Two new sesquiterpenoids, named as tyromols A and B (1 and 2), were isolated from cultures of basidiomycete Tyromyces chioneus, along with two previously reported 15-hydroxy-6 α, 12-epoxy-7β, 10αH, 11βH-spiroax-4-ene (3) and agripilol C (4). Compounds 1-4 were separated and purified by silica gel, RP-18, Sephadex LH-20 column chromatography. Their structures were elucidated on the basis of extensive spectroscopic analysis including IR, MS, 1D and 2D NMR experiments.
Basidiomycota ; chemistry ; Magnetic Resonance Spectroscopy ; Sesquiterpenes ; chemistry ; isolation & purification ; Sesterterpenes

Objective To investigate the role of activated cylic AMP(cAMP) signaling in chemical-induced podocyte injury.Methods Eight-weeks-old male BalB/C mice were randomly divided into three groups:control group,Adriamycin (ADR) group and Forskolin+ADR group.ADR nephropathy models were established by tail intravenous injection,and part of them were injected Forskolin,an agonist of adenylate cyclase,intraperitoneally.Phosphorylation of cAMP response element binding protein (CREB) was detected by laser confocal microscopy,morphology of foot processes were determined with transmission electron microscope,and WT-1 expression in glomeruli were detected by immunohistochemistry.Conditionally immortalized podocytes were treated with puromycin aminonucleoside (PAN),Exchange protein directly activated by cAMP (Epac) agonist 8-pCPT-2-O-Me-cAMP (2Me),protein kinase A (PKA) antagonist H89 and its agonist pCPT-cAMP(pCPT).Western blot was used to detect the expression levels of Epac,caspase3 and cleaved caspase3.PKA activity was assayed using cAMP-dependent protein kinase detection system.Cell viability was determined by a cell count kit and podocyte apoptosis was estimated by TUNEL staining.Mitochondrial membrane potential was evaluated by JC-1 staining.Results (1)Compared with ADR group,the urine albumin decreased significantly (P ＜ 0.05) among Forskolin + ADR group and the WT-1 positive cells per glomerulus increased obviously (P ＜ 0.05).(2)PAN decreased podocyte number in a time-dependent manner (P ＜ 0.05),pre-treatment with pCPT obviously inhibited PAN induced podocyte decrease (P ＜0.05),but H89 prevented the effect of pCPT in a dose-dependent manner (P ＜ 0.05).(3)JC-1 staining showed that the percentage of podocyte with green fluorescence for control,PAN and pCPT+PAN group were (12.67±2.15)％,(31.35±4.60)％ and (16.96 ± 2.51)％ respectively (P ＜ 0.05),and pretreatment with H89 inhibited the effect of pCPT (P ＜ 0.05).(4) PAN promoted podocyte apoptosis and cleaved caspase3 expression (P ＜ 0.05),and pretreatment with pCPT significantly prevented PAN-induced podocyte apoptosis and cleaved caspase3 expression (P ＜ 0.05).Conclusions cAMP signaling activation ameliorated podocyte injury in ADR nice and PAN-induced podocyte apoptosis,and cAMP/ PKA pathway may mediate these processes.

Objective To introduce a new method performing umbilicus abdominal access during laparoscopy. Methods In a prospec-tive,362 patients received laparoscopic appendectomy in October 2012 to October 2014 were oberserved in this study. The clinical data,the time of the progress of making umbilicus abdominal access,complications and the state of the wound were recorded. Results The performing time of the trocar in umbilicus was (42. 3 ± 27. 1)s. Conclusion The method Cut-open,is simple,fast and save,which is worth to promoting in laparoscopic surgery.

Objective To investigate the bacterial distribution and drug resistance in urinary tract infection from Sichuan Provin‐cial Antimicrobial Resistant Investigation Net during 2011-2012 .Methods The distribution and drug resistance data of pathogens isolated from urine specimens of urinary tract infection cases were collected from the members of Sichuan Provincial Antimicrobial Resistant Investigation Net ,and the results were counted and analyzed .Results There were 54 hospitals enrolling in the investiga‐tion .A total of 12 420 pathogenic strains were isolated from urinary tract infection in the survey .The top 5 predominant bacteria were Escherichia coli(46 .5% ) ,Excrement enterococcus (7 .0% ) ,K lebsiella pneumoniae (5 .8% ) ,Dung enterococcus (5 .7% ) and Pseudomonas aeruginosa(3 .7% ) .The resistant rates of Escherichia coli ,K lebsiella pneumoniae and Pseudomonas aeruginosa to imipenem were 16 .0% ,16 .7% and 16 .0% ,and to levofloxacin were 55 .2% ,28 .2% and 27 .7% ,respectively .The resistant rates of Excrement enterococcus and Dung enterococcus to vancomycin were 4 .1% and 1 .4% respectively .Conclusion Escherichiacoli and Enterococcus are still the predominant organism in urinary tract infection cases .Clinical treatment should refer to the results of drug sensitive test .

Objective:This study aimed to establish an eXtreme Gradient Boosting(XGBoost) model that can predict the recurrence of hepatocellular carcinoma(HCC)patients after laparoscopic hepatectomy (LH) surgery.Methods:A total of 440 patients with primary HCC who received LH treatment for the first time from January 2013 to September 2016 in Affiliated Hospital of Chengde Medical University were selected as the research objects. The diagnosis method was pathological diagnosis. Research objects were divided into training group ( n=88) and verification group ( n=352) at a ratio of 2∶8 by random number table method. The Kaplan-Meier method was used to draw the recurrence-free survival curve, and the Log-rank test was used to compare the survival of the two groups; the training group was used to establish the COX regression model and the XGBoost model to screen independent predictors of recurrence after LH; receiver operating characteristic(ROC) curve was used to analyze the predictive abilities of the two models, and conducted internal verification in the verification group; Hosmer and Lemeshow Test was used to evaluate the calibration of the two models, and P>0.05 was used as a good fit between the model and the actual situation. Results:Both the COX regression model and the XGBoost model screened out tumor thrombus, low degree of differentiation, tumor microvascular infiltration (MVI), number of tumors, large tumors, and positive hepatitis B surface antigen were independent predictors of tumor recurrence( HR=2.477, 0.769, 1.786, 1.905, 1.544, 1.805; 95% CI: 1.465-4.251, 0.619-0.819, 1.263-2.546, 1.354-2.704, 1.272-1.816, 1.055-2.555). The XGboost model scores were 32 points, 29 points, 24 points, 18 points, 16 points, 11 points, respectively. In the training group, the area under the curve (AUC) of the COX regression model and XGBoost model for predicting recurrence were 0.746 (0.730-0.762) and 0.802 (0.785-0.818), respectively. The XGBoost model had strong predictive ability and was confirmed in the validation cohort. Conclusions:This study had established and verified the XGBoost model that can predict the recurrence of HCC patients after receiving LH for the first time. It can be used in clinics to assist doctors in formulating personalized postoperative monitoring programs for patients. Early detection, early diagnosis and early treatment of tumors and strengthening of postoperative follow-up are important measures to improve the prognosis of patients.

AIMTo prepare heart-protecting musk pH-dependent gradient-release pellets and investigate the drug release in vitro and in vivo.

METHODSThe pH-dependent gradient-release pellet system was prepared by using HPMC, Eudragit L-30D-55 and Eudragit L100-Eudragit S100 (1:5) combinations as coater. The release of borneol and total ginsenoside from pH-dependent gradient-release pellets were determined according to the method of Pharmacopoeia of the People's Republic of China (2000) in the simulated gastrointestinal pH conditions. The gastrointestinal transit and disintegration of pellets was investigated by using gamma-scintigraphic trace in volunteers. The pharmacokinetics of borneol of heart-protecting musk pH-dependent gradient-release pellets was studied in 6 healthy volunteers by GC methods.

RESULTSThe f2 value of release data of borneol and total ginsenoside of the heart-protecting musk pH-dependent gradient-release pellets was 79.6 in the simulated gastrointestinal pH conditions. The gamma-scintigraphic trace evaluation demonstrated that the pellets coated with HPMC, Eudragit L-30D-55 or Eudragit L100-Eudragit S100 (1:5) combinations can disintegrate in stomach, duodenum and jejunum or ileum. The gastrointestinal transit time of pellets was about 5 hours in fasted state and about 6 hours in fed state. The concentration-time curves of borneol of heart-protecting musk pills fit in two-compartment model. The pharmacokinetics data showed that borneol had a short time of absorption and elimination. The mean residence time (MRT) of borneol of heart-protecting musk pills was 2.61 hours. The plasma concentration of borneol of heart-protecting musk sustained-release capsule which consisted of three kinds of pellets coated with HPMC, Eudragit L-30D-55 or Eudragit L100-Eudragit S100 (1:5) combinations was steadier than those of heart-protecting musk pills, its Cmax was lower than and Tmax was near to those of heart-protecting musk pills, its MRT was 4.0 hours, and its relative bioavailability was 96%.

CONCLUSIONThe lipidsoluble borneol and watersoluble total ginsenoside of heart-protecting musk pH-dependent gradient-release pellets can release simultaneously while sustained-releasing in vitro. The heart-protecting musk pH-dependent gradient-release pellets had the characteristics of pH-dependent gradient-releasing and disintegration while transiting in gastrointestinal tract. A characteristic of gradient sustained-release was shown in the concentration-time curves of borneol of heart-protecting musk sustained-release capsule in volunteers.

Adult ; Bornanes ; pharmacokinetics ; Delayed-Action Preparations ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Fatty Acids, Monounsaturated ; administration & dosage ; Gastrointestinal Transit ; Ginsenosides ; pharmacokinetics ; Humans ; Hydrogen-Ion Concentration ; Lactose ; analogs & derivatives ; Male ; Materia Medica ; administration & dosage ; pharmacokinetics ; Methylcellulose ; analogs & derivatives ; Oxazines ; Polymethacrylic Acids ; Random Allocation

Objective To investigate the effect of leptin on the tolerance of cultured rat brain astrocytes to ischemia and hypoxia.Methods The brain astrocytes isolated from neonatal SD rats,after purification and identification,were incubated in serum-and glucose-flee medium in the presence of 5%CO2+95%N2 for 90 min to induce isehemic and hypoxic injury. RT-PCR was performed to detect the expressions of the leptin receptors Ob-Ra and Ob-Rb in the cells, and colorimetry was used to measure the content of malonaldehyde(MDA) and lactate dehydrogenase(LDH) activity in the cell supematant.The expression level ofglial fibrillary acidicprotein(GFAP)in the cells was detected with fluorescence immunocytochemistry.Results Ischemic and hypoxic exposure of the cells induced obvious cell necrosis.Compared with the cells without the exposure,significantly decreased Ob-Rb expression(0.52±0.01 vs 1.32±0.01,P<0.05)and increased MDA,LDH and GFAP levels(709.68±47.16 vs 516.13±29.08,3.94±0.36 vs 1.81±0.21,and 0.122±0.016 vs 0.057±0.006,respectively,P<0.05) occurred after the exposure,whereas the expression level of Ob-Ra underwent no significant changes(3.87±0.13 vs 3.96±0.24,P>0.05). Compared with the exposed cells,the leptin-treated cells showed a significant reduction in MDA levels(3.94±0.36 vs 3.19±0.25,P<0.05) with significantly increased GFAP expression(0.057±0.006 vs 0.109±0.008, P<0.05)after the exposure, and the cells maintained basically intact cell morphology.Conclusion With neuroprotective effects against ischemic neuronal injuries,leptin canimprove the tolerance of rat brain astrocytes to ischemia and hypoxia.

OBJECTIVETo rapidly and sensitively detect the four virulence-associated factors of Streptococcus suis, a multiplex PCR was developed.

METHODSIn the process of this reaction, four distinct DNA targets were amplified. One target was based on the serotype 2 (and 1/2) specific cps gene and the others were based on Streptococcus suis mrp, epf (epf*) and sly gene, encoding the MRP, EF(EF*) and Sly proteins of Streptococcus suis. 72 isolates, which including 48 strains of Streptococcus suis and 24 strains of negative control, and 49 clinical specimens were detected by the multiplex PCR assay.

RESULTSAll PCR products were detected by electrophoresis on 1.2% agarose gels. With the 48 Streptococcus suis strains, the positive detection rates of cps2+, mrp+, epf+, epf*+ and sly+ were 16/48, 14/48, 12/48, 3/48 and 26/48,respectively. The results were confirmed by bacteriological examination. There were no specific amplification products including 49 clinical specimens and 24 negative control strains.

CONCLUSIONThe results demonstrated that multiplex PCR was a highly specific and sensitive diagnostic tool for the detection of virulence-associated factors of streptococcus suis.

Bacterial Proteins ; genetics ; Polymerase Chain Reaction ; methods ; Streptococcus suis ; genetics ; pathogenicity ; Virulence Factors ; genetics

OBJECTIVE: To explore clinical efficacy of limited external fixation with plastic paperboard in treating senile proximal comminuted humeral fracture. METHODS: From June 2015 to December 2017, 32 senile patients with proximal comminuted fracture of humerus were treated with plasticized cardboard after manual external fixation. Among them, including 13 males and 19 females aged from 55 to 85 years old with an average of(68.22±8.36) years old; 18 patients on the left side and 14 patients on the right side; all patients were regularly review shoulder X-rays and performed appropriate functional exercises. Constant-Murley shoulder joint scoring was used to evaluate clinical effects. RESULTS: Thirty-two patients were followed up for 3 to 12 months with an average of (4.97±2.39) months. All patients were underwent functional exercise under guidance of physicians. Nine patients were treated with topical Chinese herbal moist heat compresses to promote shoulder function recovery. Thirty-one patients were obtained fracture healing, the time ranged from 5 to 12 weeks with an average of(7.44±1.72)weeks. One patient was not healed due to comminuted fracture of fracture end and the separation was large, the blood supply to humeral head was insufficient for necrosis absorption. Postoperative Constant-Murley shoulder score at 3 months was 87.56±6.93; 15 patients got excellent results, 14 good, 2 fair and 1 poor. CONCLUSIONS Limited external fixation with plastic paperboard for the treatment of senile proximal comminuted humeral fracture could ensure biomechanical stability of fracture, promote early recovery of shoulder joint function and shorten recovery time.
Aged ; Aged, 80 and over ; Female ; Fracture Fixation, Internal ; Fractures, Comminuted ; surgery ; Humans ; Humeral Fractures ; surgery ; Male ; Middle Aged ; Plastics ; Shoulder Fractures ; Treatment Outcome

OBJECTIVETo update the clinical characteristics of mycosis fungoides in Chinese patients.

METHODWe retrospectively analyzed the clinical data of 51 patients (29 men and 22 women) with mycosis fungoides in PUMC hospital from 1984 to 2006, to determine the ages at diagnosis, clinicopathologic characteristics of skin lesions, systemic manifestation, misdiagnosis and treatment of these patients.

RESULTSThe mean age was (44.24 +/- 2.05) years at the diagnosis. Most patients were characterized by the typical evolution of patches, plaques and tumors, with some variations and subtypes. Clinical manifestations included generalized lesions (68.6%) and itchy (70.6%). Epidermotropism (68.6%) and Pautrier's microabscesses (52.9%) were common histopathologic features. The positive rate of T-cell receptor gene rearrangement was 81.3%, and was independent of the histological features. Previous misdiagnosis rate was 64.7%. Skin-targeted therapies and biologic therapies were effective approaches to relieve the skin rash at early stage, and combined chemotherapy was typically applied in more advanced cases.

CONCLUSIONMycosis fungoides has various clinical characteristics and careful differential diagnosis should be made in clinical practice.

Diagnostic Errors ; Female ; Gene Rearrangement ; Humans ; Male ; Mycosis Fungoides ; diagnosis ; pathology ; Receptors, Antigen, T-Cell ; genetics ; Retrospective Studies ; Skin Neoplasms ; diagnosis ; pathology