1.Diagnosis and treatment process of a case of Streptomyces thermoviolaceus pneumonia and literature review
Pan LIU ; Xiaotian DAI ; Tingting LIU ; Hao JIANG ; Lan LIANG
China Pharmacy 2025;36(8):981-985
OBJECTIVE To report the diagnosis and treatment process of 1 case of Streptomyces thermoviolaceus pneumonia, and provide reference for the diagnosis and treatment of this type of infection by combining literature on Streptomyces pneumonia. METHODS A case study was conducted on a patient with S. thermoviolaceus pneumonia treated at the First Affiliated Hospital of Army Medical University. Additionally, a systematic literature review of Streptomyces pneumonia cases was performed. RESULTS The patient with S. thermoviolaceus presented with left lung consolidation and mass-like opacity. Initial diagnosis via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry failed, but 16S rRNA gene amplification and sequencing confirmed S. thermoviolaceus as the causative pathogen. Six-month therapy with Amoxicillin capsules (1 g orally, three times daily) resulted in near-complete lesion resolution. The literature analysis of Streptomyces pneumonia revealed that 13 patients with Streptomyces pneumonia were included (including the patient reported in the article), age range of 18-77 years, more males (8 cases), and mostly suffering from underlying diseases. In terms of clinical symptoms, all enrolled cases exhibited cough, and some cases were accompanied by variable dyspnea. Imaging findings included that there was no characteristic predilection site for Streptomyces pneumonia lesions, and CT images commonly showed lung consolidation and bilateral nodules. Definitive diagnosis relied on 16S rRNA sequencing. Treatment regimens included tetracyclines, β -lactam drugs combined with enzyme inhibitors, ceftriaxone, aminoglycosides, macrolides, or carbapenems, administered for prolonged duration (6 months). Follow-up indicated a good prognosis, and only one mortality occurred. CONCLUSIONS 16S rRNA gene sequencing should be prioritized for diagnosing S. pneumonia. Effective antimicrobial options include tetracyclines,β-lactam drugs combined with enzyme inhibitors, ceftriaxone, aminoglycosides, macrolides, and carbapenems. Prolonged therapy correlates with favorable prognosis.
3.Application of different grafts in anterior cruciate ligament revision
Guoli LIU ; Liang LI ; Kunnan XIE ; Xianghui YIN ; Yanrui ZHANG ; Fan YI ; Shifeng DAI
Chinese Journal of Tissue Engineering Research 2024;28(17):2647-2652
BACKGROUND:The type of graft selected during anterior cruciate ligament revision is considered one of the main factors affecting the postoperative outcome,but there are few reports on the comparison between different graft materials. OBJECTIVE:To explore the medium-to-long-term clinical efficacy after anterior cruciate ligament revision with autologous ligament,allogeneic ligament,and LARS artificial ligament. METHODS:A total of 67 patients with the first anterior cruciate ligament revision admitted to the Department of Joint and Sports Medicine,The Second Hospital of Tangshan from May 2011 to May 2020 were selected,including 41 males and 26 females,with a mean age of(45.83±7.39)years.They were divided into three groups according to different grafts used:autologous ligament group(n=24),allogeneic ligament group(n=22),and LARS artificial ligament group(n=21).Follow-up for more than 36 months after revision was performed to evaluate the effect of revision. RESULTS AND CONCLUSION:(1)International Knee Documentation Committee(IKDC)score,Lysholm knee score,and Tegner motor score 1 year after surgery and at the last follow-up in the three groups were higher than those before surgery(P<0.05).There were no significant differences in IKDC score,Lysholm knee score,and Tegner motor score among the three groups 1 year after surgery and the last follow-up(P>0.05).(2)The lateral differences of KT-1000 at 1 year after surgery and the last follow-up among the three groups were lower than those before surgery(P<0.05).The lateral difference of KT-1000 and the positive rate of the axial shift test in the last follow-up of the LARS artificial ligament group were higher than those in the autologous ligament group and allogeneic ligament group(P<0.05).(3)At the last follow-up,X-ray films showed no obvious enlargement of the reconstructed bone tunnel and no obvious failure of the graft fixation device.There was no obvious aggravation of osteoarthritis,but bone density decreased significantly in some elderly patients.(4)These findings suggest that anterior cruciate ligament revision with LARS artificial ligaments can obtain good initial stability,but with the extension of time,the stability of partial cases tends to decrease,even with reconstructed ligament failure.Both allogeneic and autogenous ligaments can obtain good clinical efficacy in anterior cruciate ligament revision.
4.The Effect of Shenqi Jianxin Formula (参芪健心方) on Cardiomyocyte Pyroptosis in Chronic Heart Failure Model Rats Based on the NLRP3/Caspase-1 Signaling Pathway
Guoqing LIANG ; Ran XIA ; Yinyan WANG ; Pan LIU ; Jun ZHANG ; Xiaohua DAI
Journal of Traditional Chinese Medicine 2024;65(1):94-102
ObjectiveTo investigate the possible mechanism of Shenqi Jianxin Formula (参芪健心方) in the treatment of chronic heart failure (CHF) from the perspective of pyroptosis. MethodsFifty-two rats were randomly divided into sham operation group (n=8) and modeling group (n=44). In the modeling group, the anterior descending branch of the left coronary artery was ligated to construct CHF rat model. Forty successfully-modelled rats were randomly divided into model group, Entresto group, Shenqi Jianxin Formula group, MCC950 group and the combination group (Shenqi Jianxin Formula plus MCC950), with 8 rats in each group. In Shenqi Jianxin Formula group, 7.4 g/(kg·d) of Shenqi Jianxin Formula was given by gavage, while in Entresto group, 68 mg/(kg·d) of Entresto suspension was given by gavage; in MCC950 group, MCC950 was injected intraperitoneally with 10 mg/kg once every other day, and in the combination group, 7.4 g/(kg·d) of Shenqi Jianxin Formula was given by gavage, and MCC950 was injected intraperitoneally with 10 mg/kg once every other day; 10 ml/(kg·d) of saline was given by gavage in the sham operation group and the model group. After 3 weeks of continuous intervention, serum brain B-type natriuretic peptide (BNP), creatine kinase isoenzyme MB (CK-MB), interleukin 1β (IL-1β), and interleukin 18 (IL-18) levels were detected by ELISA; HE staining and MASSON staining were used to observe pathological changes in rat myocardium. Except for the Entresto group, western blot technique was used to detect the expression of NOD-like receptor protein 3 (NLRP3), caspase-1, and apoptosis-associated speck-like protein possessing a caspase-recruiting domain (ASC); RT-PCR was used to detect the expression of NLRP3 and caspase-1 mRNA. ResultsCompared with the sham operation group, HE staining of rats in the model group showed obvious myocardial injury, while MASSON staining showed increased area of collagen fibrosis, and serum BNP, CK-MB, IL-1β, IL-18, myocardial tissue NLRP3, caspase-1, ASC protein expression and NLRP3, caspase-1 mRNA expression were all elevated (P<0.05). Compared with those in the model group, cardiomyocyte injury of rats and collagen fibrosis area were reduced, and serum BNP, CK-MB, IL-1β, and IL-18 contents were all reduced in Shenqi Jianxin Formula group, Entresto group, MCC950 group, and the combination group; except for Entresto group, myocardial tissue NLRP3, caspase-1, ASC protein expression and NLRP3, caspase-1 mRNA expression were reduced in the remaining three medication group (P<0.05). Compared with Shenqi Jianxin Formula group, the MCC950 group and the combination group showed decreased serum IL-1β and IL-18 content, collagen fibrosis area, myocardial tissue NLPR3, caspase-1 protein expression, and caspase-1 mRNA expression, and decreased ASC and NLRP3 mRNA expression was shown in the combination group (P<0.05). Compared with MCC950 group, collagen fibrosis area was reduced, and serum IL-18 content, NLRP3, caspase-1 mRNA expression were reduced in the combination group (P<0.05). ConclusionShenqi Jianxin Formula can effectively improve the myocardial injury and heart failure in rats with CHF, and its mechanism may be related to the inhibition of cardiomyocyte pyroptosis through NLPR3/Caspase-1 pathway to reduce the level of intramyocardial inflammation. The combined use of MCC950 with Shenqi Jianxin Formula could more effectively inhibite myocardial pyroptosis, with better therapeutic result than single use of each part.
5.Targets and validation of Salvia miltiorrhiza in myopia through network pharmacology
Xiaonan LU ; Jie LI ; Guangqi AN ; Zhenhui LIU ; Chunyu LIANG ; Shuzhen DAI
Chinese Journal of Experimental Ophthalmology 2024;42(4):322-328
Objective:To explore and validate the targets of Salvia miltiorrhiza in myopia using network pharmacology and molecular docking technology. Methods:The TCMSP database was used to extract the targets of Salvia miltiorrhiza.GeneCards, DisGeNET, Malacard and OMIM databases were used to extract the myopia-related targets.The target intersection was taken, and the intersecting targets were selected to extract the corresponding active ingredients of traditional Chinese medicine (TCM) and construct the pharmacological regulatory network of TCM using Cytoscape.The protein interaction network map for the key target genes was constructed using the String database, and the relevant proteins were selected to download the three-dimensional structures of the active ingredients from the PubChem database, and molecular docking was performed using AutoDockvina software.Twelve 3-week-old guinea pigs were induced with lens-induced myopia (LIM) in the right eye and randomly divided into normal saline group and sodium danshensu group, with 6 animals in each group.During the maintenance of LIM, periocular injection of 1 ml normal saline or sodium danshensu was performed daily.The contralateral eye was used as a negative control.On days 0, 14, and 28 of the experiment, the axial length of both eyes was measured by A-scan ultrasonography, and the refractive status was assessed with a streak retinoscope.To avoid individual differences, relative spherical equivalent (treated eye-contralateral eye) and relative axial length (treated eye-contralateral eye) were compared.On day 28, the relative expression levels of hypoxia-inducible factor-1α (HIF-1α) and transforming growth factor-β1 (TGF-β1) proteins were determined by Western blot.The feeding and use of laboratory animals followed the 3R principle, and the research program was approved by the Ethics Committee of Experimental Animal Center of Zhengzhou University (No.ZZU-LAC 202320405[02]). Results:Sixteen intersecting key targets were screened for myopia and TCM components derived from Salvia divinorum.A TCM network pharmacology map and protein interaction map were constructed with Salvia divinorum as a drug candidate, and the corresponding proteins of target genes, such as MMP2, TGFB1, and MMP9 were screened to perform molecular docking with the active ingredients, such as lignocellulosic acid, danshensu, tanshinone ⅡA, and so on.After 14 days of induction, the relative spherical equivalent and relative axial length were (-4.67±1.03)D and (0.67±0.26)mm in sodium danshensu group, and (-6.30±1.22)D and (1.08±0.34)mm normal saline group, indicating slower myopia progression and axial elongation in sodium danshensu group, and the differences were statistically significant ( t=2.412, P=0.039; t=2.750, P=0.049). The relative expression levels of HIF-1α protein were 0.20±0.01, 1.29±0.05 and 0.63±0.02, and the relative expression levels of TGF-β1 protein were 0.93±0.05, 0.25±0.01 and 0.74±0.05 in the negative control, normal saline and sodium danshensu groups, respectively.The expression of HIF-1α protein was higher in sodium danshensu group than in negative control group but lower than in the normal saline group, and the expression of TGF-β1 protein was lower in sodium danshensu group than in negative control group but higher than in the normal saline group, showing statistically significant differences (all at P<0.05). Conclusions:Natural compounds extracted from Salvia divinorum extracts may serve as potential drug candidates to combat scleral hypoxia and improve scleral extracellular matrix remodeling.
6.Nanomaterial-based Therapeutics for Biofilm-generated Bacterial Infections
Zhuo-Jun HE ; Yu-Ying CHEN ; Yang ZHOU ; Gui-Qin DAI ; De-Liang LIU ; Meng-De LIU ; Jian-Hui GAO ; Ze CHEN ; Jia-Yu DENG ; Guang-Yan LIANG ; Li WEI ; Peng-Fei ZHAO ; Hong-Zhou LU ; Ming-Bin ZHENG
Progress in Biochemistry and Biophysics 2024;51(7):1604-1617
Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.
7.Effects of vecuronium bromide down-regulation of lncRNA FGD5-AS1 on the proliferation and apoptosis of gastric cancer cell HGC-27
Bin FU ; Ke ZHANG ; Xing LIU ; Chuan-Xing DAI ; Zu-Qi CHEN ; De-Liang QIU
The Chinese Journal of Clinical Pharmacology 2024;40(2):205-209
Objective To investigate the effect of vecuronium bromide on the malignant biological behavior of gastric cancer cells and its molecular mechanism.Methods Gastric cancer cells HGC-27 were divided into control group,experimental-L,-M,-H groups,si-NC group,si-FGD5-AS1 group,pcDNA-FGD5-AS1 group,pcDNA group,experimental-H+pcDNA group,experimental-H+pcDNA-FGD5-AS1 group.The control group was cultured conventionally;experimental-L,-M,-H groups were treated with 5,10 and 20μmol·mL-1 vecuronium bromide,respectively;si-FGD5-AS1 group and the si-NC group were transfected with lncRNA FGD5-AS1 interference expression vector and negative control plasmid,respectively;pcDNA-FGD5-AS1 group and pcDNA group were transfected with lncRNA FGD5-AS1 overexpression vector and negative control plasmid,respectively;lncRNA FGD5-AS1 overexpression vector and negative control plasmid were transfected into HGC-27 cells in the experimental-H+pcDNA-FGD5-AS1 group and experimental-H+pcDNA group,and then treated with 20 μmuol·mL-1 vecuronium bromide.Methyl thiazolyl tetrazolium(MTT),flow cytometry and real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)were applied to dectect cell viability,apoptosis and lncRNA FGD5-AS1 expression.Results The cell activity of control group,experimental-L,-M,-H groups,si-NC group,si-FGD5-AS1 group,pcDNA group,PCDNA-FGD5-AS1 group,experimental-H+pcDNA group and experimental-H+PCDNA-FGD5-AS1 group were 1.31±0.07,0.58±0.03,1.31±0.06,0.51±0.03,1.29±0.08,1.68±0.15,0.59±0.03 and 1.16±0.06;the apoptosis rates were(6.49±0.44)%,(23.52±0.98)%,(6.42±0.44)%,(26.75±0.97)%,(6.72±0.38)%,(2.56±0.19)%,(23.56±1.04)%and(11.65±0.47)%;the expression levels of lncRNA FGD5-AS1 were 1.00±0.05,0.37±0.02,0.99±0.05,0.21±0.02,1.00±0.03,2.98±0.12,0.38±0.02 and 0.87±0.05,respectively.The above indexes were compared with the control group and experimental-H group,those in the si-FGD5-AS1 group were compared with the si-NC group,those in the pcDNA-FGD5-AS1 group were compared with the pcDNA group,and those in the experimental-H+pcDNA-FGD5-AS1 group were compared with the experimental-H+pcDNA group,the differences were statistically significant(all P<0.05).Conclusion Vecuronium bromide may inhibit the proliferation of HGC-27 cells and promote cell apoptosis by down-regulating lncRNA FGD5-AS1.
8.Research status of the correlation between ferroptosis and renal fibrosis
Li-Juan LIANG ; En-Lai DAI ; Jun-Yuan BAI ; Can LIU ; Zhao-Ran DING ; Jie ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2278-2282
Renal fibrosis is a common pathological manifestation of all chronic kidney diseases.Ferroptosis is closely related to the pathogenesis of renal fibrosis and can influence the onset of renal fibrosis,and it is the most critical step in the development of renal fibrosis.The paper describes the relationship between ferroptosis and renal fibrosis,discusses the research progress of ferroptosis on renal fibrosis,and further summarizes,analyzes,and describes the effective and highly targeted natural active ingredients of traditional Chinese medicines against ferroptosis,and concludes that the reversal of renal fibrosis is achieved through the regulation of the key targets of ferroptosis,with a view to providing a broad new direction for its prospects in the field of renal fibrotic disease prevention and treatment;and to provide a scientific guide for clinical treatment and basis for clinical treatment.
9.National bloodstream infection bacterial resistance surveillance report (2022) : Gram-negative bacteria
Zhiying LIU ; Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(1):42-57
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period,9 035 strains of Gram-negative bacteria were collected from 51 hospitals,of which 7 895(87.4%)were Enterobacteriaceae and 1 140(12.6%)were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli( n=4 510,49.9%), Klebsiella pneumoniae( n=2 340,25.9%), Pseudomonas aeruginosa( n=534,5.9%), Acinetobacter baumannii complex( n=405,4.5%)and Enterobacter cloacae( n=327,3.6%). The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus spp. were 47.1%(2 095/4 452),21.0%(427/2 033)and 41.1%(58/141),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(58/4 510)and 13.1%(307/2 340);62.1%(36/58)and 9.8%(30/307)of CREC and CRKP were resistant to ceftazidime/avibactam combination,respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 59.5%(241/405),while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 18.4%(98/534). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions,with statistically significant differences in the prevalence of CRKP and CRPA( χ2=20.489 and 20.252, P<0.001). The prevalence of CREC,CRKP,CRPA,CRAB,ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals( χ2=11.953,81.183,10.404,5.915,12.415 and 6.459, P<0.01 or <0.05),while the prevalence of CRPA was higher in economically developed regions(per capita GDP ≥ 92 059 Yuan)than that in economically less-developed regions(per capita GDP <92 059 Yuan)( χ2=6.240, P=0.012). Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend,and Escherichia coli is ranked in the top,while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different,and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.
10.Quality evaluation for Beidougen Formula Granules
Gui-Yun CAO ; Xue-Song ZHUANG ; Bo NING ; Yong-Qiang LIN ; Dai-Jie WANG ; Wei-Liang CUI ; Hong-Chao LIU ; Xiao-Di DONG ; Meng-Meng HUANG ; Zhao-Qing MENG
Chinese Traditional Patent Medicine 2024;46(3):717-723
AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

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