[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[P.F. von Siebold and his destiny with Chinese materia medica (Ben Cao)].

P. F. von Siebold (1796-1866) was a physician at the Dutch Business Centre (Shang Wu Hui Guan) located at Nagasaki, Japan, in the Edo period. He collected a great amount of botanical and mineral specimens, books, and living wares when he stayed in Japan. He brought these materials to Europe and kept some of them at the Japan Museum Siebold Huis in Leiden in Netherlands. This collection showed the role of Siebold in connecting scientific and cultural exchanges between East and West and provided references in the research of the transmission of traditional Chinese medicine worldwide in the 19th century.

Impact of drinking water supplemented 2-hydroxy-4-methylthiobutyric acid in combination with acidifier on performance, intestinal development, and microflora in broilers.

In addition to offering methionine, 2-hydroxy-4-methylthiobutyric acid (HMTBa) is also an organic acid and shows excellent bacteriostasis. Therefore, 3 experiments were conducted to determine the influence of drinking water supplemented HMTBa in combination with acidifier on performance, intestinal development, and microflora in broilers. The addition of different concentration (0.02-0.20%) of the blend of HMTBa and other acids significantly reduced the pH of water and exerted antimicrobial activity in dose-dependent manner in vitro. The outcomes from animal trial consisting of the drinking water with blended acidifier at 0.00, 0.05, 0.10, 0.15, and 0.20% indicated that the water with 0.15 or 0.20% acidifier resulted in linear and quadratic higher body weight at 42 d, gain and water consumption during 1 to 42 d (P < 0.05). In experiment 3, responding to graded blended acidifier in drinking water, birds receiving 0.10, 0.15, and 0.20% acidifier decreased the internal pH of gastrointestinal tract and muscle, and exhibited increased duodenal weight, length, villus high, and the ratio of villus high to crypt depth. Drinking water with 0.2% blended acidifier increased the abundance of probiotics (Bacteroidaceae, Ruminococcaceae, and Lachnospiraceae) and decreased the account of pathogenic bacteria such as Desulfovibrionaceae. Alternations in gut microflora were closely related to the metabolism of carbohydrate, amino acid, and vitamins. These findings, therefore, suggest that drinking water with 0.10 to 0.13% the combination HMTBa with acidifier might benefit to intestinal development and gut microbiota, and the subsequent produce a positive effect on the performance of broilers.

[Chaihu Guizhi decoction produces antidepressant-like effects via sirt1-p53 signaling pathway].

OBJECTIVE: To investigate the mechanism of the antidepressant-like effects of Chaihu Guizhi decoction (CGD). OBJECTIVE: Chaihu Guizhi decoction at the daily dose of 17 g/kg and solvent vehicle were administered by gavage in 12 and 14 male C57BL/6J mice for 7 consecutive days, respectively. Forced swimming test (FST), elevated plus maze (EPM) test, open field test (OFT) and novelty-suppressed feeding test (NSF) were performed to assess the depression- and anxiety-like behaviors and motor ability of the mice. We further used chronic social defeat stress (CSDS) and social interaction test to evaluate the antidepressant-like effects of CGD in comparison with the solvent vehicle. Western blotting and RT-qPCR were performed to detect the expressions of sirt1, p53, acetylated p53, and the neuron plasticity-related genes including synapsin I (Syn1), Rab4B, SNAP25 and tubulin beta4b in the hippocampus of the mice. OBJECTIVE: In FST, the immobility time of CGDtreated mice was decreased significantly (P < 0.05); no significant differences were found in the performances in EPM, NSF and OFT tests between the two groups. In social interaction test, the mouse models of CSDS treated with CGD showed significantly increased time in the interaction zone (P < 0.05). Compared with those in the vehicle group, the CGD-treated mouse models exhibited significantly increased protein level of SIRT1 and decreased p53 acetylation (P < 0.05) with up-regulated synapsin I mRNA expression in the hippocampus (P < 0.05); no significant difference were found in Rab (P=0.813), SNAP (P=0.820), or Tubb mRNA expressions (P=0.864) between the two groups. OBJECTIVE: CGD produces antidepressant-like effects in mice possibly through the sirt1-p53 signaling pathway and synaptic plasticity.

Protective effects of dietary fish-oil supplementation on skin inflammatory and oxidative stress biomarkers induced by fine particulate air pollution: a pilot randomized, double-blind, placebo-controlled trial.

BACKGROUND: Exposure to fine particulate matter (with an aerodynamic diameter ≤ 2·5 µm, PM2·5 ) air pollution has been associated with skin-related diseases or disorders. OBJECTIVES: To evaluate the potential skin-protective effects of fish-oil supplementation against PM2·5 exposure. MATERIALS AND METHODS: This is an exploratory analysis based on a pilot randomized, double-blind, placebo-controlled trial among 65 healthy young adults between September 2017 and January 2018 in Shanghai, China. We randomly assigned participants to take either fish oil or placebo 2·5 g daily for four consecutive months. Four rounds of skin D-Squame® tape samples were collected in the last 2 months, and five secondary biomarkers of skin inflammation and oxidative stress were measured. Fixed-site PM2·5 concentrations on campus were measured in real time. We used linear mixed-effect models to analyse the associations between short-term PM2·5 exposure and biomarkers in each group. RESULTS: The 24-h average PM2·5 concentration was 34·68 ± 15·83 µg m-3 . There were generally weaker associations between PM2·5 and biomarkers in the fish-oil group than in the placebo group, but the associations and the between-group differences varied by biomarkers and lag periods. Compared with the placebo group, for a 10-µg m-3 increase in PM2·5 concentration, the increments of interleukin-1α and carbonyl protein in the fish-oil group were 41·55% smaller [95% confidence interval (CI) 4·61-78·48%] at lag 0-48 h and 22·01% smaller (95% CI 11·25-32·77%) at lag 0-24 h, respectively. No significant between-group differences were observed for other biomarkers. CONCLUSIONS: This study suggested that dietary fish-oil supplementation may improve biomarkers of skin inflammation and oxidative-stress response to short-term PM2·5 exposure.

Colistin and tylosin enhances disaccharidase activities, and improves morphology and permeability of the intestine of broilers.

1. The present study focused on the potential effects of antibiotics on intestinal digestion and integrity in broilers in terms of disaccharidase activity, electrophysiological properties and morphology. 2. One-day-old Arbour Acres birds were randomly allocated to one of four treatment groups for 42 days; control, colistin (20 mg/kg), tylosin (55 mg/kg) or chlortetracycline (CTC, 55 mg/kg) groups. Colistin and tylosin supplementation, but not CTC supplementation, caused an increase in body weight gain. 3. Colistin and tylosin elevated the activities of maltase and sucrase in the mucosa of the jejunum on d 42. Age caused a gradual decrease in the short-circuit current (Isc) and conductance (Gt) of the ileum, as a measure of permeability. The Isc and Gt of the ileum were higher in the colistin-supplemented broilers than in the control birds on d 42. Tylosin- and CTC-supplemented birds displayed Isc and Gt values similar to those of the control birds. 4. Colistin supplementation increased the villus area in the jejunum and thinned the muscularis mucosae in the ileum compared with the control group. Tylosin supplementation decreased the thickness of the muscularis mucosae and the depth of crypt in the jejunum. CTC thickened the muscularis mucosae in the jejunum and ileum. 5. Colistin and tylosin exhibited a beneficial effect on intestinal digestion and integrity by enhancing disaccharidase activities and improving gut morphology and permeability.

The influence of morphological distribution of melanin on parameter selection in laser thermotherapy for vascular skin diseases.

Port wine stains (PWSs) are congenital vascular malformations that progressively darken and thicken with age. Currently, laser therapy is the most effective way in clinical management of PWS. It is known that skin pigmentation (melanin content) affects the radiant exposure that can be safely applied to treat PWS. However, the effect of melanin distribution in the epidermis on the maximum safe radiant exposure has not been studied previously. In this study, 10 different morphological distributions of melanin were proposed according to the formation and migration characteristics of melanin, and the two-scale heat transfer model was employed to investigate the influence of melanin distribution on the threshold radiant exposure of epidermis and blood vessels. The results show that melanin distributions do have a strong effect on laser parameter selection. When uniform melanin distribution is assumed, the threshold radiant exposure to damage a typical PWS blood vessel (50 µm diameter) is 8.62 J/cm2 lower than that to injure epidermis. The optimal pulse duration is 1-5 ms for a typical PWS blood vessel of 50 µm when melanin distribution is taken into consideration. PWS blood vessels covered by non-uniformly distributed melanin are more likely to have poor response to laser treatment.

[Biography of Chen Zi].

Chen Zi(1878-1927), who also styled himself as "Yi Qing" or "Yi Qin" , was a famous ophthalmologist in the early period of the Republic of China.He compiled and translated serial of classical Japanese modern medical books thus promoted western medicine propagation to the east in the early period of the Republic of China, and founded the first Chinese-established eye hospital in China to serve the patients from Shanghai as well as other places in China.Also, Dr. Chen devoted himself to the combination of traditional Chinese medicine and Western medicine for his whole life.He wrote the book of Zhong Xi Yan Ke Hui Tong(, Combination of Western and Eastern Medicine in Ophthalmology)which has promoted traditional Chinese medicine into modernization.In Dr.Chen's life, he was associated with some figures from army and in political circles at that time. Besides, he did a lot of things to support the education in his hometown.Dr. Chen was a typical model to understand the clinical doctors in the early period of the Republic of China.

Chinese Medicine in Cancer Treatment - How is it Practised in the East and the West?

Chinese medicine therapies in cancer treatment are very common in the East. Although it is usually classified as a form of complementary and alternative therapy in the West, Chinese medicine is an independent medical profession in Hong Kong and mainland China. It has a different perspective in understanding health and diseases compared with Western medicine. In oncology practice, whereas Western medicine focuses on direct tumour eradication by surgery, radiation therapy and systemic therapies, Chinese medicine focuses on restoring body balance and enhancing the body's defences (immunity), in addition to some cytotoxic herbal therapies. Most often patients, especially those in the East, receive both treatments. Chinese medicine is also commonly used to reduce side-effects from chemotherapy or radiation therapy, to aid recovery after an operation, to palliate symptoms and to address survivorship issues. However, this raises concerns of drug-herb interactions and toxicity in combination therapies. Commonly used Chinese medicine treatment modalities include acupuncture, moxibustion, diet therapy, prescribed Chinese medicine herbal decoction, single Chinese medicine herbs or supplements and tai chi. Although there is an increasing trend of Chinese medicine use in cancer patients in both the East and the West, the scientific evidence of safety and efficacy is often questioned by oncologists. This article reviews the current evidence in different Chinese medicine therapies in cancer management in both the East and the West.

Rehmanniae Radix Preparata suppresses bone loss and increases bone strength through interfering with canonical Wnt/ß-catenin signaling pathway in OVX rats.

Rehmanniae Radix Preparata (RRP) improves bone quality in OVX rats through the regulation of bone homeostasis via increasing osteoblastogenesis and decreasing osteoclastogenesis, suggesting it has a potential for the development of new anti-osteoporotic drugs. INTRODUCTION: Determine the anti-osteoporotic effect of RRP in ovariectomized (OVX) rats and identify the signaling pathway involved in this process. METHODS: OVX rats were treated with RRP aqueous extract for 14 weeks. The serum levels of tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear factor kappa-Β ligand (RANKL), alkaline phosphatase (ALP), and osteoprotegerin (OPG) were determined by ELISA. Bone histopathological alterations were evaluated by H&E, Alizarin red S, and Safranin O staining. Bone mineral density (BMD) and bone microstructure in rat femurs and lumbar bones were determined by dual-energy X-ray absorptiometry and micro-computed tomography. Femoral bone strength was detected by a three-point bending assay. The expression of Phospho-glycogen synthase kinase 3 beta (p-GSK-3ß), GSK-3ß, Dickkopf-related protein 1 (DKK1), cathepsin K, OPG, RANKL, IGF-1, Runx2, ß-catenin, and p-ß-catenin was determined by western blot and/or immunohistochemical staining. RESULTS: Treatment of OVX rats with RRP aqueous extract rebuilt bone homeostasis demonstrated by increasing the levels of OPG as well as decreasing the levels of TRAP, RANKL, and ALP in serum. Furthermore, RRP treatment preserved BMD and mechanical strength by increasing cortical bone thickness and epiphyseal thickness as well as improving trabecular distribution in the femurs of OVX rats. In addition, RRP downregulated the expression of DKK1, sclerostin, RANKL, cathepsin K, and the ratio of p-ß-catenin to ß-catenin, along with upregulating the expression of IGF-1, ß-catenin, and Runx2 and the ratio of p-GSK-3ß to GSK-3ß in the tibias and femurs of OVX rats. Echinacoside, jionoside A1/A2, acetoside, isoacetoside, jionoside B1, and jionoside B2 were identified in the RRP aqueous extract. CONCLUSION: RRP attenuates bone loss and improves bone quality in OVX rats partly through its regulation of the canonical Wnt/ß-catenin signaling pathway, suggesting that RRP has the potential to provide a new source of anti-osteoporotic drugs.

A novel FGFR1-binding peptide attenuates the degeneration of articular cartilage in adult mice.

OBJECTIVE: We previously reported that genetic ablation of (Fibroblast Growth Factors Receptors) FGFR1 in knee cartilage attenuates the degeneration of articular cartilage in adult mice, which suggests that FGFR1 is a potential targeting molecule for osteoarthritis (OA). Here, we identified R1-P1, an inhibitory peptide for FGFR1 and investigated its effect on the pathogenesis of OA in mice induced by destabilization of medial meniscus (DMM). DESIGN: Binding ability between R1-P1 and FGFR1 protein was evaluated by enzyme-linked immuno sorbent assay (ELISA) and molecular docking. Alterations in cartilage were evaluated histologically. The expression levels of molecules associated with articular cartilage homeostasis and FGFR1 signaling were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC). The chondrocyte apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. RESULTS: R1-P1 had highly binding affinities to human FGFR1 protein, and efficiently inhibited extracellular signal-regulated kinase (ERK)1/2 pathway in mouse primary chondrocytes. In addition, R1-P1 attenuated the IL-1ß induced significant loss of proteoglycan in full-thickness cartilage tissue from human femur head. Moreover, this peptide can significantly restore the IL-1ß mediated loss of proteoglycan and type II collagen (Col II) and attenuate the expression of matrix metalloproteinase-13 (MMP13) in mouse primary chondrocytes. Finally, intra-articular injection of R1-P1 remarkably attenuated the loss of proteoglycan and the destruction of articular cartilage and decreased the expressions of extracellular matrix (ECM) degrading enzymes and apoptosis in articular chondrocytes of mice underwent DMM surgery. CONCLUSIONS: R1-P1, a novel inhibitory peptide for FGFR1, attenuates the degeneration of articular cartilage in adult mice, which is a potential leading molecule for the treatment of OA.

Effects of dietary vitamin C, vitamin E, and alpha-lipoic acid supplementation on the antioxidant defense system and immune-related gene expression in broilers exposed to oxidative stress by dexamethasone.

Vitamin C, vitamin E, and alpha-lipoic acid (ALA) are potent nutritional antioxidants, which are important for enhancing immunity. This study compared the effects of supplementation with vitamin C, vitamin E, or ALA on the antioxidant defense system and the expression of immune-related genes under oxidative stress induced by dexamethasone (DEX) in broilers. In total, 240 one-day-old female Recessive White Rock chickens were assigned randomly to either a basal diet (control group) or basal diet supplemented with vitamin C (200 mg/kg diet), vitamin E (100 mg/kg), or ALA (500 mg/kg) for 28 d starting from hatching. At 21 d of age, birds fed the ALA-supplemented diet had the highest plasma total antioxidant capacity (T-AOC) and superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) enzyme activities, and the lowest plasma malondialdehyde (MDA) activity, as well as the lowest mRNA gene expression levels of interferon gamma (IFN-γ) and lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF). At 23 d of age, the broilers in the 3 treatment groups were injected in the thigh muscle with DEX for 3 alternating days. In addition, the control group was divided into 2 equal groups, in which one was injected with saline and the other was injected with DEX. At 28 d of age, the DEX-ALA group (P < 0.05) had the highest activity levels for T-AOC, T-SOD, and GSH-PX in the plasma and liver (P < 0.05), and the greatest reduction in the MDA level. Dietary ALA significantly decreased the mRNA expression levels of the interleukin 1 ß (IL-1ß), IL-6, IFN-γ, and LITAF genes compared with the other groups during oxidative stress by DEX. In conclusion, this study suggests that in broilers, ALA is more effective for normalizing the oxidative stress induced by DEX than vitamin C or vitamin E.

Quick rehabilitation nursing improves the recovery of colon cancer patients after laparoscopy.

Colon cancer is a common malignant tumor with particularly high morbidity and mortality. The aim of this study was to compare the effect of quick rehabilitation nursing and routine nursing in postoperative recovery of patients with colon cancer after laparoscopic surgery. Two hundred forty patients with colon cancer were classified into four random groups (A, B, C and D, with 60 patients in each group). All patients underwent surgery to remove the colon tumor by laparoscopy under general anesthesia. Patients in groups A and B received quick rehabilitation nursing for post-surgery recovery. In group C patients, local anesthesia associated with quick rehabilitation nursing for post-surgery recovery was used. Group D was used as control group and the patients were treated based on routine nursing. Time to get out of bed, first bowel movement time and the average time of hospitalisation in group A was lower than group D (p less than 0.05), postoperative leukocyte level as well as the occurrence rate of nausea and vomiting, ankylenteron and pelvic adhesion was decreased in group A compared to group D (p less than 0.05), but the postoperative albumin and total protein level was higher than group D (p less than 0.05). The serum level of C-Reactive Protein (CRP) and interleukin 6 (IL-6) in group A was decreased compared to group D several days after surgery (p less than 0.05); group B had 4 cases of intestinal obstruction after surgery that could be cured through conservative treatment, while group D had 10 cases of intestinal obstruction, 8 of which could be cured through conservative treatment and two needed surgery (p less than 0.05); VAS for pain degree of group C in active state was clearly lower at 1h, 5h, 7h, 15h, 30h and 42h after surgery, and side effects of postoperative analgesia were clearly reduced. Time to get out of bed was obviously decreased, while there was no evident effect on postoperative dosage, chronic pain and complications. Adopting quick rehabilitation nursing can effectively reduce occurrence of complications and postoperative pain, speed up the recovery of gastrointestinal function, shorten the length of stay, and improve patients’ satisfaction.

Lenalidomide as second-line therapy for advanced hepatocellular carcinoma: exploration of biomarkers for treatment efficacy.

BACKGROUND: Lenalidomide has immunomodulatory and anti-angiogenic effects and showed moderate anti-tumour efficacy in patients with. advanced hepatocellular carcinoma (HCC) AIM: To explore potential biomarkers of lenalidomide efficacy as second-line therapy for HCC. METHODS: Eligible patients were diagnosed with advanced HCC, documented progression on sorafenib, and Child-Pugh class A liver function. Patients received 25 mg/day lenalidomide orally on days 1-21 every 4 weeks. The primary endpoint was 6 month progression-free survival rate. Early α-fetoprotein response was defined as a > 20% decline of α-fetoprotein levels from baseline within the first 4 weeks of treatment. Vascular response, evaluated using dynamic contrast-enhanced magnetic resonance imaging, was defined as a > 40% decline in Ktrans after 2 weeks of treatment. The percentage of peripheral blood lymphocyte subsets were also analysed. RESULTS: Fifty-five patients were enrolled. The response rate was 13%, and the disease-control rate was 53%. The 6 month progression-free survival rate was 9.1%. The median progression-free and overall survival was 1.8 months and 8.9 months respectively. Early α-fetoprotein response was significantly associated with higher disease-control rate (76% vs 22%, P = .001) and longer progression-free survival (P = .020). Vascular response was not associated with any treatment outcomes. Patients with a high pre-treatment B cell percentage were more likely to have disease control (70% vs 36%, P = .010) and exhibited longer progression-free survival (P < .001) and overall survival (P = .042). CONCLUSIONS: Lenalidomide exhibited moderate activity as second-line therapy for advanced HCC. Its immunomodulatory effects should be further explored (www.clinicaltrials.gov NCT01545804).

Berberine binds RXRα to suppress ß-catenin signaling in colon cancer cells.

Berberine, an isoquinoline alkaloid, is a traditional oriental medicine used to treat diarrhea and gastroenteritis. Recently, we reported that it could inhibit the growth of intestinal polyp in animals and in patients with the familial adenomatous polyposis by downregulating ß-catenin signaling. However, the intracellular target mediating the effects of berberine remains elusive. Here, we provide evidence that berberine inhibits ß-catenin function via directly binding to a unique region comprising residues Gln275, Arg316 and Arg371 in nuclear receptor retinoid X receptor alpha (RXRα), where berberine concomitantly binding to and synergistically activating RXRα with 9-cis-retinoic acid (9-cis-RA), a natural ligand binding to the classical ligand-binding pocket of RXRα. Berberine binding promotes RXRα interaction with nuclear ß-catenin, leading to c-Cbl mediated degradation of ß-catenin, and consequently inhibits the proliferation of colon cancer cells. Furthermore, berberine suppresses the growth of human colon carcinoma xenograft in nude mice in an RXRα-dependent manner. Together, our study not only identifies RXRα as a direct protein target for berberine but also dissects their binding mode and validates that berberine indeed suppresses ß-catenin signaling and cell growth in colon cancer via binding RXRα, which provide new strategies for the design of new RXRα-based antitumor agents and drug combinations.

The effect of percutaneous endoscopic lumbar discectomy under different anesthesia on pain and immunity of patients with prolapse of lumbar intervertebral disc.

OBJECTIVE: To explore the effect of percutaneous transforaminal endoscopic discectomy under different anesthesia on pain and immunity of patients with lumbar disc herniation. PATIENTS AND METHODS: 92 cases of patients with lumbar disc herniation in the Affiliated Hospital of Qingdao University from February 2015 to January 2016 were collected. These patients were randomly divided into control group and observation group (n = 46). Patients in the control group underwent percutaneous transforaminal endoscopic discectomy with the use of local anesthesia, while patients in the observation group used continuous epidural anesthesia. Oswestry Disability Index (ODI) and Visual Analogue Scale of Pain (VAS) were used to compare the surgical effect and the degree of pain of patients in the two groups. Adverse reactions (nausea, vomiting, dizziness, drowsiness) of patients in two groups were compared. T lymphocytes subset level (CD4+, CD8+) and inflammatory cytokines (IL-2, TNF) in the immune system were compared on the 1st, 3rd, and 10th day post-operatively. RESULTS: The pain degree of patients in the two groups had no significant difference before their operations (p > 0.05). The intraoperative pain rate of patients in the observation group was significantly lower than the control group (p < 0.05). Patients in both groups achieved a remarkable decrease of pain intensity on month 1 and month 3 post-operatively (p < 0.05). There is no significant difference between the two groups (p > 0.05). ODI scores of patients in the two groups had no significant difference pre-operatively (p > 0.05). Patients in both groups achieved a remarkable decrease of ODI scores after surgery (p < 0.05), and there is no significant difference between the two groups (p > 0.05). The occurrence of adverse reactions in the observation group was significantly lower than the control group (p < 0.05). On day 1 and 3 post-operatively, CD4+ and CD8+ levels of patients in both groups were lower than before operation, and data in the control group decreased more than the observation group (p < 0.05). IL-2 and TNF-α levels of patients in the two groups were significantly higher than pre-operatively, and data in the control group was higher than the observation group (p < 0.05). On day 10 post-operatively, all the indexes returned to the preoperative level. CONCLUSIONS: Both continuous epidural anesthesia and local anesthesia can reduce or avoid perioperative pain, but continuous epidural anesthesia has more advantages than local anesthesia, and it can improve the immune function for patients undergoing PTED for LDH.

Simultaneous determination of phenolic acids and flavonoids in Chenopodium formosanum Koidz. (djulis) by HPLC-DAD-ESI-MS/MS.

A high performance liquid chromatography-diode array detection-tandem mass spectrometry method (HPLC-DAD-MS/MS) was developed for simultaneous determination of phenolic acids and flavonoids in djulis (Chenopodium formosanum Koidz.), a traditional Chinese herb reported to possess vital biological activities. A high yield of phenolic acids and flavonoids was attained by employing 50% ethanol in water as the extraction solvent and shaking in a 60°C water bath for 3h. A total of 8 phenolic acids and 14 flavonoids were separated and identified within 55min by using a Poroshell 120 EC-C18 column with detection at 280nm, flow rate at 0.8mL/min, column temperature at 35°C, and a gradient solvent system of 0.1% formic acid in water and acetonitrile. Two internal standards caffeic acid and kaempferol-3-O-rutinoside were used for quantitation of phenolic acids and flavonoids in djulis respectively. The amounts of phenolic acids ranged from 11.5±0.8µg/g (caffeoyl-putrescine-derivative (2)) to 1855.3±16.9µg/g (hydroxylphenylacetic acid pentoside), while the flavonoids ranged from 19.93±2.29µg/g (quercetin-3-O-(coumaryl)-rutinoside-pentoside (1)) to 257.3±2.05µg/g (rutin-O-pentoside (2)). A high recovery (89.68-97.20%) and high reproducibility was obtained for both phenolic acids and flavonoids with the relative standard deviation (RSD) for the latter ranging from 0.09-8.22% (intra-day variability) and 0.80-8.48% (inter-day variability). This method may be applied to determination of both phenolic acids and flavonoids in food products and Chinese herbs.

Effects of tanshinone nanoemulsion and extract on inhibition of lung cancer cells A549.

Danshen (Salvia miltiorrhiza), a Chinese medicinal herb, consists of several functional components including tanshinones responsible for prevention of several chronic diseases. This study intends to prepare tanshinone extract and nanoemulsion from danshen and determine their inhibition effect on lung cancer cells A549. A highly stable tanshinone nanoemulsion composed of Capryol 90, Tween 80, ethanol and deionized water with the mean particle size of 14.2 nm was successfully prepared. Tanshinone nanoemulsion was found to be more effective in inhibiting A549 proliferation than tanshinone extract. Both nanoemulsion and extract could penetrate into cytoplasm through endocytosis, with the former being more susceptible than the latter. A dose-dependent response in up-regulation of p-JNK, p53 and p21 and down-regulation of CDK2, cyclin D1 and cyclin E1 expressions was observed with the cell cycle arrested at G0/G1 phase. The cellular microcompartment change of A549 was also investigated. The study demonstrated that tanshinone nanoemulsion may be used as a botanic drug for treatment of lung cancer.

Electroacupuncture at Zusanli (ST36) ameliorates colonic neuronal nitric oxide synthase upregulation in rats with neurogenic bowel dysfunction following spinal cord injury.

Study designExperimental study.ObjectiveTo determine the effects of electroacupuncture (EA) at Zusanli (ST36) on colonic motility and neuronal nitric oxide synthase (nNOS) expression in rats with neurogenic bowel dysfunction (NBD) after spinal cord injury (SCI).SettingSecond School of Clinical Medical, Nanjing University of Chinese Medicine, Jiangsu, China.MethodsWe divided 30 adult Sprague-Dawley rats into a sham group (10 rats), a model group (SCI alone, 10 rats) and a EA group (SCI+EA at ST36, 10 rats). Defecation time was recorded as the time from activated carbon administration (on day 15) to evacuation of the first black stool. Immunohistochemical, real-time PCR and western blot analyses were performed to assess changes in nNOS-immunoreactive cells, and nNOS messenger RNA (mRNA) and protein, respectively, after 14 experimental days.ResultsDefecation time was lower in the EA group than in the model group (P<0.01). On immunohistochemical analysis, nNOS was localized in the myenteric plexus of the colon. The number of nNOS-immunoreactive cells and the intensity of nNOS staining were greater in the model group than in the sham group and lesser in the EA group than in the model group. Consistent with the immunohistochemical findings, nNOS mRNA and protein expression was higher in the model group than in the sham group and lower in the EA group than in the model group (P<0.05 for both).ConclusionIncreased colonic nNOS expression can induce/aggravate NBD in SCI rats. EA at ST36 ameliorated NBD, possibly by downregulating colonic nNOS expression.