1.Dapagliflozin on acute kidney injury and prognosis in patients with diabetes mellitus type 2 and acute coronary syndrome after percutaneous coronary intervention
Huifang HAO ; Xiufeng ZHAI ; Qing LI ; Shicheng YANG ; Peng ZHANG
China Pharmacy 2025;36(4):469-474
OBJECTIVE To investigate the impact of dapagliflozin on contrast-induced acute kidney injury (CIAKI) and prognosis in patients with diabetes mellitus type 2 (T2DM) and acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). METHODS Retrospective selection of data on T2DM patients with ACS who underwent PCI treatment in the Cardiology Department of Tianjin Chest Hospital from January 1st 2021 to December 31st 2022. The patients were divided into dapagliflozin group (96 cases) and control group (148 cases) based on whether they received dapagliflozin or not. Renal function indicators were measured for all enrolled patients before PCI and at 48 h and 1 week after PCI, including blood urea nitrogen (BUN), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and β2-microglobulin (β2-MG). All patients were followed up for at least 1 year. The incidence of CIAKI and major adverse cardiac event (MACE) during follow-up were recorded for both groups. Logistic regression was used to analyze the impact of dapagliflozin on the occurrence of CIAKI, while the Log-rank test was applied to compare the incidence of MACE between the two groups. Cox regression was employed to analyze the impact of dapagliflozin on prognosis. RESULTS At 48 h and 1 week after PCI, serum levels of Cys-C, KIM-1 and β2-MG were significantly lower in the dapagliflozin group compared to the control group (P<0.05). The incidence of CIAKI was lower in the dapagliflozin group compared to the control group (6.25% vs. 14.86%, P=0.042). Logistic regression analysis revealed that dapagliflozin was an independent protective factor against CIAKI (OR=0.280, 95%CI 0.101-0.780,P=0.015). During the follow-up period, the incidence of MACE was lower in the dapagliflozin group compared to the control group (7.29% vs. 17.57%, P=0.049). Cox regression analysis indicated that dapagliflozin reduced the occurrence of MACE after PCI (HR=0.374, 95%CI 0.161-0.866, P=0.022). CONCLUSIONS With adequate hydration, the use of dapagliflozin does not increase the risk of CIAKI following PCI in T2DM patients with ACS.
2.Parabacteroides distasonis promotes liver regeneration by increasing β-hydroxybutyric acid (BHB) production and BHB-driven STAT3 signals.
Manlan GUO ; Xiaowen JIANG ; Hui OUYANG ; Xianglong ZHANG ; Shuaishuai ZHANG ; Peng WANG ; Guofang BI ; Ting WU ; Wenhong ZHOU ; Fengting LIANG ; Xiao YANG ; Shicheng FAN ; Jian-Hong FANG ; Peng CHEN ; Huichang BI
Acta Pharmaceutica Sinica B 2025;15(3):1430-1446
The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.
3.Erratum: Publisher erratum to "Fenofibrate-promoted hepatomegaly and liver regeneration are PPARα-dependent and partially related to the YAP pathway" Acta Pharmaceutica Sinica B 14 (2024) 2992-3008.
Shicheng FAN ; Yue GAO ; Pengfei ZHAO ; Guomin XIE ; Yanying ZHOU ; Xiao YANG ; Xuan LI ; Shuaishuai ZHANG ; Frank J GONZALEZ ; Aijuan QU ; Min HUANG ; Huichang BI
Acta Pharmaceutica Sinica B 2025;15(6):3354-3354
[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].
4.Clinical retrospective analysis of 41 cases of chronic recurrent parotitis
ZHANG Wen ; ZHANG Zhiyong ; ZHANG Luxin ; WU Xiaolin ; LI Xiaomin ; JIA Bo ; BAO Lijie
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(12):1053-1061
Objective:
To explore the clinical manifestations and treatment plans of chronic recurrent parotitis (CRP), and to provide a reference for the clinical diagnosis and treatment of CRP.
Methods:
Approval was obtained from the hospital’s Medical Ethics Committee, and a retrospective analysis and summary of the clinical features, imaging characteristics, diagnosis, and treatment of 41 CRP patients with complete data were performed.
Results:
Among the 41 patients with CRP, 14 were male and 27 were female, with a male-to-female ratio of approximately 1:2 (14/27). The age at first-time onset ranged from 3 to 23 years, with a median age of 6 years, and there were 38 patients (92.7%, 38/41) with the first onset age of under 18 years old. The age of the first visit to our hospital ranged from 4 to 72 years old, with an average age of (41.0 ± 17.3) years; the disease duration was 0.5 to 66 years, with an average of 35.0 ± 16.1 years. Twenty-five cases had bilateral parotid gland involvement (61.0%, 25/41). The clinical manifestations of CRP are repeated swelling of one or both parotid glands, along with discomfort, and this may be accompanied by mild edema or skin flushing and pus or jelly-like secretions at the duct openings. The typical manifestations of parotid angiography are: the dominant duct and branch ducts of the parotid gland do not have specific dilation or narrowing, and the peripheral ducts show characteristic “punctate, spherical, or cavitary” dilation and delayed emptying. Of the cases, 34 had abnormal enlargement of the main duct orifice (82.9%, 34/41), and 37 presented with abnormal anterior displacement of the accessory glands (90.2%, 37/41). The treatment plan of “antibiotic perfusion + aspiration and removal of obstruction (or aspiration after obstruction dissolution)+ postprandia massage along the direction of the parotid duct (from posterior to anterior) with multiple courses for consolidation”achieved favorable outcomes. The mean follow-up period of this group was(71.1+21.9)months, and no recurrence was observed during the follow-up period.
Conclusion
CRP is more prevalent in young females and frequently presents with bilateral involvement. Congenital anatomical defects, such as abnormal enlargement of the main duct orifice and abnormal anterior displacement of the accessory glands, are important predisposing factors. The multi-course comprehensive therapy centered on antibiotic infusion, removal and dissolution of obstructions, and post-prandial massage along the direction of the parotid duct has significant therapeutic effects and deserves clinical application.
5.Protective effect of Lonicerae japonicae flos extract against doxorubicin-induced liver injury in mice
Yuming ZHANG ; Shicheng XIA ; Linlin ZHANG ; Mengxi CHEN ; Xiaojing LIU ; Qin GAO ; Hongwei YE
Journal of Southern Medical University 2024;44(8):1571-1581
Objective To explore the mechanism underlying the protective effect of Lonicerae japonicae flos(LJF)extract against doxorubicin(DOX)-induced liver injury in mice.Methods Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets,based on which the protein-protein interaction(PPI)network was constructed using STRING database for screening the core targets using Cytoscape software.DAVID database was used for bioinformatics analysis,and the core components and core targets were verified using molecular docking study.In a mouse model of DOX-induced liver injury,the effect of LJF extract on liver pathologies,serum levels of ALT and AST,and hepatic expressions of HYP,ROS,TNF-α,IL-6,COL-IV and P53 proteins were evaluated using HE and Masson staining,ELISA,and Western blotting.Results We identified 12 core targets from 43 intersection genes involving cancer pathway,IL-17 signaling pathway,and TNF signaling pathways.Molecular docking study suggested that 10 core components of LJF could bind to different core targets.The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis,increased ROS content,and enhanced expressions of TNF-α,IL-6,HYP,COL-IV and P53 proteins in the liver tissue.All these changes in the mouse models were significantly alleviated by treatment with LJF extract,suggesting obviously lowered levels of oxidative stress,inflammation and fibrosis in the liver tissues.Conclusion LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53,TNF and IL-6 to reduce liver oxidative stress,inflammation and fibrosis.
6.Study of DNA Transfer from Hand Exfoliated Cells with Non-permeable Carriers
Li YUAN ; Kainan ZOU ; Shicheng HAO ; Haixiao DENG ; Jinpei ZHANG ; Libin WU ; Hang HE
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(5):818-825
[Objective]To investigate primary and secondary transfer of exfoliated cells from human hands on non-porous substrates such as plastic steering wheel or computer mouse.[Methods]DNA detection sensitivity and detection limit for mixed DNA profiling were examined to understand our laboratory's ability to test for trace DNA.Forensic swabs were used to collect samples from volunteers'one-hour-long unwashed hands,substrates touched by volunteers'immediately or 30 min following shaking hands,and individual A's daily-use substrates touched by individual B and then by individual A again.Simulations were conducted to assess the potential for introduction of another person's exfoliated cells from hands into routine casework samples.[Results]Our laboratory can obtain a full DNA profile from as little as 0.020 ng of DNA and detect minor components in a 1:9 mixed DNA sample.85%of samples from unwashed hands yielded a full DNA profile.Primary transfer of a full DNA profile was found in 77%of substrates touched by volunteers'dominant hand 30 min after hand washing,allowing differentiation between good and poor shedders,with no significant difference in genders and substrate types.75%of substrates touched 30 min after hand washing and then immediately following handshaking yielded the other individual's DNA profile(secondary transfer),with the number of short tandem repeat(STR)loci detected ranging from 0 to 23;the percentage and number decreased substantially when the substrates were touched 30 minutes later.No foreign DNA was detected in routine casework samples with introduced exfoliated cells from hands.When two individuals took turns touching items with their hands,the major contributor to the DNA profile was not always the individual who made the last contact.[Conclusions]Primary and secondary DNA transfer can be detected on non-porous substrates,and based on the deposit of hand exfoliated cells,individuals can be categorized as good or poor shedders,which is an important factor affecting detection of DNA transfer.Besides considering the laboratory's DNA detection sensitivity,if DNA is detected on substrates by hand contact,we need to take into account the potential for secondary transfer at different levels of activity when interpreting the results.
7.Protective effect of Lonicerae japonicae flos extract against doxorubicin-induced liver injury in mice
Yuming ZHANG ; Shicheng XIA ; Linlin ZHANG ; Mengxi CHEN ; Xiaojing LIU ; Qin GAO ; Hongwei YE
Journal of Southern Medical University 2024;44(8):1571-1581
Objective To explore the mechanism underlying the protective effect of Lonicerae japonicae flos(LJF)extract against doxorubicin(DOX)-induced liver injury in mice.Methods Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets,based on which the protein-protein interaction(PPI)network was constructed using STRING database for screening the core targets using Cytoscape software.DAVID database was used for bioinformatics analysis,and the core components and core targets were verified using molecular docking study.In a mouse model of DOX-induced liver injury,the effect of LJF extract on liver pathologies,serum levels of ALT and AST,and hepatic expressions of HYP,ROS,TNF-α,IL-6,COL-IV and P53 proteins were evaluated using HE and Masson staining,ELISA,and Western blotting.Results We identified 12 core targets from 43 intersection genes involving cancer pathway,IL-17 signaling pathway,and TNF signaling pathways.Molecular docking study suggested that 10 core components of LJF could bind to different core targets.The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis,increased ROS content,and enhanced expressions of TNF-α,IL-6,HYP,COL-IV and P53 proteins in the liver tissue.All these changes in the mouse models were significantly alleviated by treatment with LJF extract,suggesting obviously lowered levels of oxidative stress,inflammation and fibrosis in the liver tissues.Conclusion LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53,TNF and IL-6 to reduce liver oxidative stress,inflammation and fibrosis.
8.Clinical study on the influence of source of infection on the pathophysiology and prognosis of sepsis
Mengyu LI ; Xingqin ZHANG ; Shicheng GAO ; Senqing YE ; Weixian XU ; Bin ZHANG
China Modern Doctor 2024;62(33):28-31,95
Objective To investigate the similarities and differences in the pathophysiological responses caused by different infection sites in sepsis patients and to evaluate the clinical significance of the source of infection on the prognosis of patients.Methods A total of 159 patients with a clear source of infection in Foshan Hospital of Traditional Chinese Medicine from January 1,2021 to January 1,2023 were selected and divided into survival group(n=98)and death group(n=61)based on their survival status within 28 days.The independent risk factors affecting the prognosis of sepsis patients were determined by multivariate Logistic regression analysis.The 28-day mortality rates of different infection source groups were compared,and the distribution differences of serum biomarkers in different infection source groups were explored by analysis of variance.Results Among the 159 patients,the frequency of infection source distribution was as follows in descending order:Respiratory tract(62.89%),urinary tract(13.84%),abdomen(13.21%),skin and soft tissue(10.06%).Multivariate Logistic regression analysis showed that age,procalcitonin,sepsis-related organ failure assessment score,and respiratory tract infection source were significant risk factors affecting the 28-day mortality of sepsis patients(P<0.05).Different infection source groups showed different degrees of differences in inflammation,coagulation,and organ dysfunction,with heterogeneity.Conclusion The differences in the source of infection lead to significant differences in the pathophysiological features(inflammatory response,coagulation activation,and organ dysfunction)and short-term prognosis(28-day mortality)of sepsis.
9.Exploration of the Mechanism of Baihe Dihuang Decoction in Treating Insomnia with Intestinal Flora Disturbance in Mice Based on TLR4/NF-κB/MLCK Pathway
Yajing WANG ; Weili YANG ; Yanrui LIU ; Haoyue LI ; Shicheng HAN ; Mengjie ZHANG ; Xi WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(5):681-693
Objective Based on TLR4/NF-κB/MLCK pathway,the therapeutic effect and mechanism of Baihe Dihuang Decoction on insomnia with intestinal flora disturbance in mice induced by p-chlorophenlalanine(PCPA)and multi-factor stimulation were studied.The aim is to provide theoretical basis for clinical use.Methods Eighty-four KM mice were randomly divided into normal group,model group,positive group(Diazepam,1.38 mg·kg-1),Baihe group(2.25 g·kg-1),Dihuang group(2.25 g·kg-1)and Baihe Dihuang Decoction group(4.5 g·kg-1).Insomnia mouse model was established by intraperitoneal injection of PCPA for 2 days combined with 4 weeks of multi-factor stimulation,including stimulating the tail with forceps clip for 2 minutes,reversing day and night for 24 hours,wetting the padding for 24 hours,tilting the cage at 45° for 24 hours,alternating the cages for 24 hours,fasting food for 24 hours,and getting cold bath for 3 minutes,etc.After successfully modeling,corresponding drug treatment was given.The anxiety-like behavior of mice was observed by elevated cross maze system.The latency and duration of sleep were observed by righting reflex experiment.16sRNA sequencing was used to analyze the composition and structure of intestinal flora in mice.The concentration changes of γ-aminobutyric acid(GABA),glutamic acid(Glu),tryptophan(Trp),5-hydroxytryptophan(5-HTP)and 5-hydroxytryptamine(5-HT)in brain and colon were detected by liquid chromatography-mass spectrometry(LC-MS).Immunohistochemical method was used to detect the expressions of zona atresia protein 1(ZO-1)and Occludin in colon.Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect the genes including interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),ZO-1,Occludin,Toll-like receptor 4(TLR4),nuclear factor κB(NF-κB)and myosin light chain kinase(MLCK)in colonic tissue.Western Blot was used to detect the expressions of TLR4,NF-κB,phosphorylated nuclear factor κB(p-NF-κB),MLCK,myosin light chain(MLC)and phosphorylated myosin light chain(p-MLC)in colonic epithelial tissue.Results Compared with the normal group,the distance of entering the open arm and the duration of stay in the open arm of model group in the elevated cross maze were significantly shortened(P<0.05).The sleep latency was significantly prolonged,and the sleep duration was significantly shortened(P<0.05).The richness and uniformity of intestinal flora were decreased(P<0.05,P<0.01).The concentration of neurotransmitters GABA,Trp,5-HTP and 5-HT in the brain decreased significantly(P<0.01),while the concentration of Glu increased significantly(P<0.01).The concentration of GABA and Glu in colon decreased significantly(P<0.01),while the concentration of Trp,5-HTP and 5-HT increased significantly(P<0.01).The expression levels of inflammatory factors IL-1β,IL-6 and TNF-α in colonic tissue were significantly increased(P<0.01),and the expression levels of ZO-1 and Occludin genes and proteins were significantly decreased(P<0.01).The gene expression levels of TLR4,NF-κB and MLCK were significantly increased(P<0.01),and the protein expression levels of TLR4,p-NF-κB,MLCK and p-MLC were significantly increased(P<0.01).Compared with the model group,Baihe Dihuang Decoction could significantly prolong the distance of entering the open arm and the duration of stay in the open arm of insomnia mice in the elevated cross maze(P<0.05).The sleep latency was significantly shortened,and the sleep duration was significantly increased(P<0.05).The richness and uniformity of intestinal flora were increased(P<0.05,P<0.01).The concentration of neurotransmitters GABA,Trp,5-HTP and 5-HT in brain was increased(P<0.05,P<0.01),and the concentration of Glu was decreased(P<0.01).The concentration of GABA and Glu in colon was increased(P<0.01),while the concentration of Trp,5-HTP and 5-HT was decreased(P<0.05,P<0.01).The expression levels of IL-1β,IL-6 and TNF-α genes were down-regulated(P<0.01),the expression levels of ZO-1 and Occludin genes and proteins were up-regulated(P<0.01),TLR4,NF-κB,MLCK gene expression levels and TLR4,p-NF-κB,MLCK,p-MLC protein expression levels were down-regulated in the pathway(P<0.01).Conclusion Baihe Dihuang Decoction can effectively treat insomnia with intestinal flora disorders.Its mechanism of action may be related to the regulation of brain and intestinal neurotransmitter disorders,down-regulating TLR4/NF-κB/MLCK signaling pathway,and up-regulating tight junction proteins expression,reducing inflammatory responses,and then repairing the mechanical barrier of intestinal mucosa.
10.Impact of dapagliflozin on incidence of contrast-induced nephropathy and cardiovascular prognosis in elderly T2DM patients after PCI
Shicheng YANG ; Peng ZHANG ; Hongliang CONG ; Naikuan FU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(6):632-636
Objective To investigate the impact of dapagliflozin on the incidence of contrast-induced nephropathy(CIN)and prognosis in elderly patients(>60 years old)with type 2 diabetes mellitus(T2DM)undergoing percutaneous coronary intervention(PCI).Methods A retrospective study was conducted on 296 elderly T2DM patients who underwent PCI in our department from January 2021 to June 2022.With a propensity score matching at a ratio of 1∶1,according to ad-ministration of dapagliflozin or not,they were divided into a dapagliflozin group(148 cases)and a control group(148 cases).Changes in renal function,including blood urea nitrogen(BUN),serum creatinine(Cr),estimated glomerular filtration rate(eGFR),β2-microglobulin(β2-MG),cystatin C(Cys C),and neutrophil gelatinase-associated lipocalin(NGAL),were detected and calculated in both groups before and in 72 h after PCI.The incidence of CIN was recorded in the two groups,and logistic regression analysis was used to determine the effect of dapagliflozin on the occurrence of CIN.The occurrence of major adverse cardiac events(MACE)was observed in the two groups during follow-up period,and Kaplan-Meier curve analysis and Log-rank test were applied to com-pare the differences in the occurrence.Results There were no significant differences in the general clinical data between the two groups(P>0.05).Serum levels of Cys C,β2-MG,and NGAL were increased in both groups in 72 h after PCI,with these levels obviously lower in the dapagliflozin group than the control group(P<0.05,P<0.01).The dapagliflozin group experienced a lower incidence of CIN than the control group(4.7%vs 12.2%,P=0.035).Logistic regression analysis indicated that dapagliflozin was an independent protective factor for CIN(OR=0.256,95%CI:0.083-0.796,P=0.019).In a follow-up period of 14.25±2.15 months,a lower incidence rate of MACE was observed in the dapagliflozin group than the control group(Log rank x2=5.257,P=0.022;HR=0.460,95%CI:0.237-0.893).Conclusion Dapagliflozin may reduce the occurrence of CIN and MACE in elderly patients with T2DM after PCI.


Result Analysis
Print
Save
E-mail