Can Tibetan medicine Honghua Ruyi pills relieve endometriosisassociated dysmenorrhea?Protocol for a randomized placebocontrolled trial

Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated dysmenorrhea.Methods:This study constitutes a multicenter,randomized,double-blind,placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period.A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio.The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale(VAS)scores and quality of life,whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain,duration of pain episodes(in days),frequency and quantity of the consumption of ibuprofen sustained-release capsules(or other non-steroidal anti-inflammatory drugs),and days off work/study for staff/student due to dysmenorrhea,ovarian cyst,and/or pelvic nodule size.The safety was monitored throughout the treatment period.All the analyses were based on the intention-to-treat principle.For continuous outcomes,simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups,with categorical data expressed as the number and percentage of occurrences.Differences were compared using the chi-square test or Fisher's exact test.The predefined analysis was adjusted for concomitant treatment,a variable considered to be associated with outcomes but unaffected by treatment allocation.Estimates of treatment effects were reported with 95%confidence intervals.Two-tailed P values≤.05 were considered statistically significant.Conclusion:Positive results from this trial,upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

Integration of network pharmacology and bone marrow mesenchymal stem cells experimental research to reveal the molecular mechanisms for Hai Honghua medicinal liquor against osteoporosis

Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to promote fracture healing.However,the underlying mechanisms of HHML in the treatment of osteoporosis(OP)are still unclear.Methods:Firstly,Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to screen the targets of the active compounds of HHML.At the same time,OP targets were identified through GeneCards,Online Mendelian Inheritance in Man,DisGeNET,Therapeutic Target Database,Comparative Toxicogenomics Database and Human Phenotype Ontology databases.Next,protein-protein interaction and pathway networks were constructed for compound-disease common targets,and core targets and compounds were screened for molecular docking.Furthermore,rat bone marrow mesenchymal stem cells were extracted as model cells,and the osteogenic effects of HHML were verified via in vitro experiments.Results:Total of 343 common targets of HHML-OP and the top 10 target proteins in the protein-protein interaction network are TP53,AKT1,STAT3,HSP90AA1,ESR1,TNF,IL6,MAPK1,MAPK3 and MAPK8.Enrichment analysis yielded that the key molecular pathway was the PI3K/Akt signaling pathway.Molecular docking analysis showed that baicalein,erysodienone and naringenin docked with the target proteins AKT1,STAT3 and TP53,respectively,with low binding energy and high affinity.In addition,In vitro experiments demonstrated that HHML promoted the proliferation of bone marrow mesenchymal stem cells;compared with the control group,HHML-treated cells showed enhanced alkaline phosphatase staining,promoted the expression of OCN,RUNX2,BSP,and COL1 mRNAs as well as the expression of PI3K and AKT phosphorylated proteins.Secondly,the expression of target proteins revealed that HHML promoted the phosphorylation of STAT3 protein and inhibited the expression of P53.Conclusions:Our study investigated that HHML treatment with OP promotes bone formation possibly through activation of the PI3K/Akt signaling pathway and may involve STAT3 and TP53 target interactions.

Relationships between bird communities and vegetation structure in Honghuaerji, northern Inner Mongolia

The survey on bird communities was conducted by the belt-style method in six different sample plots in the Honghua抏rji Forests area in the northern Inner Mongolia in June 2001 and totally 28 bird species were recorded. Vegetation investigation was carried out in five 10 m×10 m quadrats at each plot. The asymptotic regression function formulae were adopted to identify the relationships between the vegetation coverage and the numbers of bird species and individuals. The analytical results showed that the changes of species number and density of bird as well as the formation of bird communities follow the changes of forest type and the total foliage. Both the number of bird species and their density decreased with the de-crease of total foliage. The similarity of bird community was very low at the breeding time. In the same classification of cluster, no similarity was higher than 0.65, which indicated that the composition of species had a great difference between all the bird communities. The bird breeding density was closely related to forest growth stage. From the bare grassland ecosystem to cli-max ecosystem, the density of bird species showed a gradually increasing trend.

Effects of Honghua preserved amniotic membrane on scar healing in experimental glaucoma surgery

AIM:To investigate the efficacy and safety of Honghua preserved amniotic membrane(AM)for preventing scar formation of the filtering bleb in a rabbit model of glaucoma trabeculectomy surgery.METHODS:Totally 36 rabbits(36 eyes)were randomly divided into 3 groups:the experimental group(ocular trabeculectomy in combination with Honghua preserved AM transplantation),the control group(ocular trabeculectomy surgery in combination with AM implantation),and the blank group(single trabeculectomy).Clinical observations[including intraocular pressure(IOP),filtering blebs and complications],MassonTrichrome staining,real-time quantitative reverse transcription-polymerase chain reaction(real-time PCR),Western blot were performed on different time points(D1,D7,D14,D21 and D56)after the surgery.RESULTS:After operated for 14d,there were statistically significant differences in the filtering blebs compared to the situation before operation(P【0.05),whereas no statistically difference on that among three groups(P】0.05).After 21d,the IOP of experimental group was lowest(P【0.05).There was significant difference between control group and blank group(P【0.05).On postoperative D14,the mean number of fibroblasts in the experimental group was significantlylower(40.6±10.2)compared to those in the control group(54.4±10.8)and blank group(68.2±11.6)(P【0.05,respectively).The mean numbers of the macrophage in the experimental and control groups were respcitively significantly lower versus the blank group(P【0.05,P【0.05,respectively).Compared to that in blank group,the level of transforming growth factor-β(TGF-β1)expression in sclera and conjunctival areas was reduced in the experimental and control groups on protein and mRNA level(P【0.05),but not significant difference between these two groups(P】0.05).CONCLUSION:The trabeculectory surgery with Honghua preserved AM can control IOP,sustain the functional filtration bleb,inhibit the proliferation of fibroblasts and open the filtrating pathway on the rabbit glaucoma models.

Pharmacokinetic parameters investigation on interaction between Danshen injection and Honghua injection

OBJECTIVE Danshen injection and Honghua injection,traditional Chinese medicine(TCM)injections,made from the extracts of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.,have a potential to be developed into the useful drugs for the.As the common TCM injections,Danshen injection is often combined with Honghua injection to treat cardiovascular disease.The purpose of this study was to investigate the pharmacokinetic parameters of Honghua injection combined with Danshen injection when they were coadministered intravenously in human and rats through the tail vein.METHODS Single and multiple doses of Danshen injection to study Danshen injection on Honghua injection pharmacokinetics parameters and single and multiple doses of Honghua injection to study Honghua injection on Danshen injection pharmacokinetics parameters.The plasma concentrations of hydroxysafflor A(HSYA)and tanshinol and salvianolic acid B were determined by the reliable high-performance liquid chromatography(HPLC)method.The concentrations of HSYA in urine of rats and human were also determined by HPLC method.DAS 2.1.1software was adopted for calculating the pharmacokinetic parameters.RESULTS The simultaneous intravenous Honghua injection and salvia miltiorrhiza injiection significantly altered the pharmacokinetic parameters of both injections when compared with the individual intravenous administration of each injection.The area under the concentration-timecurve(AUC)and maximum plasma concentration(Cmax)of HSYA and tanshinol and salvianolic acid B were significantly increased.The cumulative urine excretion of HSYA in human and rats during 24 h was decreased after two drugs were administered simultaneously by the intravenous.CONCLUSION Honghua injection and Danshen injection interact with each other following simultaneous intravenous and they have a synergistic action.This experiment has identified the pharmacokinetic parameters and provided a rationale for the clinical use of the drug combination.

Research of the molecular mechanism of Hai Honghua medicinal liquor in the treatment of fracture based on network pharmacology combined with molecular docking

Background:Hai Honghua medicinal liquor(HHML),a famous hospital formula composed of 19 traditional Chinese medicines,has been successfully applied in treating soft tissue injury,fresh closed fracture,limb dysfunction after fracture healing,shoulder,neck and leg pain,knee joint pain and other clinical multiple diseases for 30 years in clinical.However,research on the material basis of HHML for the treatment of fracture healing-related disorders is still in a gap.Therefore,it is particularly important to explore the active ingredients,core targets and potential pharmacological mechanisms of HHML to promote fracture healing.Methods:We screened the core active components of each traditional Chinese medicine in formula and its action targets through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine database.The fracture related targets were retrieved from several different public databases,including GeneCards,Online Mendelian Inheritance in Man,DisGeNET and Therapeutic Target Database.Bioinformatics analysis to obtain key bioactive components,underlying targets and signaling pathways,containing the Venn diagram of the intersection with components and diseases gene targets,protein–protein interaction,as well as the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis,and finally molecular docking.Results:A total of 249 bioactive ingredients of HHML and 325 HHML-fracture-related targets were screened.The network analysis revealed that quercetin,luteolin,kaempferol,Licochalcone A,naringenin and 8-Isopentenyl-kaempferol may be potential candidate agents.Multiple targets are involved including TP53,MAPK3,STAT3,AKT1,MAPK1,HSP90AA1,ESR1 and PIK3CA may be closely linked targets.PI3K-AKT signaling pathway may play a significant role of HHML in treatment of fracture.What’s more,molecular docking suggested that 8-isopentenyl kaempferol,glycyrrhiza chalcone A,and naringenin bound to AKT1,PIK3CA,and ESR1,respectively,exhibiting lower energy and more stable characteristics.Conclusions:The findings indicate the potential active ingredients,target proteins and molecular mechanisms of HHML for the treatment of fractures to provide the exact idea for the next research on the mechanism of action of HHML formula for fracture treatment.

红花大金元烟叶中性致香成分含量与感官质量预测分析

以42个红花大金元（Nicotiana tabacum L.cv.Honghua Dajinyuan）烟叶样品为供试材料,采用双重筛选逐步回归法等分析了感官质量指标与中性致香成分的关系,并建立了预测模型。结果表明,1感官质量指标香气质、香气量、杂气、成团性的预测效果较好,决定系数（R2）范围在0.9984-0.999 8,留一交叉验证相关系数（q2）范围在0.823-0.937。其中预测模型y1（香气质）=-2.501 4 x1＋0.9377x8–0.0693 x12–0.6815x14-0.1547x15＋2.8024x16–0.1524x19＋1.860 1x23＋2.5547x27＋1.3390 x29＋17.3163,R^2为0.9998,q^2为0.937,这为利用中性致香成分针对红花大金元预测感官质量指标提供了参考依据。2苯丙氨酸类降解产物苯甲醇和苯乙醛含量与香气量得分之间、美拉德反应产物中2-乙酰基吡咯和5-甲基糠醛含量与香气量和杂气得分之间、类胡萝卜素类降解产物法尼基丙酮和6-甲基-5庚烯-2酮含量与回甜感得分之间、4-乙烯基-2甲氧基苯酚含量与成团性得分之间、其他类芳樟醇含量与香气质和杂气得分之间均呈正相关;苯丙氨酸类降解产物苯甲醛含量与香气质得分之间、美拉德反应产物2-乙酰呋喃含量与杂气、香气量、回甜感、干燥感、成团性得分之间、类胡萝卜素类降解产物β-紫罗兰酮含量与香气质得分之间、新植二烯含量与香气量得分之间均呈负相关。

复方丁香罗勒油的稳定性研究

目的:研究复方丁香罗勒油的稳定性。方法:考察复方丁香罗勒油在冷、热和常温条件下的质量变化。结果:在低温(-20℃)和高温(80℃)区间,以及常温贮存0～18个月的条件下,复方丁香罗勒油性状、鉴别、相对密度、折光率和含量未见变化。结论:在高温、冷冻和常温条件下贮存,复方丁香罗勒油的质量稳定。

Effect of local blocking on osteoarthritis of the hip

Objective:To provide an effective treatment for the Osteoarthritis of the hip by observing the effect of local blocking of HongHua injection on relieving hip pain.Methods:Methods from June 2015 to May 2017,60 patients with Osteoarthritis of the hip in Wangjing Hospital of Chinese Academy of Sciences were randomly divided into treatment group and control group,30 cases in each group.The treatment group was given local blockingof HongHua injection treatment,control group using Compound Betamethasone Injection local closed treatment.Visual analogue scale(VAS)score,pericoxal local tenderness and hip mobility were used to evaluate the therapeutic effect.The therapeutic indicators at six different time points after 1 days,3 days,7 days,2 weeks and 1 months after treatment were compared.Results:All the 60 cases completed treatment and follow-up,and there were no cases of abscission.There was no significant difference in gender,age,etiology,classification and Harris score before treatment between the two groups(P>0.05),which was comparable.VAS score:There was no significant difference between the two groups on the 1st,3rd,7th and 2nd week after treatment(P>0.05),but the treatment group was lower than the control group on the 1st month after treatment(P<0.01).Hip joint activity:There was no significant difference in hip joint activity between the two groups 1 day,3 days,7 days,2 weeks and 1 month after treatment(P>0.05).Local tenderness around hip:The efficacy of the midpoint inguinal tenderness score was similar between the two groups at 1 day,7 days,2 weeks and 1 month after treatment(P>0.05);the treatment group was lower than the control group at 3 days after treatment(P<0.01);the adductor starting tenderness score had no significant difference at 1 day,3 days,7 days,2 weeks and 1 month after treatment(P>0.05).Conclusion:Local blockingof HongHua injection is effective and effective in treating hip pain in Osteoarthritis of the hip.The HongHua injection has many advantages,such as good safety and wide indications.It is worthy of further clinical application.