Effects of Shaoyao gancao decoction on intestinal flora in rats with acute lung injury / 中国药房

OBJECTIVE To study the improvement effects of Shaoyao gancao decoction （SGD） on acute lung injury （ALI） in rats and its effects on the intestinal flora. METHODS Sixty SD rats were randomly divided into normal group （CON group， normal saline）， model group （MOD group， normal saline）， positive control group （DEX group， 5 mg/kg dexamethasone）， SGD low-dose， medium-dose and high-dose groups （SGD-L， SGD-M， SGD-H groups， 5.8， 11.6， 23.2 g/kg， calculated by crude drug）， with 10 rats in each group. Each group was given relevant medicine 10 mL/kg intragastrically， for 7 consecutive days. Thirty minutes after the last administration， CON group was given constant volume of normal saline via airway infusion， and other groups were given lipopolysaccharide （5 mg/kg） via airway infusion to induce ALI model. After 12 hours of modeling， the lung tissue wet/dry weight ratio was calculated， and the contents of interleukin 1β （IL-1β）， IL-6 and tumor necrosis factor α（TNF-α） in rat bronchial alveolar lavage fluid （BALF） were all detected； the pathological changes of lung tissue were observed after hematoxylin-eosin staining. The intestinal flora of rat feces was analyzed by 16S rRNA sequencing technology， and the correlation of differential bacteria genera with inflammatory factors was also analyzed. RESULTS Compared with MOD group， the infiltration of inflammatory cells in the lung tissue of rats in each SGD dose group was decreased， and the thickening of alveolar septum and pulmonary edema improved； lung tissue wet/dry weight ratio， the levels of IL-1β， IL-6 and TNF-α in BALF significantly decreased （P＜0.05 or P＜0.01）. SGD （low dose） could improve the intestinal flora disorder in ALI rats， restore the diversity and richness of intestinal flora， regulate the structure of flora， reduce the abundance of Lactobacillus， Streptococcus and Escherichia-Shigella， and increase the abundance of Firmicutes， Lachnospira， Ruminococcus， Clostridia，Dubosiella and Akkermansia. Through correlation analysis， it was found that the relative abundance of Lactobacillus， Streptococcus and Escherichia-Shigella was positively related to the levels of inflammatory factor IL-1β， IL-6 and TNF-α （P＜0.05 or P＜0.01）. The relative abundance of Lachnospira， Dubosiella， Firmicutes was significantly negatively correlated with the levels of inflammatory factors mentioned above （P＜0.05 or P＜0.01）. CONCLUSIONS SGD may improve ALI by reducing lung tissue injury and inflammatory response and regulating flora structure in rats.

Association of periconceptional folate supplements and FOLR1 and FOLR2 gene polymorphisms with risk of congenital heart disease in offspring: A hospital-based case-control study / 中南大学学报(医学版)

OBJECTIVES@#Maternal periconceptional folic acid supplement is by far the most effective primary prevention strategy to reduce the incidence of congenital heart disease (CHD) in offspring. It was revealed that the underlying mechanisms are complex, including a combination of genetic and environmental factors. The purpose of this study is to investigate the association between periconceptional folic acid supplement, the genetic polymorphisms of maternal folic acid receptor 1 gene (FOLR1) and folic acid receptor 2 gene (FOLR2) and the impact of their interaction on the risk of CHD in offspring, and to provide epidemiological evidence for individualized folic acid dosing in hygienic counseling.@*METHODS@#A case-control study on 569 mothers of CHD infants and 652 mothers of health controls was performed. The interesting points were periconceptional folate supplements, single nucleotide polymorphisms (SNPs) of maternal FOLR1 gene and FOLR2 gene.@*RESULTS@#Mothers who took folate in the periconceptional period were observed a decreased risk of CHD [adjusted odds ratio (aOR)=0.58, 95% CI 0.35 to 0.95]. Our study also found that polymorphisms of maternal FOLR1 gene at rs2071010 (G/A vs G/G: aOR=0.67, 95% CI 0.47 to 0.96) and FOLR2 gene at rs514933 (T/C vs T/T: aOR=0.60, 95% CI 0.43 to 0.84; C/C vs T/T: aOR=0.55, 95% CI 0.33 to 0.90; the dominant model: T/C+ C/C vs T/T: aOR=0.59, 95% CI 0.43 to 0.81; and the addictive model: C/C vs T/C vs T/T: aOR=0.70, 95% CI 0.56 to 0.88) were significantly associated with lower risk of CHD [all P<0.05, false discovery rate P value (FDR_P)<0.1]. Besides, significant interaction between periconceptional folate supplements and rs2071010 G→A (aOR=0.59, 95% CI 0.41-0.86) and rs514933 T→C (aOR=0.52, 95% CI 0.37 to 0.74) on CHD risk were observed (all P<0.05, FDR_P<0.1).@*CONCLUSIONS@#Periconceptional folate supplements, polymorphisms of FOLR1 gene and FOLR2 gene and their interactions are significantly associated with risk of CHD. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.

Study on the Preparation of Brucine Bilayer Polymer Soluble Microneedle and Its in vitro Transdermal Perme- ability under Different Drug Loading Modes / 中国药房

OBJECTIVE：To prepare Brucine （shorted for “Bru”）bilayer polymer soluble microneedles ，and to investigate their in vitro transdermal permeation characteristics under different drug loading modes. METHODS ：Taking the degree of difficulty of microneedle film uncovering ，array integrity ，bubble amount ，needle shape ，tip hardness and backing toughness as the indexes ， tip and backing materials were screened. The swelling method and drying method of matrix were screened using the morphology of microneedles as index. The double-layer polymer soluble microneedle was prepared by two-step method ，then it was characterized and evaluated in the safety. The in vitro transdermal permeation characteristics of tip-loaded ，backing-loaded and full-loaded Bru bilayer polymer soluble microneedles were investigated by Franz diffusion cell. The in vitro skin penetration curve was drawn ，and the cumulative permeability amount （Q）and cumulative permeability rate were calculated. RESULTS ：The optimal preparation technology of bilayer polymer soluble microneedles included chondroitin sulfate （CS）and polyvinylpyrrolidone K 30（PVP K 30） （1∶1，m/m）as tip materials ，15％ polyvinyl alcohol （PVA）as backing material ，matrix swelling in the refrigerator at 4 ℃ for 1 h，and drying at room temperature for 24 h in dryer. Prepared microneedle array was complete and had good mechanical properties，and could successfully puncture aluminum foil and rat skin. After microneedle treatment ，the skin could return to its original state within 6 h. The results of in vitro transdermal test showed that microneedle drug delivery could greatly increase the cumulative transdermal permeability amount of GNYL Bru，and the tip material could dissolve and release the drug within 10 min； the tip-loaded microneedle was basically released within 8 h，Q8h was 102.185 μg/cm2 and the cumulative permeability rate reached 94.05％ ； the drug cumulativepermeability rate of backing-loaded and full-loaded microneedlesexceeded 50％ within 8 h and exceeded 90％ within 48 h；Q48h were 840.77 and 1 156.73 μg/cm2，showing sustained-release characteristics. CONCLUSIONS ：Bru bilayer polymer soluble microneedles with hard tip and tough backing material are successfully prepared to achieve effective transdermal delivery and sustained release through full-loaded mode.

Preparation and Quality Evaluation of Breviscapine Gastric Adhesive Tablets / 中国药房

OBJECTIVE：To prepar e Breviscapine gastric adhesive tablets ，to optimize the formulation and to evaluate the quality. METHODS ：HPMC K 100M and carbomer 934P were used as bioadhesives and skeleton materials ，and lactose was used as filler，and magnesium stearate was used as glidant and lubricant to prepare Breviscapine gastric adhesive tablets by direct powder pressing method. The comprehensive scores of scores of accumulative release rate of Breviscapine gastric adhesive tablets in pH 6.8 PBS at 2，6，12 h（Q2 h，Q6 h，Q12 h，with scutellarin meter ，by HPLC method ）and in vitro adhesion force of gastric tissue were evaluated by weighting method. Taking this scores as indexes，L9（34）orthogonal test design was used to optimize the amount of HPMC K 100M，carbomer 934P and lactose in Breviscapine gastric adhesive tablets and validation tests were conducted. The properties，identification，weight difference ，fragility，release and the content of scutellarin of the gastric adhesive tablets were determined. RESULTS ：The optimal prescription of Breviscapine gastric adhesive tablets were 42％ breviscapine，10％ HPMC K100M，3％ carbomer 934P and 45％ lactose. The verification test results show that the Q2 h，Q6 h，Q12 h of 3 batches of Breviscapine gastric adhesive tablets were 20.36％，48.55％，and 87.00％ ；the average in vitro adhesion force of gastric tissue was 31.36 g/cm2；the average comprehensive score was 70.23（RSD＝1.84％，n＝3）. The gastric adhesive tablets were light yellow，tasteless or slightly salty ；the peak time was consistent with that of scutellarin control ；its weight difference were ±6％， the fragility was 0.54％，and the Q12 h was 83.51％（RSD＝2.14％，n＝6）. The content of scutellarin was 288.47 mg/g（RSD＝ 0.70％，n＝3）. CONCLUSIONS ：Breviscapine gastric adhesive tablets is prepared successfully ，and its quality evaluation conforms to the requirements of Chinese Pharmacopoeia （2015 edition）.

Effects of Gegenqinlian Colon Positioning Tablet on Colon Tissue PPAR-γ,NF-κB p65 Protein Expressions of Model Rabbits with Damp-heat Type Ulcerative Colitis / 中国药房

OBJECTIVE:To observe the effects of Gegenqinlian colon positioning tablet(GGQLJC)on colon tissue PPAR-γ, NF-κB p65 protein expressions of model rabbits with damp-heat type ulcerative colitis(UC). METHODS:56 rabbits were random-ly divided into normal group(normal saline),model group(normal saline),sulfasalazine tablet(SASP)group(positive control, 0.300 g/kg),Gegenqinlian tablet (GGQL) group (0.225 g/kg) and GGQLJC high-dose,medium-dose,low-dose groups (1.036, 0.518,0.259 g/kg),8 in each group. Except for normal group,rabbits in other groups were cultured for damp-heat-type UC mod-el,intragastrically administrated in the second day of last administration,once a day,for 14 d. Disease activity index(DAI),co-lonic mucosal damage index (CMDI),histological damage (TDI) were scored;colon,spleen and thymus indexes were deter-mined;PPAR-γ,NF-κB p65 protein expressions in colon tissue were detected. RESULTS:Compared with normal group,DAI, CMDI,TDI scores and spleen index,colon index,NF-κB p65 protein level in colon tissue in model group were significantly in-creased(P<0.01);thymus index,PPAR-γprotein level in colon tissue were significantly reduced(P<0.01). Compared with mod-el group,above-mentioned indexes in each administration group were significantly improved (P<0.05 or P<0.01). Compared with GGQL group,DAI and TDI scores,spleen index,colon index,NF-κB p65 protein level in colon tissue in SASP group, GGQLJC high-dose,medium-dose groups were significantly decreased (P<0.05);PPAR-γ protein level in colon tissue in SASP group,GGQLJC high-dose,medium-dose groups were significantly increased (P<0.05 or P<0.01). CONCLUSIONS:GGQLJC has certain improvement effects on model rabbits with damp-heat type UC,which is superior to GGQL. The mechanism may be re-lated to increasing PPAR-γprotein level and decreasing NF-κB p65 protein level in colon tissue.