Pharmacological activity and clinical progress of Triptolide and its derivatives LLDT-8, PG490-88Na, and Minnelide: a narrative review.

Triptolide, a compound isolated from a Chinese medicinal herb, has potent antitumor, immunosuppressive, and anti-inflammatory properties. Due to its interesting structural features and diverse pharmacological activities, it has attracted great interest by the Society of Organic Chemistry and Pharmaceutical Chemistry. However, its clinical potential is greatly hampered by limited aqueous solubility and oral bioavailability, and multi-organ toxicity. In recent years, various derivatives of Triptolide have made varying degrees of progress in the treatment of inflammatory diseases, autoimmune diseases, and cancer. The most researched and potentially clinically valuable of them were (5R)-5-hydroxytriptolide (LLDT-8), PG490-88Na (F6008), and Minnelide. In this review, we provide an overview of the advancements made in triptolide and several of its derivatives' biological activity, mechanisms of action, and clinical development. We also summarized some prospects for the future development of triptolide and its derivatives. It is hoped to contribute to a better understanding of the progress in this field, make constructive suggestions for further studies of Triptolide, and provide a theoretical reference for the rational development of new drugs.

[Clinical efficacy of local injection of platelet-rich plasma combined with double-layer artificial dermis in treating wounds with exposed tendon on extremity].

Objective: To investigate the clinical efficacy of local injection of platelet-rich plasma (PRP) combined with double-layer artificial dermis in treating wounds with exposed tendon on extremity. Methods: A retrospective observational study was conducted. From December 2017 to October 2022, 16 patients were admitted to Department of Orthopaedic Trauma of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, and 32 patients were admitted to Department of Burns and Plastic Surgery of Guiyang Steel Factory Staff Hospital. All the patients had wounds with exposed tendon on extremity caused by various reasons and met the inclusion criteria. There were 39 males and 9 females, aged 26 to 58 years. The patients were divided into PRP alone group, artificial dermis alone group, and PRP+artificial dermis group, with 16 patients in each group. The wounds were treated with autologous PRP, double-layer artificial dermis, or thei combination of autologous PRP and double-layer artificial dermis, followed by autologous split-thickness scalp grafting after good growth of granulation tissue. On the 7th day after the secondary surgery, the autograft survival was observed, and the survival rate was calculated. The wound healing time and length of hospital stay of patients were recorded. At 3 and 6 months after wound healing, the Vancouver scar scale (VSS) was used to score the pigmentation, height, vascularity, and pliability of scars, and the total score was calculated. Adverse reactions during the entire treatment process were recorded. Data were statistically analyzed with chi-square test, Fisher's exact probability test, one-way analysis of variance, least significant difference test, Kruskal-Wallis H test, Nemenyi test, and Bonferroni correction. Results: On the 7th day after the secondary surgery, there was no statistically significant difference in the autograft survival rate of patients among PRP alone group, artificial dermis alone group, and PRP+artificial dermis group (P>0.05). The wound healing time and length of hospital stay of patients in PRP+artificial dermis group were (20.1±3.0) and (24±4) d, respectively, which were significantly shorter than (24.4±5.5) and (30±8) d in PRP alone group (P<0.05) and (24.8±4.9) and (32±8) d in artificial dermis alone group (P<0.05). At 3 and 6 months after wound healing, the pliability scores of patients in PRP+artificial dermis group were significantly lower than those in PRP alone group (with Z values of 12.91 and 15.69, respectively, P<0.05) and artificial dermis alone group (with Z values of 12.50 and 12.91, respectively, P<0.05). There were no statistically significant differences in pigmentation, vascularity, height scores, and total score of scar of patients among the three groups (P>0.05). In artificial dermis alone group, one patient experienced partial liquefaction and detachment of the double-layer artificial dermis due to local infection of Staphylococcus epidermidis, which received wound dressing change, second artificial dermis transplantation, and subsequent treatment as before. No adverse reactions occurred in the remaining patients during the whole treatment process. Conclusions: Local injection of PRP combined with double-layer artificial dermis is effective in treating wounds with exposed tendon on extremity, which can not only significantly shorten wound healing time and length of hospital stay, but also improve scar pliability after wound healing to some extent in the long term. It is a clinically valuable treatment technique that is worth promoting and applying.

[Sharing Chinese experience in obesity prevention and treatment with African countries].

Obesity has become a global public health problem that seriously threatens population health. The Chinese government has attached great importance to prevent and control the negative impacts of obesity on individuals, families and society. China has established a policy system for obesity, and made certain achievements in behavioral intervention, drug treatment, traditional Chinese medicine treatment, and surgical treatment. This study summarizes the prevention and treatment experience of obesity in China in order to provide reference for African countries to better formulate prevention and treatment strategies for obesity in line with their local context.

[Analysis of clinical characteristics, treatment and survival of elderly patients with large diffuse B-cell lymphoma].

Objective: To analyze the clinical feature,treatment and survival outcome of elderly patients older than 80 years with large diffuse B-cell lymphoma. Methods: A total of 46 patients aged over 80 years with large diffuse B-cell lymphoma who were treated in Third Hospital of Peking University during the period from 2002 to 2018 were retrospectively analyzed, and the clinical features, laboratory data, survival and prognostic factors were included in Kaplan-Meier and prognostic analysis. Results: Patients older than 80 years old accounted for 15.7% (46/293) in all elderly patients, and the median age was 83 years old. There were 78.3% (36/46)patients who belonged to stage Ⅲ or Ⅳ, 63%(29/46) who had more than two extranodal organ involvement, and the higher proliferation index(Ki-67≥80%) was present in 53.7%(22/41) patients. Immunohistochemistry showed that 37% patients in 27 cases were double-expressed DLBCL. With a median follow-up of 25 months, the overall response rate (ORR) for the whole group was 63.0%, the complete response (CR) rate was 36.4%, the 2, 3-year progression-free survival (PFS) rate was 49.9% and 41.7%, the 2, 3-year overall survival (OS) rate was 54.6% and 43.6% respectively. The ORR for patients who received anthracycline-based therapies and non-anthracycline-based therapies were 81.8% and 55.0%, and the 3-year OS rate were 50.0% and 39.0%, respectively, but the difference was not statistically significant (P>0.05). 45.5% patients had hematologic toxicity of Grade Ⅲ or above, and 56.8% patients experienced infections during the treatment. Among the patients who died, the treatment-related mortality rate in group with high score of Charlson comorbidity index(CCI) was higher (43.8% vs 16.7%, P=0.03) . The National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score, nodal involvement area ≥3, 6 cycles of chemotherapy, CCI score, initial treatment outcome and refractory-relapsed were predictive of overall survival. Multivariate analysis indicated the CCI score (HR=6.463, P=0.008) and initial treatment outcome (HR=0.086, P=0.001) were independent prognostic risk factors. Conclusions: The clinical and pathological features of patients older than 80 years were highly aggressive with poor chemotherapy tolerance and high adverse reaction rate. Anthracycline-based therapies may be less important in the treatment of DLBCL patients aged over 80 years. Patients with high CCI score have higher treatment-related mortality and CCI can help identify elderly patients who are suitable for larger chemotherapy dose.

Reconstruction of lymphatic vessels in the mouse tail after cupping therapy.

BACKGROUND: The aim of the study was to investigate the regulatory mechanism of local lymphatic reconstruction after cupping therapy in a mouse model. MATERIALS AND METHODS: The lymphatic reconstruction process in the mouse tail after cupping therapy as well as the expression levels of the vascular endothelial identification molecule CD34, prospero homeobox protein 1 (PROX1), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) were investigated for a duration of 4 days through immunohistochemistry experiments. RESULTS: On day 1 after cupping therapy, the CD34+ and LYVE-1+ cell densities were significantly increased, and the formed CD34+LYVE-1+ tubular structure started to express PROX1. This was followed by a decrease in both the CD34+ and LYVE-1+ stem cell densities to basal levels on the second day after cupping therapy. Both the CD34+ and LYVE-1+ cell densities subsequently increased again on the third day after cupping therapy. The increase in the LYVE-1+ density was accompanied by tubular structure formation, which is characteristic of lymphangiogenesis. In addition, the colocalisation of CD34+ and LYVE-1+ cells by immunohistochemistry suggests that the CD34+ stem cells differentiated into new lymphatic endothelial cells. CONCLUSIONS: Our findings indicate that the mechanism underlying the therapeutic effect of cupping therapy involves upregulation of vascular and lymphatic endothelial markers (CD34+, LYVE-1+, and CD34+LYVE-1+) in local tissues, which in turn promotes local new lymphatic vessel formation through the expression of PROX1.

Dual functions of eicosapentaenoic acid-rich microalgae: enrichment of yolk with n-3 polyunsaturated fatty acids and partial replacement for soybean meal in diet of laying hens.

Microalgae (Nannochloropsis sp., NS), with high contents of eicosapentaenoic acid (EPA) and crude protein, may be one of the important n-3 polyunsaturated fatty acid (PUFA) sources and potential protein feed ingredient. The purposes of this study were to enrich yolk with n-3 PUFA by dietary EPA-rich NS supplementation and to evaluate whether it is feasible to partly substitute for soybean meal in laying hens diet. A total of 360 37-wk-old healthy Lohmann Brown laying hens, with similar laying rate and body weight, were randomly allotted to 5 groups (6 replicates, 12 birds/replicate) and fed 5 experimental diets (0, 1, 2, 4, and 8% NS) for 4 wk. The hen performance and egg quality (except yolk color) were not affected (P > 0.05) by the NS supplemental diets. Yolk color score was increased as NS supplementation in diets (P < 0.001), and peaked on about the seventh day in all NS supplemental groups. The concentration of total n-3 PUFA was increased (P < 0.001), while total n-6 PUFA and n-6/n-3 ratio were decreased (P < 0.001) in yolk with increasing NS levels in diets. The 8% NS group had highest docosahexaenoic acid (DHA) and total n-3 PUFA levels, reaching 111.6 mg DHA and 148.6 mg total n-3 PUFA per egg. Maximum DHA, total n-3 PUFA, very long-chain (LC-) n-3 PUFA, and LC-PUFA levels were all observed at day 13 of NS supplementation. In conclusion, dietary NS supplementation enriched yolk with n-3 PUFA (especially DHA) and enhanced yolk color score without adverse effects on performance and egg quality, and indicated the practical feasibility of partial replacement for soybean meal in laying hens diet.

[Effect of postoperative precision nutrition therapy on postoperative recovery for advanced gastric cancer after neoadjuvant chemotherapy].

Objective: To investigate the effect of postoperative precision nutrition therapy on postoperative recovery (PR) of patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NC). Methods: 71 subjects were randomly divided into 2 groups. The 34 patients of research group were treated with postoperative precision nutrition treatment according to the indirect energy measurement method. The 31 patients of control group were treated with traditional postoperative nutrition treatment. All participants were measured for body mass index (BMI), NRS2002, PG-SGA and relevant laboratory test within the 1st day before surgery and 7th day after surgery. Moreover, the difference between two groups in short-term effects were evaluated. Results: The daily energy supply of control group was 30.1%-43.74% higher than that of the experimental group (P<0.05). The resting energy expenditure (REE) of the research group after surgery was lower than that before operation. The levels of prealbumin, albumin and lymphocyte count were higher in research group than the controls at the 7th day after surgery whereas the opposite was true for the creatinine, urea nitrogen, C-reactive protein and procalcitonin (P<0.05). Similarly, the rate of malnutrition and nutritional risk became lower in the research group (P<0.05). The gastrointestinal function recovery of patients in the research group was comparable to that of the control group (P>0.05). Moreover, the complication rate and hospitalization costs of in research group were significantly lower than that of in control group (P<0.05). For patients with or without nutritional risks before surgery, the nutritional index and inflammatory index in the research group were better than those in the control group. Conclusion: Postoperative precision nutrition therapy may improve the postoperative nutritional status and short-term effects of patients with AGC after NC.

Prediction of fecal nitrogen and phosphorus excretion for Chinese Holstein lactating dairy cows.

Mathematical models for predicting nitrogen and phosphorus excretion play a key role in manure application and environment monitoring. An analysis for prediction of fecal nitrogen (FN, g/d) and fecal phosphorus (FP, g/d) excretion for Chinese Holstein lactating dairy cows was conducted using a data set from 15 dairy farms in northern China. The whole independent-variable data set, obtained with questionnaires, consisted of 110 sets of average diet nutrient compositions, including DMI (kg/d), CP content (% DM), OM intake (OMI, kg/d), nitrogen intake (NI, g/d), and phosphorus intake (PI, g/d), and animal characteristics, including average days in milk (DIM, d), average milk yield (MY, kg/d), and average BW (kg). In addition, 110 fecal samples in total were collected to analyze FN and FP excretions, which were considered dependent variables of prediction equations. Correlations between diet and animal variables were examined, and several variable subpools were derived that were used to develop equations to predict FN and FP excretions by stepwise regression analysis. The results showed that among all variables, OMI was the best predictor for FN excretion (root-mean-square prediction error [RMSPE] = 9.58%, = 0.70), followed by NI (RMSPE = 10.19%, = 0.67). However, when both DMI and CP were used as independent variables, the equation showed more accurate prediction for FN excretion (RMSPE = 8.55%, = 0.77) in comparison with univariate prediction equations. Simultaneously, PI was the best predictor of FP excretion (RMSPE = 10.28%, = 0.67). Evaluation results using 3-fold cross validation and comparison with extant equations indicated that the proposed equations were accurate with low prediction errors, which could be recommended for use to estimate FN and FP excretions from Chinese Holstein lactating dairy cows.

Effects of dietary energy and lysine levels on growth performance and carcass yields of Pekin ducks from hatch to 21 days of age.

A 2 × 6 factorial experiment, using 2 dietary apparent metabolizable energy (AME) levels (2,750 and 3,050 Kcal/kg) and 6 supplemental lysine (Lys) levels (0, 0.10, 0.20, 0.30, 0.40, and 0.50%), was conducted to study the effects of dietary energy and lysine levels on growth performance and carcass yields of Pekin ducks from hatch to 21 d of age. A total of 576 one-day-old male White Pekin ducks was randomly allotted to 12 dietary treatments, each containing 6 replicate pens with 8 birds per pen. At 21 d of age, body weight gain, feed intake, and feed/gain were measured, and then 2 ducks selected randomly from each pen were slaughtered to evaluate the yields of abdominal fat, breast meat, and leg meat. As a result, birds that were fed basal diets with no Lys supplementation showed growth depression, and significant positive effects of dietary Lys supplementation on body weight gain (P < 0.001), feed intake (P < 0.001), and feed/gain (P = 0.002) were observed as dietary Lys increased gradually among all the groups. In addition, increasing energy levels did not affect overall body weight gain (P > 0.05), but feed intake (P = 0.001) and feed/gain (P = 0.009) decreased significantly between the groups. Dietary Lys levels influenced the yields of breast (P < 0.001) and leg (P = 0.001) meat among all the groups, but dietary energy levels had a significant positive effect only on abdominal fat yield (P = 0.014). The interaction between dietary energy and Lys influenced body weight gain of ducks significantly (P = 0.004). According to the broken-line regression analysis, Lys requirements of Pekin ducks for weight gain at 2,750 and 3,050 Kcal of AME/kg were 0.94 and 0.98%, respectively. It suggested that Lys requirement was higher at 3,050 Kcal of AME/kg than at 2,750 Kcal of AME/kg. Dietary energy content determined feed intake of the ducks, and high-energy diets will require a higher amino acid concentration to compensate for a lower feed intake.

Effects of low-protein diets on growth performance and carcass yields of growing French meat quails (France coturnix coturnix).

A dose-response experiment with 5 analyzed dietary crude protein (CP) levels (17.61, 19.73, 21.58, 23.24, and 25.32%) was conducted to investigate the effects of low-protein diets on growth performance and carcass yields of French meat quails from 15 to 42 d of age. All diets were formulated to contain a similar dietary energy level and amino acid profile. A total of 400 fifteen-day-old French quails were divided into 5 experimental treatments and each treatment contained 4 replicate pens of 20 birds (10♂+10♀). At 42 d of age, weight gain, feed intake, CP intake, feed/gain, and the yields of breast part with bone, leg part with bone, and liver of quails from each pen were measured. The results showed significant effects of the low-CP diets on CP intake, weight gain, feed intake, and feed/gain at different experiment periods except for the sixth wk of age (P < 0.05). In addition, as dietary CP decreased from 25.32 to 17.61%, feed intake and feed/gain were increased linearly (P < 0.05), whereas CP intake showed the opposite trend and decreased gradually. On the other hand, the carcass yields of quail were not influenced by reducing dietary CP at 42 day of age (P > 0.05). Based on broken-line regression, 23.0%, 22.5%, and 20.4% were the minimum dietary CP to keep weight gain similar to the quails fed with 25.32% CP diets during the third, fourth, and fifth wk of age, respectively. In summary, with crystalline amino acid supplementation based on a similar amino acid profile, it was possible to formulate the low-protein diets containing about 22.0% CP for growing meat quails without adverse effects on growth and carcass yields of meat quails.

Effects of Dietary Methionine Levels on Choline Requirements of Starter White Pekin Ducks.

A 2×5 factorial experiment, using 2 dietary methionine levels (0.28% and 0.48%) and 5 dietary choline levels (0, 394, 823, 1,239, and 1,743 mg/kg), was conducted to study the effects of dietary methionine status on choline requirements of starter white Pekin ducks from 7 to 28 days of age. Four hundred eighty 7-d-old male White Pekin ducks were randomly allotted to ten dietary treatments, each containing 6 replicate pens with 8 birds per pen. At 28 d of age, weight gain, feed intake, and feed/gain were measured and the legs of all ducks from each pen were examined for incidence of perosis. Perosis and growth depression were observed in choline-deficient ducks and supplementation of choline reduced perosis and significantly increased weight gain and feed intake regardless of dietary methionine levels (p<0.05). In addition, significant positive effects of dietary methionine supplementation on weight gain, feed intake, and feed/gain were observed at any choline level (p<0.05). Supplementation of 1,743 mg/kg choline in diets alleviated the depression of weight gain and feed intake caused by methionine deficiency at 0.28% methionine level. The interaction between choline and methionine influenced weight gain and feed intake of ducks (p<0.05). At 0.28% methionine level, 1,743 mg/kg choline group caused 4.92% and 3.23% amount of improvement in weight gain and feed intake compared with 1,239 mg/kg choline group, respectively. According to the broken-line regression, the choline requirements of starter Pekin ducks for weight gain and feed intake were 1,472 and 1,424 mg/kg at 0.28% methionine level and 946 and 907 mg/kg at 0.48% methionine level, respectively. It suggested the choline recommendations of starter Pekin ducks on a semi-purified diet were 1448 mg/kg at 0.28% methionine level and 927 mg/kg at 0.48% methionine level, respectively. Compared with the adequate methionine level, menthionine deficiency markedly increased the choline requirements of ducks.

Protective effect of thymoquinone on cholestatic rats with liver injury.

The aim of this study was to investigate the protective effects of thymoquinone treatment on cholestatic rats with liver injury. Thirty-two Sprague-Dawley rats were divided randomly into four groups: normal control, bile duct ligation model control, low-dose thymoquinone (25 mg/kg), and high-dose thymoquinone (50 mg/kg). Thymoquinone gavage was administered continuously 3 days before bile duct ligation, and saline, at the same volume, was administered to the control group. The rats were sacrificed after 2 weeks of treatment, and the liver tissues were obtained and frozen. The contents of hydroxyproline (HP), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the homogenate of the liver tissues were determined to evaluate the changes in hepatic tissue pathology by fibrosis scoring. The HP and MDA levels were significantly lower and the SOD and GPx levels were significantly higher in the thymoquinone-treatment group than the corresponding levels in the model control group, and the differences were statistically significant (P < 0.05) and dose-dependent. The hepatic necrosis areas and hepatic fibrosis scores of the thymoquinone-treatment groups were significantly lower than those of the model group (P < 0.05). Thymoquinone increased the antioxidative capacity of liver and reduced the oxidative stress damage to the liver. Thymoquinone can be used as a liver protectant in patients with cholestasis.

Acute restraint stress alters sound-evoked neural responses in the rat auditory cortex.

Stress is known to elicit various adaptive or maladaptive responses in the nervous system function. Psychophysical studies have revealed that stress exposure induced the changes in auditory response that can be interpreted as a transient, stress-induced hypersensitivity to sounds. However, the underlying neural mechanism remains unresolved. Thus, in this study, we explored the neural activities of the auditory cortex (AC) in response to stress. We elicited stress by physically immobilizing rats and recorded the extracellular single-unit activities through the electrodes chronically implanted in the AC of rats. By comparing the spike activities of the same rat before, during and after immobilization, we found temporal and significant changes in the sound-evoked neural activities. In most cases, acute restraint stress enhanced neural responses evoked by pure-tones and click-trains, but in a minority of neurons, stress suppressed responses. The immobilization-induced enhancement was more frequently found in the neurons that originally had a low responsibility for sound stimuli. The enhancement effects on pure-tone response were reflected by an increase of response magnitude, decrease of response latency, and extension of bandwidth of tuning curve (BW). But the spontaneous firing rate and best frequency (BF) remained unchanged. Stress also increased the ability of neural response to synchronize to click-trains, even in the neurons whose response magnitude was not significantly increased. Taken together, these results provide direct evidence that stress alters the function of auditory system at the level of AC.

First-in-human study of pbi-05204, an oleander-derived inhibitor of akt, fgf-2, nf-κΒ and p70s6k, in patients with advanced solid tumors.

BACKGROUND: PBI-05204, a Nerium oleander extract (NOE) containing the cardiac glycoside oleandrin, inhibits the α-3 subunit of Na-K ATPase, as well as FGF-2 export, Akt and p70S6K, hence attenuating mTOR activity. This first-in-human study determined the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of PBI-05204 in patients with advanced cancer. Methods Forty-six patients received PBI-05204 by mouth for 21 of 28 days (3 + 3 trial design). Dose was escalated 100% using an accelerated titration design until grade 2 toxicity was observed. Plasma PK and mTOR effector (p70S6K and pS6) protein expressions were evaluated. Results Dose-limiting toxicities (grade 3 proteinuria, fatigue) were observed at dose level 8 (0.3383 mg/kg/day). Common possible drug-related adverse were fatigue (26 patients, 56.5%), nausea (19 patients, 41.3%) and diarrhea (15 patients, 32.6 %). Electrocardiogram monitoring revealed grade 1 atrioventricular block (N = 10 patients) and grade 2 supraventricular tachycardia (N = 1). The MTD was DL7 (0.2255 mg/kg) where no toxicity of grade ≥ 3 was observed in seven patients treated. Seven patients (15%) had stable disease > 4 months. Mean peak oleandrin concentrations up to 2 ng/mL were achieved, with area under the curves 6.6 to 25.5 µg/L*hr and a half-life range of 5-13 h. There was an average 10% and 35% reduction in the phosphorylation of Akt and pS6 in PBMC samples in 36 and 32 patients, respectively, tested between predose and 21 days of treatment. Conclusions PBI-05204 was well tolerated in heavily pretreated patients with advanced solid tumors. The recommended Phase II dose is 0.2255 mg/kg/day.

Suspected Lythrum hyssopifolia (lesser loosestrife) poisoning of cattle.

CASE REPORT: Morbidity and mortality in two herds of cattle in southern New South Wales were associated with ingestion of lesser or hyssop loosestrife (Lythrum hyssopifolia). Clinical signs in adult cows included depression, listlessness, inappetence, anorexia and recumbency. Deaths occurred in 16/48 (33.3%) and 4/60 (6.7%) adult cows, but calves in both herds were unaffected. Elevated concentrations of urea and creatinine were present in the serum of one clinically affected cow and an elevated concentration of urea was detected in the aqueous humour of one cow that died. On histopathological examination, there was severe, acute necrosis of the proximal convoluted tubular epithelial cells in the kidneys of both affected cattle examined. CONCLUSION: There is strong evidence that lesser loosestrife is nephrotoxic for cattle.

Prospective randomised evaluation of traditional Chinese medicine combined with chemotherapy: a randomised phase II study of wild toad extract plus gemcitabine in patients with advanced pancreatic adenocarcinomas.

BACKGROUND: An intravenous formulated extract of the venom of the wild toad Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, huachansu, is currently used in China for the treatment of lung, liver, pancreatic, and colorectal cancers. We performed a randomised, single-blinded, phase II clinical study of huachansu plus gemcitabine versus placebo plus gemcitabine in patients with locally advanced and/or metastatic pancreatic adenocarcinomas. METHODS: Patients with tissue-proven locally advanced and/or metastatic pancreatic adenocarinoma were randomly assigned to receive either gemcitabine 1000 mg m(-2) on days 1, 8, and 15 with huachansu 20 ml m(-2) daily for 21 days (arm A) or placebo (arm B); treatment cycles were 28 days in length. Primary end point was 4-month progression-free overall survival (PFS); secondary end points were objective radiographical response rate (ORR), time to progression (TTP), and toxicity. RESULTS: A total of 80 subjects were enrolled; 76 patients were evaluable (received at least 1 week therapy). Median overall survival was 160 days for arm A and 156 days for arm B (P=0.339); ORR was 9 and 3% in arms A and B, respectively (P=0.332), median TTP was 98 and 115 days, respectively (P=0.825); the median 4-month PFS was 99 and 98 days, respectively (P=0.679). CONCLUSION: Huachansu when combined with gemcitabine did not improve the outcome of patients with locally advanced and/or metastatic pancreatic cancer.

Ginsenoside Rg1 attenuates lipopolysaccharide-induced inflammatory responses via the phospholipase C-γ1 signaling pathway in murine BV-2 microglial cells.

BACKGROUND AND PURPOSE: Microglial activation plays an important role in neurodegenerative diseases by producing an array of proinflammatory enzymes and cytokines. Ginsenoside Rg1 (Rg1), a well-known Chinese herbal medicine, has been well recognized for its anti-inflammatory effect. This study sought to determine the anti-inflammatory effects of Rg1 and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells. EXPERIMENTAL APPROACH: Murine BV-2 microglial cells were treated with Rg1 (10, 20, and 40 µM) and/or LPS (1 µg·ml(-1)). The mRNA and protein levels of proinflammatory proteins and cytokines were analysed by RT-PCR assay and double immunofluorescence labeling, respectively. Phosphorylation levels of mitogen-activated protein kinases (MAPKs) cascades, inhibitor κB-α (IκB-α) and cyclic AMP- responsive element (CRE)-binding protein (CREB) were measured by western blot. U73122 (5 µM), a specific phospholipase C (PLC) inhibitor, was used to determine if PLC signaling pathway might be involved in Rg1's action on activated BV-2 cells. KEY RESULTS: Pretreatment with Rg1 significantly attenuated the LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and nuclear factor-κB (NF-κB) in BV-2 cells. U73122 blocked the effects of Rg1 on LPS-induced microglial activation. In addition, PLC-γ1 inhibition partially abolished the inhibitory effect of Rg1 on the phosphorylation of IκB-α, CREB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). CONCLUSION AND IMPLICATIONS: This investigation demonstrates that Rg1 significantly attenuates overactivation of microglial cells by repressing expression levels of neurotoxic proinflammatory mediators and cytokines via activation of PLC-γ1 signaling pathway.

Bioprocessing papaya processing waste for potential aquaculture feed supplement--economic and nutrient analysis with shrimp feeding trial.

Papaya processing waste (PPW), a major fruit processing waste in the Hawaii islands, served as substrate for yeast (Saccharomyces cerevisiae) growth. The fermented PPW products containing nutrients of 45% crude protein and various fat, fiber, lignin, cellulose, and minerals were advantages to nutrients of yeast alone. Three experimental diets controlled at 35% protein formulation containing different levels of inclusion of PPW products and a commercial control diet were fed to shrimps for 8 weeks. The 50% inclusion of PPW diets were comparable to commercial feed in weight, growth, feed conversion ratio (FCR) and survival rate. Such bioprocess treatment system would be economically feasible with the control of annual cost and increase of the amount of PPW treated. The selling price of PPW products and annual operation and maintenance cost were the most influential factors to additional profits. This study presented a promising alternative for environmental-friendly treatment of organic wastes as well as the sustainability of local agriculture and aquaculture industries.

Adding moxifloxacin is associated with a shorter time to culture conversion in pulmonary tuberculosis.

OBJECTIVE: To investigate whether adding moxifloxacin (MXF) to the standard anti-tuberculosis regimen can shorten the time to sputum culture conversion in pulmonary tuberculosis (PTB). METHODS: Adults with culture-positive PTB were divided into two treatment groups by their choice: standard regimen alone (HERZ group) and standard regimen plus daily 400 mg MXF in the first 2 months (MXF group). Sputum samples were collected thrice weekly in the first 8 weeks. The propensity score was calculated to estimate the conditional probability of entering the MXF group. Factors influencing time to culture conversion were investigated using Cox proportional hazards regression analysis stratified by propensity score. RESULTS: Sixty-two patients were enrolled in the MXF group and 88 in the HERZ group; respectively 51 and 72 completed the study. The regimen was modified before culture conversion in respectively 6 (12%) and 12 (16%; P = 0.47) patients, due to adverse effects. The time to culture conversion was shorter in the MXF group (HR 2.1, 95%CI 1.4-3.2). The culture conversion rate after 6 weeks of treatment was respectively 82% and 61% (P = 0.011, <0.05/4, calculated using the modified Bonferroni method). CONCLUSIONS: Adding MXF to the standard anti-tuberculosis regimen in the first 2 months was associated with a shorter time to culture conversion, a higher 6-week culture conversion rate and reduced transmission of tuberculosis.