Investigations on the antifatigue and antihypoxic effects of Paecilomyces hepiali extract.

Paecilomyces hepiali, one of the most valuable and effective Chinese medicinal herbs, possesses potential antioxidant, immunomodulatory, antitumor and anti­inflammatory properties. The present study aimed to investigate the antifatigue and antihypoxic effects of Paecilomyces hepiali extract (PHC) in a mouse model. Using a rotating rod, forced swimming and running assessment, the antifatigue activity of PHC was determined. PHC administration for 7 days had no effect on mouse horizontal or vertical movement, indicating no neurotoxicity at the selected doses was observed. Using a normobaric hypoxia, sodium nitrite toxicosis and acute cerebral ischemia assessments, PHC was confirmed to possess antihypoxic effects. PHC treatment for 7 days significantly enhanced the serum and liver levels of adenosine triphosphate, superoxide dismutase and glutathione peroxidase, prior to and following 60 min of swimming. The levels of antioxidant­associated proteins in the livers of the mice were analyzed using western blotting. PHC effectively increased the expression levels of phosphorylated (p)­5'­monophosphate (AMP)­activated protein kinase (AMPK), p­protein kinase B (AKT) and p­mammalian target of rapamycin (mTOR). The results of the present study demonstrated that PHC efficiently enhanced endurance from fatigue and had antihypoxic effects through elevation of the antioxidant capacity in the serum and liver, at least in part through the AMPK and AKT/mTOR pathways. These results indicate the potential of this natural product as an antioxidant in the treatment of fatigue, hypoxia and their associated diseases.

Study of the analgesic activities, chronic toxicity and addictive potential of Jia-Yuan-Qing pill in rats.

Jia-Yuan-Qing pill (JYQP) composed of Porcellio laevis Latreille, Corydalis Rhizoma and Radix Cynanchi Paniculati at a ratio of 9:7:7 has been found to be an effective analgesic agent. The present study aimed to evaluate the safety, addictive potential and anti-cancer pain activity of JYQP in a rat model. During the 6-month chronic toxicity test, no significant changes in general behavior, defecation, postural abnormalities, dietary or water intake or blood biochemical parameters were observed in male and female rats. Although a high dose of JYQP (5 g/kg) caused swelling of the liver, spleen and kidney in male and female rats, no pathological changes were observed in all organs examined via hematoxylin and eosin staining. The analgesic effect of JYQP on bone cancer pain was successfully confirmed in a rat model of Walker 256 cell-induced bone cancer. In contrast to morphine, in a physical dependence test, JYQP produced no withdrawal symptoms following chronic administration. The data from this study provide experimental evidence supporting the clinical use of JYQP as an effective, safe and non-addictive agent for the treatment of bone cancer pain.

Enzymo-chemical preparation, physico-chemical characterization and hypolipidemic activity of granular corn bran dietary fibre.

Corn bran dietary fibre (CF) was paid more attention for its anticancer and hypolipidemic activities. In this paper, corn bran was firstly decomposed to the threadlike fibre (CF1) by multiple enzymes and then further modified to the granular fibre (CF2) by alkali under high pressure and high temperature (APT). The two types of fibres were characterized by scanning electron microscope (SEM) and near-infrared spectrophotometer (IR), and investigated by hydration measurements and nitrite adsorption assays. The results showed that CF2 had more much specific surface area, and displayed 4.7, 6.3 and 30-fold increases in water retention (WR), swelling capacity (SC) and nitrite absorption (NA), compared with CF1, respectively. The rat feeding trials showed that the granular fibre could decrease total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDLC) by 41.4 %, 20.7 % and 56.5 %, respectively. These excellent physiological activities indicate that CF2 will be a potentially available dietary ingredient in functional food industries, and meanwile imply that the enzymochemical method is a desired strategy for CF processing.

Studies on the analgesic activities of Jia-Yuan-Qing pill and its safety evaluation in mice.

The analgesic activity of Porcellio laevis Latreille, Rhizoma Corydalis, and Radix Cynanchi Paniculati have been reported in recent years. A new formula named Jia-Yuan-Qing pill (JYQP) is therefore created by combining the three herbs at 9:7:7 ratio according to traditional Chinese theories. The present study aims to evaluate the effect of JYQP as a novel painkiller in various models. Acute toxicity test was applied to evaluate the safety of JYQP. Acetic-acid-induced writhing, hot plate test, formalin test, and naloxone-pretreated writhing test were employed to elaborate the analgesic activity of JYQP and its possible mechanism. A bone cancer pain mouse model was performed to further assess the effect of JYQP in relieving cancer pain. Test on naloxone-precipitated withdrawal symptoms was conduct to examine the physical dependence of mice on JYQP. Data revealed that JYQP reduced writhing and stretching induced by acetic acid; however, this effect could not be blocked by naloxone. JYQP specifically suppressed the phase II reaction time in formalin-treated mice; meanwhile, no analgesic effect of JYQP in hot plate test was observed, indicating that JYQP exerts analgesic activity against inflammatory pain rather than neurogenic pain. Furthermore, JYQP could successfully relieve bone cancer pain in mice. No physical dependence could be observed upon long-term administration in mice. Collectively, our present results provide experimental evidence in supporting clinical use of JYQP as an effective and safe agent for pain treatment.

[Study on the detection of active ingredient contents of Paecilomyces hepiali mycelium via near infrared spectroscopy].

Partial least squares (PLS) and radial basis function neural network (RBFNN) combined with near infrared spectros- copy (NIR) were applied to develop models for cordycepic acid, polysaccharide and adenosine analysis in Paecilomyces hepialid fermentation mycelium. The developed models possess well generalization and predictive ability which can be applied for crude drugs and related productions determination. During the experiment, 214 Paecilomyces hepialid mycelium samples were obtained via chemical mutagenesis combined with submerged fermentation. The contents of cordycepic acid, polysaccharide and adenosine were determined via traditional methods and the near infrared spectroscopy data were collected. The outliers were removed and the numbers of calibration set were confirmed via Monte Carlo partial least square (MCPLS) method. Based on the values of degree of approach (Da), both moving window partial least squares (MWPLS) and moving window radial basis function neural network (MWRBFNN) were applied to optimize characteristic wavelength variables, optimum preprocessing methods and other important variables in the models. After comparison, the RBFNN, RBFNN and PLS models were developed successfully for cordycepic acid, polysaccharide and adenosine detection, and the correlation between reference values and predictive values in both calibration set (R2c) and validation set (R2p) of optimum models was 0.9417 and 0.9663, 0.9803 and 0.9850, and 0.9761 and 0.9728, respectively. All the data suggest that these models possess well fitness and predictive ability.

At-line monitoring of key parameters of nisin fermentation by near infrared spectroscopy, chemometric modeling and model improvement.

An analytical procedure has been developed for at-line (fast off-line) monitoring of 4 key parameters including nisin titer (NT), the concentration of reducing sugars, cell concentration and pH during a nisin fermentation process. This procedure is based on near infrared (NIR) spectroscopy and Partial Least Squares (PLS). Samples without any preprocessing were collected at intervals of 1 h during fifteen batch of fermentations. These fermentation processes were implemented in 3 different 5 l fermentors at various conditions. NIR spectra of the samples were collected in 10 min. And then, PLS was used for modeling the relationship between NIR spectra and the key parameters which were determined by reference methods. Monte Carlo Partial Least Squares (MCPLS) was applied to identify the outliers and select the most efficacious methods for preprocessing spectra, wavelengths and the suitable number of latent variables (n (LV)). Then, the optimum models for determining NT, concentration of reducing sugars, cell concentration and pH were established. The correlation coefficients of calibration set (R (c)) were 0.8255, 0.9000, 0.9883 and 0.9581, respectively. These results demonstrated that this method can be successfully applied to at-line monitor of NT, concentration of reducing sugars, cell concentration and pH during nisin fermentation processes.

Biodegradable poly(D, L-lactide-co-glycolide) (PLGA) microspheres for sustained release of risperidone: Zero-order release formulation.

The preparation and investigation of sustained-release risperidone-encapsulated microspheres using erodible poly(D, L-lactide-co-glycolide) (PLGA) of lower molecular weight were performed and compared to that of commercial Risperdal Consta™ for the treatment of schizophrenia. The research included screening and optimizing of suitable commercial polymers of lower molecular weight PLGA50/50 or the blends of these PLGA polymers to prepare microspheres with zero-order release kinetics properties. Solvent evaporation method was applied here while studies of the risperidone loaded microsphere were carried out on its drug encapsulation capacity, morphology, particle size, as well as in vitro release profiles. Results showed that microspheres prepared using 50504A PLGA or blends of 5050-type PLGAs exerted spherical and smooth morphology, with a higher encapsulation efficiency and nearly zero-order release kinetics. These optimized microspheres showed great potential for a better depot preparation than the marketed Risperdal Consta™, which could further improve the patient compliance.

[Application of near infrared spectroscopy in screening Cordyceps militaris mutation strains and optimizing their fermentation process].

To fast screen high-yield Cordyceps militaris mutations strains and optimize their fermentation process, near infrared (NIR) spectroscopy technology combined with chemometrics has been applied to establishing models for simultaneous determination of adenosine, protein, polysaccharide and Cordyceps militaris acid contents in Cordyceps militaris powder samples. Fermentations were implemented in Erlenmeyer flask with 468 Cordyceps militaris mutations strains under various fermentation conditions and Cordyceps militaris powder samples were collected. Then their NIR spectra were obtained using UV-VIS-NIR spectrometer and their adenosine, protein, polysaccharide and Cordyceps militaris acid contents were determined using reference methods. Partial least squares (PLS) method was employed to model the relationships between NIR spectra and the above mentioned components' contents in Cordyceps militaris powder samples. Monte Carlo partial least square (MCPLS) was applied to identify the outliers and select suitable number of calibration samples. Moving window partial least square (MWPLS) was applied to select the characteristic wavelength of the components. The degree of the approaching (Da) was employed as criterion for selecting effective pretreatment methods investigated. The optimum models for determination of adenosine, protein, polysaccharide and Cordyceps militaris acid contents in Cordyceps militaris powder samples were obtained with the above mentioned optimization. Their correlation between actual and predictive values of calibration samples (Re) was 0.92943, 0.98479, 0.90785, and 0.85131, respectively. Their root mean square error of prediction set (RMSEP) was 0.66714, 0.02065, 0.01131, and 0.01159, respectively. The obtained results demonstrated that the fitting and the predictive accuracy were satisfactory. It is feasible to apply this method to screen the high yield Cordyceps militaris mutation strains and optimize their fermentation process.

Pregnancy outcomes of repeat cesarean section in Peking Union Medical College Hospital.

OBJECTIVE: To evaluate the effect of elective repeat cesarean section on the maternal and neonatal outcomes. METHODS: A retrospective clinic- and hospital-based survey was designed for comparing the maternal and neonatal outcomes of elective repeat cesarean section [RCS group (one previous cesarean section) and MRCS group (two or more previous cesarean sections)] and primary cesarean section (FCS group) at Peking Union Medical College Hospital from January 1998 to December 2007. RESULTS: The incidence of repeat cesarean section increased from 1.26% to 7.32%. The mean gestational age at delivery in RCS group (38.1+/-1.8 weeks) and MRCS group (37.3+/-2.5 weeks) were significantly shorter than that in FCS group (38.9+/-2.1 weeks, all P<0.01). The incidence of complication was 33.8% and 33.3% in RCS group and MRCS group respectively, and was significantly higher than that in FCS group (7.9%, P<0.05). Dense adhesion (13.5% vs. 0.4%, OR=7.156, 95% CI: 1.7-30.7, P<0.01) and uterine rupture (1.0% vs. 0, P<0.05) were commoner in RCS group compared with FCS group. Neonatal morbidity was similar among three groups (P>0.05). CONCLUSIONS: Repeat cesarean section is associated with more complicated surgery technique and increased frequency of maternal morbidity. However, the incidence of neonatal morbidity is similar to primary cesarean section.

[Effect of pregnancy and spontaneous delivery on the morphology of levator ani muscle and expression of vaginal nerve fibers].

OBJECTIVE: To investigate the effect of pregnancy and spontaneous delivery on the morphologic characteristics of the levator ani muscle and innervation of the vaginal mucosa. METHODS: Eight nullipara without pelvic floor dysfunction (PFD) and 64 normal primipara undergoing spontaneous delivery were enrolled in this study during July to December 2006 in Peking Union Medical College Hospital. Biopsy specimens of levator ani muscle (LAM) and anterior and posterior vaginal walls were obtained from the puerpera as well as from the 8 nullipara undergoing vaginal operation. The structures of LAM were examined with histological techniques. Vaginal mucosa specimens were examined using immunohistochemistry staining for protein gene product 9.5 (PGP 9.5), vasoactive intestinal peptide (VIP) and ne uropeptide Y (NPY), and the positive stained nerve fibers were calculated respectively. RESULTS: The LAMs of the puerpera undergoing spontaneous delivery presented myogenetic and neurogenetic changes, both acute and chronic. Type I muscular fibers were predominant (79%) with both types increasing in diameters [(86 +/- 9) microm and (79 +/- 15) microm]. Significantly different (P < 0.05) innervation of PGP 9.5, VIP, and NPY nerve fibers was observed between epithelial lamina of anterior vaginal wall (5.9 +/- 3.3, 7.6 +/- 3.1 and 8.2 +/- 3.2, respectively) and that of posterior vaginal wall (3.8 +/- 2.9, 5.9 +/- 3.1 and 6.0 +/- 3.0, respectively), with the nerve fibers being more in epithelial lamina of anterior vaginal wall, while no difference in the innervation of nerve fibers was observed in the lamina propria. Significantly different (P < 0.05) innervation of PGP 9.5 and VIP nerve fibers was observed in the lamina propria of the anterior vaginal wall in puerperal undergoing vaginal delivery (6.9 +/- 3.2 and 4.9 +/- 2.1) compared with those in nullipara (3.9 +/- 3.6 and 3.1 +/- 1.2). CONCLUSIONS: Pathologic changes occur in LAMs and pelvic floor nerves during labor and delivery. LAM fibers become hypertrophy to adapt to the physiological changes during pregnancy. Richer innervation of PGP 9.5 and VIP nerve fibers in the lamina propria of the anterior vaginal wall in puerpera undergoing spontaneous delivery is beneficial for dilation of the blood vessels and smooth muscles and makes preparation for delivery.

[Effect of induction delivery on maternal-neonatal outcomes in 41 gestational weeks primiparae].

OBJECTIVE: To estimate the maternal-neonatal morbidity associated with induction deliveries compared with spontaneous deliveries in 41 gestational weeks uncomplicated primiparae. METHODS: Three hundred and seventy-four uncomplicated primiparous deliveries at 41 gestational weeks at Peking Union Medical College Hospital from Sept 2002 to Apr 2007 were reviewed, including 225 women undergoing induced labor and 149 women undergoing spontaneous labor. The induction methods included drug induction (173), rupture of membrane induction (5) and combined drug with rupture of membrane induction (47). The maternal morbidity, delivery method, maternal cost on hospital stay and neonatal asphyxia associated with induction deliveries or spontaneous deliveries were retrospectively analyzed. RESULTS: (1) There was no maternal death. The caesarean section rate in the induction group (44.0%, 99/225) was significantly higher than that of spontaneous group (18.1%, 27/149; P<0.05). (2) No statistically significant difference (P>0.05) was observed between induction group and spontaneous group in the following puerperal complications: postpartum hemorrhage (2.7%, 6/225 and 1.3%, 2/149 respectively), puerperal morbidity (0.9%, 2/225 and 0.7%, 1/149 respectively), severe amniotic fluid contamination (11.6%, 26/225 and 13.4%, 20/149 respectively), wound infection (0.9%, 2/225 and 0.7%, 1/149 respectively) ,urinary retention(4.4%, 10/225 and 3.4%, 5/149 respectively), traumata (0.4%, 1/225 and 0 respectively) and neonatal asphyxia (1.3%, 3/225 and 2.0%, 3/149 respectively). (3) The average duration of first stage of labor in the induction group (413 min) was not significantly different from that of spontaneous group (461 min; P>0.05). In the induction group, more women had precipitate labors (P<0.05) and the average duration of the second stage of labor was shorter than that of spontaneous group (40 min and 48 min, P<0.05). (4) Spontaneous group had shorter maternal hospital stay [(5.7 +/- 1.9) days vs (6.9 +/- 2.7) days, P<0.05] and caesarean section after induction had the highest hospital expense (P<0.05). CONCLUSIONS: Induction delivery at 41 weeks of gestation increases the rates of caesarean section, precipitate labor, clinical workload and hospital costs. Induction delivery as a prevention method of over due labor needs to be further discussed. Uncomplicated pregnancies of 41 weeks should be intentionally monitored if continued surveillance is possible. They should wait for spontanous delivery, and decision of induction should be made based on its benefit to the case.

[Application of near infrared spectroscopy in rapid and simultaneous determination of essential components in five varieties of anti-tuberculosis tablets].

Since 1980s, tuberculosis has become increasingly serious. Rifampicin tablets, isoniazide tablets, pyrazinamide tablets, rifampicin and isoniazide tablets and rifampicin isoniazide and pyrazinamide tablets are currently relatively efficacious antituberculosis drugs. In the present paper, near infrared spectroscopy (NIRS) with partial least squares (PLS) was applied to the simultaneous determination of rifampicin (RMP), isoniazide (INH) and pyrazinamide (PZA) contents in 5 varieties of anti-tuberculosis tablets. As the results showed, all of the models for the determination of RMP, INH and PZA contents applied the original NIR spectra. The most efficacious wavelength range for the determination of RMP contents was 1981-2195 nm, it was 1540-1717 nm and 2086-2197 nm for the determination of INH contents, and it was 1460-1537 nm, 1956-2022 nm and 2268-2393 nm for determination of PZA contents. The root mean square error of the calibration set obtained by cross-validation (RMSECV) of the optimum models for the quantitative analysis of RMP, INH and PZA contents was 0.0494, 0.0257 and 0.0307, respectively. Using these optimum models for the determination of RMP, INH and PZA contents in prediction set, the root mean square error of prediction set (RMSEP) was 0.0182, 0.0166 and 0.0134, respectively. The correlation coefficient (r(p)) between the predicted values and actual values was 0.9864, 0.9989 and 0.9993, respectively. These results demonstrated that this method was precise and reliable, and is significative for in situ measurement and the on-line quality control for anti-tuberculosis tablets production.

[Application of wavelet transform-radial basis function neural network in NIRS for determination of rifampicin and isoniazide tablets].

A calibration model (WT-RBFNN) combination of wavelet transform (WT) and radial basis function neural network (RBFNN) was proposed for synchronous and rapid determination of rifampicin and isoniazide in Rifampicin and Isoniazide tablets by near infrared reflectance spectroscopy (NIRS). The approximation coefficients were used for input data in RBFNN. The network parameters including the number of hidden layer neurons and spread constant (SC) were investigated. WT-RBFNN model which compressed the original spectra data, removed the noise and the interference of background, and reduced the randomness, the capabilities of prediction were well optimized. The root mean square errors of prediction (RMSEP) for the determination of rifampicin and isoniazide obtained from the optimum WT-RBFNN model are 0.00639 and 0.00587, and the root mean square errors of cross-calibration (RMSECV) for them are 0.00604 and 0.00457, respectively which are superior to those obtained by the optimum RBFNN and PLS models. Regression coefficient (R) between NIRS predicted values and RP-HPLC values for rifampicin and isoniazide are 0.99522 and 0.99392, respectively and the relative error is lower than 2.300%. It was verified that WT-RBFNN model is a suitable approach to dealing with NIRS. The proposed WT-RBFNN model is convenient, and rapid and with no pollution for the determination of rifampicin and isoniazide tablets.

[Effect of different delivery modes on the short-term function of the pelvic floor].

OBJECTIVE: To investigate the effect of different delivery modes and related obstetric factors on the short-term function of the pelvic floor. METHODS: One hundred and twenty healthy primiparae women were interviewed at 6-8 weeks postpartum, with 72 women in the vaginal delivery group and 48 women in the elective cesarean section group. Questionnaire on stress urinary incontinence and measurement of diastolic and contractive function of the pelvic floor muscles by electromyogram (EMG) were used for the evaluation and comparison. RESULTS: The prevalence of stress urinary incontinence in the vaginal delivery group and the elective cesarean section group was 21% and 10% (P = 0. 134) ,respectively. The values of the right act, right work, and average work surveyed by EMG in vaginal delivery group were significantly lower than those in cesarean section group (right act, 12.9 +/- 0.8 vs. 17.3 +/- 1.7, P < 0.05; right work, 59 +/- 5 vs. 95 +/- 17, P = 0.02; average work, 78 +/- 5 vs. 109 +/- 15, P < 0.05). Maternal age, body mass index (BMI) before labor, incontinence during pregnancy, neonatal birth weight and longer duration of second stage were risk factors for stress urinary incontinence postpartum. Incision length of episiotomy, duration of the first stage, and BMI before and (or) after pregnancy affected function of pelvic floor muscles markedly. CONCLUSION: The prevalence of stress urinary incontinence after different delivery modes is similar. Some obstetric factors have effects on both stress urinary incontinence postpartum and the function of pelvic floor.

[Clinical analysis of maternal and neonatal outcomes in uncomplicated term nulliparous after different routes of delivery].

OBJECTIVE: To compare maternal and neonatal outcomes after induction, elective cesarean section and spontaneous onset of labor in uncomplicated term nulliparous women. METHODS: A total of 3751 uncomplicated term nullipara who delivered in Peking Union Medical College Hospital from Sept 2002 to April 2007 were retrospectively analyzed. They were divided into three groups: the induction group, the elective cesarean section group, and the spontaneous onset of labor group. Their general conditions (such as age, weeks of pregnancy, hospital days and cost), postpartum complications (such as postpartum hemorrhage, puerperal morbidity, urinary retention, blood transfusion, delayed healing, and trauma), and Apgar score were compared by statistic methods. RESULTS: (1) Among 3751 women, 501 (13.3%) of them underwent induction( the induction group), 1634 (43.6%) delivered by cesarean section (cesarean section group), the other 1616 (43.1%) women underwent spontaneous onset of labor (the spontaneous onset of labor group). (2) Results of general conditions: the spontaneous onset of labor group had the shortest hospital days, which was longer in the induction group, and the longest in the selective cesarean section group (P < 0.01). The selective cesarean section group had the most cost during hospitalization, which was less in the induction group, and least in the spontaneous onset of labor group (P < 0.01). Women who undergwent emergent cesarean section after induction spent more money on hospitalization than those who were in the selective cesarean section group and the spontaneous onset of labor group (P < 0.01). (3) Puerperal complications: (1) postpartum hemorrhage: the incidence of postpartum hemorrhage was 3.0% (15/501) in the induction group, 0.6% (9/1634) in the selective cesarean section group and was 1.2% (19/1616) in the spontaneous onset of labor group (P < 0.01). (2 Urinary retention: the incidence of urinary retention was 4. 6% (23/501) in the induction group, 0 in the selective cesarean section group, and 3.3% (54/1616) in the spontaneous onset of labor group. So the rate of urinary retention was lower in the cesarean section group than in the other two groups (P < 0.01). (3) Blood transfusion: the incidence of blood transfusion in delivery was 2.0% (10/501) in the induction group, 0.1% (1/1634) in the selective cesarean section group, and 0.4% (6/1616) in the spontaneous onset of labor group (P < 0.01). (4) Trauma: the incidence of trauma in delivery was 0. 6% (3/501) in the induction group, 0 in the selective cesarean section group, and 0.4% (7/1616) in the spontaneous onset of labor group. So the rate of trauma was lower in the cesarean section group than in the other two groups (P < 0.01). (5) Delayed healing: the incidence of delayed healing of incision was 0.8% (4/501) in the induction group, 0 in the selective cesarean section group, and 0.2% (4/1616) in the spontaneous onset of labor group (P < 0.01). (6) Puerperal morbidity: there was no difference in puerperal morbidity among the three groups (P < 0.01). (7) Neonatal asphyxia: the incidence of neonatal asphyxia was 1.2% (6/501) in the induction group, 0.1% (1/1634) in the selective cesarean section group, and 1.0% (17/1616) in the spontaneous onset of labor group. The rate of neonatal asphyxia was lower in the cesarean section group than in the other two groups (P < 0.01). CONCLUSIONS: Induction may increase incidences of postpartum hemorrhage and blood transfusion, yet, it does not decrease the incidence of urinary retention and neonatal asphyxia. Generally, selective cesarean section is safer than induction and spontaneous onset of labor, but it costs most.