1.Mechanism of Wenyang Jieyu Prescription in Regulating Activation of Mouse Hippocampal Microglia Based on JAK2/STAT3 Signaling Pathway
Ying WANG ; Zihan GONG ; Wenqing LIANG ; Jingwen YANG ; Guangxin YUE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):88-96
ObjectiveTo explore the mechanism of the Wenyang Jieyu prescription in regulating depression-like behavior in mice after maternal-infant separation combined with secondary stress. MethodsAfter birth, the rats were randomly divided into blank (NC) group, maternal-infant separation (MS) group, restraint stress (RS) group, maternal-infant separation combined with restraint stress (MRS) group, Wenyang group, Jieyu group, Wenyang Jieyu (XSF) group, and minocycline group. Maternal-infant separation was performed on day 5 (PD5), followed by weaning at PD21 and prophylactic administration. The dose of Wenyang group, Xiaoyao group, XSF group and minocycline group were 5.85, 12.03, 16.71 g·kg-1 and 50 mg·kg-1, respectively. Restraint stress was applied on PD90. The model was evaluated using glucose, social interaction, open field, and O-maze behavior tests, as well as high-performance liquid chromatography to measure serotonin, dopamine, and other neurotransmitters. The expression level of ionized calcium-binding adaptor molecule-1 (Iba-1) protein, a marker of hippocampal microglia, was detected by immunohistochemistry. Protein expression levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) in the hippocampus were analyzed by an automatic protein expression analysis system. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of M1 markers, JAK2/STAT3 pathway-related genes, and cytokines in hippocampal microglia in each group. ResultsCompared with the NC group, the MRS group exhibited depression-like behavior, with significantly decreased levels of neurotransmitters in the hippocampus (P<0.05, P<0.01), increased expression of Iba-1 (P<0.01), and elevated protein levels of JAK2 and STAT3 (P<0.05). The mRNA expression levels of CD68, CD11b, IL-1β, JAK2, and STAT3 were significantly increased (P<0.01), while IL-10 mRNA expression was significantly decreased (P<0.01). Compared with the MRS group, the XSF and minocycline groups showed some improvement in depression-like behavior. In these groups, the hippocampal neurotransmitter content was significantly increased (P<0.05, P<0.01), and Iba-1 expression was significantly decreased (P<0.01). The protein levels of JAK2 and STAT3 in the XSF group showed a downward trend. The mRNA expression levels of CD68, CD11b, JAK2, STAT3, and IL-1β in the hippocampus were significantly decreased in the XSF and minocycline groups (P<0.05, P<0.01), while IL-10 mRNA expression was significantly increased (P<0.05, P<0.01). ConclusionWenyang Jieyu prescription can regulate depression-like behavior in maternal-infant separation mice combined with secondary stress by inhibiting the polarization of hippocampal microglia to the M1 phenotype. The regulation of hippocampal microglia polarization by Wenyang Jieyu prescription may be associated with the JAK2/STAT3 pathway.
2.Chest CT Imaging Features of Indeterminate Pulmonary Nodules and Outcomes in Patients with High-grade Soft Tissue Sarcoma: A Single-center Retrospective Study
Yuanrong WANG ; Liming ZHANG ; Daji SONAM ; Yan ZHU ; Gentao FAN ; Yicun WANG ; Xin SHI ; Sujia WU ; Guangxin ZHOU
Cancer Research on Prevention and Treatment 2024;51(2):99-103
Objective To explore the imaging features, clinical outcome, and prognosis of indeterminate pulmonary nodules (IPN) in patients with high-grade soft tissue sarcoma. Methods A retrospective study of 82 patients with high-grade soft tissue sarcoma who have IPNs. The clinical characteristics, imaging features of IPN, and survival of patients were analyzed with statistical software. Results The IPN size of 82 patients was 6.453±0.864 mm. IPN diameter, shape, density, and nodule discovery interval may be CT imaging features related to malignancy tendency. Age (
3.Elastase quantitative analysis of elastin effect on mechanical response of anterior cruciate ligament
Wentian ZHANG ; Yuping DENG ; Xiaoyun LIU ; Caijuan LI ; Mian WANG ; Zeyu LIANG ; Liang XIONG ; Gang HUANG ; Guangxin CHEN ; Zitao LI ; Wenhua HUANG
Chinese Journal of Tissue Engineering Research 2024;28(22):3451-3456
BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.
4.Syndromes and Mechanisms of Depression Induced by Second Hit in Mice
Zihan GONG ; Ying WANG ; Jingwen YANG ; Wenqing LIANG ; Danhua MENG ; Kaijie SHE ; Yuan LIANG ; Guangxin YUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):29-38
ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation (MS) combined with chronic restraint stress (RS) in mice. MethodOn postnatal day 0 (PD0), the offspring mice were randomized into a blank group (NC) and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21, the modeled mice were randomized into model, Wenyang, Jieyu, Wenyang Jieyu, and fluoxetine groups, with 15 mice in each group. The sucrose preference, tail suspension, and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine (5-HT) system, hypothalamic-pituitary-adrenal (HPA) axis, and brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B (TrkB) in the hippocampus. ResultCompared with the NC group, the model group exhibited depression-like behavior, which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group, the model group showed elevated levels of CORT and ACTH in the plasma (P<0.01), which, however, were lowered by Wenyang Jieyu prescription and fluoxetine (P<0.05, P<0.01). Compared with the NC group, the model group showed inhibited expression of neurotransmitters in the hippocampus (P<0.05, P<0.01), while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters (P<0.05, P<0.01). Compared with NC group, the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis, and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group, the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus (P<0.05, P<0.01), which, however, were recovered in Wenyang, Jieyu, Wenyang Jieyu, and fluoxetine groups (P<0.05, P<0.01). ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis, thereby alleviating depression-like behavior in mice.
5.Wenyang Jieyu Prescription Regulates Hippocampal Neural Plasticity in Depressed Mice via NLRP3/Caspase-1/IL-1β Pathway
Danhua MENG ; Kaijie SHE ; Xiaoying MENG ; Zinhan GONG ; Wenqing LIANG ; Ying WANG ; Yuan LIANG ; Guangxin YUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):39-47
ObjectiveTo explore the effects of Wenyang Jieyu prescription (WJP) on neuroinflammation and synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 (PD0) were randomized into a control group and a modeling group. Maternal separation combined with restraint stress was employed to establish the mouse model of depression. After the removal of female mice, the modeled mice were randomized into model, Wenyang prescription (5.85 g·kg-1), Jieyu prescription (12.03 g·kg-1), WJP (16.71 g·kg-1), and fluoxetine (2.6 mg·kg-1) groups on the weaning day (PD21), with 15 mice in each group. The mice were administrated with corresponding drugs mixed with the diet from PD21 to PD111. The sucrose preference test, open field test, O-maze test, and novel object recognition test were then carried out to evaluate the depression state, memory, and learning ability of the mice. Immunohistochemistry (IHC) was employed to observe the ionized calcium-binding adapter molecule-1 (Iba-1) in hippocampal microglia. High performance liquid chromatography (HPLC) was employed to measure the content of noradrenaline (NE) and epinephrine (E) in the hippocampus. Enzyme-linked immunosorbent assay (ELISA) was employed to determine the content of interleukin (IL)-18 and IL-1β in the hippocampus. Western blot was employed to determine the protein levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartate-specific protease-1 (Caspase-1), IL-1β, synaptophysin (Syn), and postsynaptic density 95 (PSD95). ResultCompared with control group, the model group showed decreased sucrose preference rate, time spent in central zone within 5 min, total movement distance, time spent in the open arm, and cognition index (P<0.05, P<0.01). The microglia in the model group presented amoeba-like appearance, the Iba1 increased. Moreover, the model group showed decreased content of NE and E (P<0.01), elevated levels of IL-1β and IL-18 (P<0.01), down-regulated protein levels of PSD95 and Syn (P<0.05, P<0.01), and up-regulated protein levels of NLRP3, ASC, Caspase-1, and IL-1β (P<0.05, P<0.01). Compared with model group, WJP and fluoxetine increased the sucrose preference rate, time spent in central zone within 5 min, total movement distance, time spent in the open arm, and cognition index (P<0.05, P<0.01). They recovered the microglia and the Iba1 decreased. Moreover, the drugs increased the content of NE and E (P<0.05, P<0.01), lowered the levels of IL-1β and IL-18 (P<0.01), up-regulated the protein levels of PSD95 and Syn (P<0.01), down-regulated the protein levels of NLRP3, ASC, Caspase-1, and IL-1β (P<0.05, P<0.01). ConclusionWJP can treat the depressive behavior induced by maternal separation combined with restraint stress in mice, with the performance outperforming Wenyang prescription and Jieyu prescription. It may alleviate the neuroinflammation induced by microglia and improve the synaptic plasticity by regulating the NLRP3 pathway and increasing neurotransmitters in the hippocampus.
6.Wenyang Jieyu Prescription Regulates Hippocampal Neuron Apoptosis and Improves Synaptic Plasticity in Depressed Mice via BDNF/Akt/mTOR Pathway
Danhua MENG ; Kaijie SHE ; Xiaoying MENG ; Zihan GONG ; Wenqing LIANG ; Ying WANG ; Yuan LIANG ; Guangxin YUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):48-57
ObjectiveTo explore the mechanism of Wenyang Jieyu prescription in regulating hippocampal neuron apoptosis and improving synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 (PD0) were randomly assigned into a control group (n=10) and a modeling group (n=50). Maternal separation combined with restraint stress was adopted to establish the mouse model of depression, and the modeled mice were randomized into model, Wenyang prescription, Jieyu prescription, Wenyang Jieyu prescription, and fluoxetine groups (n=10) on the weaning day (PD21). From PD21 to PD111, the mice were fed with the diets mixed with corresponding medicines. The sucrose preference test, open field test, O-maze test, and novel object recognition test were then conducted to evaluate the depression, memory, and learning abilities of mice. Immunohistochemistry (IHC) was employed to measure the atomic absorbance (AA) of postsynaptic density protein 95 (PSD95) in the hippocampus. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling (TUNEL) was employed to detect the apoptosis of hippocampal neurons. Western blot was employed to determine the protein levels of brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine kinase receptor B/tyrosine kinase receptor B (p-TrkB/TrkB), phosphorylated protein kinase B/protein kinase B (p-Akt/Akt), phosphorylated mammalian target of rapamycin/mammalian target of rapamycin (p-mTOR/mTOR), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cysteinyl aspartate-specific proteinase-3 (Caspase-3), synaptophysin (Syn), and PSD95. ResultCompared with the control group, the modeling decreased the sucrose preference rate, time spent in central zone within 5 min, total movement distance, time spent in the open arm, and cognition index (P<0.01). Furthermore, it decreased the expression of PSD95, increased the neuron apoptosis in the hippocampus (P<0.01), down-regulated the protein levels of BDNF, p-TrkB/TrkB, p-Akt/Akt, p-mTOR/mTOR, Bcl-2, PSD95, and Syn (P<0.01), and up-regulated the protein levels of Bax and Caspase-3 (P<0.05) in the hippocampus. Compared with the model group, Wenyang Jieyu prescription and fluoxetine increased the sucrose preference rate, time spent in central zone within 5 min, total movement distance, time spent in the open arm, and cognition index (P<0.05, P<0.01). Moreover, the drugs increased the expression of PSD95, reduced the neuron apoptosis (P<0.01), up-regulated the protein levels of BDNF, p-TrkB/TrkB, p-Akt/Akt, p-mTOR/mTOR, Bcl-2, PSD95, and Syn (P<0.01), and down-regulated the protein levels of Bax and Caspase-3 (P<0.01). ConclusionWenyang Jieyu prescription outperformed Wenyang prescription and Jieyu prescription in the treatment of the depressive behavior induced by maternal separation combined with restraint stress in mice. It exerted the therapeutic effect by reducing the hippocampal neuron apoptosis and improving the synaptic plasticity via the BDNF/Akt/mTOR pathway.
7.Professor WANG Shouchuan's Experience in Differentiating and Treating Children's Epistaxis from the Perspective of “Four Excess and Three Deficiency"
Tao LI ; Lili LIN ; Jianjian JI ; Qigang DAI ; Hui CHEN ; Zhao WANG ; Guangxin TAN ; Min WANG ;
Journal of Traditional Chinese Medicine 2024;65(19):1967-1971
This paper summarized professor WANG Shouchuan's experience in differentiating and treating children epistaxis from the perspective of "four excess and three deficiency". It is believed that the pathogenesis of children epistaxis is concluded as "four excess and three deficiency", of which the four excess syndromes are exuberant heat in the lung channel, intense stomach fire, heart fire hyperactivity, and liver fire flaming upward, while the three deficiency syndromes include qi, yin and yang deficiency. Seven methods for treating children epistaxis are summarized. For exuberant heat in the lung channel syndrome, it is recommended to clear lung and direct qi downward, using self-made Xiebai Zhiniu Decoction (泻白止衄汤). For intense stomach fire syndrome, the method of clearing stomach and draining fire can be used with self-made Qingwei Zhiniu Decoction (清胃止衄汤). In terms of heart fire hyperactivity syndrome, it is better to clear heart and drain fire, using self-made Daochi Zhiniu Decoction (导赤止衄汤). For liver fire flaming upward syndrome, it is advised to clear liver and drain fire, using self-made Yimu Zhiniu Decoction (抑木止衄汤). In terms of qi deficiency syndrome, the method of fortifying spleen and boosting qi and containing blood should be used with self-made Futu Zhiniu Decoction (扶土止衄汤). If there is yin deficiency syndrome, it is advised to supplement kidney, enrich yin and clear heat, using self-made Zishui Zhiniu Decoction (滋水止衄汤). If there is yang deficiency syndrome, the method of boosting qi, warming yang and nourishing blood can be used, using self-made Wenpi Zhiniu Decoction (温脾止衄汤).
8.Study on Content Determination and Immunomodulatory and Cardioprotective Effects of Sporoderm-Removed Ganoderma Lucidum Spore Powder Tablet
Jihong YANG ; Guoliang ZHANG ; Congshu LI ; Guangxin LUO ; Jing XU ; Ying WANG ; Yuejiao SHI ; Zhenhao LI
Chinese Journal of Modern Applied Pharmacy 2024;41(2):203-212
OBJECTIVE
To investigate the potential therapeutic effect of the sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" from the perspective of immunomodulation and cardioprotection.
METHODS
Chemical components of the sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" were analyzed by UPLC-Q-TOF-MS and colorimetric methods. Examined tablet’s effects on zebrafish models of macrophage reduction, heart failure, H2O2-induced oxidative stress in myocardial and endothelial cells, and a microglial inflammation model induced by lipopolysaccharide. Immune regulation and cardioprotective effects were evaluated through multiple indicators, including macrophage formation and phagocytosis abilities, anti-neuroinflammation ability, cardiac systolic and diastolic functions, and anti-oxidative stress injury ability in myocardial and endothelial cells.
RESULTS
The sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" improved macrophage formation and phagocytosis, cardiac systolic and diastolic functions, reduced neuroinflammation, and alleviated oxidative stress in myocardial and endothelial cells, resulting in immunomodulatory and cardioprotective effects.
CONCLUSION
The sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" maybe a potential therapeutic agent for regulating the immune system and protecting cardiac function.
9.The application value of emergency bedside echocardiography in the diagnosis and treatment of reverse-Takotsubo syndrome
Chaofeng GUO ; Xiaojing WANG ; Aiju LI ; Hongyu WANG ; Guangxin SUN ; Ling WANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(2):162-166
Objective To explore the clinical application value of emergency bedside echocardiography(EB-Echo)in the diagnosis and treatment of reverse-Takotsubo syndrome(r-TTS).Methods A retrospective study method was conducted,the EB-Echo imaging and clinical data of 10 patients already diagnosed with r-TTS and admitted to the department of critical care medicine of Zhengzhou People's Hospital from January 2014 to December 2021 were selected.The r-TTS group,while data from 33 concurrently admitted patients with classic Takotsubo syndrome(TTS)were selected as the classic TTS group.Comparisons were made in terms of EB-Echo detection rates,diagnosis times,cardiac function indicators[left ventricular ejection fraction(LVEF),left ventricular stroke volume(LVSV)],blood volume indicators[inferior vena cava diameter(IVCD),collapse degree of inferior vena cava(cIVC)],complications[acute left ventricular outflow tract obstruction(ALVOTO),acute mitral regurgitation(AMR),and pulmonary hypertension(PH)],and prognosis between the two groups.Results The detection rate of EB-Echo in the r-TTS group was significantly higher than that in the classic TTS group[100.0%(10/10)vs.66.7%(22/33),P<0.05],and the diagnosis time was significantly shorter(minutes:26.80±3.77 vs.41.18±6.61,P<0.05).In terms of cardiac function indicators,both LVEF and LVSV were significantly lower in the r-TTS group compared to the classic TTS group[LVEF:0.36±0.05 vs.0.41±0.04,LVSV(mL):36.43±4.30 vs.40.65±5.09,both P<0.05].However,there were no significant differences in blood volume indicators(IVCD and cIVC)between the r-TTS group and the classic TTS group[IVCD(mm):15.02±1.88 vs.14.94±1.75,cIVC:(0.43±0.06)%vs.(0.44±0.07)%,both P>0.05].Concerning complications,the incidence of ALVOTO was slightly lower in the r-TTS group compared to the classic TTS group[0%(0/10)vs.21.2%(7/33),P>0.05],while the incidences of AMR and PH were similar between the two groups[AMR incidence:40.0%(4/10)vs.24.2%(8/33),PH incidence:30.0%(3/10)vs.18.2%(6/33),both P>0.05].After a follow-up ranging from 6 months to 3 years,no deaths were reported in the r-TTS group,whereas there was one fatality in the classic TTS group.Nevertheless,the mortality difference between the groups was not statistically significant.Conclusion EB-Echo demonstrates significant clinical value in the early diagnosis,guiding therapy,and enhancing prognosis of r-TTS.
10.Clinical application of ultrasound combined with DSA-guided implantation of totally implantable venous access port via upper arm vein approach in chemotherapy for patients with malignant tumors
Guangxin JIN ; Fangqin ZHANG ; Yawen WANG ; Yan GUO ; Xiaoxia QIU ; Xuebin ZHANG
Journal of Interventional Radiology 2024;33(7):733-737
Objective To evaluate the technical feasibility and safety of upper arm vein approach in the implantation of totally implantable venous access port(TIVAP)under the guidance of ultrasound combined with DSA.Methods The clinical data of 1 546 patients with malignant tumors,who received TIVAP implantation via upper arm vein access under the guidance of ultrasound combined with DSA at the Affiliated Renji Hospital,School of Medicine of Shanghai Jiao Tong University of China between January 2020 and January 2022,were retrospectively analyzed.The implantation success rate,single-puncturing success rate,operation time,and complications were compared between the PICC catheterization room and the DSA operating room.Results The technical success rate in the 1546 patients was 100%,with a single-puncturing success rate of 99.48%.In 766 patients the TIVAP implantation was performed in the PICC catheterization room(PICC group),and in 780 patients the TIVAP implantation was carried out in the DSA operating room(DSA group).The mean operation time in the DSA group was(20.1±1.3)min,which was obviously shorter than(25.4±1.9)min in the PICC group,and the incidence of primary catheter misplacement in the DSA group was 0%,which was remarkably lower than 0.78%in the PICC group(P<0.05).No statistically significant differences in the incidences of complications,including infection,thrombosis,upper limb movement disorder,catheter occlusion,exposure of infusion port body,and overturn of infusion port body,existed between the two groups(P>0.05).Conclusion Ultrasound-guided TIVAP via upper arm vein approach is a safe and effective infusion route for patients with malignancy receiving chemotherapy.The combination use of ultrasound guidance and intraoperative DSA guidance can reduce the operation time as well as the incidence of operation-related complications.


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