Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori

BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to eradication.It has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in vitro.METHODS In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients.In vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,respectively.The most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation.This assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation.Crystalline violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains.The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction.Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups.RESULTS HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the strain.QHD had strong bacteriostatic and bactericidal effects on HP,with MICs of 32-64 mg/mL.QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains,disrupt the biofilm structure,lower the accumulation of(p)ppGpp,decrease the expression of biofilm-related genes including LuxS,Spot,glup(HP1174),NapA,and CagE,and reduce the expression of efflux pump-related genes such as HP0605,HP0971,HP1327,and HP1489.Based on metabolomic analysis,QHD induced oxidative stress in HP,enhanced metabolism,and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate(AMP),thereby affecting HP growth,metabolism,and protein synthesis.CONCLUSION QHD exerts bacteriostatic and bactericidal effects on HP,and reduces HP drug resistance by inhibiting HP biofilm formation,destroying its biofilm structure,inhibiting the expression of biofilm-related genes and efflux pump-related genes,enhancing HP metabolism,and activating AMP in HP.

Effect of Qingre Huayu Decoction on Autophagy and Apoptosis of Neurons in Rats with Ischemic Brain Injury by Regulating Ca^(2+)/CaMKKβ-AMPK-mTOR Pathway

[Objectives]To explore the neuroprotective mechanism of Qingre Huayu Decoction on rats with acute cerebral ischemia injury.[Methods]SD rats were divided into sham operation group,ischemia model group,low,medium and high dose groups of Qingre Huayu De-coction,with 10 rats in each group.Referring to the MCAO operation model,both the sham operation group and the model group were given normal saline by gavage,and the Qingre Huayu Decoction group was given different doses of Qingre Huayu Decoction by gavage.After the op-eration,the rats were scored for neurological deficit,neurons were stained with HE,apoptotic cells were detected with TUNEL,and the levels of autophagy and apoptotic proteins in the Ca^(2+)/CaMKKβ-AMPK-mTORpathway in brain tissue were detected with Western-blot.[Results]Compared with the model group,the neurological function score of Qingre Huayu Decoction Group decreased significantly(P<0.05),the pathological damage of neurons in Qingre Huavu Decoction Group decreased.the proportion of apoptosis-positive cells detected by TUNEL de-creased(P<0.05),and the expression of CaMKKβand AMPK increased,expression of mTOR decreased,expression of Beclin-1 and LC3 increased,and expression of Caspase-3decreased in Qingre Huayu Decoction Group(P<0.05).[Conclusions]Qingre Huayu Decoction may play a neuroprotective role by activating Ca^(2+)/CaMKKβ-AMPK-mTOR pathway and regulating the level of apoptosis and autophagy.

Study of Quality Standards of Xiao’er Qingre Enema Preparation in Hospitals

Objective:To establish the quality standards for the preparation of Xiao’er Qingre enema in hospitals.Method:Thin-layer chromatography(TLC)was used to identify Radix Isatidis and Glycyrrhizae in the prescription.The content of(R,S)-Goitrin was determined by high-performance liquid chromatography(HPLC).Results:In TLC identification,there was no interference between the negative controls of Radix Isatidis and glycyrrhizae,and the spots were well-separated.The HPLC results of(R,S)-Goitrin showed a good linear relationship between the peak area and concentration within the range of 0.476-95.2μg·mL-1(r=0.9999).Conclusion:The TLC and HPLC methods established in this experiment are simple,reproducible,and specific,making them suitable for the quality control Xiao’er Qingre enema preparation in hospitals.

Yiqi Qingre Xiaozheng formula protects against diabetic nephropathy by restoring autophagy in mice

Objective:To evaluate the protective effect of Yiqi Qingre Xiaozheng formula(YQQRXZF)via the regulation of autophagy in diabetic nephropathy(DN)mice induced by injection of streptozotocin(STZ)after high fat diet(HFD).Methods:The composition of YQQRXZF was analyzed by high performance liquid chromatographyelectrospray ionization/mass spectrometry(HPLC-ESI/MSn).The DN model was induced by intraperitoneally injection of 50 mg/kg STZ within 5 days,followed by HFD feeding for 8 weeks in C57BL/6J mice.Mice were randomly separated into DN group,YQQRXZF group,irbesartan group,and control group.Blood glucose was calculated,and body weight was measured every 2 weeks.An enzyme-linked immunosorbent assay was used to measure the urinary albumin-to-creatinine ratio(uACR)before and after treatment,and the serum concentrations of total cholesterol(TC),low-density lipoprotein(LDL),triglycerides(TG),high-density lipoprotein(HDL),blood urea nitrogen(BUN),and serum creatinine(Scr)were measured.In addition,hematoxylin-eosin(H&E)staining,periodic acid-Schiff(PAS)staining,Masson's trichrome staining,and transmission electron microscopy(TEM)were used to observe pathological changes in renal tissue.Autophagy levels were determined by immunofluorescence staining.Results:In this study,21 dominant chemical constituents were identified in YQQRXZF.The treatment group reduced u ACR in a more significant way than the DN group(P=.018).The treatment group reduced TC,TG,and LDL concentrations after YQQRXFF treatment(P=.021,P=.014 and P=.026,respectively).H&E,PAS,and Masson staining showed that pathological damage to mice kidneys improved,the volume of renal glomeruli was reduced,and glomerular sclerosis and fibrosis were reduced.Immunofluorescence analysis revealed that expressions of LC3-Ⅱprotein increased in the treatment group(P=.013).In contrast,the protein expressions of P62 were reduced after treatment(P=.025).

The mechanism of Qingre Quzhuo capsule in the treatment of nonalcoholic steatohepatitis by inhibiting ferroptosis

Objective:To explore the effect of Qingre Quzhuo Capsule(QRQZ)in the treatment of nonalcoholic steato-hepatitis(NASH)and to explore its mechanism from the perspective of inhibiting ferroptosis.Methods:60 C57BL/6J mice were randomly divided into 6 groups:Control,model,ferroptosis inhibitor(Fer-1,10 mg/kg,gavage),low-dose QRQZ(QRQZL,482 mg/kg,gavage),medium-dose QRQZ(QRQZM,964 mg/kg,gavage),and high-dose QRQZ(QRQZH,1929 mg/kg,gavage).The control group was given normal diet,and the other experimental groups were given MCD diet.The whole administration process lasted for 6 weeks.The body weight of mice was counted every week.After 6 weeks,the blood of mice was collected,and the serum was separated to determine ALT and AST.The liver of mice was weighed and fixed.The same part was stained with HE and Oil Red O to observe the pathological changes of liver tissue.The levels of TC,TG,total iron,GSH and GSSG in liver tissue were measured by kit.The expression of Gpx4 mRNA was detected by RT-qPCR,and the expression of FTH1,FTL and GPX4 protein was detected by Western blotting.Results:Compared with the model group,after treatment with Fer-1 and QRQZ,the body weight and liver index of NASH mice increased,the liver tissue lesions were alleviated,TC,TG,ALT and AST were improved,the liver tissue iron level decreased significantly,the relative levels of FTH1 and FTL proteins in-creased significantly,GSH/GSSG increased significantly,and the expression of Gpx4 mRNA and GPX4 protein increased significantly.Conclusion:QRQZ alleviates liver injury in NASH mice by promoting the expression of GSH/GPX4 antioxidant system and inhibiting ferroptosis.

Mechanism of Qingre Yangyin Chushi Pill in the treatment of gout based on NLRP3/GSDMD pyroptosis pathway

Background:The study was conducted with the interest of exploring the effects of Qingre Yangyin Chushi pill as anti-inflammatory agent in gout treatment based on the NLRP3/GSDMD coke death pathway.Methods:In this study,48 male SD rats were randomly divided into 6 groups,namely model group,blank control group(BC),Qingre Yangyin Chushi pill low-dose treatment group(MSD1),medium-dose treatment group(MSD2),high-dose treatment group(MSD3),and colchicine group(PC),with eight members in each group.The BC and model groups were administered with saline twice a day.The MSD1,MSD2,and MSD3 groups were administered with Qingre Yangyin Chushi pill at a dose of 1.8 g·kg^?1,3.6 g·kg^?1,and 7.2 g·kg^?1 twice a day.The colchicine group was administered with a colchicine suspension at a dose of 0.6×10^?3 g kg^?1 twice a day for 7 days.After gavage of animals in each group for 4 days,the rats'ankle joints were injected with sodium urate suspension×3 days to induce a gouty arthritis model.Then,serum and tissue samples were collected on the third and seventh day after gavage.The synovial tissue from the rat ankle joints was taken,and immunohistochemical technique was used to detect NOD-like receptor protein 3(NLRP3),inflammatory bodies,cysteine protease-1(Caspase-1),and Gasdermin-D protein(GSDMD)expression.Image-Pro Plus image analysis system was used to measure the average integrated absorbance and calculate IHS.Integral enzyme-linked immunosorbent assay was used to determine the interleukin 1β(IL-1β)and interleukin 18(IL-18)expression of tumor necrosis factor-α(TNF-α).Western blot was used to detect NLRP3,Caspase-1,GSDMD,and apoptosis-associated speck-like protein containing a CARD(ASC)expression levels.Results:After 48 hours of modeling,compared with the PC group,the arthritis indices of the MSD1,MSD2,and MSD3 groups were insignificant(P>0.05).The levels of IL-1β,IL-18,and TNF-αwere lower in the PC and MSD2 groups compared with the BC group.However,compared with the control group,MSD1,MSD2,and PC groups had lower levels of IL-1βand IL-18.Regarding TNF-αlevels(P<0.05);compared with the PC group,the levels of IL-1β,IL-18,and TNF-αin MSD2 decreased more significantly(P<0.05).The levels of NLRP3,Caspase-1,GSDMD,ASC,IHS score,and mRNA were lower in the PC and MSD2 groups(P<0.05)compared with the control group.The MSD1 and MSD2 groups had lower levels of NLRP3,Caspase-1,GSDMD,ASC protein levels,IHS points,and mRNA levels(P<0.05)compared with the PC group.Moreover,NLRP3,Caspase-1,GSDMD,ASC protein levels,IHS points,and mRNA levels were more reduced in the MSD2 group(P<0.05).Conclusion:Qingre Yangyin Chushi pill can inhibit the activation of the NLPR3 inflammatory complex,reduce the production of GSDMD protein,regulate the occurrence of pyroptosis,reduce the expression of inflammatory factors,and thus reduce arthritis.All these processes are achieved through the NLRP3/GSDMD pathway.

Effect of Qingre Buyi Decoction (清热补益汤) on Nitric Oxide and Histomorphology of Intestinal Mucosa in Rats with Radiation Enteritis

Objective: To explore the mechanism of Qingre Buyi Decoction (清热补益汤,QBD) in prevention and treatment of radiation enteritis in rats. Methods: Forty-eight Wistar rats were randomly divided into four groups, the TCM group, the WM group, the model group and the control group, 12 in each group. Rats in the former three groups were given orally with QBD, norfloxacin and normal saline once a day for 7 successive days, after being irradiated with X-ray at single dose of 10 Gy for modeling of radiation enteritis, while rats in the control group were untreated. Animals were sacrificed at the end of the medication. NO concentration, mean height and number of villi per centimeter in their small intestinal mu-cosa were measured. Results: The intestinal NO concentration was significantly lower in the TCM and WM groups than that in the model group(P<0.05), while the number of villi was significantly more and the height higher in the former two groups than those in the model group (P<0.01 for both), but no significant difference was shown between the TCM group and the WM group. Conclusion: QBD could inhibit the production of NO, increase the number and height of intestinal villi in rats with radiation enteritis, suggesting that it could reduce the inflammatory reaction of intestinal mucosa to irradiation, protect muco-sa from radiation damage, and promote the regeneration of mucosa.

Effect of "Fuzheng Qingre Tonglin" prescription on rats with complicated urinary tract infection caused by ESBLs-producing Escherichia coli

Objective: To observe the effect of traditional Chinese medicine "Fuzheng Qingre Tonglin"prescription on rats with complicated urinary tract infection caused by extended-spectrumβ-lactamases (ESBLs)-producing Escherichia coli and its possible mechanism. Methods:Specific-pathogen-free female SD rats with 7-9 weeks old were randomly divided into model group, levofloxacin group, low-dose Fuzheng Qingre Tonglin group, high-dose Fuzheng Qingre Tonglin group, levofloxacin+Fuzheng Qingre Tonglin group (n=8 in each above group), and also there was a control group with 5 rats. Each group was administered intragastrically 2 days after model establishment for 14 consecutive days. The general condition of the rats was observed. Renal pathological changes were observed by light microscopy under hematoxylin-eosin staining. The number of white blood cells and the percentage of neutral particles (NEUT%) were detected. ELISA was used for the determination of C-reactive protein (CRP), CD4+, CD8+ in the blood, and secretory immunoglobulin A (SIgA), N-acetyl-β-D-glucosidase (NAG) molecules in urine. Results: There were a large number of inflammatory cells in the kidney of the model group and the levofloxacin group. The inflammatory cells in the treatment group were significantly reduced. The NEUT% and CRP in the blood of each treatment group and the NAG in the urine were significantly lower than those in the model group (P<0.05), except levofloxacin group. Compared with the model group, except for the levofloxacin group, serum CD4 concentration and CD4/CD8 ratio in the other treatment groups were significantly decreased, and CD8 molecules were significantly increased (P<0.05). Conclusion: "Fuzheng Qingre Tonglin" can alleviate systemic and local inflammation of complicated urinary tract infections in rats. It may also have the effect of re-sensing the insensitive antibacterial drug to bacteria and may have the function of regulating immune function and protecting kidney function in rats.

Clinical efficacy of Qingre Quzhuo capsule in the treatment of non-alcoholic fatty liver disease

Background:To observe the clinical effect of Qingre Quzhuo capsule in the treatment of non-alcoholic fatty liver disease.Methods:90 patients with non-alcoholic fatty liver disease in our hospital from January 2021 to January 2022 were randomly divided into observation group and control group,45 cases in each group.All patients received routine lifestyle intervention and the control group received oral polyene phosphatidylcholine capsules 2 capsules/time(456 mg),three times daily;45 cases in the observation group were given Qingre Quzhuo capsule(Jiyao Z2017040,0.5 g/grain)2.5 g/time,3 times/day,for 12 weeks.The clinical efficacy,liver function,liver transient elastography controlled attenuation index value,lipid metabolism,oxidation and antioxidant indexes were compared between the two groups after treatment.Results:The observation indexes of the two groups after treatment were better than those before treatment(P<0.05).After treatment,the total effective rate of the observation group was higher than that of the control group.Lipid metabolism indexes and oxidation indexes were lower than those in the control group.All antioxidant indexes were higher than control group.The decrease of liver transient elastography controlled attenuation index value was better than that of the control group and the difference was statistically significant(P<0.05).There was no significant difference in the decrease of alanine aminotransferase between the observation group and the control group after treatment.The decrease of r-glutamyltransferase was statistically significant(P<0.05).Conclusion:Qingre Quzhuo capsule in the treatment of non-alcoholic fatty liver disease can improve liver function,regulate lipid metabolism indexes of patients,improve the antioxidant capacity of liver cells and improve the controlled attenuation index value of liver transient elastography.In addition,it is superior to polyene phosphatidylcholine in regulating lipid metabolism,antioxidant capacity and controlled attenuation index value of patients with non-alcoholic fatty liver disease which is safe and worthy of promotion.

Qingre Lishi Tuihuang therapy for acute icteric hepatitis B: A systematic review

Objective:To assess the efficacy of Qingre Lishi Tuihuang therapy (QLTT) for acute icteric hepatitis B infection.Methods:Eight electronic databases were searched from inception to December 2016 with no language restrictions for reports of randomized controlled trials evaluating the effect of QLTT treating acute icteric hepatitis B.Two researchers independently extracted detailed data and assessed methodological quality.ReviewManager 5.3.0 software was used to analyze the data.Results:A total of 13 randomized controlled trials involving 2238 participants were included in this review.The methodological quality was generally poor.The results indicated that supplemented Yinchenhao decoction combined with non-specific treatments was more effective in improving the cure rate (risk ratio =1.80;95% CI 1.21-2.68) and reducing the serum levels of total bilirubin (mean difference =-29.74;95% CI-31.91 to-27.57) and aspartate aminotransferase.Other self-made prescriptions conforming to QLTT plus non-specific treatments had beneficial effect for acute icteric hepatitis B in curing this disease (risk ratio =1.48;95% CI 1.27-1.73),as well as for negative seroconversion of HBeAg (risk ratio =1.39;95% CI 1.11-1.74).Supplemented Yinchenhao decoction plus non-specific treatments was more effective than other self-made prescriptions conforming to QLTT in reducing serum total bilirubin level.Conclusion:Qingre Lishi Tuihuang therapy appears to improve effect based on non-specific treatments for the treatment of acute icteric hepatitis B.However,it is premature to draw confirmative conclusions,owing to the poor methodological quality and high clinical heterogeneity of the included trials.Further well-designed clinical randomized controlled trials with large sample sizes should be undertaken.

A study of ultrasonography for the treatment of Qingre Liangxue decoction on blood-heat psoriasis

Objective:The clinical effectiveness of blood-heat psoriasis treated by Qingre Liangxue decoction and ultrasound imaging changes of lesions was observed.Methods:Patients with blood-heat psoriasis were selected and randomly grouped into two groups:the treatment group taking the Qingre Liangxue decoction orally,the control group taking the Compound Glycyrrhizin Tablets orally,both groups applying topical emollient lotion for a 12-week treatment period.Ultrasound images of target lesions and healthy skin were collected at different treatment times.Results:The epidermal thickness thought,the dermal density incremented as well as the subepidermal low-echogenic band(SLEB)width narrowed in both groups during the treatment.Conclusion:Qingre Liangxue decoction has signified efficiency in the treatment of blood-heat psoriasis,and high-frequency ultrasound has the advantages of non-invasive,timely and objective in the evolution.

Observation on the Therapeutic Effects of Qingre Shengji Ointment(清热生肌膏)on Acute Radiation Dermatitis After Modified Radical Mastectomy

Objective:To observe the curative effect of Qingre Shengji Ointment(清热生肌膏)on acute radiation dermatitis caused by radiotherapy after modified radical mastectomy.Methods:100 patients with radiotherapy after modified radical mastectomy in our hospital from June 2019 to December 2020 were randomly divided into treatment group and control group,with 50 cases in each group.The treatment group was given Qingre Shengji Ointment(清热生肌膏)on the basis of routine nursing,and the intervention began until one week after radiotherapy,while the control group was given routine nursing.Observe and record the occurrence time of acute radiation dermatitis,the degree of acute radiation dermatitis,changes of skin erythema,pruritus,pain,changes of interleukin-6(IL-6)and curative effect were evaluated.The degree of dermatitis was evaluated by RTOG grading standard,the erythema was evaluated by TCM symptom score,and pruritus and pain were evaluated by visual analogue scale(VAS).Blood routine,liver and kidney function,electrocardiogram and other safety indicators and adverse reactions were recorded before and after the study.Results:The time of acute radiation dermatitis was 6-11 days(median 8 days)in the treatment group and 8-14 days(median 10 days)in the control group(P<0.01).The degree and probability of acute radiation dermatitis in the treatment group were 82%(41/50)in grade I,16%(8/50)in grade II and 2%(1/50)in grade III.The degree and probability of acute radiation dermatitis in the control group were 54%(27/50)in grade I,40%(20/50)in grade II and 6%(3/50)in grade III(P<0.05).The highest TCM symptom score of skin erythema in the treatment group was lower than that in the control group(P<0.01).The results of generalized estimation equation show that,The VAS scores of pruritus and pain were(1.34±0.01)and(2.08±0.02)(Waldχ^(2)=1198.123,P<0.01)in the treatment group and(2.08±1.74)(Wald^(2)=1547.804,P<0.01)in the control group,respectively.Compared with the control group,the VAS scores of pruritus and pain were(1.14±0.01)and(2.08±1.74)(Wald^(2)=1547.804,P<0.01)in the treatment group.After observation,the curative effect of the treatment group was better than that of the control group(P<0.05),and the subjective symptoms of patients were obviously improved.After treatment,the level of IL-6 in the treatment group was significantly lower than that before treatment,and was lower than that in the control group(P<0.01).Conclusion:Qingre Shengji Ointment(清热生肌膏)can prevent and treat acute radiation dermatitis to some extent,and its mechanism may be to inhibit the release of inflammatory cytokines,reduce the degree of dermatitis,improve the quality of life of patients,and its safety is good.VAS score can subjectively evaluate the changes of itching and pain,and it is easy to use,so it is worthy of clinical application.

Clinical Evaluation of Yangyin Qingre Shengji Decoction(养阴清热生肌汤)in Preventing and Treating Acute Radiation Esophagitis

Objective:To explore the prevention and treatment effect of Yangyin Qingre Shengji Decoction(养阴清热生肌汤)on acute radiation esophagitis.Methods:From May 2020 to February 2021,60 patients with malignant tumor who underwent radiotherapy were selected as the research objects.They were divided into two groups by odd and even number drawing,30 cases in the control group and 30 cases in the observation group.The control group took mixed solution orally,while the observation group took Yangyin Qingre Shengji Decoction.The clinical effects,occurrence time,duration,grading of acute radiation esophagitis and TCM syndrome scores of dry mouth and constipation were compared between the two groups.Results:The effective rate of the observation group was significantly higher than that of the control group(P<0.05);Compared with the control group,the time of acute radiation esophagitis was prolonged and the duration of symptoms was shortened in the observation group(P<0.05);The incidence of above gradeⅡin the observation group was significantly lower than that in the control group,and the incidence of below gradeⅠwas significantly higher than that in the control group(P<0.05);There was no significant difference in the scores of dry mouth and constipation between the two groups before treatment(P>0.05),the scores of the two groups were decreased after treatment,and the observation group was lower than the control group(P<0.05).Conclusion:Yangyin Qingre Shengji Decoction(养阴清热生肌汤)has a positive effect on prevention and treatment of acute radiation esophagitis in patients with malignant tumor undergoing radiotherapy,which can be popularized.

Dry eye disease due to meibomian gland dysfunction treated with Pinggan Yuyin Qingre formula(平肝育阴清热方):a stratified randomized controlled trial

OBJECTIVE:To observe the clinical efficacy on improving the quality of meibum in patients suffer from dry eye disease(DED)due to meibomian gland dysfunction(MGD)with hyperactivity of Yang due to Yin deficiency pattern after being treated with Pinggan Yuyin Qingre formula(平肝育阴清热方,PGYYQR).METHODS:Totally 120 patients who met the inclusion criteria were included and stratified into three levels according to the level of MGD(1-3),and patients in each level was randomly allocated into the treatment group and control group according to a 1∶1 ratio.Both groups were treated with sodium hyaluronate eye drops,and the treatment group was also given PGYYQR granules.Both groups were treated continuously for eight weeks.The score of the properties of meibomian gland(MG)secretion,the score of the palpebral margins,the average noninvasive tear breakup time(NITBUTav),lipid layer thickness(LLT),and Traditional Chinese Medicine(TCM)syndrome efficacy were compared between the two groups after treatment.RESULTS:A total of 116 cases were included in the statistical analysis.The differences were statistically significant in the score of the properties of MG secretion,the score of the palpebral margins,and NITBUTav between the two groups after treatment,the treatment group was superior to the control group;there was no evidence of a difference in LLT.In terms of TCM syndrome efficacy,the total effective rate was 84.7%in the treatment group and 50.9%in the control group,with the statistically significant difference.None of the included cases had adverse reactions.CONCLUSIONS:PGYYQR is effective in improving the quality of meibum,and the tear film stability which thereby relieving the ocular symptoms in MGD-related DED patients with hyperactivity of Yang due to Yin deficiency pattern.

Effect of Huangqin Qingre Chubi Capsule on Bone Metabolism and Serum TLR4NF-kB in Rats with Rheumatoid Arthritis

Objective:To elucidate the effects of Huangqin Qingre Chubi capsule(HQC)on bone metabolism and serum TLR4 and NF-kB in rats with rheumatoid arthritis(RA),and to provide experimental bases for the treatment of RA with HQC.Methods:A total of 40 SD rats were randomly divided into the normal group,model group,western medicine treatment group,and HQC group,with 10 rats in each group,and the RA model was induced by complete adjuvant in all groups except the normal group.After successful modeling,they were treated for 4 weeks to compare the degree of joint swelling;meanwhile,micro-CT was used to evaluate bone microstructural parameters,and changes in serum TLR4 and NF-kB expression levels were detected by ELISA.Results:There was no statistical significance in comparing the degree of joint swelling among the model group,western medicine treatment group and HQC group(P>0.05);Micro-CT results showed that bone microstructural parameters deteriorated in the osteoporosis model group compared with the normal group.Both western medicine and traditional Chinese medicine HQC could improve the bone microjunction of RA rats,and the HQC group was better than the western medicine treatment in improving the number of bone trabeculae(2.58±0.19)·mm^(-1);the serum results showed that RA was accompanied by the up-regulation of the expression of TLR4 and NF-kB.Both western drugs and HQC down-regulated the high expression of serum TLR4 and NF-kB in osteoporotic rats,and the down-regulation of serum TLR4(9.90±0.55)ng·ml^(-1)and NF-kB(350.29±3.14)ng·L^(-1)by HQC was more obvious.Conclusion:Chinese herbal medicine HQC can significantly improve the bone microstructure of RA rats,and its effect is better than that of western medicine in some aspects.The mechanism of action of HQC is related to the inhibition of the activation of the TLR4/NF-kB pathway,and this study provides an experimental basis for the further development and utilization of HQC.

A One-year Evaluation of Radiographic Progression in Patients with Rheumatoid Arthritis Treated by Qingre Huoxue Decoction(清热活血方)

Objective： TO investigate the effects of Qingre Huoxue Decoction （清热活血方, clearing heat and promoting blood flow; QRHXD）, on the radiographic progression in patients with rheumatoid arthritis （RA） by X-ray imaging. Methods： Eighty-six patients with active RA diagnosed as damp-heat and blood stasis syndrome were randomized into a QRHXD group and a QRHXD plus methotrexate （MTX） group, with 43 cases in each group. After one-year of treatment, 21 cases in each group （42 in total） were evaluated. Radiographs of hands were obtained at the baseline and after 12 months of treatment. Images were evaluated by investigators blinded to chronology and clinical data, and assessed according to the SharpNan der Heijde methods. Results： High intrareader agreements were reached （mean intraobserver intraclass coefficients： 0.95）. No significant change in any imaging parameters of joint destruction was observed at 12 months in either group; and the differences between the two groups were not significant （P〉0.05）. The mean of the changing score in the QRHXD group was 3.5 ± 4.1, and 2.4 ± 3.5 in the QRHXD＋MTX group, while the baseline radiographic score of patients in the QRHXD group was relatively higher （18.9± 19.1 vs. 14.0± 14.0）. The mean rates of the changing scores of the two groups were similar （0.24 ± 0.28 vs. 0.25± 0.44, P=0.40）. The severity of progression in the two groups was also similar （P=0.46）, 7 cases without radiographic progression in the QRHXD group and 8 in the QRHXD＋MTX group, 3 cases with obvious radiographic progression in the QRHXD group and 1 in the QRHXD＋MTX group. Conclusion： Radiographic progression of RA patients in both groups is similar, indicating that the QRHXD Decoction has a potential role in preventing bone destruction.

Study of Qingre Liyan Decoction(清热利咽汤)in Treating and Preventing Acute Radioactive Oral Mucositis

Objective： To study the effect of Qingre Liyan Decoction （清热利咽汤 QRLYD） in the prevention and treatment of acute radiative oral mucositis （AROM）, and to explore the mechanism of QRLYD by detecting epidermal growth factor （EGF） and T lymphocytes （CD3, CD4, and CD8）. Methods： Sixty patients conforming with the standard were randomly assigned to two groups, 30 patients in each group. Patients in the trial group were treated with QRLYD, and those in the control group were treated with Dobell＇s solution, both groups receiving conventional radiation treatment. The treatment course for both groups was 6 weeks on average. Blood routine test, CD3, CD4, and CD8 in the peripheral blood and EGF in the saliva were detected one day before and on the 14th and 28th day of radio-therapy. Results： Patients in the trial group were in good condition with normal spirits and intake of food and drinks. The incidence of AROM is lower and the effect in preventing AROM is higher in the trial group than those in the control group （P〈0.05）. The EGF in saliva, and CD4 and CD8 in the blood of patients in the trial group were higher than those in the control group （P〈0.05）. Conclusion： QRLYD can cure and prevent AROM. The mechanism may be related with its effects in enhancing body immunity and promoting salivary EGF.

Efficacy of Qingre Huashi decoction(清热化湿方) on infection of Helicobacter pylori:inhibiting adhesion,antioxidant,and anti-inflammation

OBJECTIVE: To investigate the phytochemical profile of Qingre Huashi decoction( 清 热 化 湿 方, QHD) and evaluate the mechanisms rationalizing the use of QHD against Helicobacter pylori(H. pylori)-associated gastritis. METHODS: QHD is composed of 11 herbs, which was prepared by a fixed Pharmacy and concentrated into clear paste. High-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(HPLC-QTOF/MS) was used to detect the phytochemical profile of QHD. The toxicity of QHD against H. pylori and human gastric epithelial cells was evaluated by the toxicology test and cell counting kit-8 assay. The adhesion model was constructed by incubating H. pylori and gastric mucosal epithelial cells for 2 h. The urease assay was used to examine the antiadhesion effects of QHD, and gene expression of adhesins was evaluated by quantitative polymerase chain reaction. The antioxidant activity was assessed by DCFHDA labeling. To evaluate the anti-inflammatory effect, the levels of pro-inflammatory cytokines in the culture supernatant were detected by enzyme-linked immunosorbent assay. RESULTS: HPLC-QTOF/MS profiling indicated the presence of primary compounds 1-20 in QHD. Drug concentration was determined as 1, 2, and 5 mg/m L by the toxic concentration of QHD against H. pylori and human gastric epithelial cells. QHD prevented H. pylori adhesion to the human gastric epithelial cells and reduced levels of reactive oxygen species. QHD also reduced the level of interleukin-8 and other proinflammatory cytokines that were upregulated by H. pylori infection. CONCLUSION: QHD could inhibit H. pylori adhesion, and exert antioxidant and anti-inflammatory effects in vitro.

Inhibition of methicillin-resistant Staphylococcus aureus by the compound Qingre granules

Background The infection rate of methicillin-resistant Staphylococcus aureus （MRSA） is increasing yearly due to the overprescription of antibiotics. Traditional Chinese compound medicines are less inclined to induce bacterial resistance in the clinical setting because of their multi-acting mechanisms. However, most current research is limited to bacteriostasis in vitro using single extracts or formulations. Plasma pharmacology is an in vitro method, using what is called ＂medicine serum＂. The aim of this study was to investigate whether the medicine serum of compound Qingre granules （QRKL） alone or in combination with antibiotics may treat MRSA infection in the clinic. Methods An animal model of MRSA resistance was created by injecting rabbits with the standard strain of MRSA ATCC43300. Infected rabbits were treated with QRKL by intragastric administration. Sixty minutes after the last intragastric administration, serum was obtained from the rabbits by heart puncture to obtain what is termed ＂medicine serum＂. The minimum inhibitory concentration （MIC） of QRKL, medicine serum alone, or serum combined with antibiotics was assessed by agar dilution. Results were compared with the growth of sixteen isolates of MRSA. Results The MIC of QRKL to the standard strain ATCC43300 was 10.00 mg/ml. The MICgo of vancomycin was 1.00 pg/ml, which, when combined with QRKL, dropped to 0.50 lJg/ml. The MICg0 of cefuroxime alone was 512.00 pg/ml. This level also decreased to 256.00 tJg/ml when combined with QRKL. The addition of QRKL thus significantly reduced the MIC of both cefuroxime and vancomycin compared with antibiotics alone （P 〈0.01）. The MICgo of vancomycin with medicine serum decreased to 0.50 pg/ml, and the MIC of vancomycin with medicine serum also descended compared with using vancomycin alone （P 〈0.01）. Conclusions The growth of MRSA can be inhibited by QRKL or medicine serum of QRKL in vitro. The addition of QRKL results in increased sensitivity of MRSA to vancomycin and this may provide a novel treatment for patients with MRSA infection.

Effectiveness of Qingre Lishi Yishen decoction on the glomerular fibrosis of immunoglobulin A nephropathy in a rat’s model

OBJECTIVE: To investigate the effect of the clinical effective prescription of Qingre Lishi Yishen decoction(QRLS) on the activation of mesangial cells in immunoglobulin A nephropathy(IgAN) rats.METHODS: IgAN rat’s model was established by combine with intragastric administration of bovine serum albumin(BSA) + intravenous injection of lipopolysaccharide(LPS) by + subcutaneous injection of carbon tetrachloride(CCL4). Then the animals were randomly divided into four groups: control group, IgAN model group, IgAN model with Valsartan(Val) treatment group and IgAN model with QRLS treatment group. To observe the indexes of 24-h urine protein, renal function, deposition of immune complexes, expression of activation factor, fibrosis marker and inflammatory cytokines in four different groups.RESULTS: The Val or QRLS treatment group:(a) it reduced the immune complexes deposition of IgA in glomerular mesangial and inhibited mesangial cell proliferation;(b) it decreased the expression of smooth muscle actin(α-SMA), fibronectin(FN) and tumor necrosis factor alpha(TNF-α).CONCLUSION: The study suggested that QRLS ameliorate renal structure and function in IgAN rat’s model. Furthermore, we also observed that QRLS alleviated mesangial cells activation and matrix accumulation partly by decreasing the α-SMA,then to downregulated the expression of FN and TNF-α.