1.Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis
Jian LIU ; Hongchun ZHANG ; Chengxiang WANG ; Hongsheng CUI ; Xia CUI ; Shunan ZHANG ; Daowen YANG ; Cuiling FENG ; Yubo GUO ; Zengtao SUN ; Huiyong ZHANG ; Guangxi LI ; Qing MIAO ; Sumei WANG ; Liqing SHI ; Hongjun YANG ; Ting LIU ; Fangbo ZHANG ; Sheng CHEN ; Wei CHEN ; Hai WANG ; Lin LIN ; Nini QU ; Lei WU ; Dengshan WU ; Yafeng LIU ; Wenyan ZHANG ; Yueying ZHANG ; Yongfen FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):182-188
The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis (GS/CACM 337-2023) was released by the China Association of Chinese Medicine on December 13th, 2023. This expert consensus was developed by experts in methodology, pharmacy, and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine (CACM) and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine (pulmonary diseases) and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung, acute bronchitis, and acute attack of chronic bronchitis from the aspects of applicable populations, efficacy evaluation, usage, dosage, drug combination, and safety. It is expected to guide the rational drug use in medical and health institutions, give full play to the unique value of Qinbaohong Zhike oral liquid, and vigorously promote the inheritance and innovation of Chinese patent medicines.
2.Mechanism of Danshenol A in Alleviating Myocardial Ischemia-reperfusion Injury-induced Ferroptosis of Cardiomyocytes
Lei ZHANG ; Jiangang LIU ; Peili WANG ; Tao GENG ; Die LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):135-144
ObjectiveTo investigate the mechanism of danshenol A (DA) pretreatment in alleviating myocardial ischemia-reperfusion injury (MIRI) by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats, and an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank, model (OGD/R), DA, ferroptosis inducer (erastin), and ferroptosis inhibitor (Fer-1) groups. Cell viability was assessed by the methyl thiazolyl tetrazolium (MTT) assay. Biochemical assays were performed to measure the superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and ferrous ion (Fe2+) levels. Dihydroethidium (DHE) fluorescence assay was adopted to quantify the reactive oxygen species (ROS) level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels, respectively, of prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and acyl-coA synthetase long-chain family 4 (ACSL4). Sixty SPF-grade healthy male SD rats were randomly assigned to control, model (MIRI), DA, erastin, and Fer-1 groups. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the serum levels of cardiac troponin I (cTnI), lactate dehydrogenase (LDH), and creatine kinase (CK). Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin (HE) staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL). The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment: compared with the blank group, the OGD/R model group showed reduced cell viability, elevated levels of ROS, MDA, and Fe2+, up-regulated mRNA and protein levels of ACSL4, lowered levels of SOD and GSH, and down-regulated mRNA and protein levels of PTGS2, GPX4, and FTH1 (P<0.05,P<0.01). The DA and Fer-1 groups exhibited consistent trends: cell viability, SOD and GSH levels, and the mRNA and protein levels of PTGS2, GPX4, and FTH1 were significantly restored, while the ROS, MDA, and Fe2+ levels, and the mRNA and protein levels of ACSL4 were reduced (P<0.05,P<0.01). In vivo experiment: Compared with the control group, the MIRI model group showed elevated serum levels of cTnI, LDH, and CK, increased cardiomyocyte apoptosis rate, risen levels of ROS, MDA, and Fe2+, and up-regulated mRNA and protein levels of ACSL4. However, both DA and Fer-1 groups exhibited reductions in the indicators above (P<0.05). Compared with the control group, the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2, GPX4, and FTH1 (P<0.05). In contrast, both DA and Fer-1 upregulated these indicators (P<0.05), effectively reversing the trends in the model group. In addition, the MIRI model group showed swelling of cardiomyocytes, disarrangement of cardiac muscle fibers, and massive inflammatory cell infiltration, which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation, demonstrating therapeutic potential in acute myocardial infarction.
3.Mechanism of Danshenol A in Alleviating Myocardial Ischemia-reperfusion Injury-induced Ferroptosis of Cardiomyocytes
Lei ZHANG ; Jiangang LIU ; Peili WANG ; Tao GENG ; Die LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):135-144
ObjectiveTo investigate the mechanism of danshenol A (DA) pretreatment in alleviating myocardial ischemia-reperfusion injury (MIRI) by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats, and an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank, model (OGD/R), DA, ferroptosis inducer (erastin), and ferroptosis inhibitor (Fer-1) groups. Cell viability was assessed by the methyl thiazolyl tetrazolium (MTT) assay. Biochemical assays were performed to measure the superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and ferrous ion (Fe2+) levels. Dihydroethidium (DHE) fluorescence assay was adopted to quantify the reactive oxygen species (ROS) level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels, respectively, of prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and acyl-coA synthetase long-chain family 4 (ACSL4). Sixty SPF-grade healthy male SD rats were randomly assigned to control, model (MIRI), DA, erastin, and Fer-1 groups. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the serum levels of cardiac troponin I (cTnI), lactate dehydrogenase (LDH), and creatine kinase (CK). Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin (HE) staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL). The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment: compared with the blank group, the OGD/R model group showed reduced cell viability, elevated levels of ROS, MDA, and Fe2+, up-regulated mRNA and protein levels of ACSL4, lowered levels of SOD and GSH, and down-regulated mRNA and protein levels of PTGS2, GPX4, and FTH1 (P<0.05,P<0.01). The DA and Fer-1 groups exhibited consistent trends: cell viability, SOD and GSH levels, and the mRNA and protein levels of PTGS2, GPX4, and FTH1 were significantly restored, while the ROS, MDA, and Fe2+ levels, and the mRNA and protein levels of ACSL4 were reduced (P<0.05,P<0.01). In vivo experiment: Compared with the control group, the MIRI model group showed elevated serum levels of cTnI, LDH, and CK, increased cardiomyocyte apoptosis rate, risen levels of ROS, MDA, and Fe2+, and up-regulated mRNA and protein levels of ACSL4. However, both DA and Fer-1 groups exhibited reductions in the indicators above (P<0.05). Compared with the control group, the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2, GPX4, and FTH1 (P<0.05). In contrast, both DA and Fer-1 upregulated these indicators (P<0.05), effectively reversing the trends in the model group. In addition, the MIRI model group showed swelling of cardiomyocytes, disarrangement of cardiac muscle fibers, and massive inflammatory cell infiltration, which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation, demonstrating therapeutic potential in acute myocardial infarction.
4.Formulation Characteristics and Efficacy Classification of Chinese Patent Medicines for Cardiovascular and Cerebrovascular Diseases Based on Diagram of Tangye Jingfa Tu
Yuguang WANG ; Runtao ZHUANG ; Yanqing LIU ; Shen LI ; Xiaolan LIN ; Rui JIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):224-233
ObjectiveChinese patent medicines for cardiovascular and cerebrovascular diseases are diverse and complex in their efficacy. The traditional classification method based on efficacy categories has certain limitations and cannot meet the clinical needs for individualized drug selection and variety comparison. This article, based on the formulation compatibility analysis technology of "Tangye Jingfa Tu", clarifies the composition and efficacy characteristics of common Chinese patent medicines used for cardiovascular and cerebrovascular diseases, providing support for the precise selection of these medicines. MethodsFifty-six representative Chinese patent medicines, covering all the efficacy subcategories of "stasis-resolving agents" in the National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance Drug Catalogue (2023) (more than 50% of the total), were selected for the study. Within the knowledge system of "Tangye Jingfa Tu", the compatibility structure of herbal flavors and the proportion structure of herbal quantities for each Chinese patent medicine were determined. The correlation between these structures and the efficacy categories was analyzed to identify the similarities and differences among the selected Chinese patent medicines. Additionally, the efficacy was reclassified and compared according to the theoretical framework of tonifying and purging methods of five Zang organs in the "Tangye Jingfa Tu". ResultsThe representative Chinese patent medicines included in the analysis were Shexiang Baoxin pills, Danshen tablets, Qili Qiangxin capsules, Breviscapine tablets, etc., covering all the efficacy subcategories of "stasis-resolving agents". Among the 56 representative Chinese patent medicines, salty flavor was the most common (48), followed by pungent (33), and sweet (26). According to the dominant herbal flavor, salty flavor was the most common (37), followed by pungent (9), and sour (5). According to the dominant herbal quantity, salty flavor was the most common (27), followed by sour (7), and pungent (5). Furthermore, Chinese patent medicines with different efficacy subtypes showed different flavor characteristics. For example, most Qi-invigorating and blood-activating agents contained sweet drugs for tonifying the spleen (9/10), most Qi-moving and blood-activating agents contained pungent drugs for tonifying the liver (7/8), and all kidney-invigorating and blood-activating agents contained bitter drugs for tonifying the kidneys (6/6). However, the efficacy classification of individual medicines did not always align with the compatibility characteristics of their formulas, as seen with Dengyin Naotong capsules. ConclusionThe formulations of Chinese patent medicines for cardiovascular and cerebrovascular diseases predominantly feature salty, sour, and pungent flavors, which largely conform to the therapeutic principles of "nourishing the heart with salt and soothing the heart with sour" and the liver-heart, heart-spleen mother-child treatment relationship shown in the "Tangye Jingfa Tu". Using the "Tangye Jingfa Tu" framework to conduct research on the structure and efficacy characteristics of Chinese patent medicines is objective and effective.
5.Formulation Characteristics and Efficacy Classification of Chinese Patent Medicines for Cardiovascular and Cerebrovascular Diseases Based on Diagram of Tangye Jingfa Tu
Yuguang WANG ; Runtao ZHUANG ; Yanqing LIU ; Shen LI ; Xiaolan LIN ; Rui JIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):224-233
ObjectiveChinese patent medicines for cardiovascular and cerebrovascular diseases are diverse and complex in their efficacy. The traditional classification method based on efficacy categories has certain limitations and cannot meet the clinical needs for individualized drug selection and variety comparison. This article, based on the formulation compatibility analysis technology of "Tangye Jingfa Tu", clarifies the composition and efficacy characteristics of common Chinese patent medicines used for cardiovascular and cerebrovascular diseases, providing support for the precise selection of these medicines. MethodsFifty-six representative Chinese patent medicines, covering all the efficacy subcategories of "stasis-resolving agents" in the National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance Drug Catalogue (2023) (more than 50% of the total), were selected for the study. Within the knowledge system of "Tangye Jingfa Tu", the compatibility structure of herbal flavors and the proportion structure of herbal quantities for each Chinese patent medicine were determined. The correlation between these structures and the efficacy categories was analyzed to identify the similarities and differences among the selected Chinese patent medicines. Additionally, the efficacy was reclassified and compared according to the theoretical framework of tonifying and purging methods of five Zang organs in the "Tangye Jingfa Tu". ResultsThe representative Chinese patent medicines included in the analysis were Shexiang Baoxin pills, Danshen tablets, Qili Qiangxin capsules, Breviscapine tablets, etc., covering all the efficacy subcategories of "stasis-resolving agents". Among the 56 representative Chinese patent medicines, salty flavor was the most common (48), followed by pungent (33), and sweet (26). According to the dominant herbal flavor, salty flavor was the most common (37), followed by pungent (9), and sour (5). According to the dominant herbal quantity, salty flavor was the most common (27), followed by sour (7), and pungent (5). Furthermore, Chinese patent medicines with different efficacy subtypes showed different flavor characteristics. For example, most Qi-invigorating and blood-activating agents contained sweet drugs for tonifying the spleen (9/10), most Qi-moving and blood-activating agents contained pungent drugs for tonifying the liver (7/8), and all kidney-invigorating and blood-activating agents contained bitter drugs for tonifying the kidneys (6/6). However, the efficacy classification of individual medicines did not always align with the compatibility characteristics of their formulas, as seen with Dengyin Naotong capsules. ConclusionThe formulations of Chinese patent medicines for cardiovascular and cerebrovascular diseases predominantly feature salty, sour, and pungent flavors, which largely conform to the therapeutic principles of "nourishing the heart with salt and soothing the heart with sour" and the liver-heart, heart-spleen mother-child treatment relationship shown in the "Tangye Jingfa Tu". Using the "Tangye Jingfa Tu" framework to conduct research on the structure and efficacy characteristics of Chinese patent medicines is objective and effective.
6.Analysis of Animal Model Construction Methods of Different Subtypes of Gastroesophageal Reflux Disease Based on Literature
Mi LYU ; Kaiyue HUANG ; Xiaokang WANG ; Yuqian WANG ; Xiyun QIAO ; Lin LYU ; Hui CHE ; Shan LIU ; Fengyun WANG
Journal of Traditional Chinese Medicine 2025;66(13):1386-1394
ObjectiveTo collate and compare the characteristics and differences in the methods for constructing animal models of different subtypes of gastroesophageal reflux disease (GERD) based on literature, providing a reference for researchers in this field regarding animal model construction. MethodsExperimental studies related to GERD including reflux esophagitis (RE), nonerosive reflux disease (NERD) and Barrett's esophagus (BE) model construction from January 1, 2014 to January 27, 2024, were retrieved from databases such as CNKI, Wanfang, VIP, Web of Science, and Pubmed. Information on animal strains, genders, modeling methods including disease-syndrome combination models, modeling cycles were extracted; for studies with model evaluation, the methods of model evaluation were also extracted; then analyzing all those information. ResultsA total of 182 articles were included. SD rats were most frequently selected when inducing animal models of RE (88/148, 59.46%) and NERD (9/14, 64.29%). For BE, C57BL/6 mice were most commonly used (11/20, 55.00%). Male animals (RE: 111/135, 82.22%; NERD: 11/14, 78.57%; BE: 10/12, 83.33%) were the most common gender among the three subtypes. The key to constructing RE animal models lies in structural damage to the esophageal mucosal layer, gastric content reflux, or mixed reflux, among which forestomach ligation + incomplete pylorus ligation (42/158, 26.58%) was the most common modeling method; the key to constructing NERD animal models lies in micro-inflammation of the esophageal mucosa, visceral hypersensitivity, and emotional problems, and intraperitoneal injection of a mixed suspension of ovalbumin and aluminum hydroxide combined with acid perfusion in the lower esophagus (8/14, 57.14%) was the most common modeling method; the key to constructing BE animal models lies in long-term inflammatory stimulation of the esophageal mucosa and bile acid reflux, and constructing interleukin 2-interleukin 1β transgenic mice (7/25, 28.00%) was the most common modeling method. Adverse psychological stress was the most common method for inducing liver depression. ConclusionsThe construction key principles and methodologies for RE, NERD, and BE animal models exhibit significant differences. Researchers should select appropriate models based on subtype characteristics (e.g., RE focusing on structural damage, NERD emphasizing visceral hypersensitivity). Current studies show insufficient exploration of traditional Chinese medicine disease-syndrome combination models. Future research needs to optimize syndrome modeling approaches (e.g., composite etiology simulation) and establish integrated Chinese-Western medicine evaluation systems to better support mechanistic investigations of traditional Chinese medicine.
7.Determination method of clopidogrel and its metabolites in rat plasma and its pharmacokinetic study
Huan YI ; Lan MIAO ; Changying REN ; Li LIN ; Mingqian SUN ; Qing PENG ; Ying ZHANG ; Jianxun LIU
China Pharmacy 2025;36(13):1599-1603
OBJECTIVE To establish a method for determining the contents of clopidogrel (CLP), clopidogrel carboxylate (CLP-C), clopidogrel acyl-β-D-glucuronide (CLP-G) and contents of clopidogrel active metabolite (CAM) in rat plasma, and to investigate their in vivo pharmacokinetic characteristics. METHODS The Shisedo CAPCELL ADME column was used with a mobile phase consisting of water and acetonitrile (both containing 0.1% formic acid) in a gradient elution. The flow rate was 0.4 mL/min, and the column temperature was maintained at 20 ℃. The injection volume was 2 μL. The analysis was performed in positive ion mode using electrospray ionization with multiple reaction monitoring. The ion pairs for quantitative analysis were m/z 322.1→211.9 (for CLP), m/z 308.1→197.9 (for CLP-C), m/z 322.1→154.8 (for CLP-G), m/z 504.1→154.9 [for racemic CAM derivative (CAMD)]. Six rats were administered a single intragastric dose of CLP (10 mg/kg). Blood samples were collected before medication and at 0.08, 0.33, 0.66, 1, 2, 4, 6, 10, 23 and 35 hours after medication. The established method was used to detect the serum contents of various components in rats. Pharmacokinetic parameters were then calculated using WinNonlin 6.1 software. RESULTS The linear ranges for CLP, CLP-C and CAMD were 0.08-20.00, 205.00-8 000.00, and 0.04-25.00 ng/mL, respectively (r≥0.990). The relative standard deviations for both intra-day and inter-day precision tests were all less than 15%, and the relative errors for accuracy ranged from -11.68% to 14.40%. The coefficients of variation for the matrix factors were all less than 15%, meeting the requirements for bioanalytical method validation. The results of the pharmacokinetic study revealed that, following a single intagastric administration of CLP in rats, the exposure to the parent CLP in plasma was extremely low. Both the area under the drug concentration-time curve (AUC0-35 h) and the peak concentration of the parent CLP were lower than those of its metabolites. The AUC0-35 h of the active metabolite CAM was approximately 43 times that of CLP, though it had a shorter half-life (2.53 h). The inactive metabolite CLP-C exhibited the highest exposure level, but it reached its peak concentration the latest and was eliminated slowly. The AUC0-35 h of CLP-G was about four times that of CAM, and its half-life was similar to that of CLP-C. CONCLUSIONS This study successfully established an liquid chromatography-tandem mass spectrometry method for the determination of CLP and its three metabolites, and revealed their pharmacokinetic characteristics in rats. Specifically, the parent drug CLP was rapidly eliminated, while the inactive metabolites CLP-C and CLP-G exhibited long half-lives, and active metabolite CAM displayed a transient exposure pattern.
8.Hypertension Chronic Disease Management Platform-Assisted Traditional Chinese Medicine Comprehensive Antihypertensive Regimen for the Treatment of Primary Hypertension: A Prospective Cohort Study
Lin ZHAO ; Shuchen DING ; Mei XUE ; Hao XU
Journal of Traditional Chinese Medicine 2025;66(16):1687-1694
ObjectiveTo observe the effect of the hypertension chronic disease management platform-assisted traditional Chinese medicine (TCM) comprehensive antihypertensive regimen on blood pressure control in the real world, and evaluate patients' satisfaction with this regimen. MethodsA total of 160 patients with primary hypertension were recruited, and the patients were asked to use the hypertension chronic disease management platform for self-management and to decide whether to apply TCM comprehensive antihypertensive regimen (including Baduanjin for lowering blood pressure, acupoint massage, and Chinese medicinal tea). One month later, the changes in patients' blood pressure and the application rate of each treatment regimen were investigated. Logistic regression analysis was used to analyze the correlation between each regimen and blood pressure changes. Sensitivity analysis was performed by excluding some patients with comorbidities that might affect the use of the regimens to verify the reliability of the research results. Interaction analysis was conducted to explore whether there was a synergistic effect between the regimens, and patient satisfaction was also surveyed. ResultsA total of 149 patients were finally included. Compared with patients who did not use TCM comprehensive antihypertensive regimen regularly, those who used it regularly had a more significant decrease in diastolic blood pressure (P<0.05). The results of Logistic regression analysis showed that the decrease in systolic blood pressure was associated with the use of TCM decoctions, and the decrease in diastolic blood pressure was associated with the use of TCM decoctions and regular use of TCM comprehensive antihypertensive regimen (P<0.05). Sensitivity analysis suggested that the above research results were stable. The results of interaction analysis showed that there was no interactive effect between antihypertensive Baduanjin and acupoint massage, antihypertensive Baduanjin and Chinese medicinal tea, or acupoint massage and Chinese medicinal tea on systolic and diastolic blood pressure (P>0.05). One hundred and thirty patients (130/149, 87.25%) thought the hypertension chronic disease management platform was helpful or very helpful, and 111 patients (111/149, 74.50%) thought TCM comprehensive antihypertensive regimen was helpful or very helpful. ConclusionRegular use of TCM comprehensive antihypertensive regimen helps reduce the diastolic blood pressure level in patients with primary hypertension, and patients have a high degree of satisfaction with the use of the hypertension chronic disease management platform and TCM comprehensive antihypertensive regimen.
9.Analysis on Quality of Sojae Semen Praeparatum Based on Traditional Quality Evaluation
Yihan WANG ; Wangmin LIN ; Shuili ZHANG ; Bing YU ; Tiegui NAN ; Liping KANG ; Guofeng LI ; Xiyuan HE ; Zhilai ZHAN ; Luqi HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):31-42
ObjectiveBased on the quality evaluation experience of "it is better to have a fragrant and strong aroma" summarized by materia medica of past dynasties, the chemical components of Sojae Semen Nigrum(SSN) and Sojae Semen Praeparatum(SSP) were systematically compared and analyzed, and the main fermentation products in different fermentation time were quantitatively analyzed, so as to clarify the transformation law of internal components in the processing process and provide scientific basis for the modern quality control of SSP. MethodUltra performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used for the structural identification of the chemical constituents of SSN and SSP, and with the aid of Progenesis QI v2.3 software, the negative ion mode was employed for principal component analysis(PCA) pattern recognition, and the data were analyzed with the aid of orthogonal partial least squares-discriminant analysis(OPLS-DA) for two-dimensional data to obtain S-plot, and components with |P|>0.1 were selected as the differential constituents. The contents of isoflavonoids in SSP during fermentation was determined by UPLC, and the samples were taken every 8 h in the pre-fermentation period and every 2 d in the post-fermentation period, and the dynamic changes of isoflavonoid contents in different fermentation stages were analyzed. The contents of amino acids and nucleosides in SSP and SSN from different fermentation stages were quantitatively analyzed by phenyl isothiocyanate(PITC) pre-column derivatization and high performance liquid chromatography(HPLC) gradient elution, and the contribution of flavor substances to the "delicious" taste of SSP was discussed by taste intensity value(TAV). ResultA total of 19 kinds of differential components were screened out, mainly soybean saponins and isoflavones, and their contents decreased significantly or even disappeared after fermentation. In the pre-fermentation process of SSP, glycoside bond hydrolysis mainly occurred, and isoflavone glycosides in SSN were degraded and converted into the corresponding aglycones, the content of flavor substances such as amino acids increased gradually. In the post-fermentation process, protein degradation mainly occurred, after 8 d of post-fermentation, the content of isoflavones was basically stable, while the total content of amino acids increased by 8-40 times on average. Different amino acids form the special flavor of SSP, such as the TAV of glutamate is always ahead of other flavor substances, and sweet substances such as alanine and valine have made relatively great contributions to SSP. ConclusionBased on the law of constituent transformation, combined with the traditional evaluation index of "fragrant and strong", it is difficult to control the fermentation degree of SSP by the existing standards in the 2020 edition of Chinese Pharmacopoeia. It is suggested that description of the characteristics of SSP be refined and changed to "fragrant, delicious and slightly sweet", and at the same time, the post-fermentation index compounds such as glutamic acid, alanine and valine should be added as the quality control indicators of SSP, so as to standardize the production process and improve the quality of SSP.
10.Meta-Analysis of the Placebo Effect of Chinese Herbal Medicine in Clinical Trials of Traditional Chinese Medicine for Functional Dyspepsia
Kaiyue HUANG ; Jinke HUANG ; Fengyun WANG ; Xiangxue MA ; Xudong TANG ; Lin LYU
Journal of Traditional Chinese Medicine 2024;65(5):479-488
ObjectiveTo analyse the current implementation status of Chinese herbal medicine (CHM) placebo and systematically evaluate the placebo effect in randomised controlled trials (RCTs) of traditional Chinese medicine (TCM) for the treatment of functional dyspepsia (FD). MethodsA combination of medical subject terms and free words was used to search six databases, including PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Wanfang, for RCTs with CHM placebo group for FD published from January 31st, 1994 to September 30th, 2023. The dosage forms, composition, and methodological quality were collected and evaluated. The quality of the included articles was evaluated by Cochrane risk of bias assessment tool, and meta-analysis was performed on the CHM placebo response rate of patients with FD, and subgroup analysis and meta-regression was performed according to diagnostic criteria, efficacy criteria, duration of treatment, type of placebo, whether it contained active ingredient, and whether it evaluated placebo effects. ResultsA total of 34 publications were included involving 5046 participants, of which 2221 FD patients received CHM placebo treatment. Granules were the predominant placebo preparation, accounting for 71% (24/34); 32.35% (11/34) of the studies added real CHM to the placebo, and only 12 (35%) of the studies described appearance, odour, and taste. The placebo response rate in FD patients in the placebo group was 41% (95% CI: 0.35 to 0.47; P<0.01, I2 = 87%); there was significant difference between groups with different diagnostic criteria and different treatment durations (P<0.05 or P<0.01), but there was no significant difference between the different efficacy evaluation criteria, the different placebo preparation, the presence of a low-dose active ingredient, and the presence or absence of placebo assessment (P>0.05). ConclusionThere was a significant CHM placebo effect in patients with FD, with granules as the main preparation of placebop. Different diagnostic criteria and different treatment times may affect the response rate of patients, and the addition of low-dose real medicine to the CHM placebos has not been seen to have an effect on the response rate. Clinical investigators have not paid enough attention to placebos, and there is a lack of uniform standards and norms for the preparation and evaluation of CHM placebos.

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