1.Mechanism of Xiangsha Liujunzi Decoction in improving autophagy in interstitial cells of Cajal of rats with functional dyspepsia by regulation of IRE1/ASK1/JNK pathway.
Ming-Kai LYU ; Yong-Qiang DUAN ; Jin JIN ; Wen-Chao SHAO ; Qi WU ; Yong TIAN ; Min BAI ; Ying-Xia CHENG
China Journal of Chinese Materia Medica 2025;50(8):2237-2244
This study explored the mechanism of Xiangsha Liujunzi Decoction(XSLJZD) in the treatment of functional dyspepsia(FD) based on inositol-requiring enzyme 1(IRE1)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway-mediated autophagy in interstitial cells of Cajal(ICC). Forty-eight SPF-grade male SD suckling rats were randomly divided into a blank group and a modeling group, and the integrated modeling method(iodoacetamide gavage + disturbance of hunger and satiety + swimming exhaustion) was used to replicate the FD rat model. After the model replications were successfully completed, the rats were divided into a model group, high-dose, medium-dose, and low-dose groups of XSLJZD(12, 6, and 3 g·kg~(-1)·d~(-1)), and a positive drug group(mosapride of 1.35 mg·kg~(-1)·d~(-1)), and the intervention lasted for 14 days. The gastric emptying rate and intestinal propulsion rate of rats in each group were measured. The histopathological changes in the gastric sinus tissue of rats in each group were observed by hematoxylin-eosin(HE) staining. The ultrastructure of ICC was observed by transmission electron microscopy. The immunofluorescence double staining technique was used to detect the protein expression of phospho-IRE1(p-IRE1), TNF receptor associated factors 2(TRAF2), phospho-ASK1(p-ASK1), phospho-JNK(p-JNK), p62, and Beclin1 in ICC of gastric sinus tissue of rats in each group. Western blot was used to detect the related protein expression of gastric sinus tissue of rats in each group. Compared with those in the blank group, the rats in the model group showed decreased body weight, gastric emptying rate, and intestinal propulsion rate, and transmission electron microscopy revealed damage to the endoplasmic reticulum structure and increased autophagosomes in ICC. Immunofluorescence staining revealed that the ICC of gastric sinus tissue showed a significant elevation of p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins and a significant reduction of p62 protein. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. Compared with the model group, the body weight of rats in the high-dose and medium-dose groups of XSLJZD was increased, and the gastric emptying rate and intestinal propulsion rate were increased. Transmission electron microscopy observed amelioration of structural damage to the endoplasmic reticulum of ICC and reduction of autophagosomes, and the p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins in the ICC of gastric sinus tissue were significantly decreased. The p62 protein was significantly increased. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. XSLJZD can effectively treat FD, and its specific mechanism may be related to the inhibition of the expression of molecules related to the endoplasmic reticulum stress IRE1/ASK1/JNK pathway in ICC and the improvement of autophagy to promote gastric motility in ICC.
Animals
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Male
;
Drugs, Chinese Herbal/administration & dosage*
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Autophagy/drug effects*
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Rats
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Rats, Sprague-Dawley
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Interstitial Cells of Cajal/metabolism*
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Dyspepsia/physiopathology*
;
Protein Serine-Threonine Kinases/genetics*
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MAP Kinase Kinase Kinase 5/genetics*
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MAP Kinase Signaling System/drug effects*
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Humans
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Endoribonucleases/genetics*
;
Multienzyme Complexes
2.Neurodevelopment and cerebral blood flow in children aged 2-6 years with autism spectrum disorder
Jia-Bao YIN ; Gan-Yu WANG ; Gui-Qin DUAN ; Wen-Hao NIE ; Ming-Fang ZHAO ; Ting-Ting JIN
Chinese Journal of Contemporary Pediatrics 2024;26(6):599-604
Objective To investigate the neurodevelopmental characteristics of children with autism spectrum disorder(ASD),analyze the correlation between neurodevelopmental indicators and cerebral blood flow(CBF),and explore the potential mechanisms of neurodevelopment in ASD children.Methods A retrospective study was conducted on 145 children aged 2-6 years with newly-diagnosed ASD.Scores from the Gesell Developmental Diagnosis Scale and the Autism Behavior Checklist(ABC)and CBF results were collected to compare gender differences in the development of children with ASD and analyze the correlation between CBF and neurodevelopmental indicators.Results Fine motor and personal-social development quotient in boys with ASD were lower than those in girls with ASD(P<0.05).Gross motor development quotient in ASD children was negatively correlated with CBF in the left frontal lobe(r=-0.200,P=0.016),right frontal lobe(r=-0.279,P=0.001),left parietal lobe(r=-0.208,P=0.012),and right parietal lobe(r=-0.187,P=0.025).The total ABC score was positively correlated with CBF in the left amygdala(r=0.295,P<0.001).Conclusions Early intervention training should pay attention to gender and developmental structural characteristics for precise intervention in ASD children.CBF has the potential to become a biological marker for assessing the severity of ASD.
3.Interactions of Vitamin D Receptor Polymorphisms with Hypertriglyceridemia and Obesity in Chinese Individuals Susceptible to Hypertension and Diabetes Comorbidity.
Hua Lei SUN ; Tong ZHAO ; Dong Dong ZHANG ; Ming Ming FENG ; Ze XU ; Hao Yue HUANG ; Luo Ya ZHANG ; Wen Jie LI ; Xing LI ; Jia Yu DUAN ; Jia LI
Biomedical and Environmental Sciences 2023;36(2):196-200
4. Relationship between Fok polymorphism of vitamin-D receptor gene and hypertensive disorder complicating pregnancy in Han nationality of Qinghai province
Zhen WU ; Qian DUAN ; Ming YUAN ; Xue-Ni WANG ; Wen-Jing CHEN ; Jian-Hua LI ; Zhen WU ; Yu-Qin LI ; Yu-Qin E-LUO-JI
Acta Anatomica Sinica 2023;54(3):313-318
[ Abstract] Objective To investigate the relationship between single nucleotide polymorphism (SNP) Fok (rs2228570 / rs10735810) of vitamin D receptor (VDR) gene and hypertensive disorder complicating pregnancy (HDCP) in Han nationality women of Qinghai province. Methods A total of 137 Han nationality HDCP subjects (HDCP group) and 146 Han nationality normal pregnant subjects (control group) were selected from Qinghai province. The Fok polymorphism typing in HCDP group and control group was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) . The mutation was confirmed by sequencing. SPSS 19. 0 statistical software was used to test whether there were significant differences between two groups in general clinical data, genotype and allele frequency distribution. Results The frequency of FF Ff ff genotype of Fok in HDCP group and control group were 51. 82%, 37. 96%, 10. 22% and 34. 93%, 43. 15%, 21. 92% respectively (
5. Molecular analysis of interleukin 10 promoter region-592A/C polymorphism in hypertensive disorders of pregnancy in Qinghai Han nationality
Qian DUAN ; Jian-Hua LI ; Wen-Jia LI ; Ru WANG ; Zhen WU ; Ming YUAN
Acta Anatomica Sinica 2023;54(1):63-69
Objective To investigate the association between the interleukin 10 (IL-10) gene promoter region-592A/C (rs1800872) polymorphism and hypertensive disorders of pregnancy (HDP) in Han women of Qinghai province and to determine the expression of this gene in two groups (HDP group and healthy control group) preliminarily. Methods A total of 140 HDP patients (HDP group) and 140 normal pregnant women (control group) in Qinghai Province were selected. Using blood DNA as template, the IL-10-592A/C polymorphism typing of HDP group and control group was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and verified by sequencing. The expression of IL-10 mRNA in the placental tissues of the two groups was detected by Real-time PCR. Plasma IL-10 levels of the two groups were detected by ELISA. Results The frequencies of AA, AC and CC genotypes of IL-10 gene in HDP group and control group were 24. 29%, 44. 29%, 31. 42% and 13. 57%, 41. 43%, 45. 00% respectively, the difference in genotype distribution between the two groups was statistically significant (P<0. 05);AA genotype frequency in HDP group(24. 29%)was higher than that of control group(13. 57%)(P<0. 05), CC genotype frequency in HDP group (31. 42%) was lower than that in control group (45. 00%) (P < 0. 05), while there was no significant difference in genotype frequency of AC between the two groups (P<0. 05); The distribution of A and C allele frequencies of IL-10592A/C polymorphism was different between the two groups, and the A allele frequency of HDP group was higher than that of control group (
6.Oxidative Damage to BV2 Cells by Trichloroacetic Acid: Protective Role of Boron via the p53 Pathway.
Chong WANG ; Wei HUANG ; Li LI ; Chao WANG ; Ying SHI ; Song TANG ; Wen GU ; Yong Jun XU ; Li Xia ZHANG ; Ming ZHANG ; Lian DUAN ; Kang Feng ZHAO
Biomedical and Environmental Sciences 2022;35(7):657-662
This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-β production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.
Animals
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Apoptosis
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Boron/toxicity*
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Mice
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Oxidative Stress
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Reactive Oxygen Species/metabolism*
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Trichloroacetic Acid/toxicity*
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Tumor Suppressor Protein p53/metabolism*
7.Stable angina pectoris of coronary heart disease treated with different acupuncture and moxibustion therapies: a network Meta-analysis.
Ruo-Qi LI ; Li WAN ; Ming-Jie ZI ; Wen-Hui DUAN ; Li-Yun HE ; Rong-Rong GAO
Chinese Acupuncture & Moxibustion 2022;42(12):1431-1438
To compare the clinical efficacy among different acupuncture and moxibustion therapies on stable angina pectoris (SAP) of coronary heart disease by means of network Meta-analysis. The articles of randomized controlled trial (RCT) for SAP of coronary heart disease treated with acupuncture and moxibustion therapies were searched from PubMed, Web of Science, Cochrane Library, CNKI, Wanfang database and VIP database from May 1, 2002 to May 1, 2022. The quality of them was assessed with the risk of bias assessment tool of Cochrane 5.3, and the network Meta-analysis was undertaken with Stata 13.1 software. A total of 29 articles were included with the acupuncture and moxibustion therapies involved, e.g. acupuncture, acupoint application and moxibustion. In comparison with the simple routine western medication, the effective rate was better on SAP treated with the combined treatments, in which, acupoint application, moxibustion, acupuncture and intradermal needling were combined with routine western medication (P<0.05). Of those combined treatments, the combination of the acupoint application with routine western medication had high probability, suggesting the optimal regimen (area under the curve [SUCRA]=0.711, P<0.05). The effective rate of acupuncture combined with routine western medication for ECG improvement was better than that of routine western medication (P<0.05), and such combined treatment was high in probability, underlying its optimal treatment (SUCRA=0.800, P<0.05). Combined with routine western medication, acupuncture, acupoint application, moxibustion and intradermal needling all improve the clinical efficacy on SAP of coronary heart disease. But, with different outcomes considered, the optimal treatments may be different. It needs more multi-central and large-sample randomized controlled trials to validate these results.
Humans
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Network Meta-Analysis
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Coronary Disease/therapy*
8.Effect of Decitabine on Regulatory T Cells Relative Content in Peripheral Blood and Bone Marrow of Patients with Myelodysplastic Syndrome/Acute Myeloid Leukemia.
Rui HU ; Yuan GAO ; Yan WEN ; Kun WU ; Ci DUAN ; Yun ZENG ; Ming-Xia SHI
Journal of Experimental Hematology 2022;30(1):36-42
OBJECTIVE:
To investigate regulatory T cells (Tregs) relative content in peripheral blood and bone marrow of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with or without decitabine (DAC), analyze the immunomodulatory of Tregs in pathogenesis and remission of MDS and AML, as well as effect of DAC on Tregs.
METHODS:
From October 2018 to February 2019, 15 patients with MDS and 49 patients with AML (newly diagnosed, treated with DAC or other chemotherapy regimens) were enrolled in this study, and 14 cases with iron deficiency or megaloblastic anemia while without malignant tumor and autoimmune disease as controls. The Tregs relative contents in bone marrow and peripheral blood were analyzed by flow cytometry, meanwhile clinical data of the objects were collected.
RESULTS:
In peripheral blood and bone marrow of the patients with MDS and AML, the Tregs relative contents at newly diagnosed were higher than those of the control group (P=0.05, P=0.043). The Tregs relative content of AML patients in DAC regimen treatment group was significantly lower than that in the newly diagnosed group and non-DAC chemotherapy group (P<0.05). In DAC regimen treatment group, the Tregs relative contents was significantly lower in remission group than in non-remission group (P<0.05). There was no difference between DAC regimen treatment group and control group in Tregs relative content.
CONCLUSION
DAC may increase the body's anti-tumor immunity by consuming Tregs content, enhance the body's immune function to identify and kill tumor cells, thereby promote the patients' reliefs.
Antineoplastic Combined Chemotherapy Protocols
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Bone Marrow
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Decitabine/therapeutic use*
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Humans
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Leukemia, Myeloid, Acute/drug therapy*
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Myelodysplastic Syndromes/drug therapy*
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T-Lymphocytes, Regulatory
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Treatment Outcome
9.Mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 regimen in the treatment of pediatric Burkitt lymphoma.
Meng ZHANG ; Pan WU ; Yan Long DUAN ; Ling JIN ; Jing YANG ; Shuang HUANG ; Ying LIU ; Bo HU ; Xiao Wen ZHAI ; Hong Sheng WANG ; Yang FU ; Fu LI ; Xiao Mei YANG ; An Sheng LIU ; Shuang QIN ; Xiao Jun YUAN ; Yu Shuang DONG ; Wei LIU ; Jian Wen ZHOU ; Le Ping ZHANG ; Yue Ping JIA ; Jian WANG ; Li Jun QU ; Yun Peng DAI ; Guo Tao GUAN ; Li Rong SUN ; Jian JIANG ; Rong LIU ; Run Ming JIN ; Zhu Jun WANG ; Xi Ge WANG ; Bao Xi ZHANG ; Kai Lan CHEN ; Shu Quan ZHUANG ; Jing ZHANG ; Chun Ju ZHOU ; Zi Fen GAO ; Min Cui ZHENG ; Yonghong ZHANG
Chinese Journal of Pediatrics 2022;60(10):1011-1018
Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ2=4.16, P=0.041) and group C2 (χ2=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ2=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Burkitt Lymphoma/drug therapy*
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Child
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Disease-Free Survival
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Female
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Humans
;
Lactate Dehydrogenases
;
Lymphoma, B-Cell/drug therapy*
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Male
;
Prognosis
;
Retrospective Studies
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Rituximab/therapeutic use*
;
Treatment Outcome
10. Efficacy and safety of alfentanil hydrochloride injection in general anesthesia: A multicenter, double-blind, controlled study
Ming-Hua CHEN ; Yi FENG ; Kai-Ming DUAN ; Wen OUYANG ; Sai-Ving WANG ; Fu-Shan XUE ; Ming-Hua CHEN ; Fu-Shan XUE ; Yi FENG ; Ai-Lin LUO ; Qu-Lian GUO ; Ya-Ping WANG ; Deng-Bin AI ; Gong-Jian LIU ; Kai-Ming DUAN ; Wen OUYANG ; Sai-Ving WANG ; Ai-Lin LUO ; Qu-Lian GUO ; Ya-Ping WANG ; Deng-Bin AI ; Gong-Jian LIU
Chinese Pharmacological Bulletin 2022;38(10):1504-1510
Aim To investigate the effectiveness and safety of alfentanil in general anesthesia.Methods In this study, a multicenter randomized double-blind con¬trolled study was conducted.A total of 352 subjects were selected and randomly assigned to fentanyl group (group A, n =176) and alfentanil group (group 15, n = 176).Anesthesia induction: intravenous midazolam 0.03 mg • kg-1 + fentanyl 25 p.g • kg"'(group A) or alfentanil 4 p,g • kg-1 ( group 15) + propofol 2 mg • kg"1 + rocuronium 0.8 mg • kg"1.Sevoflurane + fent¬anyl ( group A ) or alfentanil ( group B ) + rocuronium were used for anesthesia.The vital signs of patients re¬covery time and extuhation time, anesthesia-related complications and the use of related remedial drugs during anesthesia induction and maintenance were compared between the two groups.Results During the induction and maintenance period of anesthesia, alfentanil and fentanyl could equally effectively inhibit the stress response induced by endotracheal intubation and surgical stimulation.Alfentanil also showed more effective inhibition on stress response induced by endo¬tracheal intubation and surgical stimulation than that of fentanyl ( P < 0.05 ) .However, there was no signifi¬cant difference in the incidence of intraoperative hypo¬tension and hypertension and the time of anesthesia re¬covery and extubation between the two groups.Conclu¬sions Both alfentanil and fentanyl can effectively in¬hibit the stress response induced by surgical stimulation and could be safely used in general anesthesia in sur¬gery.Alfentanil has more advantages in maintaining the stability of blood pressure and heart rate during an¬esthesia induction and maintenance.

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