1.Inhibition of NLRP3 inflammasome by sonodynamic therapy mediates CACNA1C upregulation to reduce atrial fibrillation susceptibility
Wei WANG ; Yimeng WANG ; Hanwen CUI ; Haozhen YANG ; Shuyuan GUO ; Chuyu ZHANG ; Yu WANG ; Qipin ZHOU ; Yanfeng TIAN ; Dechun YIN ; Ye TIAN
Chinese Journal of Cardiology 2025;53(11):1231-1243
Objective:To investigate the effect and underlying mechanism of sonodynamic therapy (SDT) on inflammation-related atrial fibrillation (AF) susceptibility.Methods:Lipopolysaccharide (LPS)-stimulated mouse and HL-1 mouse atrial myocyte models were used. (1) In vivo study: experimental groups included control, LPS, LPS+SDT, and SDT groups, with 20 mice in each group. Atrial fibrillation inducibility and duration were assessed by electrical stimulation. Western blot was used to analyze atrial expression of NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), interleukin (IL)-1β, and IL-18. Immunohistochemistry was used to detect calcium voltage-gated channel subunit alpha1 C (CACNA1C) expression. (2) In vitro study: cell counting kit-8 (CCK-8) and Western blot were used to determine the optimal and safe LPS concentration. The safe incubation condition for the sonosensitizer sinoporphyrin sodium was determined by CCK-8 and fluorometry. An LPS-induced inflammatory model in HL-1 atrial myocytes was used, with experimental groups including control, LPS, LPS+SDT, LPS+sinoporphyrin sodium, and LPS+ultrasound groups. NLRP3 was overexpressed using plasmid transfection, with experimental groups including control, NLRP3 plasmid, negative control plasmid, and NLRP3 plasmid+SDT groups. SDT was applied to LPS-stimulated or NLRP3-overexpressing HL-1 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to measure mRNA and protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Cleaved Caspase-1, IL-1β, IL-18, and CACNA1C. The NLRP3 inhibitor MCC950 was used to validate the relationship of NLRP3 and CACNA1C. The experimental groups included control, LPS, LPS+MCC950, and MCC950 groups. Intracellular reactive oxygen species (ROS) levels were detected using the probe DCFH-DA, and the ROS scavenger N-acetyl-L-cysteine (NAC) was used to test if the effects of SDT was ROS-dependent.Results:(1) In vivo: The LPS+SDT group exhibited a lower incidence of atrial fibrillation induction and a shorter duration of atrial fibrillation compared to the LPS group(both P<0.05). Protein expression levels of NLRP3 and IL-1β were lower than those in the LPS group (all P<0.05), while the expression of CACNA1C subunit tended to increase relative to the LPS group ( P>0.05). (2) In vitro: The safe concentration of LPS for administration was ≤20 μg/ml, with an optimal pro-inflammatory concentration of 4 μg/ml. The safe concentration of sinoporphyrin sodium for administration was 0.4 μmol/L, with an optimal incubation time of 4 hours. Compared to the LPS group or NLRP3 plasmid group, the LPS+SDT group or NLRP3 plasmid+SDT group exhibited lower expression levels of NLRP3, ASC, Cleaved Caspase-1, IL-1β, and IL-18, and higher mRNA and protein levels of CACNA1C (all P<0.05). The LPS+MCC950 group had higher CACNA1C protein expression than the LPS group ( P<0.05). SDT increased intracellular ROS levels, and NAC blocked the regulatory effects of SDT on NLRP3 and CACNA1C. Conclusion:SDT reduces atrial fibrillation susceptibility in mice by inhibiting NLRP3 inflammasome activation in atrial cardiomyocytes, thereby upregulating the L-type calcium channel subunit CACNA1C.
2.Inhibition of NLRP3 inflammasome by sonodynamic therapy mediates CACNA1C upregulation to reduce atrial fibrillation susceptibility
Wei WANG ; Yimeng WANG ; Hanwen CUI ; Haozhen YANG ; Shuyuan GUO ; Chuyu ZHANG ; Yu WANG ; Qipin ZHOU ; Yanfeng TIAN ; Dechun YIN ; Ye TIAN
Chinese Journal of Cardiology 2025;53(11):1231-1243
Objective:To investigate the effect and underlying mechanism of sonodynamic therapy (SDT) on inflammation-related atrial fibrillation (AF) susceptibility.Methods:Lipopolysaccharide (LPS)-stimulated mouse and HL-1 mouse atrial myocyte models were used. (1) In vivo study: experimental groups included control, LPS, LPS+SDT, and SDT groups, with 20 mice in each group. Atrial fibrillation inducibility and duration were assessed by electrical stimulation. Western blot was used to analyze atrial expression of NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), interleukin (IL)-1β, and IL-18. Immunohistochemistry was used to detect calcium voltage-gated channel subunit alpha1 C (CACNA1C) expression. (2) In vitro study: cell counting kit-8 (CCK-8) and Western blot were used to determine the optimal and safe LPS concentration. The safe incubation condition for the sonosensitizer sinoporphyrin sodium was determined by CCK-8 and fluorometry. An LPS-induced inflammatory model in HL-1 atrial myocytes was used, with experimental groups including control, LPS, LPS+SDT, LPS+sinoporphyrin sodium, and LPS+ultrasound groups. NLRP3 was overexpressed using plasmid transfection, with experimental groups including control, NLRP3 plasmid, negative control plasmid, and NLRP3 plasmid+SDT groups. SDT was applied to LPS-stimulated or NLRP3-overexpressing HL-1 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to measure mRNA and protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Cleaved Caspase-1, IL-1β, IL-18, and CACNA1C. The NLRP3 inhibitor MCC950 was used to validate the relationship of NLRP3 and CACNA1C. The experimental groups included control, LPS, LPS+MCC950, and MCC950 groups. Intracellular reactive oxygen species (ROS) levels were detected using the probe DCFH-DA, and the ROS scavenger N-acetyl-L-cysteine (NAC) was used to test if the effects of SDT was ROS-dependent.Results:(1) In vivo: The LPS+SDT group exhibited a lower incidence of atrial fibrillation induction and a shorter duration of atrial fibrillation compared to the LPS group(both P<0.05). Protein expression levels of NLRP3 and IL-1β were lower than those in the LPS group (all P<0.05), while the expression of CACNA1C subunit tended to increase relative to the LPS group ( P>0.05). (2) In vitro: The safe concentration of LPS for administration was ≤20 μg/ml, with an optimal pro-inflammatory concentration of 4 μg/ml. The safe concentration of sinoporphyrin sodium for administration was 0.4 μmol/L, with an optimal incubation time of 4 hours. Compared to the LPS group or NLRP3 plasmid group, the LPS+SDT group or NLRP3 plasmid+SDT group exhibited lower expression levels of NLRP3, ASC, Cleaved Caspase-1, IL-1β, and IL-18, and higher mRNA and protein levels of CACNA1C (all P<0.05). The LPS+MCC950 group had higher CACNA1C protein expression than the LPS group ( P<0.05). SDT increased intracellular ROS levels, and NAC blocked the regulatory effects of SDT on NLRP3 and CACNA1C. Conclusion:SDT reduces atrial fibrillation susceptibility in mice by inhibiting NLRP3 inflammasome activation in atrial cardiomyocytes, thereby upregulating the L-type calcium channel subunit CACNA1C.
3.Association Between Medication Compliance and Various Risky Behaviors in Patients With Schizophrenia
Luyi WEI ; Xianmei YANG ; Ruoxin FAN ; Dan WANG ; Jun LIU ; ChangJiu HE ; Yang LI ; Chuanlong ZUO ; Hanwen ZHOU ; Xiang LIU ; Yuanyuan LIU
Journal of Sichuan University (Medical Sciences) 2023;54(6):1201-1207
Objective To investigate the status of medication adherence and various types of risky behaviors of schizophrenia patients in a certain area of western China and to explore accordingly the correlation between the two.Methods A total of 292 667 patients with schizophrenia were enrolled in a follow-up survey between 2006 and 2018.In addition,based on the outcome-wide analysis strategy,a multivariate Cox proportional risk regression model was used to estimate and compare the impact of medication adherence on different types of risky behaviors in schizophrenia patients.Results In this 13-year prospective cohort,65 175 patients(31.4%)showed good medication adherence,while 142 394 patients(68.6%)showed poor medication adherence.The incidence rates of various risky behaviors during the follow-up period were as follows,minor nuisances,12.25%,violation of the Law of the People's Republic of China on Penalties for Administration of Public Security(APS law),3.82%,violation of criminal law,0.94%,suicide completed,0.28%,self-harm,1.42%,and attempted suicide,0.82%.Schizophrenia patients who had poor medication adherence had higher risks of committing violence against others and self-inflicted injury compared to patients with good medication adherence did,with the associated effects being minor nuisances(hazard ratio[HR]=1.31,95%confidence interval[CI]:1.27-1.35),violation of APS law(HR=1.47,95%CI:1.38-1.56),violation of criminal law(HR=1.17,95%CI:1.05-1.31),and self-harm(HR=1.43,95%CI:1.32-1.56),respectively,while the risk of suicide completed is lower in schizophrenia patients with poor medication adherence than that in patients with good medication adherence(HR=0.56,95%CI:0.47-0.66).There was no statistically significant association between attempted suicide and medication adherence.Conclusion There are variations in the direction and strength of the association between medication adherence and different types of risky behaviors and further research is needed to elucidate the mechanisms of the association.
4.Exploring the Pathogenesis of T2DM based on the Correlation between “Qi-fire Imbalance” and Ferroptosis
Xinhui SHEN ; Jiren AN ; Yufeng YANG ; Qingfeng WANG ; Hanwen ZHANG ; Jiaxiang YU ; Cheng ZHOU ; Hui ZHANG ; Mingdan GUAN ; Yan SHI
Journal of Traditional Chinese Medicine 2023;64(17):1759-1762
Ferroptosis is a novel iron-dependent mode of programmed cell death characterized by iron deposition and accumulation of lipid peroxidation. More and more studies have found that ferroptosis is closely related to the pathogenesis of type 2 diabetes mellitus (T2DM). The yin-fire theory is an important part of LI Gao's spleen-stomach theory, and it is believed that qi-fire imblance and yin-fire internal generation is the main pathogenesis of T2DM. Abnormal iron metabolism may be an important prerequisite for T2DM yin-fire internal generation, while oxidative stress is the specific manifestation of T2DM qi-fire imbalance. Reactive oxygen species (ROS) is the end product of qi-fire imbalance, and lipid peroxide is the pathological products of T2DM yin-fire internal generation. This study intends to explore the pathological mechanism of qi-fire imbalance and yin-fire internal generation from the perspectives of iron metabolism, oxidative stress and lipid peroxidation, enriching the modern connotation of yin-fire theory, and benefiting traditional Chinese medicine to target against ferroptosis, and prevent and treat T2DM precisely.
5.Electroencephalographic microstates in vestibular schwannoma patients with tinnitus.
Chi ZHANG ; Xiaoguang WANG ; Zhiwei DING ; Hanwen ZHOU ; Peng LIU ; Xinmiao XUE ; Wei CAO ; Yuhua ZHU ; Jiyue CHEN ; Weidong SHEN ; Shiming YANG ; Fangyuan WANG
Journal of Southern Medical University 2023;43(5):793-799
OBJECTIVE:
To explore the biomarkers of tinnitus in vestibular schwannoma patients using electroencephalographic (EEG) microstate technology.
METHODS:
The EEG and clinical data of 41 patients with vestibular schwannoma were collected. All the patients were evaluated by SAS, SDS, THI and VAS scales. The EEG acquisition time was 10-15 min, and the EEG data were preprocessed and analyzed using MATLAB and EEGLAB software package.
RESULTS:
Of the 41 patients with vestibular schwannoma, 29 patients had tinnitus and 12 did not have tinnitus, and their clinical parameters were comparable. The average global explanation variances of the non-tinnitus and tinnitus groups were 78.8% and 80.1%, respectively. The results of EEG microstate analysis showed that compared with those without tinnitus, the patients with tinnitus had an increased frequency (P=0.033) and contribution (P=0.028) of microstate C. Correlation analysis showed that THI scale scores of the patients were negatively correlated with the duration of microstate A (R=-0.435, P=0.018) and positively with the frequencies of microstate B (R=0.456, P=0.013) and microstate C (R=0.412, P=0.026). Syntax analysis showed that the probability of transition from microstate C to microstate B increased significantly in vestibular schwannoma patients with tinnitus (P=0.031).
CONCLUSION
EEG microstate features differ significantly between vestibular schwannoma patients with and without tinnitus. This abnormality in patients with tinnitus may reflect the potential abnormality in the allocation of neural resources and the transition of brain functional activity.
Humans
;
Neuroma, Acoustic/complications*
;
Electroencephalography
;
Patients
;
Probability
6.The effect of preoperative anxiety on propofol EC50 for no-movement during painless gastroscopy
Yiwen ZHANG ; Yanjing ZHANG ; Hanwen CHEN ; Jiyuan LI ; Zhiqiang CHEN ; Shile LIU ; Cuiyun ZHOU ; Zumin XING
Journal of Chinese Physician 2018;20(4):493-495
Objective To investigate the effect of preoperative anxiety on propofol EC50 for nomovement during Painless gastroscopy.Methods Thirty-one patients (without anxiety) and twenty-seven patients (with anxiety) undergoing gastroscopy under general anesthesia were enrolled on the study.Anesthesia was conducted with a target-controlled infusion (TCI) of propofol.The initial target effect-site propo fol concentration (Ceprop) was 5.0 μg/ml and was adjusted stepwise by 0.5 μg/ml by an up-down sequential method to reach no-movement.Results Propofol EC50 to induce no-movement was higher in patients with anxiety than those without anxiety (5.32 μg/ml,95% CI:4.75-5.88 μg/ml vs 4.75 μg/ml,95% CI:4.48-5.01 μg/ml,P < 0.05).Conclusions During painless gastroscopy,patients with anxiety had a higher propofol EC50 for no-movement compared with those without anxiety when intravenous injected of fentanyl 0.1 μg/kg.
7.Acute kidney injury in Xinjiang: a cross-sectional survey
Shun WANG ; Lei YANG ; Ping ZHOU ; Haiying WANG ; Hanwen LIAO ; Xinxia JIA ; Jian LIU ; Suhua LI
Chinese Journal of Nephrology 2018;34(5):340-347
Objective To evaluate the etiology,epidemiological characteristics,clinical diagnosis,and outcomes of hospitalized patients with AKI in Xinjiang,analyzing the risk factors of their clinical prognosis.Methods A multicenter retrospective survey was conducted,investigating adult patients admitted to four hospitals in Xinjiang in January and July 2013.Patients with AKI were screened out based on KDIGO's inclusion and exclusion criteria.Clinical variables of patients with AKI including demographics,clinical data,laboratory tests,treatment measures and prognosis were collected.Results Among 32,157 adult hospitalized patients,there were 722 AKI patients.Excluding those with incomplete data,719 patients were enrolled in this study.The detection rate of AKI was 2.25% (722 of 32,157) by KDIGO criteria.The main cause for AKI was pre-renal injury,led mainly by cardiac output,low blood volume,and the use of nephrotoxic drugs.The non-recognition rate of AKI was 72.4% (407/557).Multivariate binary logistic regression analysis showed that AKI stage,peripheral vasodilation and renal parenchyma were protective factors of the omission diagnosis.In the short-term prognostic analysis,the overall mortality rate was 12.8%(92/719).Among the 323 patients with AKI who survived discharge,43.7%(141) had renal function recovery;40.2%(130) did not fully recover their renal function but ceased maintenance dialysis;16.4% (53) were still on dialysis at discharge.Multivariate Cox regression model suggested that DIC,shock and department of obstetrics were independent risk factors for death during hospitalization of AKI.In addition,the risk of death for AKI from department of obstetrics and gynecology patients was higher than that of other departments.Conclusions The most common reason for AKI in hospitalized patients in Xinjiang was pre-renal injury.The main risk factors were low cardiac output and low blood volume.The omission diagnosis of AKI was serious;AKI stage,peripheral vasodilation and renal parenchymal injury however were its protective factors.Poor-DIC,shock,hospitalization in obstetrics were independent risk factors for death in patients with AKI.
8.Effects of light acute hypervolemic hemodilution on early postoperative cognitive function in elderly patients
Hanwen CHEN ; Zumin XING ; Xiaolei LIU ; Yanjing ZHANG ; Jiyuan LI ; Zhiqiang CHEN ; yun Cui ZHOU ; Yiwen ZHANG
The Journal of Practical Medicine 2017;33(21):3589-3592
Objective To investigate the effects of light acute hypervolemic hemodilution on early postop-erative cognitive function in elderly patients. Methods A total of 60 patients treated by radical surgery were equally randomized to an AHH and a non-AHH control group.Using the Mini-Mental State Examination scale (MMSE),we evaluated the cognitive function of the patients.We made comparisons between the two groups in the plasma S100β levels at T0(before anesthesia induction),T1(immediately after hemodilution),T2(immediately after operating),T(36 hour after operating)and T(424 hour after operating).Results The S-100β lever at T2、T3 and T4were markedly higher than T0in both groups(P<0.05);At T3and T4,the S-100β lever was higher in non-AHH control group than AHH group(P<0.05).There was no significant difference in the incidence of postopera-tive cognitive dysfunction between the two groups(P>0.05)There was no significant difference in the incidence of postoperative cognitive dysfunction between the two groups(P > 0.05). Conclusions AHH can significantly reduce plasma S100β in elderly patients,but there is no effect on early postoperative cognitive function.
9.The influence of preoperative anxiety on popofol EC50 for no-movement during gastroscopy
Hanwen CHEN ; Shijian SHI ; Zumin XING ; Yanjing ZHANG ; Jiyuan LI ; Zhiqiang CHEN ; Shile LIU ; Cuiyun ZHOU ; Yiwen ZHANG
The Journal of Practical Medicine 2017;33(20):3434-3436
Objective To investigate whether the median(50%)effective effect-concentration(EC50)of propofol inducing loss of consciousness (LOC) varies. Methods 56 patients undergoing gastroscopy under general anaesthesia were enrolled on the study. Anaesthesia was conducted with a target-controlled infusion(TCI) of propofol. The initial target effect-site propofol concentration (Ceprop) was 5.00 μg/mL and was adjusted stepwise by 0.50μg/mL by an up-down sequential method to reach no-movement. Results Propofol EC50 to induce no-movement was higher in patients with anxiety than those without anxiety(6.46μg/mL vs. 5.75μg/mL,P<0.05). Conclusions During general anaesthesia ,patients with anxiety had a higher propofol EC50 for no-movement compared with those without anxiety. Differences in preoperative anxiety levels may reduce anaesthetic effects.
10.Correlation between the changes in lower limb power line and pain area in the knee osteoarthritis patients: imaging evaluation
Hanwen LIN ; Junmao WEN ; Chaoyuan HUANG ; Chi ZHOU ; Hongyu TANG
Chinese Journal of Tissue Engineering Research 2017;21(7):1110-1114
BACKGROUND: The change of the axial angle of the lower limb is related to the occurrence and development of osteoarthritis.OBJECTIVE: To analyze the correlation between the change of lower limb power line and pain area in the knee osteoarthritis patients.METHODS: Totally 65 knee osteoarthritis patients were selected as pain group and 30 healthy people were selected as control group. All the participants took anteroposterior and lateral knee radiographs through PACS imaging systems to collect six imaging indexes, including install index, the degree of tibiofemoral joint subluxation, tibiofemoral inside and outside joint clearance ratio, femoral angle, tibial angle and tibiofemoral angle. Knee osteoarthritis patients in pain group were divided into two common clinical pain areas which were proparea and medial area.RESULTS AND CONCLUSION: (1) The insall index, the degree of tibiofemoral joint subluxation, tibiofemoral inside andoutside joint clearance ratio between knee osteoarthritis patients in pain group and people in healthy control group hadsignificant differences. There was no statistical significance in the femoral angle, tibial angle and tibiofemoral angle. (2) In terms of the comparison between proparea and medial area in knee osteoarthritis patients in pain group, tibiofemoral joint subluxation degree was statistically different. (3) These findings suggest that there was a higher patella in knee osteoarthritis patients who were in pain, more severe in the degree of tibiofemoral joint subluxation, and more limited in tibiofemoral inside and outside joint clearance ratio. The degree of tibiofemoral joint subluxation of proparea was more severe than medial area in pain group.

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