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.Research progress of nano drug delivery system based on metal-polyphenol network for the diagnosis and treatment of inflammatory diseases
Meng-jie ZHAO ; Xia-li ZHU ; Yi-jing LI ; Zi-ang WANG ; Yun-long ZHAO ; Gao-jian WEI ; Yu CHEN ; Sheng-nan HUANG
Acta Pharmaceutica Sinica 2025;60(2):323-336
Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.
3.Clinical trial on prognosis prediction of ovarian cancer patients based on tumor proliferation and immune-related biomarkers
Yi-Long LIU ; Xia HE ; Xue-Wu SONG ; Rong-Sheng TONG
The Chinese Journal of Clinical Pharmacology 2024;40(2):195-199
Objective To integrate tumor proliferation and immune-related biomarkers to construct a nomogram prediction model for predicting the prognosis of ovarian cancer patients.Methods We collected clinical information from patients diagnosed with epithelial ovarian cancer(EOC)between 2009 and 2013.Immunohistochemical staining was performed to detect the expression levels of KI67,epidermal growth factor receptor(EGFR)and programmed death-ligand 1(PD-Ll)in tumor tissues.We employed Lasso-Cox regression to identify variables and construct the nomogram model.We used time-dependent receiver operating characteristic(ROC)curves,concordance index,calibration curves,and decision curve analysis(DC A)curves to assess the model's discrimination,calibration,and net clinical benefit ability,respectively.Additionally,we conducted Kaplan-Meier survival analysis to assess the prognostic value of the model's risk score.Results We included a total of 131 EOC patients who were randomly assigned to the training set(n=79)and validation set(n=52)in a 6∶4 ratio.Lasso-Cox regression identified seven variables for constructing the nomogram prediction model.The AUCs for 1-,4-,and 6-year overall survival in the training set were 0.911,0.943,and 0.968,respectively,with a consistency index of 0.86[95%confidence interval(CI):0.81-0.91].In the validation set,the AUCs for 1-,4-,and 6-year overall survival were 0.830,0.797,and 0.828,respectively,with a consistency index of 0.71(95%CI:0.64-0.78).The calibration curves in both training and validation sets demonstrated strong agreement between model-predicted survival and actual outcomes(all P>0.05).DCA curves indicated that the modeled net clinical benefit outperformed TNM staging.Patients with high-risk scores in the model exhibit poorer overall survival(P<0.01)and progression-free survival(P<0.01).Conclusion The successful development and validation of a nomogram prediction model based on tumor proliferation and immune-related biomarkers offer an efficient and straightforward clinical tool.This tool holds promise for enabling personalized treatment strategies for patients with ovarian cancer.
4.Effect and mechanism of dandelion flavonoids in alleviating lipopolysaccharide-induced colon epithelial cell injury
Jia-Qi ZHANG ; Dong-Xue MEI ; Sha LI ; Sheng-Gai GAO ; Jia ZHENG ; Hong-Xia LIANG ; Yi WANG
The Chinese Journal of Clinical Pharmacology 2024;40(4):549-553
Objective To investigate the protective effect of dandelion flavone(DF)on lipopolysaccharide(LPS)-induced colon epithelial cell injury by intervening oxidative stress and inflammation with AT-specific binding protein 2(SATB2).Methods Colon epithelial cells FHC were cultured.FHC cells were randomly divided into control group(normal cultured),LPS group(10 μg·mL-1 LPS),experimental-L group(10 μg·mL-1 LPS+1 μmol·L-1 DF),experimental-H group(10 μg·mL-1 LPS+5 μmol·L-1 DF),experimental-H+sh-NC group(transfected with sh-NC+10 μg·mL-1 LPS+5 μmol·mL-1 DF),experimental-H+sh-SATB2 group(transfected with sh-SATB2+10 μg·mL-1 LPS+5μmol·L-1 DF).The relative expression level of SATB2 protein in FHC cells was detected by Western blotting.The survival rate of FHC cells in each group was determined by tetramethylazolium blue(MTT).The apoptosis rate of FHC cells in each group was detected by flow cytometry.The levels of malondialdehyde(MDA)and interleukin-6(IL-6)in FHC cells were detected by the kit.Results The relative expression levels of SATB2 protein in control group,LPS group,experimental-H group,experimental-H+sh-NC group and experimental-H+sh-SATB2 group were 0.83±0.09,0.19±0.03,0.66±0.05,0.62±0.07 and 0.23±0.03,respectively;cell viability rates were(100.00±1.00)%,(48.16±4.31)%,(85.31±5.83)%,(81.39±6.47)%and(58.75±5.24)%,respectively;cell apoptosis rates were(3.27±0.81)%,(41.26±2.09)%,(11.35±1.04)%,(10.29±1.26)%and(35.87±2.15)%,respectively;MDA levels were(13.16±1.73),(52.87±3.49),(23.19±2.05),(20.98±3.17)and(44.87±3.05)μmol·L-1,respectively;IL-6 levels were(507.18±103.26),(2 132.09±198.15),(883.16±136.92),(801.69±119.85)and(1 736.29±206.91)pg·mL-1,respectively.The above indicators in the LPS group showed significant differences compared to the control group(all P<0.05);the above indicators in the experimental-H group showed significant differences compared to the LPS group(all P<0.05);the above indicators in the experimental-H+sh-SATB2 group showed significant differences compared to the experimental-H+sh-NC group(all P<0.05).Conclusion DF has a protective effect on LPS-induced colon epithelial cell injury by intervening oxidative stress and inflammation through SATB2.
5.Effects of Hedysarum polybotrys polysacchcaide on NF-κB/IKKβ signaling pathway in db/db mice with diabetic cardiomyopathy
Hua-Zhi ZHANG ; Zhi-Sheng JIN ; Jin-Ning SUN ; Jing SHAO ; Xiang-Xia LUO
The Chinese Journal of Clinical Pharmacology 2024;40(6):849-853
Objective To investigate the effect of hedysarum polysacchcaide(HPS)on nuclear transcription factor-κB(NF-κB)/IκB kinase β(IKKβ)signaling pathway in cardiac tissue of db/db mice with diabetic cardiomyopathy(DCM).Methods Altogether 60 7-week-old male db/db mice were randomly divided into model group,control group and experimental-H,-M,-L groups,with 12 mice in each group.In addition,12 db/m mice of the same week age were selected as the normal group.Normal group and model group were given 0.9%NaCl by intragastric administration.Experimental-L,-M,-H groups were given 50,100 and 200 mg·kg-1 HPS suspension by intragastriction,respectively.Control group was given 4 mg·kg-1 rosiglitazone suspension by intragastric administration.Six groups of rats were given the drug once a day for 8 weeks.The contents of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in myocardial tissue were detected by enzyme-linked immunosorbent assay.The mRNA expression levels of NF-κB and IKKβ in myocardial tissue were detected by real-time fluorescence quantitative polymerase chain reaction.The correlation between the expression of NF-κB protein and the content of TNF-α and IL-6 was analyzed.Results The contents of IL-6 in myocardial tissue of normal,model,control and experimental-H groups were(1.24±0.54),(7.72±0.24),(2.90±0.50)and(2.78±0.56)ng·L-1;the contents of TNF-α were(1.96±0.52),(5.25±0.72),(2.84±0.86)and(2.82±0.58)ng·L-1;the mRNA expression levels of NF-κB were I.00±0.00,3.35±0.81,2.05±0.44 and 1.67±0.22;the mRNA expression levels of IKKβ were 1.00±0.00,2.92±0.07,1.51±0.07 and 1.41±0.08,respectively.Compared with the model group,the above indexes of the control and experimental-H groups were statistically significant(P<0.01,P<0.05).The expression of NF-κB protein was positively correlated with the content of IL-6 and TNF-α,and the correlation coefficients were 0.866 and 0.740(all P<0.01).Conclusion HPS can alleviate the damage of myocardial pathology in mice,reduce myocardial collagen deposition and fibrosis,its mechanism may be through regulating the expression of NF-κB/IKKβ signaling pathway to play a role in inhibiting the inflammatory reaction.
6.Study of action of multi-glycosides of Tripterygium wilfordii in regulating sphingosine kinases pathway to improve renal injury in IgA nephropathy rats
Zi-Lu MENG ; Chun-Dong SONG ; Yao-Xian WANG ; Xia ZHANG ; Ying DING ; Xian-Qing REN ; Wen-Sheng ZHAI
The Chinese Journal of Clinical Pharmacology 2024;40(6):879-883
Objective To study the mechanism of the amelioration of renal injury in immunoglobulin A nephropathy(IgAN)rats by multi-glycosides of Tripterygium wilfordii(GTW)based on the sphingosine kinase 1(Sphk1)/sphingosine 1-phosphate receptor 2(S1PR2)signalling pathway.Methods An IgAN rat model was established by means of bovine serum albumin gavage+castor oil and carbon tetrachloride subcutaneous injection+lipopolysaccharide tail vein injection.The rats were randomly divided into the model,control and experimental groups,with 9 rats in each group,and 10 normal rats were taken as the blank group.In the control group,6.25 mg·kg-1·d-1 prednisone was given by gavage;in the experimental group,9.375 mg·kg-1·d-1GTW was given by gavage;and in the blank and model groups,0.5 mL·100 g-1·d-1 0.9%NaCl was given by gavage,and the drugs were administered to the rats once a day in each group.At the end of the 15th week,urine samples were collected and blood albumin(ALB),blood urea nitrogen(BUN),24 hour-urine protein quantification(24 h-UTP),and urine erythrocyte counts were determined in each group,and the expression levels of Sphk1/S1PR2 proteins in each group were detected by Western blotting.Results The renal pathological changes in the control and experimental groups were significantly reduced compared with those in the model group by hematoxylin-eosin staining and immunofluorescence.The levels of ALB in the blank,model,control and experimental groups were(32.49±2.23),(22.98±0.51),(26.01±1.33)and(26.53±1.92)g·L-1;the levels of BUN were(6.11±1.71),(13.75±2.96),(6.71±1.35)and(4.77±0.99)mmol·L-1;the levels of 24 h-UTP were(5.72±1.96),(9.12±2.15),(5.78±2.05)and(4.75±1.50)mg·24 h-1;the urine erythrocyte counts were(9.73±2.40),(14.62±2.60),(9.90±1.59)and(9.46±2.94)cell·μL-1;the relative expression levels of Sphk1 protein were 0.85±0.02,1.47±0.02,1.06±0.02 and 1.09±0.02;the relative expression levels of S1PR2 protein were 0.27±0.02,0.88±0.01,0.43±0.02,and 0.42±0.02,respectively.The above indexes in the model group were statistically significant when compared with those of the control group and the experimental group(all P<0.01).Conclusion GTW may reduce the proliferation of mesangial cells by inhibiting the Sphk1/S1PR2 signalling pathway,thus attenuating kidney injury in IgAN rats.
7.Two types of coumarins-specific enzymes complete the last missing steps in pyran- and furanocoumarins biosynthesis.
Yucheng ZHAO ; Yuedong HE ; Liangliang HAN ; Libo ZHANG ; Yuanzheng XIA ; Fucheng YIN ; Xiaobing WANG ; Deqing ZHAO ; Sheng XU ; Fei QIAO ; Yibei XIAO ; Lingyi KONG
Acta Pharmaceutica Sinica B 2024;14(2):869-880
Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.
8.Establishment of SHERLOCK-HBA Detection Method and Its Application in Blood Identification
Qian-Wei YAO ; Hong-Xia HE ; Sheng HU ; Yi-Xia ZHAO ; Yu LUO ; An-Quan JI ; Qi-Fan SUN
Progress in Biochemistry and Biophysics 2024;51(8):1971-1982
ObjectiveRapid and accurate identification of body fluid traces at crime scenes is crucial for case investigation. Leveraging the speed and sensitivity of nucleic acid detection technology based on SHERLOCK, our research focuses on developing a peripheral blood SHERLOCK-HBA detection system to detect mRNA in forensic practice. MethodsShort crRNA fragments targeting the blood-specific mRNA gene HBA were designed and screened, alongside RPA primers. Optimal RPA primers were selected based on specificity and amplification efficiency, leading to the establishment of the RPA system. The most efficient crRNA was chosen based on relative fluorescence units (RFU) generated by the Cas protein reaction, and the Cas protein reaction system was constructed to establish the SHERLOCK-HBA detection method. The RPA and Cas protein reaction systems in the SHERLOCK detection system were then individually optimized. A total of 79 samples of five body fluids were tested to evaluate the method’s ability to identify blood, with further verification through species-specific tests, sensitivity tests, mixed spots detection, aged samples, UV-irradiated samples, and actual casework samples. ResultsThe SHERLOCK reaction system for the peripheral blood-specific marker HBA was successfully established and optimized, enabling detection within 30 min. The method demonstrated a detection limit of 0.001 ng total RNA, better than FOB strip method and comparable to RT-PCR capillary electrophoresis. The system could detect target body fluids in mixed samples and identify blood in samples stored at room temperature for three years and exposed to UV radiation for 32 h. Detection of 11 casework samples showed performance comparable to RT-PCR capillary electrophoresis. ConclusionThis study presents a CRISPR/Cas-based SHERLOCK-HBA detection system capable of accurately, sensitively, and rapidly identifying blood samples. Introducing CRISPR/Cas technology to forensic body fluid identification represents a significant advancement in applying cutting-edge molecular biology techniques to forensic science.The method’s simplicity, shorter detection time, and independence from specialized equipment make it promising for rapid blood sample identification in forensic cases.
9.Study on multi-component contents of Jinqi Jiangtang Capsule
Tian TIAN ; Rong SHI ; Jia-sheng WU ; Tian-ming WANG ; Jian-guo LI ; Guo-feng XIA ; An-ning LI ; Yuan-yuan LI ; Yue-ming MA
Acta Pharmaceutica Sinica 2024;59(10):2849-2856
Jinqi Jiangtang Capsule (JQJTC) is clinically used for the prevention and treatment of type 2 diabetes, but the contents of its main chemical components are not yet clear. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established for the determination of 15 components in JQJTC, including new chlorogenic acid, chlorogenic acid, cryptochlorogenic acid, formononetin, ononin, calycosin, calycosin-7-glucoside, astragaloside IV, berberine, epiberberine, berberrubine, coptisine, jatrorrhizine, palmatine and magnoflorine. The method was used to determine the contents of 15 components in the capsule and then to investigate the influence of excipients on the contents of the components in JQJTC. The separation was performed on a ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with a mobile phase consisting of 0.1% acetic acid and 5 mmol·L-1 ammonium acetate (A) and acetonitrile (B) with gradient elution at a flow rate of 0.3 mL·min-1 and a column temperature at 40 ℃. Electron spray ionization was used for mass spectrometry in positive ion mode. The established method meets the requirements of methodology of content determination in Chinese pharmacopoeia. The contents of 15 components in JQJTC varied from high to low. The top 5 contents were berberine, chlorogenic acid, magnoflorine, coptisine, and cryptochlorogenic acid, accounting for 87.31% of the total content. The contents of 10 components, including the alkaloids of coptidis rhizoma (berberine, epiberberine, berberrubine, coptisine, jatrorrhizine, palmatine and magnoflorine) and the organic acids of honeysuckle (new chlorogenic acid, chlorogenic acid, and cryptochlorogenic acid) in the whole formula extract without excipients was significantly lower than that in the capsule. These components accounted for 99.20% of the determined component contents. In this experiment, an accurate, sensitive and efficient UHPLC-MS/MS method for the determination of multi-components in JQJTC was established, which stably and reliably detected the contents of 15 components in the capsule and could provide the basis for more comprehensive quality analysis. It was also found that excipients had an increasing effect on the contents of detected alkaloid and organic acid components, which may be beneficial to the effectiveness of the capsules.
10.Research progress of nanomedical drug delivery system based on aerobic glycolytic regulation for tumor therapy
Yi-jing LI ; Sheng-nan HUANG ; Zi-ang WANG ; Wei-wei ZHI ; Xia-li ZHU
Acta Pharmaceutica Sinica 2024;59(9):2509-2518
Tumor is one of the serious problems threatening human health. There are some limitations in the delivery of commonly used tumor therapy technologies, and the therapeutic effect is not satisfactory, so new anti-tumor strategies need to be developed. The process of tumor cells using glycolysis to produce energy under aerobic conditions is called aerobic glycolysis, which is closely related to tumor growth, proliferation and metastasis, and can provide a new target spot for tumor treatment. Nano drug delivery system has been widely used in targeted tumor therapy because of its advantages of targeted drug delivery, improved anti-tumor efficacy and reduced toxic side effects. Numerous studies have shown that more and more nano drug delivery systems regulates aerobic glycolytic metabolism by targeting to potential targets such as signaling factors or reaction products of aerobic glycolytic process in tumors, and therefore enhance the anti-tumor effect. This paper reviews the application of nano drug delivery system in regulating tumor aerobic glycolysis, and provides theoretical references for realizing efficient targeted tumor therapy.

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