Objective:To investigate the effect of saikosaponin A on depressive-like behaviors and hippocampal cyclic adenosine monophosphate response element-binding(CREB) protein expression in olfactory bulbectomized mice.Methods:Totally thirty male SPF-grade C57BL/6J mice, six weeks old, were randomly divided into 3 groups ( n=10 in each group): the control group, the olfactory bulbectomy group, and the saikosaponin A group.Olfactory bulbectomy was performed to damage the olfactory bulbs in the mice of bulbectomy group and saikosaponin A group, while the mice of control group only had a cranial drill hole at the same coordinates without damaging the olfactory bulbs. Mice in saikosaponin A group were administered saikosaponin A solution (dose: 5 mg/kg) via gavage, while mice in the control and olfactory bulbectomy groups were given the same volume of 0.9% NaCl solution once a day for 21 days. The depressive-related behavioral changes of mice in each group were evaluated by open field test, tail suspension test, forced swimming test, and weight measurement. The expression of CREB in the hippocampus of mice were detected by Western blot. Graphpad prism 5 software was used for data analysis.The data comparison among the multiple groups was conducted by one-way ANOVA and further pairwise comparisons were conducted by Tukey test. Results:(1) The results of weight measurement showed that there was no significant difference in body weight among the three groups( F=0.468, P=0.631) on the day of the olfactory bulbectomy surgery, but there was a statistically significant difference in body weight among the three groups ( F=37.340, P<0.001) on the 28th day after the olfactory bulbectomy.The body weight of mice in the olfactory bulbectomy group was lower than that of the control group ((24.09±1.01) g, (27.22±0.58)g)( P<0.05). The body weight of mice in the saikosaponin A group((26.23±0.83)g) was higher than that of the olfactory bulbectomy group( P<0.05). There was a statistically significant difference in body weight differences among the three groups of mice ( F=48.180, P<0.001). The body weight difference of mice in the olfactory bulbectomy group was lower than that of the control group ((2.34±0.96) g, (5.57±0.72) g) ( P<0.05). The body weight difference of mice in the saikosaponin A group was higher than that of the olfactory bulbectomy group ((4.74±0.56) g, (2.34±0.96) g) ( P<0.05).(2) The results of the open field test showed that there were statistically significant differences in the central area residence time and total activity distance in mice among the three groups ( F=27.03, 10.98, both P<0.001). The central area residence time ((13.87±4.59) s) and total activity distance ((35.67±4.88) m) of mice in the olfactory bulbectomy group were both less than those of the control group ((27.44±2.76) s, (59.02±16.21) m) (both P<0.05).The central area residence time ((21.77±4.78) s) and total activity distance ((52.33±10.41) m) of mice in the saikosaponin A group were both higher than those of the olfactory bulbectomy group(both P<0.05).(3) The results of tail suspension test showed that there was a statistically significant difference in immobility time among the three groups ( F=74.57, P<0.001). The immobility time of mice in the olfactory bulbectomy group was longer than that of the control group ((148.20±8.84)s, (97.89±8.64)s) ( P<0.05). The immobility time of mice in the saikosaponin A group((135.70±11.09)s) was less than that of the olfactory bulbectomy group( P<0.05). (4) The results of forced swimming test showed that there was a significant difference in immobility time among the three groups ( F=51.73, P<0.001). The immobility time of mice in the olfactory bulbectomy group was longer than that of the control group ((61.39±5.20) s, (40.80±4.30) s) ( P<0.05).The immobility time of mice in the saikosaponin A group((53.52±4.13)s) was less than that of the olfactory bulbectomy group( P<0.05). (5) The results of Western blot showed that there was a significant difference in hippocampal CREB protein expression among the three groups ( F=13.32, P<0.001).Compared with the control group, hippocampal CREB protein expression of mice in the olfactory bulbectomy group was significantly down-regulated(0.51±0.15, 1.45±0.61) ( P<0.05).Compared with the olfactory bulbectomy group, hippocampal CREB protein expression in the saikosaponin A group(0.97±0.09) was up-regulated( P<0.05). Conclusion:Saikosaponin A can significantly alleviate the depressive-like behaviors in olfactory bulbectomized mice, and its mechanism may be related to the up-regulation of CREB protein expression in the hippocampus.

Objective:To investigate the effect of saikosaponin A on depressive-like behaviors and hippocampal cyclic adenosine monophosphate response element-binding(CREB) protein expression in olfactory bulbectomized mice.Methods:Totally thirty male SPF-grade C57BL/6J mice, six weeks old, were randomly divided into 3 groups ( n=10 in each group): the control group, the olfactory bulbectomy group, and the saikosaponin A group.Olfactory bulbectomy was performed to damage the olfactory bulbs in the mice of bulbectomy group and saikosaponin A group, while the mice of control group only had a cranial drill hole at the same coordinates without damaging the olfactory bulbs. Mice in saikosaponin A group were administered saikosaponin A solution (dose: 5 mg/kg) via gavage, while mice in the control and olfactory bulbectomy groups were given the same volume of 0.9% NaCl solution once a day for 21 days. The depressive-related behavioral changes of mice in each group were evaluated by open field test, tail suspension test, forced swimming test, and weight measurement. The expression of CREB in the hippocampus of mice were detected by Western blot. Graphpad prism 5 software was used for data analysis.The data comparison among the multiple groups was conducted by one-way ANOVA and further pairwise comparisons were conducted by Tukey test. Results:(1) The results of weight measurement showed that there was no significant difference in body weight among the three groups( F=0.468, P=0.631) on the day of the olfactory bulbectomy surgery, but there was a statistically significant difference in body weight among the three groups ( F=37.340, P<0.001) on the 28th day after the olfactory bulbectomy.The body weight of mice in the olfactory bulbectomy group was lower than that of the control group ((24.09±1.01) g, (27.22±0.58)g)( P<0.05). The body weight of mice in the saikosaponin A group((26.23±0.83)g) was higher than that of the olfactory bulbectomy group( P<0.05). There was a statistically significant difference in body weight differences among the three groups of mice ( F=48.180, P<0.001). The body weight difference of mice in the olfactory bulbectomy group was lower than that of the control group ((2.34±0.96) g, (5.57±0.72) g) ( P<0.05). The body weight difference of mice in the saikosaponin A group was higher than that of the olfactory bulbectomy group ((4.74±0.56) g, (2.34±0.96) g) ( P<0.05).(2) The results of the open field test showed that there were statistically significant differences in the central area residence time and total activity distance in mice among the three groups ( F=27.03, 10.98, both P<0.001). The central area residence time ((13.87±4.59) s) and total activity distance ((35.67±4.88) m) of mice in the olfactory bulbectomy group were both less than those of the control group ((27.44±2.76) s, (59.02±16.21) m) (both P<0.05).The central area residence time ((21.77±4.78) s) and total activity distance ((52.33±10.41) m) of mice in the saikosaponin A group were both higher than those of the olfactory bulbectomy group(both P<0.05).(3) The results of tail suspension test showed that there was a statistically significant difference in immobility time among the three groups ( F=74.57, P<0.001). The immobility time of mice in the olfactory bulbectomy group was longer than that of the control group ((148.20±8.84)s, (97.89±8.64)s) ( P<0.05). The immobility time of mice in the saikosaponin A group((135.70±11.09)s) was less than that of the olfactory bulbectomy group( P<0.05). (4) The results of forced swimming test showed that there was a significant difference in immobility time among the three groups ( F=51.73, P<0.001). The immobility time of mice in the olfactory bulbectomy group was longer than that of the control group ((61.39±5.20) s, (40.80±4.30) s) ( P<0.05).The immobility time of mice in the saikosaponin A group((53.52±4.13)s) was less than that of the olfactory bulbectomy group( P<0.05). (5) The results of Western blot showed that there was a significant difference in hippocampal CREB protein expression among the three groups ( F=13.32, P<0.001).Compared with the control group, hippocampal CREB protein expression of mice in the olfactory bulbectomy group was significantly down-regulated(0.51±0.15, 1.45±0.61) ( P<0.05).Compared with the olfactory bulbectomy group, hippocampal CREB protein expression in the saikosaponin A group(0.97±0.09) was up-regulated( P<0.05). Conclusion:Saikosaponin A can significantly alleviate the depressive-like behaviors in olfactory bulbectomized mice, and its mechanism may be related to the up-regulation of CREB protein expression in the hippocampus.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

OBJECTIVE To study the effect of different proportion compatibility of Astragali Radix and Chuanxiong Rhizoma on the extraction kinetics of flavonoids. METHODS The content determination method of flavonoids(with rutin as the control substance) was established, and the concentrations of flavonoids in the extracts of Astragali Radix membranicum and Chuanxiong Rhizoma in different proportions(1∶1, 1∶2, 1∶3, 1∶4, 1∶5, 2∶1, 3∶1, 4∶1, 5∶1) were determined dynamically within 2 h, respectively. The extraction kinetics model was established according to Feck's first diffusion law. The extraction rate constant was calculated and the difference of dissolution kinetics was compared. RESULTS The compatibility of different proportions of Astragali Radix and Chuanxiong Rhizoma had significant effects on the extraction rate and concentration of flavonoids. The extraction kinetics models of flavonoids were consistent with the characteristics of the first-order kinetic equation. The extraction rate was the fastest when Astragali Radix ∶ Chuanxiong Rhizoma was 3∶1, the extraction rate was the slowest when Chuanxiong Rhizoma∶ Astragali Radix was 2∶1. The equilibrium concentration of flavonoids was the highest when Chuanxiong Rhizoma∶ Astragali Radix was 3∶1, when the ratio of Astragali Radix∶Chuanxiong Rhizoma was 5∶1, it was the lowest. CONCLUSION The compatibility of different proportions of Astragali Radix and Chuanxiong Rhizoma has a significant effect on the extraction rate and concentration of flavonoids.

Objective:To evaluate the efficacy and safety of modified Atkins diet (MAD) in treating global growth retardation (GDD).Methods:A prospective multicenter clinical controlled study was conducted.The children were included from 8 departments of children′s rehabilitation in Henan Province from July 2017 to October 2017.A total of 154 children who met the inclusion criteria were randomly assigned into the routine treatment group (88 cases) and MAD therapy group (66 cases). A total of 62 children in MAD therapy group and 59 children in routine treatment group completed the study for 15 months.The routine treatment group was provided comprehensive rehabilitation training, and the MAD therapy group was given MAD treatment on the basis of rehabilitation training.Two-way repeated-measures ANOVA was used to compare the differences among datas at different time points. Results:After 3 months, there were significant differences in the scores of the Chinese Version of Urban Infant-Toddler Social and Emotional Assessment (CITSEA)/Achenbach Children′s Behavior Scale (CBCL) between the 2 groups (all P<0.05). Significant improvement was seen in the MAD group.After 6 months, the MAD therapy group had significantly higher scores on the Gesell Developmental Scale for language and social behavior than the routine treatment group (all P<0.05). After 9 months, the scores of the children in the MAD therapy group were better than those in the routine treatment group in the Gesell Developmental Scale adaptive energy area and the infant-junior high school student social life scale (S-M scale), and the differences were statistically significant (all P<0.05). After 15 months, the fine motor in the MAD therapy group was better than that in the routine treatment group ( P<0.05). At the early stage of MAD therapy, 28 patients showed mild adverse reactions that were reversed after symptomatic treatment.No severe adverse reactions were observed. Conclusions:MAD therapy can improve the neuro-development, emotional and social behaviors, and adaptive behaviors with no severe adverse effects.

Objective To establish a method for the simultaneous determination of Forsythoside A, Phillyrin, (R,S)-Epigoitrin, Chlorgenic Acid and Isochlorogenic Acid A by HPLC, and test 16 batches of samples from 14 manufacturers. Methods The test was performed on Kinetex EVO C18 column (150 mm × 4.6 mm, 5 μm) with the column temperature at 35 ℃ . The gradient elution was adopted with the mobile phase of acetonitrile and 0.3% phosphoric acid aqucous at a flow rate of 1.0 ml/min. The detection wavelength of (R,S)-Epigoitrin and Phillyrin were set as 236 nm, the detection wavelength of Forsythoside A, Cholorogenic Acid and Isochlorogenic Acid A were set as 327 nm. Results The good linear relationships were displayed within the linear range of 0.050 45-2.018 00 μg for Forsythoside A (r=0.999 9), 0.018 21-0.728 40 μg for Phillyrin (r=0.999 9), 0.010 16-0.406 40 μg for (R,S)-Epigoitrin (r=0.999 9), 0.006 60-0.263 90 μg for Cholorogenic Acid (r=0.999 9) and 0.0040 44~0.161 76 μg for Isochlorogenic Acid A ( r=0.999 5). The RSDs of reproducibility and stability tests were lower than 2%; recoveries were 97.01%, 98.28%, 99.35% and 96.21%, RSD were 3.19%, 1.19%, 0.81%, 2.88% and 2.96%. The content ranges of Forsythoside A, Phillyrin, (R,S)-Epigoitrin, Chlorgenic Acid and Isochlorogenic Acid A from 16 batches of samples from 14 manufacturers were 0.057 43-1.508 71 mg/g, 0.017 72-0.350 15 mg/g, 0.005 68-0.177 13 mg/g, 0.007 53-0.226 33 mg/g and 0.00308-0.11908 mg/g. Conclusions The established method is simple and accurate, and has a good repeatability. It can be used for the quality analysis of Forsythoside A, Phillyrin, (R,S)-Epigoitrin, Chlorgenic Acid and Isochlorogenic Acid A. The content of the tested chemical components from 16 batches of samples from 14 manufacturers have significant differences which indicate that a reinforcement of the quality control is needed.

Objective: To optimize the preparation process for Haoqin-Huaban granules so as to provide experimental basis for the development and utilization of the compound. Methods: Taking the extraction rate of gentiopicroside from Gentiana macrophylla Pall as the observation index, L₉(3⁴)orthogonal test was used to investigate the amount of water, extraction time, and extraction frequency for optimizing the water extracting technology of the Haoqin-Huaban granules. Then the dry paste was used for the raw material, the ratio of the diluent (dextrin) and the concentration and dosage of the binder (ethanol) were investigated by single factor, and the particles were prepared. Results: The optimum water extraction process was A2B2C3, which indicated that the prescribed medicinal materials with 8 times water were extracted 1 h for 3 times. The extract was concentrated into paste, vacuum drying, pulverizing, mixing according to the ratio of 5:1, with ethanol, made of soft material, pelletizing, drying at 60 ℃ for granulation, in order to make Haoqin-Huaban granules. Conclusions The preparation process is reasonable and feasible, which provides experimental basis for the industrial production of Haoqin-Huaban granules.

Objective To investigate the distribution characteristics of the gut microbiome in infants with different delivery mode and feeding pattern at six weeks of life.Methods A total of 60 infants delivered between June and September in 2017 at Peking University First Hospital were recruited.According to delivery modes and feeding patterns,they were respectively divided into two groups,which were vaginal delivery (n=42)and cesarean delivery (n=18) groups,and exclusively breastfeeding (n=40) and mixed-feeding (n=20) groups.Stool samples of all subjects were collected at six weeks after birth.The V3-V4 region of 16s rRNA gene was sequenced on Illumina Hiseq 2500 platform,and the results were analyzed with SILVA database and QIIME software.Independent samples t-test or Mann-Whitney U test was used for statistical analysis.Results (1)Eight bacterial phyla and 146 genera were identified in the 60 stool samples.Firmicutes,Proteobacteria,Actinobacteria and Bacteroidetes were four dominant phyla,and Bifidobacterium,Clostridium,Klebsiella,Bacteroides,Streptococcus,Escherichia-Shigella,Veillonella and Faecalibacterium were the top eight most abundant genera.(2) At the phyla level,the vaginal delivery group was characterized with reduced Firmicutes (0.56 ± 0.1 0 vs 0.42± 0.20,t=2.94,P＜0.05) and increased Actinobacteria and Bacteroidetes [0.04 (0.01-0.11)vs 0.20 (0.05-0.36),U=223,P＜0.05;0.05 (0.01-0.23) vs 0.09 (0.02-0.29),U=315,P＜0.05] as compared with the cesarean delivery group.However,there was no significant difference in the four dominant phyla between exclusively breastfeeding and mixed-feeding groups (all P＞0.05).At the genus level,the relative abundance of Bifidobacterium was higher in the vaginal delivery group than in the cesarean delivery group [0.19 (0.02-0.36) vs 0.01 (0.00-0.07),U=210,P＜0.01].Similarly,there was no significant difference in the eight dominant genus between exclusively breastfeeding and mixed-feeding groups(all P＞0.05).(3) The vaginal delivery group showed significantly lower Shannon and Simpson indexes than the cesarean delivery group [4.26 (3.61-5.52) vs 5.48± 1.19,U=227,P＜0.05;0.86±0.08 vs 0.94 (0.92-0.97),U=194,P＜0.05],while no significance was found in operational taxonomic unit (OTU) number and Chaol index (all P＞0.05).However,there was no significant difference in OTU number,Chaol,Shannon or Simpson index between the exclusively breastfeeding and the mixed-feeding groups (all P＞0.05).Conclusion The early infancy is a critical period for the establishment of gut microbiome.Significant differences in the composition and diversity of gut microbiota are found between infants born vaginally and abdominally,but not in infants with different feeding patterns.