Molecular docking technology and network pharmacology based on Rhapontici Radix-Cremastrae Pseudobulbus drug pair in treating breast cancer.

OBJECTIVE: Network pharmacology is a bioinformatics-based research strategy for identifying the mechanisms of drugs and promoting drug development. This study used network pharmacology to investigate the mechanism of the Loulu-Cremastrae Pseudobulbus drug pair treating breast cancer (BC). MATERIALS AND METHODS: The ingredients and potential targets of the drug pair were searched with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCSMP). National Center for Biotechnology Information (NCBI) and gene cards were used to search the targets of BC. Networks of "drugs-components-targets" and protein-protein interaction were constructed through Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out through common targets. Using AutoDock tool, molecular docking was performed to verify the binding between key targets and compounds. RESULTS: Finally, we selected 6 active compounds from the drug pair. A total of 61 targets were associated with the drug pair, and 15,295 targets were related to BC. 55 common targets were obtained after the intersection. The key targets included Transcription factor Jun (JUN), Heat shock protein HSP 90-alpha (HSP90AA1), and Caspase-3(CASP3). 327 terms were obtained by GO analysis. 78 pathways (p < 0.05) were identified through KEGG analysis. Molecular docking indicated that important compounds combined well with key targets. CONCLUSIONS: Various active compounds, including beta-sitosterol, 2-methoxy-9,10-dihydrophenanthrene-4,5-diol, and stigmasterol, can regulate multiple signaling pathways related to BC, such as the estrogen and prolactin signaling pathways, playing therapeutic roles in BC.

[HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems].

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

[The Museum of Western Studies on Chinese Medicine:Chinese medicine in the western societies].

The historical artifacts displayed in the Museum of Western study on Chinese Medicine at Yunnan University of Chinese Medicine came from a variety of Chinese medical schools in America and European countries. They are in the memorial galleries for some well-known figures, such as George Soulié de Morant (Su Lie), Jacques-André Lavier (La Wei Ai), Felix Mann (Man Fu Li) and Manfred Porkert (Man Xi Bo), representing the development and status of respective Chinese medical schools in America and European countries. The displayed artifacts are nearly 3,000 photos, manuscripts, documents and more than 500 hours of audiovisual materials, including instruments for acupuncture and moxibustion, books, passports, letters and even supplies for their life. The displayed artifacts demonstrate the process and the access of people in the western societies to know, learn and take use of Chinese medicine.

[Research progress on the clinical features and mechanisms of COVID-19 combined with liver injury].

The highly contagious novel coronavirus pneumonia (COVID-19) that broke out in December 2019 has brought huge threats and losses to human society, so it has been the concern of every countries government. Presently, there are no specific drugs for COVID-19; however, a variety of potentially effective antiviral drugs, vaccines, cell therapies, traditional Chinese medicine and other methods are in clinical trials. Liver injury is a common complication of patients receiving COVID-19 treatment and its possible high incidence may affect the outcome of the disease. The pathogenesis of COVID-19 combined with liver injury in existing studies is still unclear, and relevant guidelines and expert consensuses are insufficient for clinical diagnosis and treatment. Therefore, the relevant progress and issues are now reviewed here.

[Multi-disciplinary cooperative treatment and management experience of 35 patients with extremely severe burns involved in August 2nd Kunshan factory aluminum dust explosion accident].

On August 2nd, 2014, 35 patients with extremely severe burns involved in August 2nd Kunshan factory aluminum dust explosion accident, including 18 males and 17 females, aged from 21 to 50 years, were admitted to our unit. According to the patient's condition, the rescue members divided the participants into groups according to their characteristics, and used the multi-disciplinary cooperative treatment and management mode of integrating critical care medicine, anesthesia, traditional Chinese medicine, rehabilitation, and nursing led by burn medicine. Totally 27 patients were successfully treated, with a success rate of 77.14%.

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.

Changes in the range of the medicinal herb Eriocaulon buergerianum Körnicke. (Eriocaulaceae) under climate change.

Eriocaulon buergerianum Körnicke. (Eriocaulaceae) is one of the most common and least expensive herbal medicines for eye disease. This species is facing potential threats from climate change. Insufficient biogeographic knowledge of this plant species can hinder its effective management for long-term population survival. We integrated ecological niche modelling (Biomod2) with 70 records of E. buergerianum and eight environmental variables to estimate changes in distribution over time. A core area Zonation algorithm was introduced to identify conservation priority areas. Our results indicate that the range of E. buergerianum will likely decrease in the future: the overall range change on average is -44.36 ± 21.56% (-3.70% to -77.73%); values of range loss and range gain are 45.79 ± 20.30% (9.29-78.19%) and 1.43 ± 1.53% (0.18-5.59%), respectively. According to conservation priority analysis, the mandatory reserve (top 5%), negotiable reserve (0.95-0.9) and partial reserve (0.9-0.8) areas are 19,799, 19,799 and 39,597 km2 , respectively. The areas identified as conservation priority are located in the southeast, especially in northern Taiwan and the Wuyi Mountains. Based on these results, we suggest a re-evaluation of the threatened status of this species, with a potential upgrade to the vulnerable (VU) category. To overcome the adverse conditions faced by populations of E. buergerianum in China, we propose a multi-faceted conservation strategy involving more complete resource assessment, a monitoring system, medical research focused on revealing medicinal components or substitutes, and a regional development plan that considers both wildlife and socio-economic issues.

[Efficacy of Weitan Waifu patch on the postsurgical gastroparesis syndrome of gastrointestinal cancer: a multi-center trial].

Objective: To investigate the safety and efficacy of the Weitan Waifu patch on the postsurgical gastroparesis syndrome (PGS) of gastrointestinal cancer. Methods: The multi-center, double-blind, randomized controlled trial was conducted with superiority design. Patients with PGS of gastrointestinal cancer diagnosed in 4 AAA hospitals and the abdominal symptom manifested as cold syndrome by Chinese local syndrome differentiation were recruited. These patients were randomly divided into two groups according to 1∶1 proportion. Placebo or Weitan Waifu patch was applied in control group or intervention group, respectively, based on the basic treatments, including nutrition support, gastrointestinal decompression, promoting gastric dynamics medicine.Two acupuncture points (Zhongwan and Shenque) were stuck with placebo in control group or patch in treatment group. The intervention course was 14 days or reached the effective standard. Results: From July 15, 2013 to Jun 3, 2015, 128 participants were recruited and 120 eligible cases were included in the full analysis set (FAS), and 60 cases in each group. 88 cases were included in the per-protocol set (PPS), including 45 cases in the treatment group and 43 cases in the control group. In the FAS, the clinical effective rate in the treatment group was 68.3%, significantly superior than 41.7% of the control group (P=0.003). The medium time of effective therapy in the treatment group was 8 days, significantly shorter than 10 days in the control group (P=0.017). In the FAS, 3 adverse events occurred in the treatment group, including mild to moderate decrustation, pruritus and nausea. The incidence rate of adverse events was 5.0% (3/60) and these symptoms were spontaneously remitted after drug withdrawal. No severe adverse events were observed in the control group. There was no significant difference between these two groups (P=0.244). Conclusion: Weitan Waifu patch is a safely and effectively therapeutic method for patients with PGS (cold syndrome) of gastroenterological cancer. Trial registration: International Standard Randomized Controlled Trial Number Register, ISRCTN18291857.

Intensified nitrate and phosphorus removal in an electrolysis -integrated horizontal subsurface-flow constructed wetland.

A novel electrolysis-integrated horizontal subsurface-flow constructed wetland system (E-HFCWs) was developed for intensified removal of nitrogen and phosphorus contaminated water. The dynamics of nitrogen and phosphorus removal and that of main water qualities of inflow and outflow were also evaluated. The hydraulic retention time (HRT) greatly enhanced nitrate removal when the electrolysis current intensity was stabilized at 0.07 mA/cm2. When the HRT ranged from 2 h to 12 h, the removal rate of nitrate increased from 20% to 84%. Phosphorus (P) removal was also greatly enhanced-exceeding 90% when the HRT was longer than 4 h in the electrolysis-integrated HFCWs. This improved P removal is due to the in-situ formation of ferric ions by anodizing of sacrificial iron anodes, causing chemical precipitation, physical adsorption and flocculation of phosphorus. Thus, electrolysis plays an important role in nitrate and phosphorus removal. The diversity and communities of bacteria in the biofilm of substrate was established by the analysis of 16S rDNA gene sequences, and the biofilm was abundant with Comamonadaceae and Xanthomonadaceae bacteria in E-HFCWs. Test results illustrated that the electrolysis integrated with horizontal subsurface-flow constructed wetland is a feasible and effective technology for intensified nitrogen and phosphorus removal.

Effect of compound Maqin decoction on TGF-ß1/Smad proteins and IL-10 and IL-17 content in lung tissue of asthmatic rats.

In this research, compound Maqin decoction (CMD) has been shown to positively affect in airway inflammation of asthma models. We evaluated the effects of CMD on the expression of transforming growth factor (TGF)-ß1/Smad proteins, interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats were killed to evaluate the expression of TGF-ß1 and Smad proteins in lung tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by ELISA. The expression of TGF-ß1 and Smad3 protein increased, whereas expression of Smad7 protein decreased upon high-dose or low-dose treatment with CMD or by intervention with dexamethasone, compared to the control. There was a significant difference between treatment with a high dose CMD and the control treatment, but no significant difference was found between high-dose CMD treatment and dexamethasone intervention. The expression of TGF-ß1 and Smad7 protein increased, whereas the expression of Smad3 protein decreased in the model group compared to other groups. In the CMD high-dose group, low-dose group, and dexamethasone intervention group, the IL-17 concentrations in lung tissue homogenates were decreased, while IL-10 levels were increased. Again, there was a significant difference between CMD high-dose and control treatment, but not between CMD high-dose treatment and dexamethasone intervention. Thus, positive effects of CMD against asthmatic airway remodeling may be due to its regulatory effect on TGF-ß1, Smad3, and Smad7 protein levels and on cytokines such as IL-10 and IL-17.

In vitro inhibition of invasion and metastasis in colon cancer cells by TanIIA.

The purpose of this study was to investigate the effect of the traditional Chinese medicine TanIIA on the viability, invasion, and metastasis of SW480 cells. SW480 cells were treated with TanIIA for 24 h, and MTT assays were performed to determine the effect of TanIIA on cell viability. Transwell transmembrane experiments were applied to test the effect of 1.0 mg/mL TanIIA on SW480 cell invasion and metastasis abilities. Western blotting was performed to determine the expression of the tumor cell metastasis proteins E-cadherin, vimentin, and MMP-9. The cell growth inhibition rates were 0%, 26 ± 4.3%, 43.47 ± 4.0%, 63.0 ± 5.5%, and 76.8 ± 7.8% for treatment with 0, 0.5, 1.0, 2.0, and 5.0 mg/L TanIIA, respectively. The differences in the cell viability inhibitory rates among all groups were statistically significant (P < 0.05). The Transwell assay results indicated that SW620 cell invasion and metastasis abilities were strongly inhibited by 1.0 mg/mL TanII. The western blotting results showed that the expression of E-cadherin was significantly increased and that the expression levels of vimentin and MMP-9 were significantly decreased after treatment with 1.0 mg/mL TanII for 24 h (P < 0.05). Tan II can effectively inhibit the biological activity of colon cancer in vitro and prevent the invasion of colon cancer cells.

High performance of nitrogen and phosphorus removal in an electrolysis-integrated biofilter.

A novel electrolysis-integrated biofilter system was developed in this study to evaluate the intensified removal of nitrogen and phosphorus from contaminated water. Two laboratory-scale biofilter systems were established, one with electrolysis (E-BF) and one without electrolysis (BF) as control. The dynamics of intensified nitrogen and phosphorus removal and the changes of inflow and outflow water qualities were also evaluated. The total nitrogen (TN) removal rate was 94.4% in our newly developed E-BF, but only 74.7% in the control BF. Ammonium removal rate was up to 95% in biofilters with or without electrolysis integration with an influent ammonium concentration of 40 mg/L, and the accumulation of nitrate and nitrite was much lower in the effluent of E-BF than that of BF. Thus electrolysis plays an important role in TN removal especially the nitrate and nitrite removal. Phosphorus removal was significantly enhanced, exceeding 90% in E-BF by chemical precipitation, physical adsorption, and flocculation of phosphorus because of the in situ formation of ferric ions by the anodizing of sacrificial iron anodes. Results from this study indicate that the electrolysis integrated biofilter is a promising solution for intensified nitrogen and phosphorus removal.

Identification of a novel LEMD3 Y871X mutation in a three-generation family with osteopoikilosis and review of the literature.

INTRODUCTION: Osteopoikilosis is a rare and benign autosomal dominant genetic disorder, characterized by a symmetric but unequal distribution of multiple hyperostotic areas in different parts of the skeleton. Recent studies have reported loss-of-function mutations in the LEM domain containing 3 (LEMD3) gene, encoding an inner nuclear membrane protein, as a cause of osteopoikilosis. METHODS: We investigated LEMD3 gene in a three-generation family from China, with six patients affected with osteopoikilosis. Peripheral blood samples were collected from family members and 100 healthy controls. All exons of the LEMD3 gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. RESULTS: A novel heterozygous c.2612_2613insA (p.Y871X) mutation in exon 13 of LEMD3 was identified, which resulted in a frame shift predicted to generate a premature stop codon at amino acid position 871. The mutation co-segregates with the osteopoikilosis phenotype and was not found in 100 ethnically matched controls. CONCLUSION: We identified a new mutation in LEMD3 gene, accounting for the familial case of osteopoikilosis. In addition we also review the clinical manifestation, diagnosis and treatment of osteopoikilosis.

Coffee consumption and the risk of lung cancer: an updated meta-analysis of epidemiological studies.

BACKGROUND/OBJECTIVES: Coffee is one of the most popularly consumed beverages worldwide. Many epidemiological studies have investigated the association between coffee consumption and lung cancer risk, but the results are inconsistent. Hence, we conducted a systematic analysis of relevant population-based studies to examine this association and derive a more precise estimation. SUBJECTS/METHODS: The Cochrane library, PubMed and Embase databases were searched to identify studies published through Mar 2015 that met the predetermined inclusion criterion. Seventeen studies (5 cohort and 12 case-control studies) involving 12 276 cases and 102 516 controls were included. RESULTS: The summary odds ratio (OR) of lung cancer was 1.17 (95% confidence interval (CI): 1.03-1.33) for coffee drinkers compared with nondrinkers and 1.31 (95% CI: 1.11-1.55) for the highest category of coffee consumption compared with the lowest category. Compared with nondrinkers, the pooled ORs for lung cancer were 1.10 (95% CI: 0.92-1.31) for ⩽1 cup per day, 1.10 (95% CI: 0.93-1.30) for 2-3 cups per day and 1.20 (95% CI: 1.02-1.39) for ⩾3 cups per day. Further analysis showed that the ORs for hospital-based case-control studies, population-based case-control studies and prospective cohort studies were 1.36 (95% CI: 1.10-1.69), 0.99 (95% CI: 0.77-1.28) and 1.59 (95% CI: 1.26-2.00), respectively. Significant associations for high coffee intake with increased risk of lung cancer were observed in men (OR=1.41 95% CI: 1.21-1.63), but not in women (OR=1.16, 95% CI: 0.86-1.56), in American (OR=1.34 95% CI: 1.08-1.65) and Asian populations (OR=1.49 95% CI: 1.28-1.74), but not in European populations (OR=1.12, 95% CI: 0.74-1.67), and in smokers (OR=1.24, 95% CI: 1.00-1.54), but not in nonsmokers (OR=0.85, 95% CI: 0.64-1.11). Particularly over the last 5 years, studies have consistently indicated that lung cancer risk is significantly increased by 47% in the population with the highest category intake of coffee compared with that with the lowest category intake (OR=1.47, 95% CI: 1.21-1.79). CONCLUSION: The present study suggested that coffee intake was associated with an increased risk of lung cancer.

Agriculture facilitated permanent human occupation of the Tibetan Plateau after 3600 B.P.

Our understanding of when and how humans adapted to living on the Tibetan Plateau at altitudes above 2000 to 3000 meters has been constrained by a paucity of archaeological data. Here we report data sets from the northeastern Tibetan Plateau indicating that the first villages were established only by 5200 calendar years before the present (cal yr B.P.). Using these data, we tested the hypothesis that a novel agropastoral economy facilitated year-round living at higher altitudes since 3600 cal yr B.P. This successful subsistence strategy facilitated the adaptation of farmers-herders to the challenges of global temperature decline during the late Holocene.

Neurodegenerative diseases in a dish: the promise of iPSC technology in disease modeling and therapeutic discovery.

The study of stem-cell biology has been a flourishing research area because of its multi-differentiation potential. The emergence of induced pluripotent stem cells (iPSCs) open up the possibility of addressing obstructs, such as the limited cell source, inherent complexity of the human brain, and ethical constrains. Though still at its infancy phase, reprogramming of somatic cells has been demonstrating the ability to enhance in vitro study of neurodegenerative diseases and potential treatment. However, iPSCs would not thoroughly translate to the clinic before limitations are addressed. In this review, by summarizing the recent development of iPSC-based models, we will discuss the feasibility of iPSC technology on relevant diseases depth and illustrate how this new tool applies to drug screening and celluar therapy.

Pharmacogenetics of obesity drug therapy.

As the prevalence and severity of obesity and its complications have risen significantly in worldwide populations, behavioral interventions alone have been inconsistent in promoting sufficient, sustained weight loss. Consequently, there has been intense interest in the development of anti-obesity medications as treatment strategies. When coupled with structured lifestyle modifications, pharmacotherapy can enhance weight loss. While less efficacious than bariatric surgery, drug therapy may be an alternative to surgery for some obese patients, and is an emerging strategy for weight maintenance. The goal of pharmacogenetics is to help identify patients who will benefit most from drug therapies while minimizing the risk of adverse effects. In this review, we summarize the pharmacogenetic literature on obesity drugs of the past (sibutramine, rimonabant), present (orlistat, lorcaserin, phentermine, topiramate), and future (buprioprion/naltrexone).

Transcutaneous electric acupoint stimulation reduces intra-operative remifentanil consumption and alleviates postoperative side-effects in patients undergoing sinusotomy: a prospective, randomized, placebo-controlled trial.

BACKGROUND: Although opioids are widely used as analgesics in general anaesthesia, they have unpleasant side-effects and can delay postoperative recovery. Acupuncture and related techniques are effective for acute and chronic pain, and reduces some side-effects. We assessed the effect of transcutaneous electric acupoint stimulation (TEAS) on intra-operative remifentanil consumption and the incidences of anaesthesia-related side-effects. METHODS: Sixty patients undergoing sinusotomy were randomly assigned to TEAS or control group. TEAS consisted of 30 min of stimulation (6-9 mA, 2/10 Hz) on the Hegu (LI4), Neiguan (PC6), and Zusanli (ST36) before anaesthesia. The patients in the control group had the electrodes applied, but received no stimulation. Bispectral index was used to monitor the depth of anaesthesia. Perioperative haemodynamics were recorded, and peripheral blood samples were collected to measure the levels of mediators of surgical stress. The primary end point was intraoperative remifentanil consumption and the secondary endpoints were recovery quality and anaesthesia-related side-effects. RESULTS: Patients in the TEAS group required 39% less remifentanil during surgery than controls [0.0907 (SD 0.026) µg kg(-1) min(-1) vs 0.051 (0.018) µg kg(-1) min(-1)]. There were no differences in intra-operative haemodynamics or surgical stress between groups. However, the time to extubation and recall in the control group was 16.8 (6.8) min and 23.0 (5.0) min, respectively, significantly longer than that in the TEAS group (P<0.01). TEAS also decreased the incidence of dizziness and pruritus within the first 24 h after surgery (P<0.01). CONCLUSION: The use of TEAS significantly reduced intra-operative remifentanil consumption and alleviated postoperative side-effects in patients undergoing sinusotomy. CLINICAL TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT01700855).

Dissolution and pharmacokinetic properties of alkaloids and flavonoids in a Xiexin multiple-unit drug delivery system.

Alkaloids from Rhizoma coptidis and flavonoids from Radix scutellariae were prepared in 2 separate units using a Xiexin multiple-unit drug delivery system (XXMU) to avoid the interactions that occur in the Xiexin decoction (XXD), which reduce oral bioavailability. Similarity factors (f 2 ) were calculated for the release of each component, and 4 equations were fitted to describe the release mechanism. In vivo pharmacokinetic studies were undertaken in rats to compare orally administered XXMU to a XXD powder suspension. No significant differences in the in vitro release properties of the 4 main components were observed between the individual pellets and the entire XXMU delivery system. The release mechanisms for coptisine, berberine, palmatine and baicalin from XXMU involved non-Fickian transport, non-Fickian transport, Fickian diffusion and zero-order release, respectively. The AUC(0-6 h), Cmax1(0-0.5 h) and Cmax3(2-6 h) values for berberine were significantly higher for XXMU than for XXD, but significant differences between the 2 dosage forms were not observed for pharmacokinetic parameters of baicalin. Interactions between flavonoids and alkaloids were reduced in XXMU, and the oral bioavailability of berberine was improved. The successful application of a multiple-unit drug delivery system may provide a method to improve the oral bioavailability of traditional Chinese medicines with multiple components.

Central α-adrenoceptors contribute to mustard oil-induced central sensitization in the rat medullary dorsal horn.

Our previous studies have demonstrated that application of the inflammatory irritant mustard oil (MO) to the tooth pulp produces trigeminal central sensitization that includes increases in mechanoreceptive field size and responses to noxious stimuli and decrease in activation threshold in brainstem nociceptive neurons of trigeminal subnucleus caudalis (the medullary dorsal horn, MDH). The aim of the present study was to test if central noradrenergic processes are involved in the central sensitization of MDH neurons and if α1-adrenoceptors or α2-adrenoceptors or both are involved. In urethane/α-chloralose-anesthetized rats, the activity of extracellularly recorded and functionally identified single nociceptive neurons in the MDH was studied. Continuous intrathecal (i.t.) superfusion of the adrenergic modulator guanethidine and α-adrenoceptor blocker phentolamine or selective α1-adrenoceptor antagonist prazosin over the medulla strongly attenuated all three MO-induced parameters of central sensitization in the MDH nociceptive neurons, compared to phosphate-buffered saline (as vehicle control). In contrast, i.t. superfusion of the selective α2-adrenoceptor antagonist yohimbine had little effect on the mechanoreceptive field expansion and the decreased mechanical activation threshold, and indeed facilitated responses to noxious stimuli of sensitized nociceptive neurons. Superfusion of each of the four chemicals alone did not affect baseline nociceptive neuronal properties. These findings provide the first documentation of the involvement of central noradrenergic processes in MDH in the development of the central sensitization, and that α1- and α2-adrenoceptors may be differentially involved.