The chemical investigation on Ganoderma philippii led to the isolation of sixteen compounds by silica gel and Sephadex LH-20 column chromatography. On the basis of spectroscopic data analyses, their structures were elucidated as 2, 5-dihydroxyacetophenone (1), methyl gentisate (2), (S) -dimethyl malate (3), muurola-4, 10 (14) -dien-11beta-ol (4), dihydroepicubenol (5), 5-hydroxymethylfuran carboxaldehyde (6), ergosta-7, 22E-dien-3beta-ol (7), ergosta-7, 22E-dien-3-one (8), ergosta-7, 22E-diene-2beta, 3alpha, 9alpha-triol (9), 6/beta-methoxyergo-sta-7, 22E-dien-3beta, 5alpha-diol (10), ergosta-4, 6, 8(14), 22E-tetraen-3-one (11), ergosta4, 6, 8-(14), 22E-etetraen-3beta-ol (12), 5alpha, 8alpha-epidioxy-ergosta-6, 22E-dien-3beta-ol (13), 7alpha-methoxy-5alpha, 6alpha-epoxyergosta-8-(14), 22E-dien-3beta-ol (14), ergosta-8, 22E-diene-3beta, 5alpha, 6beta, 7alpha-tetraol (15), and ergosta-5, 23-dien-3beta-ol, acetate (16). All the compounds were obtained from this fungus for the first time, and compounds 4 and 5 were isolated from the Ganoderma genus for the first time.
Ganoderma ; chemistry ; Medicine, Chinese Traditional ; Organic Chemicals ; analysis ; isolation & purification

OBJECTIVETo investigate the clinical manifestations, pathological characteristics, and treatments of urothelial-type mucinous adenocarcinoma of the prostate (UMAP).

METHODSWe reported a case of UMAP, reviewed relevant literature, and analyzed the clinicopaothological features, diagnosis, treatment, and prognosis of the disease.

RESULTSThe patient was a 60-year-old male and underwent transurethral resection of the prostate for dysuria. Postoperative pathology indicated mucinous adenocarcinoma and sigmoidoscopy revealed no primary colon cancer. Immunohistochemical staining showed the negative expressions of PSA and P504s and positive expressions of CK7, CK34 β E12, CK20, and CDX2. Thus UMAP was confirmed and treated by intensity-modulated radiotherapy. Then the patient was followed up for 30 months, which showed desirable therapeutic result, with neither local progression nor distant metastasis.

CONCLUSIONUMAP has a bad prognosis and its diagnosis depends on pathological and immunohistocchemical examinations. It responds well to radical prostatectomy but is not sensitive to endocrine therapy. Radiotherapy can be considered for those who are not fit to receive radical prostatectomy.

Adenocarcinoma, Mucinous ; metabolism ; pathology ; therapy ; Humans ; Keratins ; metabolism ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; Prognosis ; Prostatectomy ; Prostatic Neoplasms ; metabolism ; pathology ; therapy ; Racemases and Epimerases ; metabolism

Administration, Oral ; Adult ; Atrial Flutter ; drug therapy ; physiopathology ; Digoxin ; therapeutic use ; Echocardiography ; Female ; Fetal Diseases ; drug therapy ; physiopathology ; Humans ; Hydrops Fetalis ; drug therapy ; physiopathology ; Infant, Newborn ; Male ; Pregnancy

Objective To study the effect of platelet-derived growth factor(PDGF)and lysosomes on lung injury in macaque with early-phase endotoxie shock.Method Eleven macaques were randomly divided into two groups,namely,control group(Co group,n=5)iand endotoxic group(En group,n=6).The macaque of the Co group injected with 1 ml/kg normal saline and the macque of the En group received a dose of 2.8 mg/kg Lipopolysaccharides(LPS)i.v.The blood gas was detected at 120 minutes after LPS challenging. Uhrastructure,cytochemistry of acid phosphatase(ACPase)detection by electronic microscopy and immunohistochemical assay of PDGF were completed in hmgs of all the macaque .Results Administration of LPS did not change the parameters of gas exchange,namely,PaO_2,PaO_2/Fi and PaCO_2.In the early phase,of endotoxic shock,ACPase activity products increased and lysosome destroyed in the alveolar cells.The pathologic changes of alveolus,such as degeneration of vessel endothelium,injury of alveolar epithelium and damage of basement membrane,and transudation of blood component were observed by electron microscopy in the En group. However,no pathological changes were found in the control group.By immunohistochemical staining,PDGF on alveolar wall in the En animals was observed,whereas no PDGF protein in the Co macaques was noticed. Conclusions Administration of LPS induced the expression of PDGF in the alveolar wall and lysosome injury in the alveolar cells,as a result of alveolar damage in early-phase endotoxin shock.In the meantime,the parameters of gas exchanges did not change.The PDGF may play an important role in the pathogenesis of lung during the early-phase of endotoxin shock.

The aim of the present study was to investigate the role of p38 MAPK in the renal tubular epithelial-mesenchymal transition (TEMT) induced by high glucose. In in vivo study, the rats were randomly divided into control (C), diabetes mellitus (DM) and insulin-treated DM groups. Immunohistochemical staining and Western blot were employed to determine the expression of p38 MAPK and p-p38 MAPK protein in renal cortex of rats. In in vitro study, primary renal tubular epithelial cells (PTECs) were cultured with normal glucose (5.5 mmol/L), high glucose (20 mmol/L D-glucose), high osmolality (20 mmol/L D-mannitol) and SB202190 (a p38 MAPK inhibitor) plus high glucose respectively for 72 h. The expressions of p38 MAPK, p-p38 MAPK, Snail1, transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA) and E-cadherin protein and mRNA were detected by immunocytochemical staining, Western blot and RT-PCR. The p38 MAPK and p-p38 MAPK were specifically upregulated by high glucose in both in vivo and in vitro studies. The p38 MAPK activation was abolished by insulin controlling hyperglycemia to normal level in DM rats and inhibited dramatically by SB202190 in high glucose-cultured PTECs. The protein and mRNA of alpha-SMA were markedly increased in PTECs cultured with high glucose and were 12-fold and 8-fold respectively over that in the normal glucose, which were significantly suppressed by SB202190. SB202190 down-regulated the high glucose-induced Snail1 protein expression in PETCs, and restored partly the depression of E-cadherin protein and mRNA. These results suggest that p38 MAPK mediates high glucose-induced TEMT via transcription factor Snail1.
Actins ; metabolism ; Animals ; Blotting, Western ; Cadherins ; metabolism ; Cells, Cultured ; Diabetes Mellitus, Experimental ; metabolism ; Epithelial Cells ; cytology ; metabolism ; Epithelial-Mesenchymal Transition ; Glucose ; pharmacology ; Imidazoles ; pharmacology ; Insulin ; pharmacology ; Kidney Tubules ; cytology ; Pyridines ; pharmacology ; Rats ; Snail Family Transcription Factors ; Transcription Factors ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism

The present study was aimed to explore the expressions of transforming growth factor-β1 (TGF-β1) and Snail1 in renal tissues of diabetic rats, and their role in tubular epithelial-mesenchymal transition (TEMT). Induced diabetic rats were randomly divided into 2-, 4-, 8-, 12-, 16-, 20-, 24-week and 16wA, 20wA, 24wA groups. The rats in 16wA, 20wA and 24wA groups were treated with insulin to control blood glucose to the normal level from the 13th week. The age-matched rats were set as controls. Blood glucose, 24-hour urine protein, serum creatinine (Scr), kidney index of rats were measured. PAS staining was used to observe the renal pathological changes. Immunohistochemical staining and (or) Western blot were employed to determine the expressions of TGF-β1, Snail1, E-cadherin, α-smooth muscle actin (α-SMA) and fibronectin (FN) proteins. The expressions of Snail1 and E-cadherin mRNAs in renal cortex were examined by RT-PCR. Blood glucose, 24-hour urine protein, Scr and kidney index increased remarkably in diabetic rats as compared with those in the control groups (P<0.05, P<0.01) and insulin-treated rats (P<0.01). TGF-β1 and Snail1 protein expressions could not be detected by immunohistochemical staining in the normal renal tissues, however, the strongly positive staining was observed in diabetic rat renal tubules. A time-dependent loss of TGF-β1 and Snail1 expressions was detected in the kidney of insulin-treated rats. In diabetic rats tubular α-SMA positive staining was seen at the 16th week. E-cadherin expression was lost in diabetic rats. The expressions of TGF-β1, Snail1 proteins and Snail1 mRNA were significantly up-regulated in diabetic rats, while down-regulated in insulin-treated rats (P<0.01). The expressions of E-cadherin protein and mRNA in the cortex were contrary to the expressions of TGF-β1 and Snail1. Therefore, TGF-β1 and Snail1 are possibly involved in the pathogenesis of TEMT in diabetic nephropathy rats.
Animals ; Diabetes Mellitus, Experimental ; metabolism ; Diabetic Nephropathies ; metabolism ; Down-Regulation ; Epithelial-Mesenchymal Transition ; Kidney ; pathology ; Kidney Tubules ; metabolism ; Rats ; Snail Family Transcription Factors ; Transcription Factors ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo establish the visual patch clamp whole-cell recording technique and study the properties and functional significance of muscarinic receptor-mediated currents in rat medial vestibular nucleus neurons (MVNn).

METHODSBrain slices containing the MVN were prepared from fifteen Wistar rats. By combining infrared differential interference contrast (IR-DIC) technique and CCD-Camera system with visual patch clamp whole-cell recording technique, twenty healthy neurons were located and muscarinic receptor-mediated currents in rat MVNn were observed and analyzed.

RESULTSVisual patch clamp technique can be used to make direct localization and to make sure of active neuron. In MVNn, a comparison of the current-voltage relationships before and during the application of muscarine, which revealed an increase in the slope of the I-V curve and the reversal potential for this response lay at (-88.4 +/- 4.9) mV (x +/- s), indicates that the activation of muscarinic cholinergic receptors leads to a decrease in potassium current. The test in the voltage sensitivity of the muscarine-induced response, which showed that the effect had a linear current-voltage relationship and reversed at (-86.7 +/- 3.5) mV, indicates that the potassium current blocked by muscarine corresponds to the voltage-insensitive leak potassium current.

CONCLUSIONSVisual patch clamp technique, which was considered better than blind patch clamp technique, can improve the success of sealing process. By the analysis of muscarinic receptor-mediated currents, the data provide support that muscarinic cholinergic mechanisms play a prominent role in the modulation of the excitability of MVNn and also offer a new idea for the efficacy of anticholinergic drugs.

Animals ; Electrophysiological Phenomena ; Neurons ; physiology ; Patch-Clamp Techniques ; Rats ; Rats, Wistar ; Receptors, Muscarinic ; physiology ; Vestibular Nuclei ; physiology

OBJECTIVETo study the membrane properties of rat medial vestibular nucleus (MVN) neurons and their firing responses to simulated input signals of peripheral vestibular system, and to discuss how the intrinsic membrane properties contribute to physiologic functions in central vestibular system.

METHODSBy using infrared differential interference contrast technique, whole-cell recordings were made from rat MVN neurons under direct observation. On the basis of their averaged action potential shapes, the MVN neurons were classified. Linear and non-linear currents were put into the neurons to simulate the input signals of peripheral vestibular system. The differences of intrinsic membrane properties and firing response dynamics were observed between two types.

RESULTSThe discharge activities were recorded in MVN neurons, which remained in low Ca2+-high Mg2+ artificial cerebrospinal fluid (ACSF). Neurons are classified as type A (33%) characterized by a single deep after-hyperpolarization (AHP) and A-like rectification, or type B (63%) characterized by double AHP, and another two neurons with all or none of the characters. The passive membrane properties were not significantly different between type A and type B neurons, while part of active membrane properties was significantly different. Both type A and B neurons well responded to simulated current inputs, but disparities existed in response range and firing dynamics.

CONCLUSIONSThe discharge activities of MVN neurons were initiated by their intrinsic membrane properties. Most MVN neurons were classified as type A and B, while several showed unrepresentative firing properties. Linear and nonlinear inputs evoked a heterogeneous range of firing responses. The differences of response range and firing dynamics between neurons may determine their different physiological functions.

Action Potentials ; Animals ; Neurons ; metabolism ; physiology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Vestibular Nuclei ; cytology ; metabolism ; physiology

OBJECTIVETo observe the alterations of the auditory function and morphology of the ear in the mouse sialidosis models which has been generated by targeted deletion of lysosomal neuraminidase gene (Neul) and closely resembled the phenotypes in corresponding human conditions, and to explore pathophysiological mechanisms of hearing impairment.

METHODSNeul homozygous (Neul -/-) mice at 3 weeks, 2 and 4 months of age, and their wildtype littermates (Neu1 +/+) were examined for auditory thresholds through auditory brainstem responses (ABR) to click, 8, 16, and 32 kHz stimuli. Morphological analyses in ears were performed by series temporal bone section and light microscopy.

RESULTSNeul -/- mice at 3 weeks of age showed an elevated ABR threshold, 50-55 dB above those of Neul +/+ mice. Up to 2 and 4 months of age, their thresholds were further elevated for 60-68 dB. There were distinct pathological changes of middle and inner ear of 3 weeks of age in Neul -/- mice, especially at 2-4 months of age there were significant cerumen occlusion in the external auditory canal and severe otitis media. Vacuolation associated with lysosomal storage was observed within ossicles and cochlear bone cells, stria vascularis cells, spiral ganglion neurons and macrophages, spiral limbus, spiral prominence, Reissner's membrane cells, and the mesothelial cells of the perilymphatic scala and basilar membrane, but not within the organ of Corti. Vestibular ganglion neurons, hair cells and supporting cells in cristae and maculae also showed vacuolation.

CONCLUSIONSThe deficiency of lysosomal neuraminidase may result in a serious hearing loss and morphological alterations of ear. The external auditory canal obstruction, otitis media and ossicle changes may cause conductive hearing loss, and the defects in lysosomal storage of neurons, stria vascularis, spiral limbus, Reissner's membrane and basilar membrane cells may contribute to sensorineural deafness.

Animals ; Ear, Middle ; anatomy & histology ; pathology ; Evoked Potentials, Auditory, Brain Stem ; Hearing Loss ; pathology ; physiopathology ; Mice ; Mice, Knockout ; Mucolipidoses ; pathology ; physiopathology ; Neuraminidase ; genetics ; Otitis Media ; pathology

The aim of this study was to investigate effects of IAT and MAT chemotherapeutic regimens treating patients with refractory and relapsed acute myeloid leukemia (AML). 99 patients with refractory and relapsed AML received IAT regimen or MAT regimen as study objects were retrospectively analyzed (56 patients with refractory AML and 43 patients with relapsed AML). Among of them, 28 patients were treated with IAT regimen, and 71 patients received with MAT regimen. The results showed that in 2 groups mentioned above the OR was 65.7%, CR was 49.5%, PR was 16.2%; in IAT group the OR was 64.3%, CR was 46.4%; in MAT group the OR was 66.2%, CR was 50.7%, no statistical difference was found between these 2 groups; The 2 years overall survival was 25% in IAT group and 15.5% in MAT group. Serious infection in IAT and MAT regime groups was 25% and 9.9%, respectively. It is concluded that both IAT and MAT regimens are effective methods for inducing CR in patients with refractory of relapsed AML. IAT and MAT regimens can be used in treatment of the refractory or relapsed MAL patients who were not respond to other regimen.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Child ; Cytarabine ; administration & dosage ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; etiology ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Vidarabine ; administration & dosage ; Young Adult