1.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.
2.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.
3.Research status on the regulation of Nrf2/HO-1 signaling pathway by active ingredients of Chinese medicine in the prevention and treatment of diabetic kidney disease
Xie NIE ; Zhi-Gang WANG ; Yong-Lin LIANG
The Chinese Journal of Clinical Pharmacology 2024;40(2):284-288
Diabetic kidney disease(DKD)is a high incidence microvascular complication caused by diabetes mellitus(DM).Persistent high glucose induces oxidative stress in the body.nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)can play an anti-inflammatory and anti-oxidative role by inhibiting the accumulation of extracellular matrix in glomerular mesangium,inhibiting epithelial-mesenchymal transition in renal tubular epithelial cells,and inhibiting iron apoptosis,so as to improve renal function damage and delay the process of DKD.This article reviews the relationship between Nrf2/HO-1 pathway and DKD and the effect of traditional Chinese medicine active ingredients on DKD through Nrf2/HO-1 signaling pathway,in order to provide a basis for the development of new drugs.
4.Role of TGF-β/Smads signaling pathway in myocardial fibrosis of heart failure and research status of traditional Chinese medicine intervention
Yao-Hui HUO ; Jing ZHANG ; Li-Rong ZHOU ; Xiao-Gang ZHANG ; Yong-Ze GAO ; Li-Ming LIU ; Kai LIU
The Chinese Journal of Clinical Pharmacology 2024;40(3):444-448
During the progression of heart failure(HF),abnormal transduction of the transforming growth factor-β(TGF-β)/Smads signaling pathway is important mechanism of myocardial fibrosis(MF)in HF.TGF-β,a key factor in MF,is in an overexpression state in the process of MF in HF,and Smads is a major effector downstream of TGF-β.The TGF-β/Smads pathway induces abnormal proliferation of myofibroblasts,aggravates myocardial extracellular matrix deposition,and reduces the ability of the cardiac tissues to resist fibrosis,which plays a complex role in the pathogenesis of MF in HF.Traditional Chinese medicine(TCM)has the efficacy of unequivocal inhibiting myocardial collagen deposition,anti-MF,protecting the myocardium and improving cardiac function in the prevention and treatment of MF in HF and so on,and the TGF-β/Smads pathway is one of the key pathways through which TCM monomers,TCM combinations,and proprietary medicines can exert their cardioprotective effects on the HF.This paper reviews the existing experimental research results of TCM intervening in the TGF-β/Smads pathway for the treatment of MF in HF over the past 10 years,with a view to providing theoretical basis for the prevention and treatment of HF MF well as the development and of new drugs.
5.Clinical trial of aspirin and low molecular weight heparin for prevention of venous thromboembolism in patients with hand and foot trauma fractures after operation
Li SUN ; Rong LIU ; Yong LI ; Jia-Gang WANG
The Chinese Journal of Clinical Pharmacology 2024;40(12):1718-1722
Objective To observe the postoperative effects of aspirin and low-molecular-weight heparin(LMWH)in preventing venous thromboembolism(VTE)and improving distal circulation in patients with hand and foot trauma fractures.Methods Retrospectivey selected patients undergoing hand and foot trauma fracture surgery into control and treatment groups.The control group received enteric-coated aspirin,0.1 g per dose,once daily;the treatment group received subcutaneous injection of calcium-enoxaparin,4 000 U per dose,twice daily,for continuous treatment for 12 days.The incidence of VTE,coagulation function,hemorheological parameters,distal collateral circulation,and drug adverse reactions were compared between the two groups.Results There were 60 patients in each of the treatment and control groups.The incidence of postoperative deep vein thrombosis was 5.00%in the treatment group and 3.33%in the control group,while the incidence of pulmonary embolism was 1.67%in both groups,with no statistically significant differences(all P>0.05).After treatment,the activated partial thromboplastin time(APTT)in the treatment and control groups were(35.01±5.96)and(36.82±6.15)s,prothrombin time(PT)were(14.95±1.54)and(15.32±1.63)s;fibrinogen(FIB)were(3.97±1.25)and(4.36±1.02)g·L-1;D-dimer(D-D)were(309.69±56.55)and(319.03±55.32)μg·L-1;whole blood viscosity(WBV)were(13.26±3.80)and(12.26±3.61)mPa·s-1;plasma viscosity(PV)were(1.76±0.35)and(1.77±0.43)mPa·s-1,hematocrit(HCT)were(60.20±7.05)%and(58.60±6.71)%,with no statistically significant differences(all P>0.05).After treatment,the flow rates(Vmax)in the treatment and control groups were(54.27±6.64)and(51.18±5.67)cm·s-1;resistance indices(RI)were 0.59±0.13 and 0.65±0.15,showing statistical significance(all P<0.05).Comparison of drug adverse reactions such as nausea,vomiting,bleeding,and injection site hematoma between the treatment and control groups showed no statistically significant difference in the overall incidence of adverse drug reactions(P>0.05).Conclusion There was no significant difference in the efficacy of aspirin and LMWH in preventing postoperative VTE in patients with hand and foot trauma fractures,but LMWH demonstrated better improvement in distal collateral circulation.
6.Analysis of inorganic elements in different batches of earthworm polypeptides by ICP-MS combined with chemometrics technology
Hong-liu YANG ; Wei-ting ZHONG ; Yu-shi GUO ; Shu-qi LI ; Jin-chai QI ; Yong-gang LIU ; Tao MA
Acta Pharmaceutica Sinica 2024;59(4):1040-1047
To establish a method for determining 26 inorganic elements in earthworm polypeptide and determine the elemental content in different batches of earthworm polypeptide, microwave digestion method was used to pre-treat the samples, and ICP-MS method was used to determine the content of 26 elements in different batches of earthworm polypeptide. The linear relationships of 26 elements were good in the range of 0-1 000 μg·L-1, with
7.Clinical evaluation of extracorporeal cardiopulmonary resuscitation in adult sudden cardiac death
Huazhong ZHANG ; Zhongman ZHANG ; Yong MEI ; Jinru LYU ; Deliang HU ; Feng SUN ; Wei LI ; Gang ZHANG ; Xufeng CHEN
Chinese Journal of Emergency Medicine 2024;33(2):204-209
Objective:To summarize the experience and effect of extracorporeal cardiopulmonary resuscitation (ECPR) on the treatment of sudden cardiac death (SCD).Methods:The data of 120 adults with SCD-ECPR in emergency department of the first affiliated hospital of Nanjing Medical University from April 2015 to April 2023 were retrospectively analyzed. The patients were grouped by Survival/death at 90 days, OHCA/IHCA (out-of-hospital/in-hospital cardiac arrest), with/without acute myocardial infarction (AMI) and divided according to 60 min of the time from cardiac arrest to extracorporeal membrane oxygenation (ECMO) initiation (CA-Pump On time). Age, sex, Charlson comorbidity index, IHCA/OHCA, initial rhythm, no-flow time, CA-Pump On time, ECMO evacuation success rate, 90-day survival rate, ECMO treatment time were analyzed.Results:①Total of 114 adult patients with SCD-ECPR were enrolled, and 45 (39.5%) patients survived at 90 days, of whom 40 (88.9%) patients had good neurological outcomes.②Age and no-flow time were significantly lower in the 90-day survival group than that in death group, and the proportion of IHCA and shockable initial rhythm was higher. ③The no flow time in IHCA group was significantly lower than that in OHCA group, and the 90-day survival rate was higher. ④OHCA and regional interhospital transport prolonged CA-Pump On time and reduced the 90-day survival rate. ⑤The AMI group was older with a higher Charlson comorbidity index, and the 90-day survival rate was significantly lower than that in non-AMI group.Conclusions:ECPR improves the prognosis of patients with SCD, there are high benefits in patients with long healthy life expectancy, IHCA, shockable initial rhythm, and short no flow time. The smooth life-saving chain of SCD-ECPR improves survival rate, by screening high benefit candidates in patients with OHCA, delayed initiation of ECPR or requiring interhospital transport, despite CA-Pump On time > 60 min, there is still survival potential.
8.The major adverse kidney events in acute myocardial infarction with extracorporeal cardiopulmonary resuscitation
Huazhong ZHANG ; Zhongman ZHANG ; Yong MEI ; Jinru LYU ; Deliang HU ; Feng SUN ; Wei LI ; Gang ZHANG ; Xufeng CHEN
Chinese Journal of Emergency Medicine 2024;33(2):222-227
Objective:To investigate the major adverse kidney events (MAKE) in acute myocardial infarction (AMI) with extracorporeal cardiopulmonary resuscitation (ECPR).Methods:The data of 75 patients with AMI-ECPR in Emergency Medicine Department of the First Affiliated Hospital of Nanjing Medical University from April 2015 to April 2023 were retrospectively analyzed. The patients were grouped by survival/death at 90 days, with/without renal replacement therapy (RRT), and whether to initiate RRT because of acute kidney injury (AKI). age, sex, Charlson comorbidity index, OHCA/IHCA (out-of-hospital/in-hospital cardiac arrest), initial rhythm, Gensini score, ECPR initial blood gas pH and lactate value, no-flow time, time from cardiac arrest to extracorporeal membrane oxygenation (ECMO) initiation (CA-Pump On time), ECMO and RRT treatment time, 90-day survival rate were analyzed. Moreover, the renal function of the survivors was followed up.Results:① Total of 68 AMI-ECPR patients were enrolled, 22 (32.4%) patients survived at 90 days, 54 (79.4%) combined with RRT, and 48 (70.6%) MAKE within 90 days. ②Compared with the death group, the 90-day survival group had a higher proportion of initial shockable heart rhythm, a lower Gensini score, a higher ECPR initial blood gas pH and a lower lactic acid value. ③The severity of coronary artery disease, ECPR initial acidosis and hyperlactacemia in the RRT group was significantly higher than that in the non-RRT group, and all the non-RRT group patients survived. ④ There was no difference between the AKI-RRT group and the non-AKI-RRT group. Of 21 patients with stage 1 AKI initiating RRT, 5 survived, one of them still needs RRT for 90 days, and 7 patients with stage 2 to 3 AKI initiating RRT died.Conclusions:The 90-day MAKE rate in AMI-ECPR patients was as high as 70.6%, and the 90-day renal insufficiency rate in AMI-ECPR survivors with AKI was as high as 20.0%. Active initiation of RRT to avoid AKI or early initiation of RRT may improve the prognosis of AMI-ECPR patients.
9.Biomechanical analysis on Vancouver BI periprosthetic femoral fractures fixed by a customized anatomical plate system
Jiaqi WANG ; Xiaozhong LUO ; Yi TONG ; Xiaobo LU ; Weixiang SHI ; Xin ZHOU ; Gang WU ; Yong DING ; Caidong ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(24):3807-3813
BACKGROUND:At present,the use of a locking bone plate combined with steel wire or steel cable for the treatment of periprosthetic femoral fracture often adopts monocortical fixation,which is not stable and the proximal end of the bone cannot be achieved anatomically fitted by plate.The customized anatomical plate system can effectively solve this problem. OBJECTIVE:To explore the biomechanical strength of a customized anatomical plate system in fixation of Vancouver BI periprosthetic femoral fracture. METHODS:CT thin layer scanning data of normal femurs of 1 006 cases were selected and input into the MIMICS 21.0 software to establish the three-dimensional reconstruction model of the femur,which was set as the three-dimensional reconstruction group.56 complete human femoral specimens were selected as the femoral specimen group.The measured results of the two groups for femoral anatomical appearance were compared.If there was no significant difference between the two groups,the approximate appearance of a customized anatomical plate system was designed based on the measurement results in MIMICS 21.0 software and NX11.0 software.The customized anatomical plate system was designed and prepared according to the above measurement results.Eight pairs of frozen human femurs were selected to make Vancouver BI periprosthetic femoral fracture,which of the left were thin layer scanned by dual-source CT to obtain data.The data were transferred to determine the customized anatomical plate system model by the above design software.Eight sets of customized anatomical plate systems were ultimately produced,relying on the instrument company.The eight pairs of models were numbered 1-8.The left side was fixed with the customized anatomical plate system(customized anatomical plate system group);the right side was fixed with a metal locking plate system-large locking plate(claw plate group).L1-L4 and R1-R4 were subjected to vertical short-cycle loading test and vertical loading test.L5-L8 and R5-R8 were subjected to horizontal short-cycle loading test and four-point bending test.The vertical loading test and four-point bending test were used to collect bending load,bending displacement,and bending strain.Two short cycle loading tests were used to collect strain displacement to compare the maximum load,maximum displacement,bending stiffness,and short-period displacement resistance of the two kinds of bone plates. RESULTS AND CONCLUSION:(1)There were no significant differences in all indexes between the three-dimensional reconstruction group and the femoral specimen group(P>0.05).Individual customized anatomical plate system was designed based on the measurement results combined with digital software.(2)In the vertical loading test,the maximum load was higher(P=0.015),the maximum bending displacement was smaller(P=0.014),and the bending stiffness was higher(P=0.005)in the customized anatomical plate system group compared with the claw plate group.(3)In the four-point bending test,the maximum load was higher(P=0.023),the bending stiffness was higher(P=0.005),and the maximum bending displacement was not significant(P=0.216>0.05)in the customized anatomical plate system group compared with the claw plate group.(4)In the vertical short-cycle loading test,the average level of bending displacement in the customized anatomical plate system group(0.23±0.10 mm)was significantly lower than that in the claw plate group(0.44±0.02 mm)(P<0.05).(5)There was no significant difference in the average level of bending displacement between the two groups in the horizontal short cycle loading test(P>0.05).(6)It is concluded that the customized anatomical plate system has personalized anatomical characteristics,and the fixation of Vancouver BI periprosthetic femoral fracture is more stable,which has certain significance for clinical treatment.
10.Dosimetric study of two-arc and dual-arc techniques in VMAT program for lower mid-thoracic esophageal cancer
Yong-Fu FENG ; Yu-Song LONG ; Jun-Wen TAN ; Xian-Tao HE ; Gang LI ; Zhan-Yu WANG
Chinese Medical Equipment Journal 2024;45(1):62-66
Objective To compare the effects of two arc(TA)and dual arc(DA)techniques on the dose distribution to the planning target volume(PTV)and organs at risk(OAR)in volumetric modulated arc therapy(VMAT)for lower mid-thoracic esophageal cancer.Methods Ten patients with lower mid-thoracic esophageal cancer who received radiation therapy at some hospital from July 2020 to June 2022 were selected retrospectively.A TA radiation therapy plan and a DA radiation therapy plan were developed for each patient using the Ray Arc module of RayStation 4.7.5.4 planning system,and the two kinds of radiation plans were compared in terms of dosimetric parameters including D2,D5,D50,D95,D98,homogeneity index(HI),conformity index(CI),beam-on time and total monitor unit for PTV and lung V5,V10,V20,V30 and Dmean and heartV30,V40 and Dmean and spine cord Dmax for OAR.SPSS 22.0 was used for statistical analysis.Results TA and DA radiation therapy plans had no significant differences in PTV CI,HI,D2,D5,D50,D95 and beam-on time(P>0.05),and DA plan had D98 and total monitor unit higher obviously than those of TA plan(P<0.05).In terms of OARs protection,DA plan had heart V30,V40 and Dmean slightly lower than those of TA plan with non-significantly differences(P>0.05),while lung V5,V30 and Dmean and spine cordDmax significantly lower(P<0.05).Conclusion DA technique gains advantages over TA technique in PTV dose distribution and dose to OAR,and the involvement of DA technique in preparing the VMAT plan for esophageal cancer contributes to enhancing the treatment efficacy.[Chinese Medical Equipment Journal,2024,45(1):62-66]

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