AIM To investigate the effects of different compatibility ratios and processing method on the content of rutin,isoquercetin,ferulic acid,quercetin,isotoosendanin,kaempferol,toosendanin,α-pinene,trans-anethole in the combination use of Toosendan Fructus and Foeniculi Fructus,and to explore the optimal compatibility ratio for its use.METHODS The analysis of HPLC-DAD was performed on a 30℃thermostatic ZORBAX SB C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the use of DAD detector.SPSS 24.0 software was used to analyze the data differences.RESULTS Nine constituents showed good linear relationships within their own ranges(r≥0.999 1),whose average recoveries were 96.19%-103.13%with the RSDs of 1.86%-2.67%.Generally higher total content of nine constituents were detected in the combination use groups when Toosendan Fructus-Foeniculi Fructus were at ratios of 1 ∶ 1,1 ∶ 2,and 2 ∶ 1 than those single uses(P<0.05),and among which the 1 ∶ 1 ratio contributed the highest total content.After salt processing,decreased content of toosendanin and isotoosendanin,α-pinene and trans-anethole(P<0.05,P<0.01)),increased isoquercetin content(P<0.01),and no significant content changes of other ingredients were detected.CONCLUSION Through this method of high accuracy and good reproducibility,we learn that the combination use of Toosendan Fructus and Foeniculi Fructus promotes the dissolution of the nine constituents,and the maximum content is achieved at ratio of 1 ∶ 1.

ObjectiveTo understand the physical development level of 3-7 years old children in Zhag′yab， and to provide reference for local health decision-making. MethodsA cross-sectional study was conducted between June 2021 and July 2021， with a sample of 1 247 Tibetan children aged 3-7 years from kindergartens in 13 districts of Zhag′yab. Their height and weight were measured and the hemoglobin was detected by a unified method. Standard statistical method was adopted （Z-score method）. Z-scores of length /height-for-age （HAZ）， Z-scores of weight-for-age （WAZ）， Z-scores of body mass index （BMI）-for-age （BAZ） and Z-scores of weight-for-height （WHZ） were calculated by WHO Anthro v3.2.2 and WHO Anthro Plus. The nutritional status of children was evaluated according to WHO diagnostic criteria for malnutrition and anemia. ResultsThe average WAZ and HAZ of children aged 3 to 7 in Zhag′yab were lower than the WHO standards，except for the WAZ of 4-year old， the differences were statistically significant （P<0.05）. The overall detection rate of malnutrition was 25.7%， stunting， underweight， wasting， overweight， obesity and anemia were 11.6%， 11.8%， 10.8%， 3.3%， 1.8% and 29.3%， respectively. The detection rates of all indicators in boys were higher than those in girls， and the differences were not statistically significant （P>0.05）. The overweight rate and obesity rate of rural children were lower than those of urban children， and the other detection rates were higher than those of urban children. The differences of underweight rate， obesity rate and anemia rate were statistically significant between urban and rural children （P<0.05）. Among the detection rates of all indicators in different age groups， there were statistically significant differences in the overweight rate and the anemia rate （P<0.05）. The overweight rate of children aged 4 and the anemia rate of children aged 5 were the highest. ConclusionsThe physical development of children aged 3 to 7 in Zhag′yab is poor， and the prevalence of malnutrition and anemia is high. Underweight and anemia are more serious in rural children， and the overweight and obesity problem of urban children is emerging. More attention should be paid to promote their nutritional status. The prevention and intervention of children’s malnutrition should be strengthened in Zhag′yab.

ObjectiveTo analyze the changes of serum levels of free triiodothyronine （FT3）， free thyroxin （FT4） and thyroid-stimulating hormone （TSH） in 3~21-day-old preterm infants born between 28 and 36 weeks of gestation. MethodsWe retrospectively reviewed the clinical data of 236 preterm infants born at 28~36 weeks of gestation in the third affiliated hospital of Sun Yat-sen university between July 2018 and June 2019. The clinical data included thyroid function parameters （FT3， FT4， TSH）， gestational age， gender， birth weight， birth length， time of examination， mode of conception， singleton or multiple birth， maternal thyroid disease and maternal gestational diabetes mellitus （GDM）. FT3， FT4 and TSH levels between 3~7-day-old and 8~21-day-old preterm infants were compared. Multiple linear regression models were used to identify the independent factors affecting FT3， FT4 and TSH levels. FT3 and FT4 levels in different gestational age groups were compared. ResultsCompared with those in 8~21-day-old preterm infants， in 3~7-day-old preterm infants， FT3 levels were significantly lower ［（3.23±0.54） pmol/L vs. （3.41±0.76） pmol/L， P=0.040］ and FT4 levels were significantly higher ［（15.36±3.40） pmol/L vs. （13.20±2.63） pmol/L， P＜0.001）］. No statistical difference was found in TSH levels. （P=0.846）. In 3~7-day-old preterm infants， FT3 levels were associated with gestational age （P < 0.001）； FT4 levels were associated with gestational age and time of examination （P < 0.001）. In 8~21-day-old preterm infants， both FT3 and FT4 levels were associated with gestational age and gender （P < 0.001， P < 0.001）. FT3 and FT4 were positively correlated with gestational age in both groups （P < 0.001， P < 0.001； P < 0.001， P = 0.001）. ConclusionGestational age affects the thyroid function of the preterm infants of 3~21 days. The younger the gestational age， the lower FT3 and FT4 levels. A reference range of FT4 or T4 related to gestational age should be established， combined with TSH， to evaluate the thyroid function in preterm infants.

【Objective】 To guide the nutritional intervention of children in the clinical practice ，by exploring the effect of over-nutrition in postnatal life on growth of the female SD rats.【Methods】We established the rat model of intra? uterine growth retardation（IUGR）through diet restriction in pregnant rats and selected female newborn rats that met the criteria as the experimental group（group I）. Group I was randomly divided into control group（group IC）and small group（group IS）. Fifty-eight female newborn rats with normal diet in pregnant period（group C）were also divided into control group（group CC）and small group（group CS）. After 21-days-lactation，group IC and group CC were randomly subdivided into 4 rats per cage，and then fed with normal diet，while group IS and group CS were fed with high fat diet. We measured the body weight and the body length of each rat every week. Serum fasting insulin，fasting blood glucose，IGF-1，IGF- BP3 levels，and rat insulin sensitivity index（ISI）were measured at different growth and development stages.【Results】 The body weight and body length of group IS were higher than those of group IC（P<0.05）；the same was true for group CS and group CC. In the different growth and development stages，the FINS，FBG，IGF- 1 and IGF- BP3 of group IS were higher than those of group IC（P < 0.05），the ISI was lower than that of group IC（P < 0.05）. Besides，the FINS，FBG of group CS were higher than those of group CC and the ISI of group CS was lower than that of group CC in the 75 days after birth（P < 0.05）.【Conclusions】We found that those small for gestational age infants can be added nutrition appropriately for rapid catch-up，but it is necessary to evaluate the growth index closely and adjust the nutrition on time. Children with normal intrauterine development also need to prevent over-nutrition.

Glioblastoma is a common brain tumor and the overall survival rate of the patients is very low, so it is an effective way to develop the potential chemotherapy or adjuvant chemotherapy drugs in glioblastoma treatment. As a well-known antimalarial drug, artesunate(ARTs) has clear side effects, and recently it has been reported to have antitumor effects, but rarely reported in glioblastoma. Different concentrations of ARTs were used to treat the glioblastoma cells, and then the inhibitory effect of ARTs on glioblastoma proliferation was detected by MTT assay; Ki67 immunofluorescence assay was used to detect the proliferation of cells; Soft agar experiment was used to explain the clonal formation abilities ; Flow Cytometry was used to detect the cell cycle; and Western blot assay was used to determine the expression of key cell cycle protein. MTT assay results indicated that ARTs-treated glioblastoma cell A172, U251, U87 were significantly inhibited in a time-and-dose dependent manner as compared to the control group(DMSO treatment group). Soft agar experiment showed that ARTs could significantly reduce the clonal formation ability of glioblastoma. Furthermore, Flow cytometry analysis showed that ARTs could obviously increase the cell proportion in G₀/G₁ phase and reduce the cell proportion in S phase. Western blot results showed that the expressions of cell cycle-related proteins CDK2, CDK4, cyclin D1 and cyclin B1 were all obviously down-regulated. Above all, ARTs may inhibit the proliferation of glioblastoma cells by arresting cell cycle in G₀/G₁ phase through down-regulating the expression of CDK2, CDK4, cyclin D1, cyclin B1. These results may not only provide a novel method for rediscovering and reusing ARTs but also provide a new potential drug for treating glioblastoma.
Antineoplastic Agents ; pharmacology ; Apoptosis ; Artesunate ; pharmacology ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin B1 ; metabolism ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 2 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Glioblastoma ; drug therapy ; pathology ; Humans

Objective To investigate the effect of reducing blood lipid in three effective parts of Rheum palmatum L.based on variation coefficient weight.Methods First of all,the SD rat model of hyperlipidemia was given the water extract,the ethanol extract and the ethyl acetate extract of Rheum palmatum L.,then the content of total cholesterol (TC),high densitylipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),triglyceride (TG) in serum were determined and general survival of rats was analyzed.Then using fuzzy matter-element model on variation coefficient weight to evaluate the comprehensive reducing blood lipid effect of different extract parts of Rheum palmatum L..In the end,combining with the result of the value of Euclid approach degree,compared the effect of normal group (M1),the model group (M2),the positive control group (Xuezhikang,M3),the water extract group(M4),the ethanol extract group (M5),the ethyl acetate extract group (M6) of blood lipid.Results Compared with model group,the water extract part and the ethanol extract part of Rheum palmatum L.could reduce the congtents of TC,LDL-C,TG and rise HDL-C.Combining with the result of the value of Euclid approach degree,the water extract was 0.74,the ethanol extract was 0.54.Combining with the result of the value of Euclid approach degree,the order of its magniude is M3 ＞ M4 ＞ M1 ＞ M5 ＞ M6 ＞ M2.Conclusion The water extract part is the effective part of reducing blood lipid.The method and model can be used to objectively evaluate the comprehensive effect of reducing blood lipid of Rheum palmatum L.'s three extracted parts.

Objective To screen the effective parts of loosening bowel and relieving constipation in mice from different extracted parts of Angelica and to investigate the utilization of fuzzy matter-element model in evaluating the effect of moisturizing intestine to relaxing the bowels of Angelica's different extracted parts.Methods Kunming mice were randomly divided into 11 groups,including normal group,model group (constipation),positive control group (Nongsuo Danggui Wan and Runchang Wan:20 μL · g-1),medicated group consisted by 7 different extracted parts of Angelica (3.4 g · kg-1 Angelica herbs).The constipation model was formed by the compound difenoxate solution 5.0 mg · kg-1 and finished after 30 min.We used the first defecation time as well as the dark stool points in 6 h,the weight of stools,the pushing rate of intestine and intestinal moisture as detection index and then using fuzzy matter-element model on variation coefficient weight to evaluate the comprehensive effect of different extract parts of Angelica.Results Time of first black stool discharge as well as the dark stool points in 6 h,the weight of stools,the pushing rate of intestine and intestinal moisture in model group were (241.90 ± 48.10) min,(9.00 ± 5.40) count,(149.10 ± 86.80) mg,(48.90 ± 16.50) ％,(1.45 ± 0.16) g,respectively.The 70％ ethanol impregnation part (part 2) on the factors were (172.60 ± 40.70) min,(17.30 ± 4.50) count,(223.70 ± 63.40) mg,(73.70 ± 13.10) ％,(1.71 ± 0.18) g,respectively.The difference between part 2 and model group was statistically significant in the factors (P ＜0.05 or P ＜0.01).Combining with the result of the value of Euclid approach degree,the maximum is 0.71 (part 2:70％ alcohol impregnation part).Conclusion The 70％ alcohol impregnation part is the effective part of loosening bowel to relieve constipation in mice.The method and model can be used to objectively evaluate the effect of moisturizing intestine to relaxing the bowels of Angelica' s different extracted parts.

Objective To select the effective parts of blood nourishing and to investigate the utilization of fuzzy matter-element model in evaluating the effect of blood nourishing of Angelica's different extracted parts.Methods KM mice half males and half females were randomly divided into 10 groups,including blank control group,model group (blood-deficiency),positive control group (Complex Prescription Glue Mucilage:0.02 mL· g-1),experimental group consisted by 7 different extracted parts of Angelica (3.4 g kg-1 Angelica herbs) Acetylphenyhydrazine (APH) and cyclophosphamide (CTX) were used to copy the blood-deficiency model mice by administration APH at the second day (20 mg · kg-1) and the fifth day (40 mg · kg-1) respectively,since the fifth day,ip CTX 40 mg · kg-1 everyday,once a day for four days.Periphera hemogram and organ index,including thymus index (TI),spleen index (SI),were detected at the 10th day.Then using Fuzzy Matter-element model on variation coefficient weight.Results The TI,SI,red blood cell (RBC),platelet count(PLT),hematokrit (HCT),hemoglobin (HGB),white blood cell (WBC) were (7.70 ± 1.81) × 10-2,(56.90 ± 12.23) × 10-2,8.44 ± 1.59,1453.10 ± 102.50,56.54 ± 6.69,170.00 ± 26.39,2.10 ± 0.49,respectively in model group.The 70％ ethanol impregnation part (part 2) for TI,SI,RBC,PLT,HCT,HGB,WBC were 0.10 ± 2.66 ×10-2,(33.83 ±8.97) × 10-2,11.94 ±2.07,1749.60 ±211.50,55.53 ±9.42,55.53 ±9.42,2.60 ± 0.47,respectively.The part 2 can increase TI,RBC,PLT,HCT,WBC and reduce SI,HGB.Compared with model group,the difference was statistically significant in SI,RBC,PLT,HCT,WBC (P ＜ 0.05 or P ＜ 0.001).There were no significant differences between part 1 and part 2 (P ＞ 0.05).Combining with the result of the value of Euclid approach degree,in part 1-7,the maximum is 0.50 (part 2),is greater than 0.40 (part 1).Conclusion The 70％ alcohol impregnation part is the effective part of blood nourishing.The method and model can be used to objectively evaluate the comprehensive effect of blood nourishing of Angelica's different extracted parts.

To study pharmacokinetic characteristics of epimedin A, B, C and icariin after intermuscular administration of Chuankezhi injection to rat. The established RRLC-MS/MS method was applied for simultaneous determination of four analytes in rat plasma and calculating their pharmacokinetic parameters. As a result, each analyte showed a good linear relationship in the concentration range of 1-1 000 μg•L⁻¹.The intra-day precise was 96.9%-107.5% with RSD<5.99%, inter-day precise was 92.3%-105.0% with RSD<10.16%. The relative recovery of four analytes was 88.1%-101.1% with RSD<7.9% and their absolute recovery was 72.0%-86.6% with RSD<6.3%. After intermuscular administration of Chuankezhi injection, the plasma concentration of four flavonoid glycosides rapidly arose to peaks at about 10 min, and then quickly declined in rat. Tmax of epimedin A, B, C and icariin was 0.21, 0.19, 0.16 and 0.49 h, respectively, and their mean elimination half-life(t1/2z) was 0.60, 0.62, 0.47 and 0.49 h. The established method was validated to be sensitive, rapid and specific for determination of the four analytes. Serum concentration of 4 species of epimedium flavonoids in Chuankezhi injection was low, and their absorption and elimination seem quickly, displaying similar pharmacokinetic characteristics in this study.

A quantitative method for epimedin A, B, C and icariin in rat plasma was established using LC-MS/MS after intermuscular administration of Chuankezhi injection to rat. Chromatographic separation was performed on an Agilent Eclipse XDB-C₁₈ column (150 mm×2.1 mm, 5.0 μm) at 40℃. Mobile phase consisted of acetonitrile -0.1% formic acid in water (35:65), and the flow rate was 0.22 mL·min^-1. The LC effluent was detected and analyzed using an ESI-triple quadrupole tandem mass spectrometer under the multiple reaction monitoring (MRM) in the negative ion mode. The plasma samples were treated with solid phase extraction prior to LC-MS/MS analysis. As a result, all of the four analytes displayed a good linearity over the concentration of 1-1000 ng·mL^-1. The RSDs of intra-day and inter-day assays were less than 5.99% and 10.16%, respectively. The relative recovery of each analyte was between 88.1%-101.1% with RSD<7.9% and the absolute recovery was between 72.0%-86.6% (RSD<6.3%). In conclusion, the established method shows good specificity, sensitivity and efficiency for quantifying the four flavonoid glycosides contained in rat plasma.