ObjectiveTo explore the impact of Gegen Qinliantang（GQT） on the fecal short-chain fatty acids（SCFAs） metabolism in antibiotic-associated diarrhea（AAD） through targeted metabolomics. MethodA total of 240 SD rats were randomly divided into six groups（n=40， half male and half female）， including blank group， model group， bifidobiogen group（0.15 g·kg^-1）， and GQT high-， medium-， and low-dose groups（10.08， 5.04， 2.52 g·kg^-1）， except for the blank group， clindamycin（250 mg·kg^-1） was given to all groups by gavage for modeling every day for 7 d. After successful modeling， each administered group was gavaged with the corresponding dose of the drug， and the blank and model groups were gavaged with an equal volume of normal saline solution， 1 time/d， for 14 d. At 0， 3， 7， 14 d after the drug intervention， eight rats were randomly selected from each group， respectively. Gas chromatography-time-of-flight mass spectrometry（GC-TOF-MS） was used to perform targeted metabolomic analysis of SCFAs in the feces of rats， and partial least squares-discriminant analysis（PLS-DA） was applied to compare the differences in metabolic profiles between groups at different treatment times， and to compare the changes in the contents of SCFAs in rat feces between groups. ResultPLS-DA results showed that the blank group could be clearly distinguishable from the model group， with GQT exhibiting a closer proximity to the blank group after 7 d of treatment. After further analyzing the composition of SCFAs， it was found that the proportion of acetic acid increased and the proportions of butyric acid， valeric acid， hexanoic acid and isovaleric acid decreased in the model group compared with the blank group. After the treatment with GQT， the proportions of butyric acid， isobutyric acid， valeric acid， and isovaleric acid increased， and the proportions of acetic acid， propionic acid and caproic acid decreased. Subsequent differential analysis revealed that GQT could significantly improve the content of butyric acid， and had a certain retrogressive effect on the contents of valeric acid and hexanoic acid. ConclusionThe medium dose group of GQT can improve the contents of SCFAs in AAD feces after 7 days of treatment， which may be related to the improvement of the composition ratio of SCFAs and the contents of butyric acid， valeric acid and caproic acid.

Objective To investigate the therapeutic mechanism of Tujia medicine Toddalia asiatica alcohol extract(TAAE)for synovial pannus formation in rats with college-induced arthritis(CIA).Methods Sixty male SD rats were randomized into normal control group,CIA model group,TGT group,3 TAAE treatment groups at low,medium and high doses(n=10).Except for those in the normal control group,all the rats were subjected to CIA modeling using a secondary immunization method and treatment with saline,TGT or TAAE by gavage once daily for 35 days.The severity of arthritis was assessed using arthritis index(AI)score,and knee joint synovium pathologies were examined with HE staining.Serum levels of TNF-α,IL-6,and IL-1β were detected with ELISA;the protein expressions of PI3K,Akt,p-PI3K,p-Akt,VEGF,endostatin,HIF-1α,MMP1,MMP3,and MMP9 in knee joint synovial tissues were determined using Western blotting,and the mRNA expressions of TNF-α,IL-6,IL-1β,VEGF,HIF-1α,PI3K,and Akt were detected with RT-PCR.Results Treatment of CIA rat models with TAAE and TGT significantly alleviated paw swelling,lowered AI scores,and reduced knee joint pathology,neoangiogenesis,and serum levels of inflammatory factors.TAAE treatment obviously increased endostatin protein expression,downregulated p-PI3K,p-Akt,MMP1,MMP3,MMP9,VEGF,and HIF-1α proteins,and reduced TNF-α,IL-6,IL-1β,PI3K,Akt,VEGF,and HIF-1α mRNA levels in the synovial tissues,and these changes were comparable between high-dose TAAE group and TGT group.Conclusion TAAE can improve joint symptoms and inhibit synovial pannus formation in CIA rats by regulating the expressions of HIF-1α,VEGF,endostatin,MMP1,MMP3,and MMP9 via the PI3K/Akt signalling pathway.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective To investigate the therapeutic mechanism of Tujia medicine Toddalia asiatica alcohol extract(TAAE)for synovial pannus formation in rats with college-induced arthritis(CIA).Methods Sixty male SD rats were randomized into normal control group,CIA model group,TGT group,3 TAAE treatment groups at low,medium and high doses(n=10).Except for those in the normal control group,all the rats were subjected to CIA modeling using a secondary immunization method and treatment with saline,TGT or TAAE by gavage once daily for 35 days.The severity of arthritis was assessed using arthritis index(AI)score,and knee joint synovium pathologies were examined with HE staining.Serum levels of TNF-α,IL-6,and IL-1β were detected with ELISA;the protein expressions of PI3K,Akt,p-PI3K,p-Akt,VEGF,endostatin,HIF-1α,MMP1,MMP3,and MMP9 in knee joint synovial tissues were determined using Western blotting,and the mRNA expressions of TNF-α,IL-6,IL-1β,VEGF,HIF-1α,PI3K,and Akt were detected with RT-PCR.Results Treatment of CIA rat models with TAAE and TGT significantly alleviated paw swelling,lowered AI scores,and reduced knee joint pathology,neoangiogenesis,and serum levels of inflammatory factors.TAAE treatment obviously increased endostatin protein expression,downregulated p-PI3K,p-Akt,MMP1,MMP3,MMP9,VEGF,and HIF-1α proteins,and reduced TNF-α,IL-6,IL-1β,PI3K,Akt,VEGF,and HIF-1α mRNA levels in the synovial tissues,and these changes were comparable between high-dose TAAE group and TGT group.Conclusion TAAE can improve joint symptoms and inhibit synovial pannus formation in CIA rats by regulating the expressions of HIF-1α,VEGF,endostatin,MMP1,MMP3,and MMP9 via the PI3K/Akt signalling pathway.

ObjectiveTo investigate the mechanism of Gegen Qinliantang（GQT） on the intestinal flora of antibiotic-associated diarrhea（AAD） by 16S rRNA sequencing and network pharmacology. MethodSixty SD rats were randomly divided into six groups（n=10）， including blank group， model group， GQT high-， medium- and low-dose groups（10.08， 5.04， 2.52 g·kg^-1） as well as Lizhu Changle group（0.15 g·kg^-1）， except for the blank group， each group was given clindamycin（250 mg·kg^-1） by gavage once a day for 7 consecutive days. After successful modeling， the blank group and the model group were given equal volumes of normal saline by gavage. The other groups were given corresponding doses of drugs by gavage for 14 days. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） was used to screen the active components and targets of GQT， GeneCards， Online Mendelian Inheritance in Man（OMIM） database， Pharmacogenetics and Pharmacogenomics Knowledge Base（PharmGKB）， DrugBank and DisGeNET were used to search for AAD disease targets. The drug-disease common targets were obtained by R software. STRING was applied to analyze the target protein-protein interaction， and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis was performed. Then hematoxylin-eosin（HE） staining was used to observe the pathological changes of the colon， and 16S rRNA sequencing of AAD colon content flora structure further verified the results of network pharmacology. ResultThrough network pharmacology， it was found that 238 active components were screened from GQT and acted on 276 component targets， among which quercetin， puerarin， wogonin and apigenin were the main core components of GQT， 1 097 AAD disease targets and 127 drug-disease intersection targets. The protein-protein interaction network mainly included core targets such as protein kinase B1（Akt1）， interleukin（IL）-6 and IL-1β， which were mainly enriched in the IL-17 signaling pathway. It was verified through animal experiments that compared with the blank group， the colon structure of the model group was seriously abnormal， the intestinal epithelial columnar cells were damaged， the goblet cells were reduced， and a large number of inflammatory cells were infiltrated. Compared with the model group， the colon structure of the GQT high-dose group improved， but there were still abnormalities， the colon structure of GQT medium- and low- dose groups and Lizhu Changle group improved significantly and reached the normal level. GQT could improve the structural diversity of AAD intestinal flora. At the phylum level， the abundance of Firmicutes was increased and the abundance of Bacteroidetes was decreased. At the genus level， the abundance of Lactobacillus was increased， and the abundances of Prevotella and Bacteroides were decreased. Among them， Lactococcus could be used as a biomarker for AAD treatment with GQT， and the prediction of functional metabolism of intestinal flora revealed that GQT could promote acetate and lactate metabolic pathways in the intestine. ConclusionGQT may activate IL-17 signaling pathway by acting on the targets of Akt1 and IL-6 through key components such as quercetin and wogonin， and improve the abundance of Lactococcus in the intestinal tract as well as acetate and lactate metabolic pathways， so as to play a role in repairing the intestinal barrier for the treatment of AAD.

Objective:To study the risk factors of necrotizing enterocolitis (NEC) after surgery for intestinal atresia.Method:From August 2013 to June 2020, children with intestinal atresia receiving surgery in our hospital were retrospectively reviewed. The patients were assigned into NEC group and non-NEC group according to the occurrence of postoperative NEC. Demographic data and clinical characteristics were summarized and the risk factors for postoperative NEC were analyzed using Logistic regression analysis method.Result:A total of 96 infants were enrolled and NEC occurred in 13 patients (13.5%) after surgery for intestinal atresia. Compared with the non-NEC group, the NEC group were diagnosed of intestinal atresia [4.0(1.5,6.0)d vs. 1.4(0,2.0)d, P<0.001] and received surgery [4.8(2.0,7.0)d vs. 3.1(1.0,4.0)d, P=0.034] at later ages. The incidences of complex intestinal atresia [76.9%(10/13) vs. 44.6%(37/83), P=0.030] and blood transfusion [46.2%(6/13) vs. 13.3%(11/83), P=0.007] in the NEC group were higher than the non-NEC group. Logistic regression analysis showed that the age of initial diagnosis of intestinal atresia ( OR=3.346, 95% CI 1.493~7.500, P=0.003), complex intestinal atresia ( OR=9.052, 95% CI 1.119~73.209, P=0.039) and blood transfusion ( OR=6.835, 95% CI 1.399~33.380, P=0.018) were independent risk factors for postoperative NEC. Conclusion:Patients with delayed diagnosis of intestinal atresia, complex intestinal atresia and blood transfusion within 48 hours after surgery should be monitored for the occurrence of postoperative NEC.

Objective:To investigate the effects of Huang-Lian-Jie-Du-Decotion containing serum for the autophagy of RAM264.7 macrophages ,and to explore its possible anti-atherosclerosis mechanism .Methods:The SD rats were intervened with large , middle and small dose Huang-Lian-Jie-Du-Decotion to prepare containing drug serum .Cell proliferation was tested by MTT assay .The gene and protein expressions of Beclin 1, mTOR was assessed by fluorescent quantitative PCR and Western blot method .Results:Compared with the normal serum group ,Huang-Lian-Jie-Du-Decotion containing serum enhanced expression of the mRNA and protein level of Beclin1,and decreased the expression of mTOR and p-mTOR(P<0.05 or P<0.01).Conclusion:Huang-Lian-Jie-Du-Decotion containing serum could regulate the expressions of Beclin 1 and mTOR.These might be one of the mechanisms for preventing atheroscle-rosis.

Objective To study the effect of Danggui Buxue Decoction on red cell immune function in mice with morphine abstinence syndrome. Methods 50 mice were randomly divided into normal group,positive control group, high, medium, low dose group,Hindlimb injection of morphine in morphine dependent mice model was established.Erythrocyte membrane were measured in five groups of mice micro viscosity, erythrocyte deformation index; Determination of red cell immune complex rosette rate using the method (CIC), red cell C3b receptor rosette rate;and to observe the five group of regulator factor enhance rate (RFER) and immune adherence inhibitor factor (RFIR) levels.Results Erythrocyte membrane microviscosity in model group were significantly higher than those in normal group, medium group and low group (P<0.05),red cell deformability index was lower than that of normal group, drug medium group and drug group low (P<0.05).Drug high group and medium group,immune complex rosette rate lower than in model group(P<0.05), C3b receptor rosette rate was significantly higher than that in the model group (P<0.05).Conclusion Low dose group and high dose group Danggui Buxue Decoction raises the red cell immune function in morphine withdrawal mice, improves the withdrawal symptoms, rapids rehabilitation of the body, has good clinical value.

Objective:To investigate effects of viola on macrophage TOLL-like receptor expression ,and tentatively explore the partial mechanism of viola intervention on macrophage function.Methods: Using viola water decoction lavage intervention in clean grade SD rats of conventional preparation containing serum ,In a certain concentration coculture with mouse peritoneal macrophages in 96-well plates.After 24 hours,cell phagocytosis activity was determined by neutral red uptake assay ,changes in expression levels of TLR-1,TLR-2,TLR-3,TLR-4,TLR-5 mRNAs were determined by RT-PCR.Results:Compared with the same concentration of normal serum group :(1 ) viola-containing serum group macrophage activity was significantly increased ( P<0.01 );( 2 ) Within certain concentration,viola containing serum group with increased or decreased expression levels of TLR -1,TLR-2,TLR-3 mRNA(P<0.05 or P<0.01 ) ,the expression level of TLR-4 was not significantly altered in each group ( P>0.05 ) ,and the expression level of TLR-5 was significantly increased in each group ( P<0.01 ).Conclusion:Viola-containing serum has obvious promoting effect on macrophage phag-ocytosis,the mechanism of which may be related to that this drug regulates and controls part of macrophage TOLL -like receptor expres-sion.

Objective: To study the effect of ecological factors on contents of gastrodine, preliminary discuss the relations between the soil ecological factor and the quality of gastrodine. Methods: To collected wild and cultivated gastrodia rhizome and growth soil sample from the different habitat in different harvesttime. To examine microorganism quantity, the contents of soil organic matter, the contents of soil metallic, the soil pH value and the contents of gastrodine in the soil, and analyze the relations between the soil ecological factor and the quality. Results: In collection samples, it’s showed negative correlation (P0.05). Conclusion: The bacteria/fungus constitution condition, the contents of soil organic matter and the soil pH value were important ecological factor that affect the gastrodia quality.