1.Exploration of Spectrum-effect Relationship of Zhuriheng Dropping Pills Against Macrophage Foaming Based on UPLC-Q-Exactive Orbitrap MS
Qiong ZHAI ; Fangyuan LIANG ; Yuewu WANG ; Ren BU ; Xin DONG ; Jingkun LU ; Peifeng XUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):176-186
ObjectiveThrough the correlation analysis between intestinal absorption profile and inhibition of macrophage foaming, the pharmacodynamic components of Zhuriheng dripping pills(ZRH) were explored to provide a basis for establishing its quality standard. MethodIntestinal absorption fluids with 0, 5, 10, 15, 20 times clinical equivalent doses were prepared by a rat everted gut sac(EGS), and the oxidized low density lipoprotein(ox-LDL)-induced RAW264.7 macrophage foaming model was used to investigate the effect of intestinal absorption fluid with different doses on the accumulation of lipids in RAW264.7 cells by oil red O staining and cholesterol content determination, and to screen for the optimal dose. Ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was used to analyze and identify intestinal absorption fractions of ZRH intestinal absorption fluids, and partial least squares-discriminant analysis(PLS-DA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were performed on different doses of ZRH intestinal absorption fluids using SIMCA 13.0 with peak area as the independent variable and the pharmacodynamic indicators as the dependent variables to screen the compounds with variable importance in the projection(VIP) value>1.0 as contributing components, and Pearson correlation analysis was used to determine the spectral effect relationship, determined the compounds and positive correlation with pharmacodynamic were as active ingredients. Molecular docking was used to verify the binding energy of peroxisome proliferator-activated receptor α(PPARα), PPARγ, PPARβ, human retinoid X receptor α(RXRA) and nuclear transcription factor-κB(NF-κB) with the active ingredients in ZRH intestinal absorption fluids. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was performed to detect the mRNA levels of PPARγ, scavenger receptor A1(SRA1) and adenosine triphosphate-binding cassette transporter A1(ABCA1) in RAW264.7 cells, Westen blot was used to detect the expression level of PPARγ protein in RAW264.7 cells, and enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-1β and NF-κB in RAW264.7 cells. ResultAccording to the results of oil red O staining and cholesterol content determination, the ZRH intestinal absorption fluids could significantly reduce macrophage foaming, and intestinal absorption fluids with 15, 20 times clinical equivalent doses had the best effect, the 15-fold ZRH intestinal absorption fluid was finally determined as the study subject. Spectral effect relationship showed that 52 corresponding peaks in the ZRH-containing intestinal fluid were positively correlated with the efficacy, including organic acids, phenylpropanoids, iridoids, flavonoids, bile acids, coumarins and chromones. Target validation results showed that 86.9%-96.2% of the total components processed good binding activities with the key targets of PPARα, PPARγ, PPARβ, RXRA and NF-κB, and the docking energy values were all less than -6.0 kcal·mol-1(1 cal≈4.19 J). The results of validation showed that, compared with the normal group, the model group showed a significant increase in the levels of SRA1 and PPARγ mRNA expression, a significant decrease in ABCA1 mRNA expression, a significant increase in the level of PPARγ protein expression, and a significant increase in the levels of IL-1β and NF-κB(P<0.01), compared with the model group, the 15-fold intestinal absorption fluid group showed a significant decrease in the levels of SRA1 and PPARγ mRNA expression(P<0.05, P<0.01), ABCA1 mRNA expression level was significantly up-regulated, the levels of IL-1β and NF-κB were significantly reduced(P<0.01), and PPARγ protein expression level was significantly reduced(P<0.05). ConclusionThis study identifies 52 components and their metabolites in ZRH intestinal absorption fluid that are positively correlated with the inhibition of macrophage foaming, which may be related to the regulation of the PPARs pathway in cells and the reduction of the levels of inflammatory factors, and can provide a reference for the quality control and clinical application of ZRH.
2.Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.
Shuo ZHANG ; Hong-Jin LI ; Chun-Mei YANG ; Liu LIU ; Xiao-Ying SUN ; Jiao WANG ; Si-Ting CHEN ; Yi LU ; Man-Qi HU ; Ge YAN ; Ya-Qiong ZHOU ; Xiao MIAO ; Xin LI ; Bin LI
Chinese journal of integrative medicine 2024;30(3):222-229
OBJECTIVE:
To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.
METHODS:
Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.
RESULTS:
TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).
CONCLUSIONS
TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male
;
Animals
;
Mice
;
Tripterygium
;
Psoriasis/drug therapy*
;
Keratinocytes
;
Skin Diseases/metabolism*
;
Cytokines/metabolism*
;
Imiquimod/metabolism*
;
Dermatitis/pathology*
;
Disease Models, Animal
;
Mice, Inbred BALB C
;
Skin/metabolism*
3.Comparison of luteal phase long protocol and GnRH antagonist protocol in PCOS patients after the first antagonist failure cycle
Tianjuan WANG ; Chao WANG ; Qiong XIN ; Yuping XU ; Wenxiang ZHANG ; Ping ZHOU ; Xiaofeng XU ; Zhaolian WEI ; Yunxia CAO
Acta Universitatis Medicinalis Anhui 2024;59(6):976-982
Objective To investigate the clinical effects and pregnancy outcomes of using luteal phase long protocol and GnRH antagonist protocol in patients with polycystic ovary syndrome(PCOS)who have failed their first GnRH antagonist protocol therapy.Methods The clinical data of 163 PCOS patients who underwent IVF/ICSI-ET were retrieved.After the failure of their first GnRH antagonist protocol treatment,they were divided into two groups in the second controlled ovarian hyperstimulation(COH)cycle:Luteal phase long protocol group(n=95)and Gn-RH antagonist protocol group(n=68).A retrospective analysis and comparison of basic clinical data,clinical and laboratory indicators,and pregnancy outcomes between two groups were conducted.Results ① There was no sta-tistically significant difference in basic clinical indicators between two group except LH.② Compared the first and second cycle treatments of patients in the luteal phase long protocol group,the initiation dose of gonadotropin(Gn),total number of Gn days,total Gn usage,estradiol(E2)on the day of hCG injection,number of retrieved eggs,oocyte maturation rate,2PN fertilization rate,2PN cleavage rate,blastocyst formation rate,high-quality blas-tocyst formation rate,and moderate to severe OHSS rate were significantly higher than those in the first GnRH an-tagonist cycle(P<0.05).The GnRH antagonist protocol group also showed similar improvements.③ The com-parison of the second COH cycle between two groups showed that the total number of Gn days,total Gn usage,and total Gn cost in the luteal phase long protocol group were significantly higher(P<0.05),while the E2 and LH on the day of hCG injection,and the maturation rate of eggs were significantly lower than those in the GnRH antagonist protocol group(P<0.05).However,there was no statistically significant difference in the number of retrieved eggs,2PN fertilization,2PN cleavage,blastocyst formation rate,high-quality blastocyst formation rate,and OHSS rate between the two groups;④ The comparison of fresh transplantation cycles for the second COH cycle between the two groups showed that the luteal phase long protocol fresh transplantation rate,implantation rate,clinical preg-nancy rate,and live birth rate were slightly higher than those of the GnRH antagonist protocol group,but the differ-ence was not statistically significant.Comparing the outcomes of pregnancy following the initial frozen-thawed em-bryo transfer(FET)between two groups,the biochemical pregnancy rate and clinical pregnancy rate of the GnRH antagonist protocol group were higher than those of the luteal phase long protocol group(P<0.05).However,no significant statistical variations were found in implantation rate,live birth rate,neonatal gestational age,and birth weight.Conclusion For PCOS patients who fail the first GnRH antagonist protocol,an appropriate increase in the initiating dose and usage of Gn can achieve satisfactory pregnancy outcomes with both protocols.Compared with change to a luteal phase long protocol,reusing the GnRH antagonist protocol still maintains its long-standing advan-tages,such as shorter total Gn days,lower costs,and better patient compliance.
4.Clinical trial of citicoline in the treatment of patients with post-stroke cognitive impairment
Chang GAO ; Yan LIU ; Qiong NIE ; Xin-Yu WANG ; Cui-Cui ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(19):2801-2805
Objective To observe the clinical efficacy of citicoline sodium tablets combined with huperzine A tablets in the treatment of patients with cognitive impairment after stroke,and to explore the influence on neurological function and serum levels of vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF).Methods Patients with cognitive impairment after stroke were classified into control group and treatment group according to cohort method.The control group was given oral administration of huperzine A tablets 0.1-0.2 mg for twice a day,while the treatment group was given 0.2 g citicoline sodium tablets orally for three times a day on the basis of the control group.Both groups of patients were treated for 12 weeks.The clinical efficacy,cognitive function[Mini-Mental State Examination(MMSE),National Institute of Health stroke scale,Barthel index],neurological function and daily living ability and serum vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)levels were compared and safety was evaluated.Results One hundred patients were enrolled in the experimental group and the control group.After treatment,the total effective rates in treatment group and control group were 92.00%(92 cases/100 cases)and 75.00%(75 cases/100 cases)with significant difference(P<0.05).The MMSE scores in treatment group and control group after treatment were(23.40±2.43)and(19.35±2.51)points;the scores of National Institutes of Health Stroke Scale were(12.25±1.24)and(15.84±1.61)points;the Barthel Index scores were(71.14±8.60)and(64.26±8.33)points;VEGF levels were(191.52±14.80)and(125.73±11.48)pg·mL-1;BDNF levels were(9.47±1.59)and(8.01±1.35)ng·mL-1.There were statistically significant differences in the above indexes between the treatment group and the control group(all P<0.05).The adverse drug reactions in the treatment group were mainly dizziness and nausea,and the adverse drug reactions in the control group were mainly dizziness and nausea.The incidence rates of adverse drug reactions in treatment group and control group were 8.00%(8 cases/100 cases)and 5.00%(5 cases/100 cases)(P>0.05).Conclusion Citicoline sodium tablets combined with huperzine A tablets have a definite efficacy in the treatment of patients with cognitive impairment after stroke,and it has a significant improvement effect on cognitive function and neurological function of patients,with good safety.
5.Clinical trial of alteplase combined with rivaroxaban in the treatment of elderly obese patients with acute lower extremity deep vein thrombosis
Ya-Nan JIA ; Ya-Qiong WANG ; Li-Xin GUO ; Ling-Tao TANG
The Chinese Journal of Clinical Pharmacology 2024;40(20):2939-2943
Objective To observe the clinical efficacy and safety of alteplase combined with rivaroxaban in the treatment of acute deep vein thrombosis(DVT)in elderly obese patients.Methods Elderly obese patients with DVT were divided into control group and treatment group according to random number table method.The control group was treated with 10 mg·d-1 rivaroxaban tablets orally.The treatment group was treated with 0.9 mg·kg-1·d-1 alteplase on the basis of the control group.Both groups were treated for 1 week.Clinical efficacy,coagulation function indexes,lower limb venous blood flow mechanics indexes,inflammatory factors and vascular endothelial function related indexes,relative expression level of miR-374b-5p,occurrence of adverse drug reactions and recurrence within 3 months were compared between the two groups.Results A total of 80 patients were enrolled in the treatment group and the control group,respectively.After treatment,the total effective rate of treatment group and control group were 92.50%(74 cases/80 cases)and 81.25%(65 cases/80 cases),respectively,and the difference was statistically significant(P<0.05).After treatment,the fibrinogen levels of treatment group and control group were(3.58±0.83)and(3.91±1.04)g·L-1,respectively;D-dimer levels were(2.18±0.74)and(2.49±0.93)μg·mL-1,respectively;platelet activating factor were(115.42±10.43)and(119.74±11.37)μg·L-1,respectively;prothrombin time were(12.95±1.16)and(13.41±1.27)s,respectively;the maximum blood flow velocity were(29.19±6.74)and(26.93±4.58)cm·s-1,respectively;the blood flow were(92.17±9.61)and(88.63±8.75)mL·min-1,respectively;endothelial vasoconstricting peptide-1 were(51.97±4.86)and(54.02±4.92)pg·mL-1;the relative expression levels of miR-374b-5p were 2.18±0.73 and 2.49±0.85,respectively.The above indexes of the treatment group were statistically significant compared with the control group(all P<0.05).Bleeding symptoms were the main adverse drug reactions in both groups.The total incidence of adverse drug reactions in treatment group and control group was 10.00%and 13.75%,respectively,with no statistical significance(P>0.05).The 3-month recurrence rates of treatment group and control group was 6.25%and 16.25%,respectively,and the difference was statistically significant(P<0.05).Conclusion Alteplase combined with rivaroxaban has good clinical efficacy in the treatment of elderly obese patients with DVT,which can improve the blood flow of patients,reduce inflammatory response,and has high safety.
6.Construction of damage control operation simulation training platform for traumatic brain injury of wartime based on mixed reality
Wen-Qiong DU ; Zhao-Wen ZONG ; Xin ZHONG ; Ren-Qing JIANG ; Yi-Jun JIA ; Can CHEN ; Chuan-Shuan WANG
Chinese Medical Equipment Journal 2024;45(2):17-21
Objective To develop a damage control operation(DCO)simulation training platform for traumatic brain injury(TBI)in wartime based on mixed reality to open up a new path for surgical skills training of military surgeons.Methods The platform mainly consisted of wartime TBI DCO simulation training software,a surgical manikin and a HoloLens 2 MR device.The simulating training software was developed with C# language and the technologies of MR,basic gestures,spatial scanning positioning and etc on the basis of constructed surgical decision-making training system,virtual surgical environment and functional modules.The surgical manikin was customized with reference to the standard body type of an adult male with a height of 180 cm,and an electronic chip was developed and placed inside the head of the manikin to execute data matching with the simulation training software.The simulation training software was installed and run in the HoloLens 2 MR device to realize TBI DCO simulation training on the virtual reality interactive model.Results The platform developed implemented the functions of virtual reality interactive model reset positioning,operation simulation training,examination and on-site demonstration,which gained advantages in stimulating learning interest and facilitating risk-free,time-and space-indepen-dent,immersive and interactive learning and was generally recognized by the trainees.Conclusion The simulation training platform can be a supplementary to other training means to improve the ability of military surgeons in damage control operation.[Chinese Medical Equipment Journal,2024,45(2):17-21]
7.Research on human life signal separation and reconstruction method based on optimized variational modal decomposition
Xian-Qiong WEN ; Xin-Yu WANG ; Ding SHI ; Kun ZHANG
Chinese Medical Equipment Journal 2024;45(3):9-15
Objective To propose a human life signal separation and reconstruction method based on optimized variational mode decomposition(VMD)to improve the accuracy and timeliness of the life detection radar in extracting and separating human life signals such as heartbeat and respiration.Methods Firstly,the particle swarm optimization algorithm was used to optimize the parameters of VMD,and the human life signal was decomposed into a series of intrinsic mode functions(IMFs);secondly,the alignment entropy of each IMF was calculated,the noise was removed based on the alignment entropy threshold,and the remaining components were reconstructed to form human life signals;finally,the method proposed was compared with infinite impulse response(IIR)filtering,VMD and complete ensemble empirical mode decomposition with adaptive nosie(CEEMDAN)to verify its performance.Results Under different noise levels the proposed method outperformed IIR filtering,VMD and CEEMDAN in evaluation metrics of signal-to-noise ratio and root-mean-square error,and behaved better than CEEMDAN in terms of computational time-consumption.Conclusion The proposed method realizes rapid separation and reconstruction of vital signals such as heartbeat and respiration while effectively filtering out the noise,which has broad application prospects in the fields of non-contact vital signs detection of bum/scald patients,infectious disease patients and newborns and the search and rescue of buried casualties after a disaster.[Chinese Medical Equipment Journal,2024,45(3):9-15]
8.Construction and application of big data sharing platform for clinical scientific research
You-Qiong CHEN ; Qing-Ke SHI ; Mi-Ye WANG ; Ren-Xin DING ; Xue-Jun ZHUO
Chinese Medical Equipment Journal 2024;45(4):27-31
Objective To construct a big data sharing platform for clinical scientific research to solve the problems of clinical research in decentralized application systems and data sharing safety.Methods A clinical research information data usage management system was developed through the formulation of management methods in line with the actual situation of the institution,normalized standard data usage processes and a data usage service team.Then a clinical scientific research big data sharing platform including the components for sharing environment construction,research application integration,data desensitization and encryption and file management was established based on the existing hospital systems,the requirements of clinical research data usage management and the habits of clinical researchers.Results The platform realized the balance between open sharing of clinical research data and data security control,which improved the efficiency of clinical researchers while reducing data security risks during data transmission and data analysis.Conclusion The clinical scientific research big data sharing platform meets the needs of clinical scientific research application and data security management,and provides references for the co-construction-sharing of medical big data resources.[Chinese Medical Equipment Journal,2024,45(4):27-31]
9.Perianal scrotal necrotizing fasciitis combined with pyomyositis caused by Candida spp.:a case report
Xue-Li XU ; Zuo-Wu XI ; Yan-Yan WANG ; Qiong-Ge ZHOU ; Ke-Xin DENG
Chinese Journal of Infection Control 2024;23(11):1445-1449
The patient,a 42-year-old male,with a history of hepatitis B and membranous nephropathy,had inter-mittent fever and chills 12 days before admission.In the first 2 days after admission,the patient's condition aggra-vated with redness,swelling and pain in the left scrotum and perineum.Immediate surgical debridement was per-formed.The patient had a persistent low fever,with blood and pus cultures showing Candida albicans positive,thus was diagnosed fungal necrotizing fasciitis and pyomyositis.The patient was treated with echinocandins mica-fungin(150 mg,qd)for antifungal infection,and was given encroaching dressing change,hyperbaric oxygen thera-py,nutritional support,etc.Two months after surgery,the patient's condition improved and he was discharged.The early clinical symptoms of necrotizing fasciitis and pyomyositis caused by Streptococcus spp.infection lack spe-cificity,thus are prone to be delayed.For patients with concomitant immune diseases,attention should be paid to the prevention and early treatment of complex infection.The appropriate selection of empirical antifungal agents at the early stage has clinical significance.
10.Acupuncture improves intestinal barrier function and visceral pain in rats with irritable bowel syndrome by blocking BDNF/TrkB signaling pathway
Min YANG ; Huan XIN ; Ran ZOU ; Qiong WANG ; Yue LI
Chinese Journal of Immunology 2024;40(6):1234-1239
Objective:To explore whether acupuncture can affect intestinal barrier and visceral pain of rats with irritable bowel syndrome(IBS)by regulating brain-derived neurotrophic factor(BDNF)and its downstream tyrosine kinase receptor B(TrkB),and to explore the possibility of BDNF/TrkB signaling pathway as a new target for acupuncture treatment.Methods:Sixty SD rats were ran-domly grouped into healthy group,IBS group,acupuncture group,positive control group and acupuncture+TrkB activation group,with 12 rats in each group.An IBS rat model was established,abdominal withdrawal reflex(AWR)was used to detect visceral pain of rats in each group;levels of TNF-α and IL-1β in colon of rats in each group were measured;expression levels of colonic mucosal cyto-plasmic Claudin 1(ZO-1)and occludin were measured with immunohistochemistry;expression levels of BDNF and TrkB mRNA and protein in colon of rats in each group were measured with fluorescence quantitative PCR and Western blot.Results:Compared with healthy group,colonic mucosa of rats in IBS group was damaged,expressions of ZO-1 and occludin were significantly reduced,AWR score,fecal water content,TNF-α and IL-1β contents,colonic BDNF,TrkB mRNA and BDNF protein expressions,and TrkB phos-phorylation were significantly increased(P<0.05);compared with IBS group,colon mucosa of acupuncture group and positive control group gradually recovered,expressions of ZO-1 and occludin were significantly increased,AWR score,fecal water content,TNF-α and IL-1β contents,colonic BDNF,TrkB mRNA and BDNF protein expressions,and TrkB phosphorylation were significantly re-duced(P<0.05);compared with acupuncture group,colonic mucosa of rats in acupuncture+TrkB activation group still had lesions,expressions of ZO-1 and occludin were significantly reduced,AWR score,fecal water content,TNF-α and IL-1β contents,colonic BDNF,TrkB mRNA and BDNF protein expressions,and TrkB phosphorylation were significantly increased(P<0.05).Conclusion:Acupuncture can regulate BDNF/TrkB pathway,inhibit expression of related proteins,improve intestinal barrier function,reduce vis-ceral pain,inflammation and relieve IBS.


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