Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

Rationality of the ethanol precipitation process in modern preparation production of Zishui-Qinggan decoction evaluated by integrating UPLC-QTOF-MS/MS-based chemical profiling/serum pharmacochemistry and network pharmacology.

INTRODUCTION: Zishui-Qinggan decoction (ZQD) is a classical traditional Chinese medicine formula (TCMF) for alleviating menopausal symptoms (MPS) induced by endocrine therapy in breast cancer patients. In the production of TCMF modern preparations, ethanol precipitation (EP) is a commonly but not fully verified refining process. OBJECTIVES: Chemical profiling/serum pharmacochemistry and network pharmacology approaches were integrated for exploring the rationality of the EP process in the production of ZQD modern preparations. MATERIAL AND METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) was applied to identify the chemical profiles and absorbed components of ZQD. Network pharmacology was used to identify targets and pathways related to MPS-relieving efficacy. RESULTS: The chemicals of ZQDs without/with EP process (referred to as ZQD-W and ZQD-W-P, respectively) were qualitatively similar with 89 and 87 components identified, respectively, but their relative contents were different; 51 components were detectable in the serum of rats orally administered with ZQD-W, whereas only 19 were detected in that administered with ZQD-W-P. Key targets, such as AKT1, and pathways, such as the PI3K-Akt signalling pathway, affected by ZQD-W and ZQD-W-P were similar, while the neuroactive ligand-receptor interaction pathway among others and the MAPK signalling pathway among others were specific pathways affected by ZQD-W and ZQD-W-P, respectively. The specifically absorbed components of ZQD-W could combine its specific key targets. CONCLUSION: The EP process quantitatively altered the chemical profiles of ZQD, subsequently affected the absorbed components of ZQD, and then affected the key targets and pathways of ZQD for relieving MPS. The EP process might result in variation of the MPS-relieving efficacy of ZQD, which deserves further in vivo verification.

[UPLC-Q-TOF-MS analysis of chemical constituents of classical prescription Yiguanjian standard decoction].

An UPLC-Q-TOF-MS method was employed to characterize and classify the chemical components of the standard decoction of Yiguanjian, a classical famous recipe. Chromatographic separation was performed on an Acquity HSS T3(2.1 mm ×100 mm, 1.8 µm) column with a mobile phase of 0.1% formic acid water-0.1% formic acid acetonitrile using gradient elution. The flow rate was 0.4 mL·min~(-1) and the column temperature was 40 ℃. Mass spectrometry was performed on electrospray ionization source(ESI) with positive and negative ion scanning modes. The potential compounds were identified by comparing the reference compounds, analyzing the mass spectrometry data and matching the published articles on Masslynx 4.1 software and SciFinder database. Finally, a total of 113 compounds, including 11 amino acids, 19 terpenoids, 13 phthalides, 11 steroidal saponins, 10 coumarins, 9 alkaloids, 7 flavonoids, 8 phenylethanoid glycosides, 8 organic acids and 17 other categories were identified. The established method systematically and accurately characterized the chemical components in Yiguanjian, which could provide experimental evidences for the subsequent studies on the pharmacodynamical material basis and quality control of Yiguanjian.

UPLC-Q-TOF-MS analysis of chemical constituents of classical prescription Yiguanjian standard decoction / 中国中药杂志

An UPLC-Q-TOF-MS method was employed to characterize and classify the chemical components of the standard decoction of Yiguanjian, a classical famous recipe. Chromatographic separation was performed on an Acquity HSS T3(2.1 mm ×100 mm, 1.8 μm) column with a mobile phase of 0.1% formic acid water-0.1% formic acid acetonitrile using gradient elution. The flow rate was 0.4 mL·min~(-1) and the column temperature was 40 ℃. Mass spectrometry was performed on electrospray ionization source(ESI) with positive and negative ion scanning modes. The potential compounds were identified by comparing the reference compounds, analyzing the mass spectrometry data and matching the published articles on Masslynx 4.1 software and SciFinder database. Finally, a total of 113 compounds, including 11 amino acids, 19 terpenoids, 13 phthalides, 11 steroidal saponins, 10 coumarins, 9 alkaloids, 7 flavonoids, 8 phenylethanoid glycosides, 8 organic acids and 17 other categories were identified. The established method systematically and accurately characterized the chemical components in Yiguanjian, which could provide experimental evidences for the subsequent studies on the pharmacodynamical material basis and quality control of Yiguanjian.

Correlation between body composition and cardiorespiratory fitness decline in physical examination population of different genders / 中华健康管理学杂志

Objective:To analyze the correlation between the body composition and cardiorespiratory fitness (CRF) decline in physical examination population of different genders.Methods:Clinical data of the cardiopulmonary exercise testing (CPET) and body composition analysis of 439 people who received physical examination in the Medical Examination Center of Peking University Third Hospital from May 2021 to September 2021 were retrospectively analyzed. The general data, physical examination, biochemical parameters, body composition and CPET results were collected. The subjects were divided into normal group and decline group according to the percentage of peak oxygen uptake (VO 2peak) levels ≥ 85% or<85%. Multivariate logistic regression was applied to investigate the influencing factors of CRF decline in subjects of different genders. Results:Among men, total cholesterol and triglyceride in the decline group were significantly higher than those in the normal group [(5.097±0.890) vs (4.865±0.856) mmol/L, (1.778±1.200) vs (1.485±0.709) mmol/L], and the blood homocysteine (Hcy) and skeletal muscle index were significantly lower than those in the normal group [13.00 (11.30, 15.90) vs 13.80 (12.05, 17.10) μmol/L, (7.89±0.65) vs (8.08±0.64) kg/m 2] (all P<0.05). Among women, skeletal muscle index in the decline group was significantly lower than that in the normal group [(6.21±0.52) vs (6.53±0.56)kg/m 2], and percent body fat was significantly higher than that in the normal group [(32.83±4.92)% vs (31.21±4.55)%] (all P<0.05). The elevation of triglyceride level ( OR=1.487, 95% CI: 1.042-2.121) and visceral fat area ( OR=1.032, 95% CI: 1.014-1.051) were positively correlated with the decline of CRF in man, the decrease of skeletal muscle index ( OR=0.215, 95% CI: 0.106-0.435) and the increase of percent body fat ( OR=1.149, 95% CI: 1.060-1.245) were positively correlated with the decrease of CRF in women (all P<0.05). Conclusions:There is a correlation between body composition and CRF decline in physical examination population of different genders. Men should control visceral fat more effectively, and women should pay attention to increase muscle mass while reducing body fat, in order to improve CRF.

Analysis of 4 Cases of Fungal Infections in Children and Literature Review / 中国药房

OBJECTIVE：To prov ide a reference for the diagnosis and treatment of invasive fungal infection in children. METHODS：Four male children with invasive fungal infection in critical condition ，aged from 3 months to 17 years，were treated in our hospital. The types of diseases included pneumonia ，endocarditis，meningitis and pulmonary infection. The pathogens involved Trichosporon asahii ，Candida portugal ，Malassezia globosa ，Pichia guilliermondii ，Alternaria alternate and Candida krusei. Clinical pharmacists comprehensively followed up the treatment and reviewed the literature to assist doctors in formulating treatment plans. They provided Fluconazole sodium chloride injection （6 mg/kg，ivgtt，qd），Caspofungin acetate for injection （loading dose 32 mg，maintenance dose 25 mg，ivgtt，qd），Fluconazole capsules （400 mg，p.o.，qd）and Voriconazole for injection（200 mg，i.v.，q12 h）+Capofungin acetate for injection （loading dose 70 mg，maintenance dose 50 mg，i.v.，qd）and other symptomatic treatment ，and closely monitored the changes of relevant indicators and the occurrence of ADR during the treatment of children. RESULTS ：The doctor adopted the clinical pharmacist ’s suggestion ，three cases were relieved and one was not cured. No serious ADR was found. CONCLUSIONS ：Once similar infections are found in clinic ，timely targeted treatment should be given in combination with the types of pathogens and drug resistance characteristics ，so as to effectively control the disease. The real cases provided in this article can provide evidence for the treatment of children with fungal infection.

A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data / 中华胃肠外科杂志

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Danggui Sini decoction protects against oxaliplatin-induced peripheral neuropathy in rats.

The effects of Danggui Sini decoction on peripheral neuropathy in oxaliplatin-induced peripheral is established. The results indicated that Danggui Sini decoction treatment significantly reduced the current amplitude of dorsal root ganglia cells undergoing agonists stimuli compared to the model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment significantly inhibited the inflammatory response of dorsal root ganglia cells compared to the model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment significantly enhanced the amounts of Nissl bodies in dorsal root ganglia cells compared to the Model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment improved ultra-microstructures of dorsal root ganglia cells. In conclusion, Danggui Sini decoction protected against neurotoxicity of oxaliplatin-induced peripheral neuropathy in rats by suppressing inflammatory lesions, improving ultra-microstructures, and enhancing amounts of Nissl bodies.

Exploring the Possible Mechanism and Drug Targets of Huang-Qi-Gui-Zhi-Wu-Wu Decoction for the Treatment of Chemotherapy-Induced Peripheral Neuropathy on Network Pharmacology.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment, which may influence its successful completion. The Huang-Qi-Gui-Zhi-Wu-Wu decoction (HQGZWWD) has been widely used to treat CIPN in China although the pharmacological mechanisms involved have not been clarified. Using the network pharmacology approach, this study investigated the potential pathogenesis of CIPN and the therapeutic mechanisms exerted by the HQGZWWD herbal formula in CIPN. The targets of HQGZWWD were identified using traditional Chinese medicine (TCM) databases (TCMSP and ETCM) and prediction platforms (PharmMapper and TargetNet), and the genes of CIPN were collected by DisGeNET, GeneCards, and literature search. The common target interaction network between herbal formula and diseases was constructed by using Cytoscape. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal the mechanism and efficacy of HQGZWWD in the treatment of CIPN. A total of 153 CIPN-related genes were screened, and a protein-protein interaction (PPI) network with 96 nodes and 424 edges was constructed. Sixty-three active components were retrieved from HQGZWWD, with a herb-composite compound-target network including 748 nodes and 5448 edges. Forty-one targets belong to the above two networks. The analysis of network results and literature review shows that the main pathological processes of CIPN may be the inflammatory response and nerve injury, and HQGZWWD plays a therapeutic role in CIPN by regulating inflammatory response and repairing nerve injury, thus verifying the reliable efficacy of this herbal formula. In addition, we found two new potential therapeutic targets (CDK7 and GSTM2) warranting further investigation. This study fully illustrates that TCM has the characteristics of a multicompound, multitarget, and multipathway treatment, which is of great significance to study the curative effect of herbal formulations.

[UPLC-Q-TOF-MS analysis on chemical constituents of classical prescription Huangqi Guizhi Wuwu Tang standard decoction].

UPLC-Q-TOF-MS technology was used to analyze the chemical constituents from classical prescription Huangqi Guizhi Wuwu Tang standard decoction. Acquity HSS T3 column(2.1 mm × 100 mm, 1.8 µm) was used as the chromatographic column, with 0.1% formic acid solution-0.1% formic acid acetonitrile as the mobile phase for gradient elution. The volume flow rate was 0.4 mL·min~(-1) and the column temperature was 40 ℃. Mass spectrometry data of Huangqi Guizhi Wuwu Tang standard decoction were collected in positive and negative ion modes. The chemical constituents from classical prescription Huangqi Guizhi Wuwu Tang standard decoction were analyzed and identified by Masslynx 4.1 software combined with SciFinder database, comparison with reference mate-rials, mass spectrometry data analysis and reference to relevant literature. A total of 110 compounds were analyzed and identified, including 33 flavonoids, 14 monoterpene glycosides, 8 triterpenoids, 8 gingerols, 17 phenylpropanoids, 12 organic acids, 7 amino acids and 11 other compounds. The results of this study provide an experimental basis for the further research on the substance basis and quality control of Huangqi Guizhi Wuwu Tang standard decoction.

A study of systematic family intervention on 1-2 years old toddlers at high risk for autism spectrum disorders / 中华实用儿科临床杂志

Objective:To examine the efficacy of systematic family intervention (a parent-implemented early start Denver model, P-ESDM) on toddlers at high risk of autism spectrum disorders (IHRASD) who were aged 1 to 2.Methods:The developmental screening for infants aged 1-2 years in Hefei city was performed by using the standardized screening method.The monitoring network of referral-assessment-P-ESDM guidance-follow up-early intervention effect assessment was conducted on the screened children with positive results.A total of 110 patients with IHRASD aged 1 to 2 years were detected.Sixty-three cases that met the inclusion criteria and volunteered to take part in this study were divided P-ESDM group (31 cases) and the control group (32 cases). They were assessed before intervention, 3 and 6 months after intervention separately.Parents of the patients in the P-ESDM group attended 12 weeks of family intervention training courses, 1 hour per week, while parents of the patients in the control group rejected interventions available from us.Results:The proportion of fathers with college degree or above (71.0% vs.43.8%, χ2=7.315, P=0.026) and proportion of mothers with high school/secondary school degree or above (83.9% vs.65.6%, χ2=5.264, P=0.072) were significantly higher in the P-ESDM group than in the control group.Three months after intervention, the P-ESDM group showed decreased Aberrant Behavior Checklist (ABC) scores [29.0(20.0, 45.0) scores vs.48.0(33.0, 50.0) scores, Z=-2.298, P=0.022]and increased Infant-Junior Middle School Social Adaptive Capacity Scale (SM) scores[ 10.0(9.0, 10.0) scores vs.9.0(8.0, 10.0) scores, Z= -2.045, P=0.041], compared with the control group.No significant improvement was found by the Gesell tests in the development quotients (EQs) of five energy areas, namely, the adaptive energy area [(83.86±18.03) scores vs.(75.34±10.49) scores, t=1.734, P=0.090], big movement energy area [(90.24±10.79) scores vs.(85.20±8.97) scores, t=1.595, P=0.118], fine movement energy area [(85.18±14.99) scores vs.(83.41 ± 9.28) scores, t=0.429, P=0.670], language energy area [(59.28±15.01) scores vs.(51.09±9.37) scores, t=1.981, P=0.054] and individual-society energy area [(67.13±14.86) scores vs.(63.50±7.85) scores, t=0.908, P=0.369]. Twelve months after intervention, the P-ESDM group demonstrated significantly decreased ABC scores[20.0(12.0, 33.0) scores vs.45.0(32.3, 52.8) scores, Z=-3.783, P=0.000], increased SM scores[10.0(9.0, 10.0) scores vs.9.0(8.3, 10.0) scores, Z=-2.974, P=0.003], increased EQ of adaptive energy area [(80.83±17.20) scores vs.(72.34 ± 13.18) scores, t=2.203, P= 0.031], increased EQ of the individual-society energy area[(71.87±17.30) scores vs.(62.18±13.91) scores, t= 2.454, P= 0.017]and increased EQ of the language energy area[(68.96±19.93) scores vs.(53.42±14.88) scores, t= 3.515, P= 0.001], compared with the control groups. Conclusions:Early screening, diagnosis, and P-ESDM intervention can improve the outcome of young children aged 1 to 2 years at high risk of ASD.P-ESDM intervention for 12 months demonstrates obvious effects in patients with IHRASD.

UPLC-Q-TOF-MS analysis on chemical constituents of classical prescription Huangqi Guizhi Wuwu Tang standard decoction / 中国中药杂志

UPLC-Q-TOF-MS technology was used to analyze the chemical constituents from classical prescription Huangqi Guizhi Wuwu Tang standard decoction. Acquity HSS T3 column(2.1 mm × 100 mm, 1.8 μm) was used as the chromatographic column, with 0.1% formic acid solution-0.1% formic acid acetonitrile as the mobile phase for gradient elution. The volume flow rate was 0.4 mL·min~(-1) and the column temperature was 40 ℃. Mass spectrometry data of Huangqi Guizhi Wuwu Tang standard decoction were collected in positive and negative ion modes. The chemical constituents from classical prescription Huangqi Guizhi Wuwu Tang standard decoction were analyzed and identified by Masslynx 4.1 software combined with SciFinder database, comparison with reference mate-rials, mass spectrometry data analysis and reference to relevant literature. A total of 110 compounds were analyzed and identified, including 33 flavonoids, 14 monoterpene glycosides, 8 triterpenoids, 8 gingerols, 17 phenylpropanoids, 12 organic acids, 7 amino acids and 11 other compounds. The results of this study provide an experimental basis for the further research on the substance basis and quality control of Huangqi Guizhi Wuwu Tang standard decoction.

The effect of ghrelin O-acyltransferase inhibitor on gastric H+-K+-ATPase activity and GOAT/ghrelin system in gastric mucosal cells in vitro.

Ghrelin is implicated in the regulation of gastric functional development. The octanoylation of ghrelin is critical for its physiological functions which dependent upon ghrelin O-acyltransferase (GOAT) catalyzation. To investigate the effect of GOAT on gastric acid secretion and expression of ghrelin in vitro. Primary cultures of gastric mucosal cells were challenged with 1.5 × 10-5, 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (The GOAT inhibitor), respectively, for 24 h in order to further clarify the effect of GOAT on H+-K+-ATPase activity. In vitro, GO-CoA-Tat significantly increased ghrelin and GOAT mRNA expression at 1.5 × 10-5, 1.5 × 10-4 and 1.5 × 10-3 mol/mL, and augmented cell total ghrelin secretion at 1.5 × 10-3 mol/mL. But cell acylated ghrelin secretion was reduced at 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). And cell acylated ghrelin synthesis was reduced at 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). In accordance with acylated ghrelin level, H+-K+-ATPase activity were decreased with 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). These results indicated that GOAT inhibitor decreases the acylated ghrelin level and H+-K+-ATPase activity in vitro.

Exploring on the elderly health management model in tropic area.

In this article, based on the characteristics of tropical area, we analyze the beneficial and the disadvantage of tropical area to human health, points out the existing problems in elderly health management pattern in the tropics area, accordingly we discuss how to establish tropical characterized elderly health management, and put forward constructive suggestions.

Exploring on the elderly health management model in tropic area

In this article, based on the characteristics of tropical area, we analyze the beneficial and the disadvantage of tropical area to human health, points out the existing problems in elderly health management pattern in the tropics area, accordingly we discuss how to establish tropical characterized elderly health management, and put forward constructive suggestions.

Exploring on the elderly health management model in tropic area

In this article, based on the characteristics of tropical area, we analyze the beneficial and the disadvantage of tropical area to human health, points out the existing problems in elderly health management pattern in the tropics area, accordingly we discuss how to establish tropical characterized elderly health management, and put forward constructive suggestions.

Determination of Mildronate Concentration in Human Plasma and Urine by LC-MS/MS and Pharmacokinet-ics Study / 中国药房

OBJECTIVE:To establish the method for the determination of mildronate in human plasma and urine,and to study the pharmacokinetic characteristics in healthy volunteers. METHODS:After precipitating plasma and urine sample,LC-MS/MS method was adopted. Dikma Diamonsil C18 column was used with mobile phase consisted of methanol-water(containing 0.2% for-mic acid,0.3% ammonium acetate)(31∶69,V/V)at the flow rate of 0.6 ml/min. ESI was adopted in MRM mode,by using nega-tive ion. The ion for quantitative analysis were m/z 147.10→58.20 (mildronate) and m/z 152.00→110.10 (internal standard,acet-aminophen). The pharmacokinetic parameters of mildronate with single administration and multiple administration were calculated by using DAS 2.1 software and compared. RESULTS:The linear range of mildronate in plasma were 0.02-20 ng/ml(r=0.999 3) and in urine were 0.05-40 ng/ml(r=0.998 2). The lowest limits of quantitation were 0.02 and 0.05 ng/ml. Precision and recovery met the requirements of biological specimen determination,and endogenous impurities hadn’t effect on the determination. The main pharmacokinetics parameters of low-dose,medium-dose and low-dose(250,500,750 mg)of mildronate in plasma with single ad-ministration were as follows:t1/2 were(3.39±0.81),(5.52±0.57)and(5.32±0.96)h;tmax were(0.80±0.45),(1.38±0.43)and (1.10±0.36)h;cmax were(4.17±1.46),(8.08±1.04)and(15.04±1.86)ng/ml;AUC0-36 h were(24.55±5.81),(45.50±7.07)and (85.60 ± 13.09)ng·h/ml. In the dose range,cmax,AUC0-36 h h had a linear relationship with dose (R2 were 0.974 5 and 0.968 3). The main pharmacokinetic parameters of low-dose of mildronate with multiple administration after keeping stable were as follows:cmin was(0.28 ± 0.10)ng/ml;AUCs was(38.78 ± 4.18)ng·h/ml;cs was(1.62 ± 0.17)ng/ml;DF was(3.81 ± 1.14);t1/2 was(6.17 ± 1.46)h;tmax was(1.20 ± 0.33)h;cmax was(6.46 ± 1.96)ng/ml;AUC0-36 h was(40.33 ± 4.65)ng·h/ml;accumulation factor of cmax and AUC were(1.73±0.90)and(1.64±0.40). Compared with single administration,t1/2,cmax and AUC of mildronate with multiple admin-istration after keeping stable all changed,and tmax had no signifi-cant difference. After single administration,26 h accumulative excretion rate of those groups were (0.004 009 ± 0.001 1)%, (0.004 026±0.001 01)% and(0.003 858±0.000 68)% respec-tively. CONCLUSIONS:Established method is sensitive,accurate and specific,and suitable for the determination of mildronate concentration in human plasma and urine and pharmacokinetics study. Mildronate capsule shows certain accumulation effect in healthy volunteers,and linear pharmacokinetic characteristics.

Association between Toll-like receptor 4 and interleukin 17 gene polymorphisms and colorectal cancer susceptibility in Northeast China.

Limited studies about the effects of TLR 4 and IL17 polymorphisms (SNPs) on the risk of colorectal cancer (CRC) have yielded inconsistent results. Totally, 601 CRC patients and 627 controls were enrolled. Unconditional logistic regression was used to estimate the association between tagSNPs and susceptibility of CRC and the interactions effects of gene and environment on the risk of CRC. IL17 rs6973569 AG and AG/AA genotypes significantly decreased the risk of CRC compared with GG genotype (ORadjusted=0.72, 95% CI 0.55-0.94 and ORadjusted=0.74, 95 % CI 0.57-0.97). The haplotype G-T-G-C-A-G accounting for the largest proportion haplotypes increased the risk of CRC (OR=1.27, 95 % CI 1.06-1.53). However, G-C-C-T-A-G and G-C-G-C-A-G haplotypes decreased the susceptibility of CRC. Synergistic interactions between TLR 4 rs1927911 CT/TT and higher pungent food intake as well as IL17 rs6973569 AG/AA genotypes and higher intake of sausage food (ORi=1.72, 95% CI 1.04-2.84 and ORi=3.38, 95% CI 1.28-8.91) on the risk of CRC were observed. IL17 rs6973569 SNP might be an independent factor of susceptibility to CRC. TLR 4 haplotype of G-T-G-C-A-G may increase risk of CRC. Higher intake of pungent and sausage food synergistically interacted with TLR 4 and IL17 SNPs on the risk of CRC.

A Comparative Study of 2 different Teaching Modes Used in Rehabilitation Medicine Continuing Education: the Physicians and Therapists Teaching Together or Separately / 中国康复理论与实践

@# Objective To compare the acceptance of 2 different teaching modes－physicians and therapists teaching together and separately in continuing education students of rehabilitation medicine. Methods A questionnaire was filled by the students who attended the lectures of both Rehabilitation of Elbow Injury and Rehabilitation of Wrist Injury in the 9th National Orthopedic Class. The former lecture was taught by the rehabilitation physician and physical therapist together (together mode), and the latter lecture was taught by the rehabilitation physician and physical therapist separately (separate mode). The questionnaire included the choices and text questions. Results There were 45 copies of effective questionnaire all together. The satisfaction of both lectures were above 90%. As to teaching modes, 77.8% students liked together mode better, and 22.2% students preferd the separate mode. 93.9% students would or maybe use together mode in their future work, and 88.9% in separate mode. Conclusion The mode of physician and therapist giving lectures together is well accepted by students.