1.Role and mechanism of IL-39 in K562 cells
Kangkang LYU ; Mingzhu XU ; Bo HU ; Yuejun LIU
Chinese Journal of Immunology 2024;40(7):1355-1358
Objective:To explore the role and mechanism of IL-39 in K562 cells.Methods:The expressions of IL-39R and STAT1/STAT3 in K562 cells were detected via qRT-PCR;the protein levels of phospho-STAT1/STAT3 and STAT1/STAT3 in K562 cells were detected by Western blot;the mRNA regulated by IL-39 in K562 cells was predicted by RNA sequencing.Results:rIL-39 significantly promoted the expression of IL-39R in K562 cells;IL-39 affected K562 cells through STAT1 pathway;IL-39 significantly regulated the expression of mRNA in K562 cells,thus potentially affecting a series of biological processes.Conclusion:IL-39 can directly act on K562 cells,alter gene transcriptional expression and inhibit tumor growth through the STAT1 pathway.IL-39 may similarly modulate gene expression profile in human leukemia cells.
2.A Whole-Course Nursing Quality Evaluation System for Liver Transplantation in Children Based on Donabedian Theory
Shi TANG ; Mingzhu HUANG ; Yefeng LU ; Wenzhuo LIU ; Beibei WANG ; Yan WANG
Acta Academiae Medicinae Sinicae 2024;46(1):55-61
Objective To build a whole-course nursing quality evaluation system for liver transplanta-tion in children,so as to provide a basis for nursing quality evaluation and management.Methods With Donabedian's"structure-process-outcome"model as the theoretical framework,we employed literature analysis,Delphi method,and hierarchical analysis to determine the contents and weights of indexes in the whole-course nursing quality evaluation system for liver transplantation in children.Results The three rounds of survey based on questionnaires showed the questionnaire recovery rate of 100% ,the expert authority coefficients of 0.95,0.96,and 0.98,and the Kendall's coefficients of concordance of 0.165,0.209,and 0.220,respectively(all P<0.001).The established nursing quality evaluation system included 3 first-level indexes,15 second-level inde-xes,and 67 third-level indexes.Conclusion The whole-course nursing quality evaluation system for liver trans-plantation in children that was built in this study can provide a basis for the evaluation of the nursing quality.
3.Research progress of active components and compounds of traditional Chinese medicine improving liver fibrosis by regulating JAK/STAT signaling pathway
Siming DENG ; Lijian LIU ; Liqun LI ; Chengning YANG ; Jinxiu WEI ; Jianfeng LI ; Mingzhu HUANG ; Lili XIE
China Pharmacy 2024;35(15):1923-1927
Hepatic fibrosis is a pathological process of chronic liver injury. Without timely intervention and treatment, liver fibrosis may eventually lead to liver cirrhosis and cancer. Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is closely associated with the occurrence and development of liver fibrosis. Based on this, this paper summarized and analyzed the mechanism and effects of active ingredients and compounds of traditional Chinese medicine improving liver fibrosis based on JAK/STAT signaling pathway. It is found that the active ingredients and compounds of traditional Chinese medicine that promote blood circulation and remove blood stasis (ingredients such as ethanol extract of Euonymus alatus and paclitaxel, as well as compounds such as Ershiwuwei songshi pill and Ganfukang), clear away heat and toxic material (ingredients such as betulinic acid, total flavonoids from Persicaria perfoliata, as well as compounds such as Pianzaihuang and Kehuang capsules), and sooth the liver and promote qi circulation (ingredients such as fraxetin and cucurbitacin B, as well as compounds such as Chaihu shugan powder and Xiaochaihu decoction) can all relieve liver fibrosis by inhibiting the activity of the JAK/STAT signaling pathway, reducing inflammatory reactions, and inhibiting the proliferation of hepatic stellate cells.
4.Reference range and impact factors of left ventricular trabecular and papillary muscle mass in Chinese adults explored by cardiac MRI
Gengxiao LI ; Zhen ZHANG ; Shanshan ZHOU ; Jianan XIE ; Yiyuan GAO ; Shurong LIU ; Zhiwei ZHAO ; Jun ZHAO ; Mingzhu ZHANG ; Kai SUN ; Kuncheng LI
Journal of Practical Radiology 2024;40(2):209-212
Objective To establish normal reference values for left ventricular trabecular and papillary muscle mass(TPMM)in Chinese adults using MRI and to explore its impact factors.Methods A total of 168 healthy Chinese adults were retrospectively included,and compacted and total left ventricular myocardial mass(LVM)were measured using traditional and dedicated methods,respectively.TPMM was calculated from the difference between total and compacted LVM.Independent sample t-tests and analysis of variance were used to explore the differences in TPMM among genders and age groups,while multiple linear regression was used to explore the independent correlation between TPMM and age,gender,heart rate,systolic blood pressure(SBP),fasting blood glucose(FBG),and body mass index(BMI).Results TPMM for men was significantly larger than that for female(P<0.001).TPMM in the elderly group was significantly larger in female(P<0.05),but not in men.Multiple linear regression showed that BMI and SBP were both independently positively correlated with TPMM,and female and heart rate were independently negatively correlated with TPMM(P<0.05).Conclusion This study provides age-and gender-specific normal reference values for TPMM in Chinese adults.Gender,heart rate,BMI,and SBP are all independently associated with TPMM.
5.Effects of electroacupuncture with"Zhi San Zhen"on Notch signaling pathway and synaptic plasticity in 5xFAD mice
Huaneng WEN ; Run LIN ; Yixiao WANG ; Bingshui WANG ; Lu LIU ; Chuanyao LIU ; Canxin CAI ; Shaoyang CUI ; Mingzhu XU
Chinese Journal of Tissue Engineering Research 2024;28(32):5148-5153
BACKGROUND:Alzheimer's disease is a degenerative neurological disorder characterized primarily by cognitive impairment.Acupuncture is a kind of traditional Chinese medicine therapy for treating Alzheimer's disease,but its mechanism is not yet clear. OBJECTIVE:To observe the effects of electroacupuncture with"Zhi San Zhen"on the Notch signaling pathway,β-amyloid protein(Aβ)and synaptic plasticity in 5xFAD mice. METHODS:Sixteen male,6-month-old 5xFAD mice,SPF-grade,were randomly divided into the electroacupuncture with"Zhi San Zhen"group(electroacupuncture group)and the model group,with eight mice in each group.Eight SPF-grade,male,6-month-old C57BL/6 mice were used as the wild control(wild)group.The electroacupuncture group received electroacupuncture with"Zhi San Zhen"intervention,5 times a week for 4 consecutive weeks.The model group and the wild group did not receive electroacupuncture intervention.The Morris water maze was used to preliminarily assess their learning and memory abilities.Thioflavin S staining was performed to detect Aβ plaque deposition.Western blot and real-time quantitative polymerase chain reaction(RT-qPCR)were used to measure the expression levels of transmembrane receptor protein Notch-1,Notch 1 intracellular domain(NICD),hairy and enhancer of split 1(Hes 1),hairy and enhancer of split 5(Hes 5),synaptophysin(SYN),postsynaptic density protein-95(PSD-95),and Aβ. RESULTS AND CONCLUSION:Compared with the model group,the wild group and the electroacupuncture group showed shortened escape latency,increased platform crossing times,and longer target quadrant dwell time(P<0.05).Compared with the wild group,the model group had significantly increased deposition of Aβ plaques,while electroacupuncture with"Zhi San Zhen"inhibited the deposition of Aβ plaques in the hippocampus of 5xFAD mice(P<0.05).Compared with the wild group,the model group had decreased mRNA levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5 in the hippocampal tissue of mice,and increased mRNA levels of Aβ(P<0.05).Electroacupuncture with"Zhi San Zhen"increased the mRNA levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5 in the hippocampal tissue,and decreased the mRNA level of Aβ(P<0.05).Compared with the Wild group,the model group had decreased protein expression levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5 in the hippocampal tissue of mice,and increased protein expression levels of Aβ(P<0.05).Electroacupuncture with"Zhi San Zhen"upregulated the protein expression levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5,and inhibited the protein expression of Aβ(P<0.05).To conclude,electroacupuncture with"Zhi San Zhen"can improve the learning and memory abilities of 5xFAD mice,possibly by inhibiting the deposition of Aβ protein and activating the Notch signaling pathway in the hippocampus to enhance synaptic plasticity.
6.Diagnostic value of ultra-wide field swept-source optical coherence tomo-graphy angiography combined with ultra-wide field scanning laser ophthal-moscopy in diabetic retinopathy
Mingzhu MAO ; Mengyu LI ; Dingyang WEI ; Li CHEN ; Yi LIU ; Jie LI ; Jie ZHONG
Recent Advances in Ophthalmology 2024;44(4):291-296
Objective To investigate the detection rate and grading diagnostic value of ultra-wide field swept-source optical coherence tomography angiography(UWF SS-OCTA)combined with ultra-wide field scanning laser ophthalmoscopy(UWF SLO)in diabetic retinopathy(DR)lesions.Methods In this cross-sectional study,diabetic patients attending the Ophthalmology Department of Sichuan Provincial Peoples Hospital were recruited.All participants underwent UWF SS-OC-TA,UWF SLO and fundus fluorescein angiography to detect DR lesions,including microaneurysms(MA),intraretinal hem-orrhages(IRH),nonperfusion areas(NPAs),intraretinal microvascular abnormalities(IRMAs),venous beading(VB),neovascularization elsewhere(NVE),neovascularization of the optic disc(NVD),and vitreous hemorrhage(VH).The re-sults of the combination of three imaging examinations(triple imaging)were used as the standards,evaluating the detec-tion rate and severity grading consistency in DR lesions of pairwise combinations of different imaging modalities.Results A total of 101 patients(175 eyes)were included.Compared with the triple imaging results,the detection rates of UWF SS-OCTA combined with UWF SLO for MA,IRH,NPAs,IRMAs,NVE,NVD and VH were 91%,83%,77%,69%,27%,10%and 12%,respectively,with Kappa values of 0.812,1.000,1.000,1.000,0.986,0.970 and 1.000.Compared with the triple imaging results,the combination of UWF SS-OCTA and UWF SLO demonstrated excellent consistency in grading the severity of DR(Kappa=0.943).Conclusion UWF SS-OCTA combined with UWF SLO can accurately identify MA,IRH,NPAs,IRMAs,NVE,NVD and VH,demonstrating high accuracy in DR screening and grading diagnosis,making it suitable for large-scale screening and management of DR in clinical practice.
7.Grey-scale Reversed T1-weighted MRI for Detecting Structural Lesions of the Sacroiliac Joint in Patients with Axial Spondyloarthritis
Ximeng LI ; Wenjuan LI ; Ke ZHANG ; Chaoran LIU ; Yunfei ZHU ; Yingying ZHAN ; Mingzhu LIANG ; Guobin HONG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(3):412-419
[Objective]To analyze the value of grey-scale reversed T1-weighted(rT1)MRI in the detection of structur-al lesions of the sacroiliac joint(SIJ)in patients with axial spondyloarthritis(ax-SpA).[Methods]Fifty-two ax-SpA pa-tients who underwent both MRI and CT in our hospital within a week from February 2020 to December 2022 were retrospec-tively included.Both sacral and iliac side of each SIJ on oblique coronal images were divided into anterior,middle and pos-terior portion.Two radiologists reviewed independently three groups of MRI including T1-weighted imaging(T1WI),rT1 and T1WI+rT1 images to evaluate the structural lesions like erosions,sclerosis and joint space changes in each of the 6 re-gions of the SIJ.One of the radiologist did the evaluation again one month later.CT images were scored for lesions by a third radiologist and served as the reference standard.Intra-class correlation coefficients(ICC)were calculated to test the inter-and intra-reader agreement for the assessment of SIJ lesions.A Friedman test was performed to compare the lesion results of MRI and CT image findings.We examined the diagnostic performance[accuracy,sensitivity(SE)and specifici-ty]of different groups of MRI in the detection of lesions by using diagnostic test.A McNemar test was used to compare the differences of three groups of MRI findings.[Results]CT showed erosions in 71 joints,sclerosis in 65 and joint space changes in 53.Good inter-and intra-reader agreements were found in three groups of MRI images for the assessment of le-sions,with the best agreement in T1WI+rT1.There were no difference between T1WI+rT1 and CT for the assessment of all lesions,nor between rT1 and CT for the assessment of erosions and joint space changes(P>0.05).T1WI+rT1 yielded better accuracy and SE than T1WI in detection of all lesions(Accuracy erosions:90.3%vs 76.9%;SE erosions:91.6%vs 76.1%;Accu-racy sclerosis:89.4%vs 80.8%;SE sclerosis:84.6%vs 73.9%;Accuracy joint space changes:86.5%vs 73.1%;SE joint space changes:84.9%vs 60.4%;P<0.05).rT1 yielded better accuracy and SE than T1WI in detection of erosions and joint space changes(Accuracy erosions:87.5%vs 76.9%;SE erosions:88.7%vs 76.1%;Accuracy joint space changes:85.6%vs 73.1%;SE joint space changes:83.0%vs 60.4%;P<0.05).[Conclusions]In the detection of SIJ structural lesions in ax-SpA,rT1 improves the diagnostic perfor-mance and T1WI+rT1 is more superior to others.
8.Identification of Pharmacodynamic Material Basis of Ruyi Zhenbaowan by Multidimensional Correlation Model of "Pharmacodynamic-target-component-pharmacokinetic"
Mingzhu XU ; Huaiping LI ; Zhaochen MA ; Tao LI ; Yudong LIU ; Ziqing XIAO ; Chu ZHANG ; Kedian CHEN ; Weihua MA ; Feng HUANG ; Na LIN ; Yanqiong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):68-77
ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2, and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them, and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that, plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points, and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry(UPLC-Q-TRAP/MS), and drug concentration-time curves were plotted, then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network, a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes, such as estrogen receptor 1(ESR1), cyclic adenosine monophosphate(cAMP)-dependent protein kinase catalytic subunit alpha(PRKACA) and protein kinase B1 (Akt1), and 10 corresponding potential effect components, such as glycyrrhizic acid and betulinic acid, were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components, gallic acid, apigenin-7-O-glucuronide, glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid, with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic, this study analyzes the main effective materials of Ruyi Zhenbaowan, such as glycyrrhizic acid, gallic acid, apigenin-7-O-glucuronide and apigenin, which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.
9.Identification of in Vitro and in vivo Chemical Constituents of Ruyi Zhenbaowan Based on UHPLC-Q Exactive Orbitrap HRMS
Kedian CHEN ; Zhaochen MA ; Bingbing CAI ; Ying LIU ; Yudong LIU ; Tao LI ; Mingzhu XU ; Haiping WANG ; Na LIN ; Yanqiong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):78-84
ObjectiveTo identify the chemical constituents of Ruyi Zhenbaowan in vitro and in vivo. MethodThe chemical constituents of Ruyi Zhenbaowan were identified based on UHPLC-Q Exactive Orbitrap HRMS. A total of 12 male SD rats were randomized into two groups: control (pure water) and Ruyi Zhenbaowan (1.8 g·kg-1). The rats were administrated with the suspension of Ruyi Zhenbaowan or pure water by gavage. After 1.5 h, the plasma and cerebrospinal fluid were collected. Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 150 mm, 1.7 μm) with a mixture of 0.1% formic acid aqueous solution (A) and acetonitrile (B) as the mobile phase. Gradient elution was carried out according to the procedure of 0~15 min,97%~80%A;15~30 min ,80%~60%A;30~40 min,60%~30%A;40~45 min,30%~5%A. The ion source was electrospray ionization, and scan range was m/z 100-1 500. The prototype components and the components in the plasma and cerebrospinal fluid were analyzed qualitatively by scanning in positive and negative ion modes and identified by comparison with the data in published literature and the information of standard substances. ResultA total of 126 chemical constituents were identified from the 80% methanol solution of Ruyi Zhenbaowan, and 14 and 7 prototype constituents were detected in the plasma and the cerebrospinal fluid, respectively. In addition, the fragmentation rules of apigenin, apigenin-7-O-glucuronide, galangin, liquiritin, piperine, glycyrrhizic acid, eugenol, gallic acid, and cholic acid were deduced. ConclusionThis study achieved rapid multicomponent characterization and identification of Ruyi Zhenbaowan in vitro and in vivo, providing theoretical support for exploring active substances and performing quality control.l.
10.Efficacy and Safety Evaluation of Glucagon-like Peptide-1 Receptor Agonists for Renal Protection in Patients with Type 2 Diabetes
Junhong LIU ; Yali GAO ; Cuilyu LIANG ; Qiying CHEN ; Mingzhu CHEN ; Yin ZHANG
Chinese Journal of Modern Applied Pharmacy 2024;41(6):823-833
OBJECTIVE
To systematically evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists(GLP-1RA) in the renal protection of type 2 diabetes(T2DM) patients, and provide evidence for clinic.
METHODS
Computer retrieval of PubMed, Embase, The Cochrane Library, Clinical Trials.gov, CNKI, WanFang Data and VIP databases, and manual retrieval of the included references. Randomized controlled trials(RCTs) for T2DM using GLP-1RA alone or GLP-1RA in combination with other conventional agents(experimental group) versus conventional treatment without GLP-1RA or placebo(control group). The search period spanned from the establishment of the database to January 30, 2022. Meta-analysis of the included data was performed using RevMan 5.4 statistical software.
RESULTS
A total of 7 studies were included, including 7 985 cases in experimental group and 6 633 cases in control group. Meta-analysis showed that the experimental group significantly reduced the incidence of renal complex endpoint events[Z=2.17, P=0.03, RR=0.79, 95%CI(0.64, 0.98)], urinary albumin creatinine ratio[Z=11.66, P<0.00001, MD=–23.74, 95%CI(–27.73, –19.74)], incidence of new macroalbuminuria[Z=5.79, P<0.000 01, MD=0.76, 95%CI(0.69, 0.83)], hemoglobin A1c[Z=12.76, P<0.000 01, MD=–0.94, 95%CI(–1.09, –0.80)] and estimated glomerular filtration rate[P=0.0007, Z=3.39, MD=–7.37, 95%CI(–11.63, –3.10)], the differences were statistically significant. One study showed that the experimental group could significantly reduce 24-hour urinary albumin excretion rate. However, there was no significant difference in the incidence of acute renal failure between the two groups[Z=0.63, P=0.53, MD=1.13, 95%CI(0.78, 1.63)]. In terms of safety, except the incidence of hypoglycemia, the incidence of adverse reactions in the experimental group was higher than that in the control group, including diarrhea, nausea, vomiting and loss of appetite, with statistically significant differences.
CONCLUSION
Existing research evidence shows that the common adverse reactions of GLP-1RA are gastrointestinal reactions and can be tolerated. Compared with placebo or conventional treatment without GLP-1RA, GLP-1RA may have a protective effect on the kidney of T2DM patients, and this conclusion needs to be further verified by RCTs.


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