rb-1 groups were significantly lower than those of the model group (P<0.01). The expression levels of Nrf2, HO-1 and NQO1 genes in the model group were significantly lower than those in the control group (P<0.05), while the expression of these genes in low-dose and high-dose Rb-1 groupswere significantly higher than those of the model group (P<0.01). The activities of CAT, GSH-Px and SOD in the model group were lower than those in the control group (P<0.01), however the activities of CAT, GSH-Px and SOD in low-dose and high-dose Rb-1 groups were higher than those of model group (P<0.05). Conclusions: Both low-dose and high-dose Rb-1 have protective effect on memory and cognitive function of Alzheimer's disease rats by reducing the damage and apoptosis of hippocampal neurons, down-regulating the expression levels of p53, Bax, Cyto C, caspase-3 and caspase-9, up-regulating the expression of Nrf2, HO-1 and NQO1 genes, and increasing the activities of CAT, GSH-Px and SOD. Moreover, the protective effect of Rb-1 on rat brain may be dose-dependent.

[Endemic situation of schistosomiasis in national surveillance sites of Anhui Province from 2015 to 2018].

OBJECTIVE: To analyze the endemic situation of schistosomiasis in national surveillance sites of Anhui Province from 2015 to 2018, so as to provide scientific evidence for schistosomiasis control and prevention in Anhui Province. METHODS: According to the National Schistosomiasis Surveillance Programme (2014 version), a total of 51 national schistosomiasis surveillance sites were assigned in Anhui Province in 2015, and Schistosoma japonicum infections in humans and livestock and snail distribution were monitored from 2015 to 2018. RESULTS: A total of 89 638 local residents and 42 609 mobile populations received serological screening of schistosomiasis in 51 national surveillance sites of Anhui Province from 2015 to 2018, and the sero-prevalence of S. japonicum infections was 1.41% to 3.69% in local residents and 0.84% to 2.13% in mobile populations, respectively. There were 5 egg-positive local residents and 1 egg-positive mobile populations detected in 2015, with occupations of farmers and fishermen. There were 6 405 livestock detected for S. japonicum infections, and no egg-positives were identified. Among an area of 12 661 hm2 surveyed in the national schistosomiasis surveillance sites of Anhui Province from 2015 to 2018, the areas of snail habitats were 2 461.27 to 2 628.96 hm2, andthemeandensityoflivingsnailswas 0.3757 to 0.4330 snails/0.1 m2, with no S. japonicum infections identified in snails. CONCLUSIONS: The endemic situation of schistosomiasis is at a low level in Anhui Province; however, the risk of schistosomiasis transmission remains in local regions of the province. The construction of the surveillance-responsesystemshouldbereinforcedtoconsolidatetheachievementsofschistosomiasis control in Anhui Province.

[Spatiotemporal distribution of Oncomelania hupensis snail habitats in Anhui Province].

OBJECTIVE: To investigate the spatiotemporal distribution of Oncomelania hupensis snails and infected snails in the endemic areas of schistosomiasis in Anhui Province. METHODS: Based on the snail survey data in Anhui Province in 2016, the distribution of snails and infected snails were analyzed, and the spatial distribution of snails and spatial cluster patterns of infected snails were investigated in snail habitats in Anhui Province from 1950 to 2016. RESULTS: A total of 22 757 snail habitats and 5 004 infected snail habitats were identified in Anhui Province from 1950 to 2016, which appeared single-peak and double-peak patterns, with an inflection point seen in 1970. There were 141 000 hm2 historically accumulative snail habitats, 88.08% of which were firstly identified from 1950 to 1979, and totally 114 500 hm2 snail habitats were eradicated, 77.17% of which were eradicated from 1970 to 1999. There were 4 830 snail habitats identified until 2016, in which 1 051 were once detected with infected snails. In addition, 78.12% of current snail habitats had been present for over 40 years, and infected snails had been eliminated in 65.75% of the infected snail habitats within 10 years. There was a spatial autocorrelation of the living snail density in current snail habitats in Anhui Province (Moran's I = 0.196, Z = 139.63, P < 0.001), and local hotspot analysis showed spatial clusters of living snails density in snail habitats, with high-value clusters in south of the Yangtze River and low-value clusters in north of the Yangtze River. The 21 high-value clusters of living snail density with statistical significance were distributed along the Yangtze River basin and its branches. Spatiotemporal scan analysis revealed spatiotemporal clusters of infected snails in 4 current snail habitats. CONCLUSIONS: The current snail habitats have been present for a long period of time, and snails are difficult to be eliminated by chemical treatment alone, which requires the combination of environment improvements. There are spatial clusters of living snail density in current snail habitats in Anhui Province. The epidemic factors and risk of human and animal infections still remain in some clusters of historical infected snail habitats revealed by spatiotemporal scan analysis, which should be consid- ered as the key target areas for snail control in Anhui Province.

[The safety study of percutaneous dilational tracheostomy in a large sample].

Objective:The aim of this study is to analyze the safety of a large number cases of percutaneous dilatation tracheostomy. Method: Retrospective analyzed the clinical data of PDT (1 200 cases) and TT (326 cases) patients which were recruited. The postoperative complications were analyzed statistically. PDT and TT randomized controlled trials (PDT and TT) were conducted with 80 cases in each group. The intraoperative conditions (including operative time, intraoperative bleeding volume and incision size) and postoperative complications in the two groups were statistically analyzed. The data were analyzed by SPSS 17.0 software. Result:①Randomized controlled study: The blood loss, incision size and operative time of two groups have significant difference. Comparison of postoperative complications: the number of postoperative bleeding and the total number of complications were statistically significant difference (P<0.05). However, granulation formation, incision infection and subcutaneous emphysema showed no significant difference (P>0.05). ②Large sample study: The postoperative follow-up results showed that there were significant differences in postoperative bleeding, postoperative infection, subcutaneous emphysema and the total number of complications (P<0.05), but there was no significant difference in the formation of tracheal granulation (P>0.05). Conclusion:This study further validates that PDT is a safe method to establish long-term artificial airway through large sample and randomized controlled study, which accords with the direction of modern minimally invasive surgery. PDT not only short operation time, and is easy to grasp, but also safe and reliable. If there is no obvious operation contraindication, we can choose PDT first for critically ill patients who need tracheotomy, and the success rate and safety are high after mastering the operation skills.

The microRNA-1908 up-regulation in the peripheral blood cells impairs amyloid clearance by targeting ApoE.

OBJECTIVE: To give a new insight into the mechanism of ApoE dysregulation and microRNA-1908 in Alzheimer's disease (AD). METHODS: Plasma ApoE levels were measured in 20 AD patients and 20 healthy controls. THP-1 was maintained in RPMI1640 with 10% fetal bovine serum. Quantitative real-time polymerase chain reaction was performed to detect 13-microRNA and ApoE mRNA in cultured cell lines. Enzyme-linked immunosorbent assay was used to measure human ApoE in the plasma or culture medium of cell lines and also used to quantify the human Aß42 in the culture medium of cell lines. RESULTS: We found plasma ApoE level reduced in AD patients (2.28 vs 3.78 µg/mL, P < .001), and microRNA-1908 was up-regulated in AD patients and was negatively associated with plasma ApoE (r = -0.32, P = .012). In human macrophage cell line THP-1 and astrocytoma cell line U87, microRNA-1908 could inhibit the mRNA and protein levels of ApoE by targeting its 3'untranslated region. Consistently, microRNA-1908 inhibits the ApoE-mediated Aß clearance. CONCLUSIONS: Our study provides new insight into the mechanism of ApoE dysregulation in AD patients, and microRNA-1908 might be a therapeutic target for AD treatment.

Planned ventral hernia following damage control laparotomy in trauma: an added year of recovery but equal long-term outcome.

PURPOSE: Significantly injured trauma patients commonly require damage control laparotomy (DCL). These patients undergo either primary fascial closure during the index hospitalization or are discharged with a planned ventral hernia. Hospital and long-term outcomes of these patients have not been extensively studied. METHODS: Patients who underwent DCL for trauma from 2003 to 2012 at a regional Level I trauma center were identified and a comparison was made between those who had primary fascial closure and planned ventral hernia. RESULTS: DCL was performed in 154 patients, 47% of whom sustained penetrating injuries. The mean age and injury severity score (ISS) were 40 and 25, respectively. Hospital mortality was 19%. Primary fascial closure was performed in 115 (75%) of those undergoing DCL during the index hospitalization. Of these, 11 (9%) had reopening of the fascia. Of the surviving patients, 22 (19%) never had primary fascial closure and were discharged with a planned ventral hernia. Patients with primary fascial closure and those with planned ventral hernia were similar in age, gender, ISS, and mechanism. Those with planned ventral hernias underwent more subsequent laparotomies (3.0 vs. 1.3, p < 0.001), and had more enteric fistulas (18.2 vs. 4.3%, p = 0.041) and intra-abdominal infections (46 vs. 15%, p = 0.007), and had a greater number of hospital days (38 vs. 25, p = 0.007) during the index hospitalization. Sixteen (73%) patients with a planned ventral hernia had definitive reconstruction (mean days = 266). Once definitive abdominal wall closure was achieved, the two groups achieved similar rates of return to work and usual activity (71 vs. 70%, p = NS). CONCLUSIONS: Following DCL for trauma, patients with a planned ventral hernia have definitive reconstruction nearly 9 months after the initial injury. Once definitive abdominal wall closure has been achieved; patients with primary fascial closure and those with planned ventral hernia have similar rates of return to usual activity.

Serum brain-derived neurotrophic factor levels and psychotic symptoms in heroin dependence.

OBJECTIVES: Psychotic symptoms are commonly observed among heroin users. Low serum brain-derived neurotrophic factor (BDNF) levels have been reported in schizophrenia and psychosis; however, studies assessing the relationship between serum BDNF levels and psychotic symptoms in heroin dependence are lacking. METHOD: A total of 31 heroin-dependent patients who had never experienced psychotic symptoms during heroin consumption and 21 patients with a history of psychotic symptoms were consecutively recruited. We measured by enzyme-linked immunosorbent assay (ELISA) serum BDNF levels during early abstinence. A gender- and age-matched sample of healthy controls was also recruited and underwent measurement of BDNF. RESULTS: BDNF levels were significantly lower in patients with psychotic symptoms than in those without psychotic symptoms (P<0.001). BDNF levels were not found to be correlated with sex, age, age of onset, duration of heroin use, average daily dose of heroin use, frequency of heroin use, SDS scores, BAI scores and BDI scores in the psychotic subsamples (all P>0.05). CONCLUSIONS: Our findings suggest that heroin-dependent patients with psychotic symptoms share some of the neurotrophic insult that characterizes schizophrenia and psychosis.

Removal of dimethyl sulfide by the combination of non-thermal plasma and biological process.

A bench scale system integrated with a non-thermal plasma (NTP) and a biotricking filtration (BTF) unit for the treatment of gases containing dimethyl sulfide (DMS) was investigated. DMS removal efficiency in the integrated system was up to 96%. Bacterial communities in the BTF were assessed by PCR-DGGE, which play the dominant role in the biological processes of metabolism, sulfur oxidation, sulfate-reducing and carbon oxidation. The addition of ozone from NTP made microbial community in BTF more complicated and active for DMS removal. The NTP oxidize DMS to simple compounds such as methanol and carbonyl sulfide; the intermediate organic products and DMS are further oxidized to sulfate, carbon dioxide, water vapors by biological degradation. These results show that NTP-BTF is achievable and open new possibilities for applying the integrated with NTP and BTF to odour gas treatment.

Development and validation of a high-performance liquid chromatography coupled with ultraviolet detection method for the determination of isocorydine in rat plasma and its application in pharmacokinetics.

A new HPLC-UV method has been developed, validated and applied for the determination of isocorydine (CAS 475-67-2) in rat plasma after oral or intravenous (i. v.) administration. Caffeine was used as the internal standard (IS). The analyte and IS were extracted from rat plasma by liquid-liquid extraction (LLE) with methyl tert-butyl ether and they were separated on an XTerra C18 column (250×4.6 mm, 5 µm, pH 1-12) with UV detection at 264 nm. The mobile phase consisted of methanol and 0.02 mol/L potassium dihydrogen phosphate-phosphoric acid buffer solution (pH 3.2) (30:70, v/v) at a flow rate of 1 mL/min for 8.5 min. The retention times of isocorydine and caffeine were approximately 6.5 and 5.1 min, respectively. The good linearity of the calibration curves was observed over the concentration range of 0.05-8 µg/mL (n=8, r 2≥0.9995). The lower limit of quantification (LLOQ) was 0.05 µg/mL [signal to noise ratio (S/N)≥10], and the limit of detection (LOD) was demonstrated as 0.01 µg/mL (S/N≥3). The mean extraction recovery ranged from 83.7% to 89.5% at 3 quality control (QC) concentrations. Intra-day and inter-day precision (relative standard deviation, RSD%) were within 4.7% and accuracy (relative error, RE%) ranged from -1.2% to 4.5%. The developed method was successfully applied to determination of the pharmacokinetic properties of isocorydine in rats after oral administration at a dose of 20 mg/kg and i. v. injection at 5 mg/kg.

Pharmacokinetic and myocardial enzyme profiles of two administration routes of epirubicin in breast cancer patients.

To evaluate the changes in myocardial enzymes and plasma epirubicin concentration following administration by micro-pump (MP) and intravenous drip (ID) in breast cancer patients.11 self-controlled breast cancer patients were recruited for a trial with epirubicin administration by MP for 48 h and by ID for 1 h during 2 cycles of treatment. Plasma concentration of epirubicin at different time points was determined using LC-MS/MS. The levels of myocardial enzymes before and after chemotherapy were compared. Another group of patients receiving epirubicin by ID (n=4) or MP (n=9) were monitored for 4 months.8 patients completed the self-controlled study. The peak concentration of epirubicin in the MP group and the ID group were 21.84±18.85 ng/mL and 294.80±225.54 ng/mL, respectively. The MP group had a longer duration (54~60 h) of plasma concentration of epirubicin not less than 10 ng/mL than that of the ID group (8~14 h). There was significant difference for the alteration of myocardial enzymes before and after chemotherapy (p<0.05) in the ID group, whereas the MP group showed no significant difference (p>0.05). The increased range of myocardial enzymes after chemotherapy in the ID group was larger than that of the MP group and the difference was significant (p<0.05). There is an increased cardiotoxicity in patients receiving epirubicin by ID during the 4-month trial.Administration of epirubicin by MP maintained an effective drug concentration for a longer period of time than by ID. The higher peak plasma concentration observed following epirubicin administration by ID may lead to cardiac toxicity.

Development and validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of acrivastine and pseudoephedrine in human plasma and its application in pharmacokinetics.

A specific, sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of acrivastine and pseudoephedrine in human plasma samples. Plasma samples were processed and analyzed on a Phenomenex Luna 3 µ CN 100A column (150 mm×2.0 mm) eluted with the mobile phase consisting of methanol and 0.01 mol/L ammonium acetate water solution containing 0.1% formic acid (45:55, v/v) at a flow rate of 0.2 mL/min. The analytes were detected by positive ion electrospray ionization in multiple reaction monitoring mode. The transitions of m/z 349→278, m/z 166→148 and m/z 256→167 were monitored for acrivastine, pseudoephedrine and diphenhydramine (IS), respectively. The method was specific and sensitive with a lower limit of quantitation (LLOQ) of 1.52 ng/mL for acrivastine and 8.13 ng/mL for pseudoephedrine. The method showed good linearity in the range of 1.52~606.0 0 ng/mL for acrivastine and 8.13~813.12 ng/mL for pseudoephedrine (r≥0.996). The mean recovery were ranged 91.82% ~ 98.46% for acrivastine and 90.77% ~ 92.05% for pseudoephedrine. Validation results, such as accuracy, precision and repeatability were within the required limits. The method was successfully applied in a pharmacokinetic study of the acrivastine and pseudoephedrine hydrochloride compound capsule in humans.

Determination of the plasma pharmacokinetic and tissue distributions of swertiamarin in rats by liquid chromatography with tandem mass spectrometry.

An LC-MS/MS method was developed for the quantification of swertiamarin (CAS 17388-39-5) in rat plasma and tissues using gentiopicroside as the internal standard (IS). Swertiamarin and an IS were extracted from plasma and tissues by a simple solid-phase extraction (SPE) procedure. Separation was achieved on a Phenomenex kinetex-C18 column (100 mm×2.1 mm, 2.6 µm) with an isocratic mobile phase consisting of methanol and water (22:78, v/v) with 0.1% acetic acid at a flow rate of 0.2 mL/min. The analyte and IS were detected by negative ion electrospray ionisation in multiple-reaction monitoring mode while monitoring the transitions of m/z 433 [M + CH3COO] - →179 and m/z 415 [M + CH3COO] - →179 for swertiamarin and the IS, respectively. The method was validated with respect to selectivity, matrix effect, linearity, accuracy, precision, recovery and stability. The method was successfully applied in a pharmacokinetic study of swertiamarin after intravenous and oral administration to rats. The pharmacokinetics of swertiamarin showed rapid absorption and elimination, and its absolute bioavailability was low at 10.3%. After oral administration to rats, swertiamarin was rapidly and widely distributed in its tissues. High concentrations were found in the liver and kidney, indicating that swertiamarin was possibly absorbed in the liver and eliminated by the kidney.

Absence of the adenosine A2A receptor confers pulmonary arterial hypertension and increased pulmonary vascular remodeling in mice.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by sustained elevation of pulmonary vascular resistance resulting from endothelial and smooth muscle cell dysfunction and collagen deposition in pulmonary vascular walls. In this study, we investigated the role of the adenosine A(2A) receptor (A(2A)R) in the development of PAH by determining the effect of genetic inactivation of A(2A)Rs on pulmonary vascular remodeling in mice. METHODS AND RESULTS: We characterized hemodynamic, histological and ultrastructural changes in pulmonary vascular remodeling in A(2A)R knockout (KO) mice compared with their wild-type (WT) littermates after exposure to normoxia and hypoxic conditions. After exposure to normoxia, compared to WT mice, A(2A)R KO mice displayed: (1) increased right ventricular systolic pressures and an elevated ratio of the right ventricle over left ventricle plus septum (Fulton index), (2) increased wall area and thickness as well as enhanced smooth muscle actin immunoreactivity in pulmonary resistance vessels, (3) increased proliferating cell nuclear antigen-positive cells in pulmonary resistance vessels and (4) increased smooth muscle cells hypertrophy and collagen deposition in the adventitia of pulmonary arteriole walls as revealed by electron microscope. By contrast, histological analysis revealed no features of hypertensive nephropathy in A(2A)R KO mice and there was no significant difference in systemic blood pressure, and left ventricular masses among the 3 genotypes. Furthermore, following chronic exposure to hypoxia, A(2A)R KO mice exhibited exacerbated elevation in right ventricular systolic pressure, hypertrophy of pulmonary resistance vessels and increased cell proliferation in pulmonary resistance vessels, compared to WT littermates. Thus, genetic inactivation of A(2A)Rs selectively produced PAH and associated increased smooth muscle proliferation and collagen deposition. CONCLUSIONS: Extracellular adenosine acting at A(2A)Rs represents an important regulatory mechanism to control the development of PAH and pulmonary vascular remodeling.

Advanced glycation endproducts induce podocyte apoptosis by activation of the FOXO4 transcription factor.

Advanced glycation endproducts (AGEs) and a receptor for AGEs (RAGE) have been linked in the pathogenesis of diabetic nephropathy. RAGE is usually localized to podocytes and is increased in diabetes. RAGE activation increases reactive oxygen species production, which mediates hyperglycemia-induced podocyte apoptosis in early diabetic nephropathy. Here, we examined the interaction of AGE and RAGE on podocyte apoptosis. When we exposed murine cultured podocytes to bovine serum albumin (BSA) that was modified by AGEs or to carboxymethyl-lysine BSA, more apoptosis was found when compared with unmodified BSA. Similarly, more podocytes underwent detachment and apoptosis when cultured on AGE-modified collagen IV than on native collagen IV. AGEs isolated from sera of patients with chronic kidney disease also caused apoptosis of podocytes. Apoptosis was diminished by small interference RNA (siRNA) for RAGE in podocytes exposed to AGE-BSA, but not to AGE-modified collagen IV. Both AGE- and carboxymethyl-lysine modified-BSA activated p38MAP kinase and inhibition of this kinase reduced the apoptotic effect of AGE-BSA. Exposure to AGE-BSA was associated with Akt dephosphorylation and FOXO4 transcriptional activation leading to an increase in the expression of an effector protein of apoptosis, Bim. siRNA for FOXO4 abolished AGE-BSA-induced apoptosis of podocytes. Our study suggests that an AGE-RAGE interaction contributes to podocyte apoptosis by activation of the FOXO4 transcription factor.