1.Mechanism of Yiqi Jiedu Formula Against Ischemic Stroke Based on Microbial-gut-brain Axis
Jialin YANG ; Bingjie CAI ; Yuhao DAI ; Shuting LI ; Keke ZHANG ; Yanhua GAO ; Qiman ZHANG ; Ying ZHANG ; Jianying SHEN ; Shaojing LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):91-100
ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula (YQ) in treating ischemic stroke (IS) from the perspective of the microbial-gut-brain axis (MGBA). MethodRats were randomly divided into five groups, with six in each group, including sham surgery group, model group, and low, medium, and high dose YQ groups (1, 5, and 25 mg·kg-1). Except for the sham surgery group, all other groups were established with a middle cerebral artery occlusion (MCAO) model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring, and the protective effect of YQ on IS was evaluated. Then, the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology, and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 (IL-6), interleukin-17A (IL-17A), and interleukin-10 (IL-10) in serum was detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue, and hematoxylin-eosin staining (HE) was used to observe pathological changes in the cerebral cortex and colon, so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats (P<0.01) and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them, significantly changed microorganisms include Morgentia, Escherichia Shigella, Adlercreutzia, and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group, the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A (P<0.01) and a decrease in the content of anti-inflammatory factor IL-10 (P<0.01). Compared with the model group, the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased (P<0.05), and that of anti-inflammatory factor IL-10 increased (P<0.01). The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats (P<0.05), while the expression levels of both increased in the treatment group (P<0.05). ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier, and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia, inhibit systemic inflammatory response, and improve the disruption of the gut-blood brain barrier, preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.
2.Exploring Mechanism of Neferine in Promoting Vascular Regeneration Against Cerebral Ischemia Based on Mitochondrial MCU Channel
Qiman ZHANG ; Yanhua GAO ; Wenjie WU ; Wei YANG ; Chen LIU ; Shuting LI ; Bingjie CAI ; Jialin YANG ; Ying ZHANG ; Jing MA ; Shaojing LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):103-113
ObjectiveTo investigate the mechanism of neferine(Nef) in promoting vascular regeneration against cerebral ischemia through modulation of mitochondrial calcium uniporter(MCU) ion channel. MethodTaking the area of subintestinal vessels in microvascular deficiency zebrafish as an index, the vascular regenerative efficacy of Nef was evaluated, and the median effective concentration(EC50) was calculated. Rats were randomly divided into a sham operation group, a model group, a positive drug group(butylphthalide, 6 mg·kg-1), and Nef low, medium, and high dose groups(0.125, 0.625, 3.125 μg·kg-1). Except for the sham operation group, the middle cerebral artery occlusion(MCAO) model was established in other groups. After modeling, the groups were administered the corresponding dose of drugs by gavage, while the sham operation and model groups received equal volumes of saline, once a day for 7 consecutive days. Neurobehavioral scores were assessed for each group of rats, and the infarct rate of ischemic brain tissue was calculated by 2,3,5-triphenyltetrazolium chloride(TTC) staining. The regional cerebral blood flow(rCBF) of each group was measured using a speckle contrast imaging. Immunofluorescence and Western blot were conducted to detect the expression of vascular endothelial growth factor(VEGF), platelet endothelial cell adhesion molecule-1(CD31), and hypoxia-inducible factor-1α(HIF-1α) proteins in each group. Human umbilical vein endothelial cells(HUVECs) were divided into the normal group, model group, positive drug group(astragaloside Ⅳ, 10 μmol·L-1), and Nef group (32 nmol·L-1). In the verification of mitochondrial protection of Nef and its mechanism in promoting vascular regeneration, the spermine(MCU agonist) and Nef+spermine group were added. HUVECs model of oxygen-glucose deprivation(OGD) was established in all groups except the normal group, the cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, and cell migration ability was evaluated through scratch and tube formation assays. Fluorescent probes(Rhod-2 AM, Fluo-3 AM, JC-1, Calcein AM) and a cellular energy metabolism analyzer were used to analyze the mitochondrial protective effects of Nef. Molecular docking was performed to predict the binding ability of Nef with MCU and HIF-1α, and Western blot was used to detect the effects of Nef on the protein expressions of MCU, B-cell lymphoma-2 associated X protein(Bax), Caspase-3 and HIF-1α in the OGD model HUVECs. ResultThe results of vascular regeneration in microvascular deficiency zebrafish showed that compared to the normal group, the area of subintestinal vessels in the model group significantly decreased(P<0.01). Compared to the model group, different concentrations of Nef could significantly increase the area of subintestinal vessels(P<0.01), with the maximum tolerated concentration of 10.24 μmol·L-1 and the EC50 of 0.23 μmol·L-1. Anti-cerebral ischemia results on MCAO rats showed that compared to the sham operation group, the model group had a significant decrease in rCBF and a significant increase in infarct rate, while CD31 expression significantly decreased(P<0.01), and VEGF and HIF-1α protein expressions significantly increased(P<0.05). Compared to the model group, the treated groups showed significant increases in rCBF, significant reductions in infarct volume, and significant increases in CD31, VEGF, and HIF-1α protein expression(P<0.01). Cell experiment results showed that compared to the normal group, the model group had decreased cell viability and migration ability, increased intracellular Ca2+ and mitochondrial Ca2+ levels, reduced mitochondrial permeability transition pore(MPTP) opening, and decreased mitochondrial energy metabolism capability, with increased expressions of MCU, Bax, Caspase-3 and HIF-1α proteins(P<0.05, P<0.01). Compared to the model group, the Nef group showed increased cell viability and migration ability, decreased intracellular Ca2+ and mitochondrial Ca2+ levels, increased MPTP opening, enhanced mitochondrial energy metabolism capability, decreased expressions of MCU, Bax and Caspase-3 proteins, and increased HIF-1α protein expression(P<0.05, P<0.01). ConclusionNef can stabilize mitochondrial membrane potential and inhibit mitochondrial apoptosis. By down-regulating the expression of MCU, it suppresses the activation of intracellular Bax and Caspase-3 while activating the HIF-1α signaling pathway, enhancing the expression of VEGF and CD31, thereby promoting vascular regeneration to treat ischemic brain injury.
3.Network analysis of campus bullying and anxiety symptoms among rural middle school students
ZHU Yiran, WANG Yuhao, WANG Yingxue, WANG Yihan, CAI Jialin, YAN Na, LUO Yunjiao, WANG Wei
Chinese Journal of School Health 2024;45(11):1594-1598
Objective:
To explore the network structure characteristics and core items of rural middle school students suffering from campus bullying and anxiety symptoms, so as to provide a reference basis for the precise prevention and intervention of the comorbidity of campus bullying and anxiety symptoms.
Methods:
From September 2021 to March 2022, a multi stage random cluster sampling method was used to select 1 920 rural middle school students from Xuzhou. The Chinese version of the Olweus Bully/Victim Questionnaire was used to investigate the situation of campus bullying, and the Chinese version of the Generalized Anxiety Disorder (GAD-7) was used to assess anxiety symptoms. The network analysis method was used to construct the network between suffering from campus bullying and anxiety symptoms of rural middle school students to evaluate the centrality, bridge strength, stability and accuracy of each item.
Results:
The total score of suffering from campus bullying symptoms of rural middle school students was (10.42±3.26) points, and the total score of anxiety symptoms was (11.47±4.93) points. The symptom with the highest strength and expected influence was "unable to stop or control one s worry emotions", and the node strength and expected influence value was 1.041 7. The nodes "feel nervous, anxious or irritable" and "unable to stop or control one s worry emotions" were most closely related. The symptoms with the highest bridge strength were "others give me ugly nicknames to scold me or make fun of and satirize me" and "unable to stop or control one s worry emotions".
Conclusions
Rural middle school students suffering from campus bullying is related to anxiety symptoms. Accurate intervention according to the intervention targets may minimize the negative impact of suffering from campus bullying and anxiety symptoms on rural middle school students.
4.Comparison of effects between different anesthesia methods under preoperative optimal measures in elderly patients with hip fracture
Meijiao LIN ; Qiufen WANG ; Jialin CAI ; Jingjia YAN
Chongqing Medicine 2024;53(18):2788-2792
Objective To compare the application effects of different anesthesia methods under preoper-ative optimization measures in elderly patients with hip fracture surgery.Methods A total of 120 elderly pa-tients (≥75 years old) with hip fracture surgery in this hospital from May 2022 to December 2023 were se-lected as the study subjects and divided into group A and group B,60 cases in each group.The two groups a-dopted the preoperative optimization measures.The group A performed "two single three low" (unilateral,once,low position,low concentration and low dose) lumbar anesthesia,while group B conducted the laryngeal mask artificial airway anesthesia.The hemodynamic changes at skin incision in operation beginning (T1),at 30 min after operation (T2),suture at operation end (T3),at the end of operation (T4) and at 30 min after opera-tion end (T5),postoperative recovery time and occurrence situation of complications such as nausea and vomi-ting,agitation,postoperative delirium (POD) were compared between the two groups.Results The systolic blood pressure and the heart rate at T1 in group B were lower than those in group A,and the differences were statistically significant (P<0.05).The systolic blood pressure and heart rate at T4 in group B were higher than those in group A,and the difference was statistically significant (P<0.05).The recovery time,agitation,nausea and vomiting and incidence rate of adverse reactions such as POD had no statistical difference between the two groups (P<0.05).Conclusion On the basis of preoperative optimization measures,selecting the "two single three low" lumbar anesthesia method in elderly patients with hip fracture surgery anesthesia has more stable hemodynamics,less complications and faster postoperative recovery.
5.Effects of dexmedetomidine acupoint injection on neurocognitive disorder and sleep quality after non-cardiac major surgery in elderly people
Jialin CAI ; Qiufen WANG ; Xiaohong LIU ; Qingwang LU ; Jingjia YAN
Chongqing Medicine 2024;53(22):3429-3434
Objective To investigate the effects of dexmedetomidine injection at the Neiguan acupoint before general anaesthesia on neurocognitive disorder and sleep quality after non-cardiac major surgery in eld-erly people.Methods Elderly patients undergoing elective thoracic and laparoscopic surgery in this hospital from February 2023 to March 2024 were selected and divided into the dexmedetomidine Neiguan acupoint in-jection group(A),saline Neiguan acupoint injection group(B)and dexmedetomidine intravenous injection group(C)by the randomised numerical table method,40 cases in each group.The postoperative neurocognitive function and sleep-related condition in the three groups were observed.Results The incidence rate of postop-erative delirium(POD)on postoperative 1 d in the group A and C was significantly decreased compared with the group B,and the difference was statistically significant(P<0.05);the incidence rate of POD on postoper-ative 2 d in the group A was significantly decreased compared with the group B(P<0.05);the incidence rate of postoperative cognitive dysfunction(POCD)on postoperative 1 d in the group A and C was significantly de-creased compared with the group B,moreover which in the group A was lower than that in the group C,and the differences were statistically significant(P<0.05);the incidence rate of POCD on postoperative 3,5 d in the group A was lower than that in the group B(P<0.05).The MMSE score on postoperative 1,3,5 d in the group B and C was significantly decreased compared with preoperative 1 d(P<0.05).The MMSE score on postoperative 1,3,5 d in the group A and C was higher than that in the group B.and the difference was statis-tically significant(P<0.05).The PSQI score on postoperative 1,3,5 d in the group A and C was increased compared with preoperative 1 d(P<0.05);compared with the group B,the PSQI score on postoperative 1,3,5 d in the group A and C was decreased,moreover the group A was lower the group C,and the differences were statistically significant(P<0.05).The incidence rate of bradycardia in the group A and C was signifi-cantly higher than that in the group B(P<0.05).The incidence rate of postoperative nausea and vomiting(PONV)in the group A was significantly lower than that in the group B and C(P<0.05),and the difference between the group B and C had no statistical significance(P>0.05).Conclusion Dexmedetomidine injection at the Neiguan acupoint before anaesthesia for minimally invasive surgery can significantly reduce periopera-tive neurocognitive dysfunction(PND)and improve the quality of sleep in elderly patients,moreover simulta-neously has the effect for preventing PONV.
6. Construction of mammary gland cell-specific SENP7 knockout mice by Cre-loxP system
Hong SUN ; Jiaqin CAI ; Jie ZHUANG ; Xiaoxia WEI ; Jialin HOU
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(4):376-381
AIM: To construct and identify the mammary gland cell-specific conditional knockout of SENP7 by the Cre-loxP system. METHODS: The homozygous SENP7
7. SUMO E3 ligase mediates androgen receptor transcription to promote tamoxifen resistance of breast cancer
Hong SUN ; Jiaqin CAI ; Xiaoxia WEI ; Jie ZHUANG ; Jialin HOU
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(3):285-291
AIM: To investigate the mechanism of the involvement of SUMO-ylated Androgen receptor (AR) in tamoxifen resistance and the role of SUMO inhibitor ginkgolic acid in resistance. METHODS: Real-Time PCR was used to detect AR mRNA levels in parental cells MCF-7W and drug-resistant cells MCF-7R, AR protein levels and SUMO levels in MCF-7W and MCF-7R cells was performed by western blot, and CB/IP was applied to detect AR interacts with SUMOE3 ligase PIAS1 and HSP27 in MCF-7R cell chromatin, the transcriptional activity of SUMO AR was also evaluated by the fluorescent reporter gene experiment, the CCK-8 method and the trypan blue exclusion method were used to detect cell viability and cell viability respectively. RESULTS: The mRNA and protein expression levels of AR in MCF-7R cells were significantly higher than those in MCF-7W cells (P<0.05), and there was highly SUMOylated AR in MCF-7R cells. Further research found that there had an obvious interaction between AR and SUMO E3 ligase PIAS1 and HSP27, that was, the SUMOylated AR was modified by E3 ligase. Moreover, androgen R1881 could enhance the transcriptional activity of the SUMOylated AR in a concentration-dependent manner. Compared with ginkgo acid alone, 10 μmol/L of ginkgolic acid combined with 10 μmol/L of enzalutamide treated MCF-7R cells for 3 days, the cell number was significantly reduced, and the number of cell death increased significantly (P<0.05). CONCLUSION: The resistance mechanism of tamoxifen may be due to the enhanced AR transcription and activity increased by the hyperactive SUMOylated AR, SUMO inhibitor ginkgolic acid combined with AR antagonist enzalutamide can be a new strategy for the treatment of tamoxifen resistance.
8.Research progress of anticoagulant management service for atrial fibrillation
Junxia WANG ; Jialin CHEN ; Lin WU ; Shu CAI
Chinese Journal of General Practitioners 2020;19(4):368-371
The morbidity and mortality caused by ischemic stroke resulted from atrial fibrillation are increasing year by year. Anticoagulation is the core strategy for the prevention and treatment of atrial fibrillation-related stroke. At present, the prominent problems in anticoagulation of atrial fibrillation in China include low rate of anticoagulation therapy, low rate of INR compliance, non-standard drug treatment, poor compliance with medication and follow-up, and so on. It has been reported that anticoagulation management service can significantly improve the effect and compliance of anticoagulation therapy, and reduce the hospitalization rate and emergency consultation rate of adverse events related to anticoagulation therapy. In this paper, the research progress of anticoagulant management service of atrial fibrillation at home and abroad is reviewed, providing reference for the establishment of anticoagulant management system under the hierarchical medical system in China.
9. Study on the health literacy and related factors of the cancer prevention consciousness among urban residents in China from 2015 to 2017
Chengcheng LIU ; Chunlei SHI ; Jufang SHI ; Ayan MAO ; Huiyao HUANG ; Pei DONG ; Fangzhou BAI ; Yunsi CHEN ; Debin WANG ; Guoxiang LIU ; Xianzhen LIAO ; Yana BAI ; Xiaojie SUN ; Jiansong REN ; Li YANG ; Donghua WEI ; Bingbing SONG ; Haike LEI ; Yuqin LIU ; Yongzhen ZHANG ; Siying REN ; Jinyi ZHOU ; Jialin WANG ; Jiyong GONG ; Lianzheng YU ; Yunyong LIU ; Lin ZHU ; Lanwei GUO ; Youging WANG ; Yutong HE ; Peian LOU ; Bo CAI ; Xiaohua SUN ; Shouling WU ; Xiao QI ; Kai ZHANG ; Ni LI ; Wanghong XU ; Wuqi QIU ; Min DAI ; Wanqing CHEN
Chinese Journal of Preventive Medicine 2020;54(1):47-53
Objective:
To understand the health literacy and relevant factors of cancer prevention consciousness in Chinese urban residents from 2015 to 2017.
Methods:
A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The self-designed questionnaire was used to collect the information of demographic characteristics and cancer prevention consciousness focusing on nine common risk factors, including smoking, alcohol, fiber food, food in hot temperature or pickled food, chewing betel nut, helicobacter pylori, moldy food, hepatitis B infection, estrogen, and exercise. The logistic regression model was adopted to identify the influencing factors.
Results:
The overall health literacy of the cancer prevention consciousness was 77.4% (24 980 participants), with 77.4% (12 018 participants), 79.9% (6 406 participants), 77.2% (1 766 participants) and 74.5% (4 709 participants) in each group (
10. Analysis on the consciousness of the cancer early detection and its influencing factors among urban residents in China from 2015 to 2017
Ayan MAO ; Jufang SHI ; Wuqi QIU ; Chengcheng LIU ; Pei DONG ; Huiyao HUANG ; Kun WANG ; Debin WANG ; Guoxiang LIU ; Xianzhen LIAO ; Yana BAI ; Xiaojie SUN ; Jiansong REN ; Li YANG ; Donghua WEI ; Bingbing SONG ; Haike LEI ; Yuqin LIU ; Yongzhen ZHANG ; Siying REN ; Jinyi ZHOU ; Jialin WANG ; Jiyong GONG ; Lianzheng YU ; Yunyong LIU ; Lin ZHU ; Lanwei GUO ; Youqing WANG ; Yutong HE ; Peian LOU ; Bo CAI ; Xiaohua SUN ; Shouling WU ; Xiao QI ; Kai ZHANG ; Ni LI ; Min DAI ; Wanqing CHEN
Chinese Journal of Preventive Medicine 2020;54(1):54-61
Objective:
To understand the consciousness of the cancer early detection among urban residents and identify the influencing factors from 2015 to 2017.
Methods:
A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. Self-designed questionnaires were used to collect population, socioeconomic indicators, self-cancer risk assessment, regular participation in physical examination and other information. The multivariate logistic regression model was used to identify the factors of people who had not regularly participated in the regular physical examination in the past five years.
Results:
The self-assessment results of 32 357 residents showed that there were 27.54% (8 882) of total study population with self-reported cancer risk, 45.48% (14 671) without cancer risk and 26.98% (8 704) with unclear judgement on their own cancer risk. Among population with cancer risk, 79.84% (7 091) considered physical examination accounted. In the past five years, there were 21 105 (65.43%) residents participated in regular physical examination and 11 148 (34.56%) participated in non-scheduled one, respectively. The multivariate logistic regression analysis showed that compared with unmarried and western region residents, divorced, middle and eastern region residents had a stronger consciousness to participate in the regular physical examination (


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