1.Sesquiterpene ZH-13 from Aquilariae Lignum Resinatum Improves Neuroinflammation by Regulating JNK Phosphorylation
Ziyu YIN ; Yun GAO ; Junjiao WANG ; Weigang XUE ; Xueping PANG ; Huiting LIU ; Yunfang ZHAO ; Huixia HUO ; Jun LI ; Jiao ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):139-145
ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide (LPS) to induce neuroinflammation. The cells were divided into the normal group, the model group, and the ZH-13 low- and high-dose treatment groups (10, 20 μmol·L-1). The model group was treated with 1 μmol·L-1 LPS. Cell viability was assessed using the cell proliferation and activity assay (CCK-8 kit). Nitric oxide (NO) release in the cell supernatant was measured using a nitric oxide kit (Griess method). The mRNA expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and interleukin-6 (IL-6) were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The phosphorylation of mitogen-activated protein kinase (MAPK) pathway proteins was assessed by Western blot. ResultsCompared with the model group, ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation (P<0.05, P<0.01). In the 20 μmol·L-1 ZH-13 treatment group, the mRNA expression levels of IL-1β, TNF-α, iNOS, and IL-6 were significantly reduced compared to the model group (P<0.05, P<0.01). In both the low- and high-dose ZH-13 groups, the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase (JNK) in the upstream MAPK pathway were significantly reduced (P<0.05). After stimulation with the JNK agonist anisomycin (Ani), both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group (P<0.01). ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.
2.Study on the Mechanism of Guanyuan Mingmen Sequential Acupuncture Activating FSHR/cAMP/PKA Pathway to Promote Granulosa Cell Proliferation in POI Model Rats
Jiang-Hong XU ; Yue-Lai CHEN ; Ping YIN ; Xue-Dan ZHAO ; Hui-Min ZHENG ; Jun-Wei HU ; Lu-Min LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):965-972
Objective To observe the therapeutic effects and mechanisms of Guanyuan Mingmen Sequential Acupuncture on rats with premature ovarian insufficiency(POI)model.Methods Female SD rats were divided into the blank group,the model group,the protein kinase A(PKA)inhibitor(H89)+acupuncture group,and the acupuncture group,with 12 rats in each group.Except for the blank group,the POI model was prepared by gavage with Tripterygium Glycosides Tablets in the other three groups of rats.After the model was successfully established,the blank group and the model group were bundled once a day;in the acupuncture group,Guanyuan(RN4)point was taken during the intermotility period,and in the pre-motility period,Mingmen(DU4)point was taken;in the H89+acupuncture group,the intervention was performed in accordance with the acupuncture protocol of the acupuncture group,and H89 was injected intraperitoneally for 30 minutes prior to each acupuncture session.Continuous intervention was performed for 20 days.Samples were taken from each group of rats in the first estrus period and in proestrus period after intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of follicle stimulating hormone(FSH)and estradiol(E2)during the estrous phase,Western Blot was used to measure the protein expressions of follicle stimulating hormone receptor(FSHR)and aromatase P450(P450arom)during the estrous phase,and the activity of granulocytes during the estrous phase and the proestrus phase were measured using the cell-counting kit 8(CCK-8)method.The immunohistochemistry method was used to detect the protein expression of pre-motility proliferating cell nuclear antigen(PCNA).Results(1)Compared with the blank group,the serum FSH level of the model group and H89+acupuncture group was significantly increased(P<0.01),and the E2 level was significantly decreased(P<0.001);there was no difference between the FSH level of the H89+acupuncture group and that of the model group(P>0.05),and the E2 level of the H89+acupuncture group was lower than that of the model group(P<0.05);the FSH level of the acupuncture group was lower than that of the model group and that of the H89+acupuncture group(P<0.05),had no difference with the blank group(P>0.05),E2 level was significantly higher than the model group and H89+ acupuncture group(P<0.01),still being lower than the blank group(P<0.05).(2)The protein expressions of FSHR and P450arom in the model group and H89 + acupuncture group was lower than those in the blank group;the protein expression of FSHR in the H89 + acupuncture group was not different from that in the model group(P>0.05),while the protein expression level of P450arom was lower than that in the model group(P<0.05);the protein expression levels of FSHR and P450arom in the acupuncture group were higher than those in the model group and H89 + acupuncture group,but still lower than those in the blank group(P<0.05).(3)Both GCs activity and average optical density value of PCNA in the model group and H89+acupuncture group were lower than the blank group(P<0.05);both GCs activity and average optical density value of PCNA in the H89+acupuncture group were lower than the model group(P<0.05);the activity of GCs and average optical density value of PCNA of the acupuncture group were significantly higher than that of the model group and H89+acupuncture group(P<0.05 or P<0.01).Conclusion Guanyuan Mingmen Sequential Acupuncture can regulate sex hormone levels,increase GCs activity and promote GCs cell proliferation by up-regulating protein expressions of follicle stimulating hormone receptor(FSHR)/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)pathway FSHR,P450arom,thus improving POI.
3.Investigation and analysis of the current status of transjugular intrahepatic portosystemic shunt treatment for portal hypertension in China
Haozhuo GUO ; Meng NIU ; Haibo SHAO ; Xinwei HAN ; Jianbo ZHAO ; Junhui SUN ; Zhuting FANG ; Bin XIONG ; Xiaoli ZHU ; Weixin REN ; Min YUAN ; Shiping YU ; Weifu LYU ; Xueqiang ZHANG ; Chunqing ZHANG ; Lei LI ; Xuefeng LUO ; Yusheng SONG ; Yilong MA ; Tong DANG ; Hua XIANG ; Yun JIN ; Hui XUE ; Guiyun JIN ; Xiao LI ; Jiarui LI ; Shi ZHOU ; Changlu YU ; Song HE ; Lei YU ; Hongmei ZU ; Jun MA ; Yanming LEI ; Ke XU ; Xiaolong QI
Chinese Journal of Radiology 2024;58(4):437-443
Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.
4.Pharmacokinetics of wogonin-aloperine cocrystal in rats
Zhong-shui XIE ; Chun-xue JIA ; Yu-lu LIANG ; Xiao-jun ZHAO ; Bin-ran LI ; Jing-zhong HAN ; Hong-juan WANG ; Jian-mei HUANG
Acta Pharmaceutica Sinica 2024;59(9):2606-2611
Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the
5.Effect of Jiuxin Pill (救心丸)on Exercise Tolerance and Quality of Life in Patients of Stable Angina Pectoris:A Randomized,Double-Blind,Placebo-Controlled,Multi-Center Clinical Trial
Xianliang WANG ; Mingjun ZHU ; Daimei NI ; Jianguang WU ; Yitao XUE ; Chenglong WANG ; Xiaohua DAI ; Qian LIN ; Jun LI ; Zhiqiang ZHAO ; Shuai WANG ; Yingfei BI ; Tongzuo LIU ; Zhou ZHOU ; Jingyuan MAO
Journal of Traditional Chinese Medicine 2024;65(24):2549-2557
ObjectiveTo evaluate the effect and safety of Jiuxin Pill (救心丸) on exercise tolerance and quality of life in patients with stable angina pectoris (SAP). MethodsA randomised, double-blind, placebo-controlled, multicentre study design was used to enroll 170 patients of SAP from nine centres, which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan, and added Jiuxin Pill or placebo respectively, 2 pills (0.05 g) each time twicely for 28 days. The main outcomes were total exercise time (TED) in the exercise treadmill test and Seattle Angina Questionnaire (SAQ) scores including physical limitation (PL), angina stability (AS), angina frequency (AF), treatment satisfaction (TS), and disease perception (DP). The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min (HRR1), metabolic equivalents (METs), maximum magnitude of ST-segment depression, and the Borg rating of perceived exertion scale, the average number of angina attacks per week, withdrawal and reduction rate of nitroglycerin, traditional Chinese medicine syndrome scores, incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment, day 28±2 in treatment period, and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set (FAS) and safety analysis set (SS). Compared with the group before treatment and with the control group after treatment, the trial group had higher TED, HRR1, and METs, and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment (P<0.01). Compared with the group before treatment and with the control group after treatment and at follow-up, the total SAQ score and scores of AS, AF, TS and DP of the trial group after treatment and at follow-up elevated, while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced (P<0.01). There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups (P>0.05). Major adverse cardiovascular events occurred in 1 case (1/84, 1.19%) in the trial group and 1 case (1/85, 1.18%) in the control group, and the difference between groups was not statistically significant (P>0.05). A total of 3 cases of adverse events occurred in the trial group (3/84, 3.57%), and a total of 6 cases of adverse events occurred in the control group (6/85, 7.06%), and there was no statistically significant difference in the incidence of adverse events between groups (P>0.05). ConclusionIn the treatment of SAP, Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance, improve quality of life, and demonstrate great safety.
6.Establishment and Preliminary Application of Competency Model for Undergraduate Medical Imaging Teachers
Tong SU ; Yu CHEN ; Daming ZHANG ; Jun ZHAO ; Hao SUN ; Ning DING ; Huadan XUE ; Zhengyu JIN
Medical Journal of Peking Union Medical College Hospital 2024;15(3):708-717
To establish a medical imaging teacher competency model and evaluate its application value in group teaching for undergraduates. Based on literature review, a competency model for teachers in medical colleges and universities was established. This study collected the self-evaluation scores and student evaluation scores of the competency model for teachers from Radiology Department of Peking Union Medical College Hospital who participated in the undergraduate medical imaging group teaching from September 2020 to November 2021, and compared the differences of various competencies before and after training, between different professional titles and between different length of teaching. A total of 18 teachers were included in the teaching of undergraduate medical imaging group, with 11 having short teaching experience (≤5 years) and 7 having long teaching experience (> 5 years). Altogether 200 undergraduate students participated in the course (95 in the class of 2016 and 105 in the class of 2017). There were 8 teachers with a junior professional title, 5 with an intermediate professional title, and 5 with a senior professional title. The teacher competency model covered a total of 5 first-level indicators, including medical education knowledge, teaching competency, scientific research competency, organizational competency, and others, which corresponded to 13 second-level indicators. The teachers' self-evaluation scores of two first-level indicators, scientific research competency and organizational competency, as well as three second-level indicators, teaching skills, academic research on teaching and research, and communication abilities, showed significant improvements after the training, compared to those before training(all The competency model of undergraduate medical imaging teachers based on teacher competency can be preliminarily applied for the training of medical imaging teachers, as it reflects the change of competency of the teachers with different professional titles and teaching years in the process of group teaching.
7.Research on regulatory countermeasures for local human genetic resources in China
Shuo GU ; Tao XUE ; Yue TANG ; Jinping ZHAO ; Xiaowei ZHANG ; Jun FENG
Chinese Medical Ethics 2024;37(4):441-447
Human genetic resources are an indispensable part of national natural science and technology resources,as well as an important strategic resource for safeguarding national security,public health,and social public interests.To promote the effective protection and rational utilization of human genetic resources,as well as improve and optimize the local human genetic resources management system in China,this paper summarized the current situation of administrative approval and supervision of national human genetic resources from 2004 to 2021 by sorting out the national human genetic resources management policies and regulations.Furthermore,the current situation and progress of local human genetic resources management in China were understood from three aspects,including development planning and programs of human genetic resources,administrative licensing and penalties,and the construction of management expert committees.The main problems of local human genetic resources management in China were discussed and analyzed,such as unclear supervision,difficulty in supervision and inspection,and capacity for services.Based on the causes of the problems and the local management work,specific countermeasures and suggestions were put forward from the perspective of clarifying the regulatory policies and procedures for human genetic resources,improving the supervision and inspection mechanisms,and improving the management and service capabilities.
8.Clinical trial of bevacizumab combined with TOMIRI chemotherapy in the treatment of patients with advanced colorectal cancer
Ye FENG ; Hai GUO ; Jun-Bin ZHAO ; Zhi-Xue LI ; Hai-Peng LIU
The Chinese Journal of Clinical Pharmacology 2024;40(15):2170-2173
Objective To observe the clinical efficacy and safety of bevacizumab injection combined with raltitrexed injection and irinotecan injection(TOMIRI)in the treatment of patients with advanced colorectal cancer.Methods Patients with advanced colorectal cancer were divided into control group and treatment group according to the cohort method.The control group received 180 mg·m-2 irinotecan with intravenous infusion for 30 to 90 min on the first day+3 mg·m-2 raltitrexed with intravenous infusion for 15 min,once every three weeks.On the basis of control group,the treatment group was given 5 mg·kg-1 bevacizumab with intravenous infusion,once every three weeks.Two groups were treated for 4 cycles with 3 weeks per cycle.The clinical efficacy,lesion diameter,Karnofsky performance status(KPS),and adverse drug reactions were compared between two groups.Additionally,based on follow-up results,the progression-free survival(PFS)within 12 months was compared between the two groups.Results The treatment and control groups enrolled 53 patients.After treatment,the total effective rates of treatment and control groups were 83.02%(44 cases/53 cases)and 54.72%(29 cases/53 cases)with statistically significant difference(P<0.05).After treatment,the tumor diameters of treatment and control groups were(2.44±0.30)and(3.35±0.38)cm;the KPS scores were(78.01±0.79)and(70.69±0.72)points;the PFS was(11.26±1.43)and(8.01±0.97)months,there were statistically significant differences of above indexes between two groups(all P<0.05).The adverse drug reactions in the treatment group were anemia,abnormal liver and renal function,nausea and vomiting,and leukopenia,which in the control group were gastrointestinal reaction,nausea and vomiting,abnormal liver and kidney function,blood toxicity,anemia and skin rash.The total incidence of adverse drug reactions in treatment and control groups were 11.32%and 28.30%(P>0.05).Conclusion Bevacizumab injection combined with TOMIRI can helps to enhance the clinical efficacy of advanced colorectal cancer and improve patients'quality of life,improve patient quality of life,prolong PFS,and without increasing the incidence of adverse drug reactions.
9.Study on baritinib improving pulmonary endothelial barrier injury in acute lung injury mice by regulating the JAK2/STAT3 pathway
Lin WANG ; Jun-Fang CHEN ; Bao-Liang ZHAO ; Xue-Li WANG
The Chinese Journal of Clinical Pharmacology 2024;40(16):2363-2367
Objective To explore the effect of barretinib on mice with acute lung injury(ALI)by regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods The male C57BL/6 mice were randomly divided into control group,model group and experimental-L,-M-H groups.Except for the control group,the other four groups were constructed ALI models by intraperitoneal injection of lipopolysaccharide.The control and model groups were given equal volume 0.9%NaCl by gavage.The experimental-H,-M,-L groups were administered with 1.00,0.50 and 0.25 mg·mL-1 barretinib solution 200 μL by gavage.Five groups were treated for 48 hours with once every 12 hours.The levels of inflammatory cytokine in bronchoalveolar lavage fluid were measured by enzyme linked immunosorbent assay.The expression levels of Occludin,JAK2 and STAT3 in mouse lung tissue were detected by Western blot.Results The levels of tumor necrosis factor-α in bronchoalveolar lavage fluid for experimental-M,-H groups,model group and control group were(228.48±25.41),(198.53±23.11),(317.32±32.85)and(48.93±2.59)ng·L-1;the levels of interleukin-6 were(118.81±14.85),(98.58±13.82),(172.23±25.94)and(49.47±3.06)ng·L-1;the relative expression levels of Occludin were 0.48±0.13,0.49±0.11,0.28±0.09 and 0.69±0.21;the phospho-JAK2/JAK2 ratios were 0.51±0.13,0.32±0.09,0.75±0.21 and 0.16±0.05;the phospho-STAT3/STAT3 ratios were 0.43±0.11,0.27±0.08,0.78±0.21 and 0.17±0.05,respectively.The differences of above indicators were statistically significant between the experimental-M,-H groups,control group and model group(all P<0.05).Conclusion Barretinib can reduce the lung inflammatory response and improves the level of tight junction protein in lung tissue to protect ALI mice by inhibiting the JAK2/STAT3 signaling pathway.
10.The role and its regulatory significance of interleukin-25 in ovalbumin induced atopic dermatitis of mice
Jiang JIN ; Xue CHEN ; Yan ZHAO ; Jun JIA ; Jianzhong ZHANG
Journal of Peking University(Health Sciences) 2024;56(5):756-762
Objective:To investigate the effect of interleukin-25(IL-25)on ovalbumin(OVA)in-duced atopic dermatitis of mice,and the significance of regulating IL-25.Methods:In this study,90 healthy male 6-week-old specific pathogen free(SPF)BALB/c mice were divided into 6 groups(15 in each group):① subcutaneous injection of phosphate buffered saline(PBS)group(normal control group);② subcutaneous injection of mouse IL-25 group(IL-25 group);③ subcutaneous injection of anti-mouse IL-25 monoclonal antibody(anti-IL-25 group),each group received subcutaneous injection once a day for 1 week,2 weeks apart,repeated daily subcutaneous injections for 1 week,2 weeks apart,and repeated daily subcutaneous injections for 1 week,for a total of 7 weeks;④OVA treated group(model group);⑤ OVA treated and IL-25 subcutaneous injection group(IL-25 treated dermatitis group);⑥ OVA treated and anti-mouse IL-25 monoclonal antibody injection group(anti-IL-25 treated dermatitis group).The ⑤ and ⑥ groups in the process of treatment with OVA,IL-25 or anti-IL-25 anti-body were given in the same way as the ② and ③ groups.Scratching behavior and skin performance of the mice were recorded during the seven-week-treatment.Twenty four hours after the final treatment,blood was taken from the mouse heart,and the serum was separated to detect the total IgE,IL-4,IL-5,IL-13,etc.The skin samples of the treatment sites were used for hematoxylin-eosin(HE)staining,im-munohistochemistry,real-time PCR and Western blot detections.A single factor(ANOVA)analysis of variance was used to compare the differences in various indicators between the groups.Results:The fre-quency of scratches in the IL-25 treated dermatitis group was higher than that in the model group,and the scratching behavior of the anti-IL-25 treated dermatitis group was significantly lower than that in the model group.The appearance of atopic dermatitis,thickening of the epidermis and the degree of dermal inflammation in the IL-25 treated dermatitis group were more serious than those in the model group and the anti-IL-25 treated dermatitis group.The levels of serum IgE,IL-4,IL-5,and IL-13 in the IL-25 treated dermatitis group were significantly higher than that in the model group and the anti-IL-25 treated dermatitis group.There were significantly more CD4+T cells in the dermis of IL-25 treated dermatitis group than that in the anti-IL-25 treated dermatitis group.The expression levels of filaggrin and defensinβ2 proteins in the IL-25 treated dermatitis group were significantly lower than those in the model group and the anti-IL-25 treated dermatitis group.Conclusion:In the OVA induced atopic dermatitis mice model,IL-25 can significantly promote the damage of the epidermal barrier function and aggravate the OVA-induced dermatitis.Antagonizing IL-25 can alleviate OVA induced dermatitis to a certain extent.

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