1.Electroacupuncture pretreatment alleviates cerebral ischemia-reperfusion injury in rats by inhibiting ferroptosis through the gut-brain axis and the Nrf2/HO-1 signaling pathway.
Anbang ZHANG ; Xiuqi SUN ; Bo PANG ; Yuanhua WU ; Jingyu SHI ; Ning ZHANG ; Tao YE
Journal of Southern Medical University 2025;45(5):911-920
OBJECTIVES:
To investigate the neuroprotective effects of electroacupuncture (EA) preconditioning against cerebral ischemia-reperfusion injury (CIRI) mediated by gut microbiota modulation, Nrf2/HO-1 pathway activation, and ferroptosis suppression.
METHODS:
Adult male SD rats were divided into sham operation group, CIRI model group, and EA preconditioning group. In the latter two groups, rat models of CIRI were established by middle cerebral artery occlusion (MCAO), and in EA preconditioning group, EA was applied at Baihui (DU20) and Zusanli (ST36) for 3 days before modeling. Neurological deficits, cerebral infarction, and hippocampal pathology of the rats were evaluated using behavioral tests, TTC staining, and Nissl and HE staining, and the oxidative stress markers (MDA, ROS, and SOD), apoptosis/ferroptosis-related proteins (Bax, Bcl-2, GPX4, and SLC7A11), and changes in gut microbiota were analyzed.
RESULTS:
EA preconditioning significantly reduced neurological deficits, decreased infarct volume, promoted hippocampal neuronal survival, and improved structural integrity of the hippocampal neurons in MCAO rats. EA preconditioning also significantly lowered MDA and ROS and increased SOD levels, upregulated Bcl-2, GPX4, and SLC7A11 expressions, and downregulated Bax expression in the hippocampal tissue of the rats, causing also activation of Nrf2/HO-1 signaling and improvement of gut microbiota composition.
CONCLUSIONS
EA preconditioning alleviates CIRI in rats by suppressing ferroptosis and apoptosis, enhancing antioxidant defenses via activating Nrf2/HO-1 signaling, and regulating the gut-brain axis.
Animals
;
Electroacupuncture
;
NF-E2-Related Factor 2/metabolism*
;
Rats, Sprague-Dawley
;
Signal Transduction
;
Reperfusion Injury/therapy*
;
Ferroptosis
;
Male
;
Rats
;
Brain Ischemia
;
Gastrointestinal Microbiome
;
Heme Oxygenase (Decyclizing)/metabolism*
;
Brain/metabolism*
;
Oxidative Stress
;
Heme Oxygenase-1/metabolism*
;
Apoptosis
2.Heme oxygenase-1 enhances the anti-HBV effect of IFN-αby inducing the expression of antiviral proteins
Wei DA ; Qin WANG ; Anbang WEI ; Hao ZHANG ; Renbing WANG ; Qian LIU ; Qiang ZHOU
Acta Universitatis Medicinalis Anhui 2024;59(2):324-330
Objective To investigate the role of heme oxygenase-1(HO-1)on HBV replication and the antiviral effect of HO-1 combined with α-interferon(IFN-α).Methods HepG2.2.15 cells and HBV1.3-transfected HepG2 cells(HepG2-HBV1.3)were used as HBV replicating cell models;Hemin treated HepG2.2.15 and HepG2-HBV1.3 cells,to induce the expression of HO-1 molecules.CCK-8 method was used to assess the toxic effects of Hemin on HepG2 and HepG2.2.15;chemiluminescence method was used to analyze HBsAg and HBeAg in the supernatants of Hemin-treated group and si-HO-1 and other experimental groups;RT-qPCR was used to ana-lyze HO-1,IFN-β and HBV-DNA;Western blot was used to analyze the expression of IRF-3 and the expression of related molecules in the JAK/STAT signaling pathway;Hemin combined with IFN-α treated HepG2.2.15 to moni-tor whether HO-1 had synergistic IFN-α antiviral effect.Results Hemin dose-dependently induced HO-1,and HO-1 was induced to exert a significant anti-HBV effect,while the expression of IFN-β,IRF-3,and IRF-9 and MxA,downstream molecules of the JAK/STAT signaling pathway,were all increased.Silencing HO-1 expression reversed the antiviral effect in the Hemin-induced group,and at the same time,type Ⅰ interferon IFN-β showed low expression,and the expression of IRF-9 and MxA in the JAK/STAT signaling pathway was inhibited as well.He-min combined with IFN-α exerted stronger antiviral effects.Conclusion HO-1 can exert an anti-HBV effect,which may be due to increased phosphorylation of IRF-3 to induce type Ⅰ interferon expression and thus activate the JAK/STAT signaling pathway to exert an antiviral effect;HO-1 can synergize with IFN-α to exert an antiviral effect.
3.Electroacupuncture pretreatment alleviates post-stroke spasticity in rats by inhibiting NF-κB/NLRP3 signaling pathway-mediated inflammation and neuronal apoptosis
Xiuqi SUN ; Jing CAI ; Anbang ZHANG ; Bo PANG ; Chunyan CHENG ; Qiqi CHA ; Fei QUAN ; Tao YE
Journal of Southern Medical University 2024;44(11):2102-2109
Objective To explore the mechanism of electroacupuncture pretreatment(EP)for relieving post-stroke spasticity in rats.Methods Eighteen rats were randomized equally into sham-operated group,middle cerebral artery occlusion(MCAO)group,and MCAO+EP group.In MCAO+EP group,the rats received electroacupuncture at the acupoints Qubin and Baihui for 3 consecutive days prior to MCAO.Neurological deficits and cognitive function of the rats were evaluated,and pathologies in the hippocampus were examined using HE,Nissl,and TUNEL staining.The expressions of IL-4,IL-6,TNF-α,and TMAO in the brain tissues were detected with ELISA,and the mRNA and protein expression levels of NF-κB p65,NLRP3,caspase-3,and caspase-9 were determined with qRT-PCR,Western blotting,and immunohistochemistry.Results The rats receiving MCAO had significantly increased neurological deficit scores and showed increased muscle tension,number of apoptotic neurons,and expressions of IL-6,TNF-α,NF-κB p65,NLRP3,caspase-3 and caspase-9 in the hippocampus and significantly reduced length of time for new object recognition.Microscopically,the cells in the hippocampus of the MCAO rats showed uneven and loosened arrangement and unclear cell boundaries.In contrast,the rats in I/R+EP group showed significantly lowered neurological deficit scores and dystonia rating scores,reduced cell apoptosis,lowered hippocampal expressions of IL-6,TNF-α,caspase-3,caspase-9,and NF-κB p65,increased time for new object recognition,tightly arranged and uniformly stained hippocampal cells with clear boundaries,with also an increased number of active neurons and enhanced expression of IL-4 in the hippocampus.Conclusion EP alleviates post-stroke spasticity in rats by inhibiting inflammatory responses and hippocampal neuronal apoptosis mediated by the NF-κB/NLRP3 signaling pathway.
4.Electroacupuncture pretreatment alleviates post-stroke spasticity in rats by inhibiting NF-κB/NLRP3 signaling pathway-mediated inflammation and neuronal apoptosis
Xiuqi SUN ; Jing CAI ; Anbang ZHANG ; Bo PANG ; Chunyan CHENG ; Qiqi CHA ; Fei QUAN ; Tao YE
Journal of Southern Medical University 2024;44(11):2102-2109
Objective To explore the mechanism of electroacupuncture pretreatment(EP)for relieving post-stroke spasticity in rats.Methods Eighteen rats were randomized equally into sham-operated group,middle cerebral artery occlusion(MCAO)group,and MCAO+EP group.In MCAO+EP group,the rats received electroacupuncture at the acupoints Qubin and Baihui for 3 consecutive days prior to MCAO.Neurological deficits and cognitive function of the rats were evaluated,and pathologies in the hippocampus were examined using HE,Nissl,and TUNEL staining.The expressions of IL-4,IL-6,TNF-α,and TMAO in the brain tissues were detected with ELISA,and the mRNA and protein expression levels of NF-κB p65,NLRP3,caspase-3,and caspase-9 were determined with qRT-PCR,Western blotting,and immunohistochemistry.Results The rats receiving MCAO had significantly increased neurological deficit scores and showed increased muscle tension,number of apoptotic neurons,and expressions of IL-6,TNF-α,NF-κB p65,NLRP3,caspase-3 and caspase-9 in the hippocampus and significantly reduced length of time for new object recognition.Microscopically,the cells in the hippocampus of the MCAO rats showed uneven and loosened arrangement and unclear cell boundaries.In contrast,the rats in I/R+EP group showed significantly lowered neurological deficit scores and dystonia rating scores,reduced cell apoptosis,lowered hippocampal expressions of IL-6,TNF-α,caspase-3,caspase-9,and NF-κB p65,increased time for new object recognition,tightly arranged and uniformly stained hippocampal cells with clear boundaries,with also an increased number of active neurons and enhanced expression of IL-4 in the hippocampus.Conclusion EP alleviates post-stroke spasticity in rats by inhibiting inflammatory responses and hippocampal neuronal apoptosis mediated by the NF-κB/NLRP3 signaling pathway.
5.Optimisation of fixed daily dose regimens for amikacin based on PPK auxiliary system of JPKD
Yulin ZHU ; Shan GAO ; Tingting HOU ; Lei HONG ; Anbang JIANG ; Yong ZHANG ; Ran SANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(12):1353-1358
AIM:To examine the predictive perfor-mance of the PPK software JPKD for the steady-state concentrations of amikacin and recommend the applicable conditions under fixed daily dosage of 400 mg and 600 mg.METHODS:Inpatients using amikacin in the First Affiliated Hospital of Bengbu Medical University from July 2022 to February 2024 were enrolled,and the measured concentra-tions of amikacin were detected by LC-MS/MS;Ver-ified the predictive performance of JPKD software for peak and trough concentrations of amikacin;JP-KD software was applied to predict the steady-state concentrations of amikacin in the patients at the infusion time of 0.5,1.0,1.5,2.0,2.5,and 3.0 h,and then compared the variability of steady-state concentrations with different levels of renal function at optimal infusion time,then the C max/MIC values were measured.RESULTS:A total of 69 patients were enrolled,including 18 patients with steady state trough concentrations and 17 patients with steady state peak concentrations.It was found that JPKD had a poor predictive ability for steady state trough concentrations but a good predictive ability for peak concentrations,the WRES<10%be-tween predictive and measured concentrations,and a strong correlation existed between them(r=0.806).With the shortening infusion time,the high-er peak concentrations.The predicted peak concen-trations at 0.5 h and 1.0 h infusion time groups were(34.81±6.87)μg/mL and(32.51±6.07)μg/mL,respectively.With the decline of the renal function,the peak concentrations showed a increasing trend.On the same level of renal function,the peak concentrations in the 600 mg group was high-er than that of the 400 mg group.When MIC ≤2 μg/mL,400 mg daily dose was chosen;when MIC=4 μg/mL,400 mg daily dose could be used for CKD3b stage patients,and 600 mg daily dose could be used for CKD1,CKD2,and CKD3a stage patients;when MIC=8 μg/mL,it was predicted that a higher dose was needed to achieve the expected target.CONCLUSION:Amikacin is preferably administered intravenously for 0.5 to 1.0 h,fixed daily doses of 400 mg and 600 mg are indicated for some pa-tients according to the target bacterial MIC and re-nal function.
6.Optimisation of fixed daily dose regimens for amikacin based on PPK auxiliary system of JPKD
Yulin ZHU ; Shan GAO ; Tingting HOU ; Lei HONG ; Anbang JIANG ; Yong ZHANG ; Ran SANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(12):1353-1358
AIM:To examine the predictive perfor-mance of the PPK software JPKD for the steady-state concentrations of amikacin and recommend the applicable conditions under fixed daily dosage of 400 mg and 600 mg.METHODS:Inpatients using amikacin in the First Affiliated Hospital of Bengbu Medical University from July 2022 to February 2024 were enrolled,and the measured concentra-tions of amikacin were detected by LC-MS/MS;Ver-ified the predictive performance of JPKD software for peak and trough concentrations of amikacin;JP-KD software was applied to predict the steady-state concentrations of amikacin in the patients at the infusion time of 0.5,1.0,1.5,2.0,2.5,and 3.0 h,and then compared the variability of steady-state concentrations with different levels of renal function at optimal infusion time,then the C max/MIC values were measured.RESULTS:A total of 69 patients were enrolled,including 18 patients with steady state trough concentrations and 17 patients with steady state peak concentrations.It was found that JPKD had a poor predictive ability for steady state trough concentrations but a good predictive ability for peak concentrations,the WRES<10%be-tween predictive and measured concentrations,and a strong correlation existed between them(r=0.806).With the shortening infusion time,the high-er peak concentrations.The predicted peak concen-trations at 0.5 h and 1.0 h infusion time groups were(34.81±6.87)μg/mL and(32.51±6.07)μg/mL,respectively.With the decline of the renal function,the peak concentrations showed a increasing trend.On the same level of renal function,the peak concentrations in the 600 mg group was high-er than that of the 400 mg group.When MIC ≤2 μg/mL,400 mg daily dose was chosen;when MIC=4 μg/mL,400 mg daily dose could be used for CKD3b stage patients,and 600 mg daily dose could be used for CKD1,CKD2,and CKD3a stage patients;when MIC=8 μg/mL,it was predicted that a higher dose was needed to achieve the expected target.CONCLUSION:Amikacin is preferably administered intravenously for 0.5 to 1.0 h,fixed daily doses of 400 mg and 600 mg are indicated for some pa-tients according to the target bacterial MIC and re-nal function.
7.Robotic single-port radical cystectomy: initial experience with 9 cases report
Jiazi SHI ; Zhijun WANG ; Guanqun JU ; Anbang WANG ; Ming CHEN ; Zhenjie WU ; Zongqin ZHANG ; Hong XU ; Bing LIU ; Dongliang XU ; Linhui WANG
Chinese Journal of Urology 2020;41(11):811-814
Objective:To assess the safety and feasibility of single-port robotic radical cystectomy.Methods:During May 2019 and August 2019, nine patients (8 males, 1 female) received single-port robotic radical cystectomy by the same surgeon. The average age was 65.6(56-78)years. After a 4.5-5.5 cm trans-umbilical incision was made, Lagiport was inserted. Da Vinci Si system 1 #, 2 # arms and 30° lens were applied. Radical cystectomy and bilateral pelvic lymphadenectomy were performed without additional ports. Urinary diversion was completed outside the body. Uterus and vaginal anterior walls were also resected for female patient. Results:All 9 surgeries were successfully conducted without additional ports or conversion to laparoscopic and open surgery. The average operation time was 437.8(280-600)min. Urinary diversion methods included 2 orthotopic ileal neobladder, 5 ideal conduit and 2 cutaneous ureterostomy. Average estimated blood loss was 227.8(100-450)ml, without blood transfusion. Average intestinal recovery time was 3.1(2-4)days, drainage duration was 8.3(3-16) days, and postoperative hospital stays was 7.7(6-13) days. Pathological TNM stage: T 2aN 0M 0 6 cases, T 2bN 0M 0 1 case, T 3aN 3M 0 1 case, T isN 0M 0 1 case. All surgical margins were negative. One bowel obstruction was cured with fasting and indwelling gastric tube. During 9-12 months’ follow-up, no tumor recurrence and metastasis were observed. There was no hydronephrosis or ureterostenosis. All surgical incision healed well. Conclusions:For experienced surgeons, single-port robotic radical cystectomy is safe and feasible with small incision and fast recovery. Short-term clinical result is satisfied.
8.Comparison of efficacy between early enteral nutrition and total parenteral nutrition after esophageal cancer surgery based on propensity score matching
Xugang ZHANG ; Weiqing LI ; Baozhong LI ; Anbang QIAO ; Zhitian LI ; Fusheng JIANG
Chinese Journal of Clinical Oncology 2019;46(16):832-835
Objective: To evaluate and compare the clinical value of early enteral nutrition (EEN) and total parenteral nutrition (TPN) af-ter esophageal cancer surgery. Methods: We retrospectively analyzed 237 patients who underwent esophageal cancer surgery at Bei-jing Shijitan Hospital from March 2011 to March 2019. They were assigned into two groups based on the postoperative nutritional sup-port used: EEN (136 cases) and TPN (101 cases). Nutritional status, liver function, recovery of gastrointestinal function, days of hospital-ization, and postoperative complications were compared between the two groups after propensity score matching. Results: Using 1 :1 nearest neighbor matching, we successfully matched 91 pairs of patients. The prealbumin (PA) level was significantly higher in the EEN group than in the TPN group 7 days after surgery (P<0.05); however, there was no significant difference in albumin (ALB) level before surgery, 3 or 7 days after surgery. Additionally, the levels of ALT and AST in the EEN group were significantly lower than those in the TPN group 3 and 7 days after surgery (P<0.05). The incidence of acid reflux, vomiting, and diarrhea in the EEN group was higher than that in the TPN group, while the incidence of pulmonary edema and pulmonary infection was lower in the EEN group than in the TPN group (P<0.05). Conclusions: Compared with TPN, EEN is associated with a high incidence of acid reflux, vomiting, and diarrhea after esophageal cancer surgery, but it has a lower impact on liver function. EEN can promote the recovery of intestinal function, improve nutritional indicators, and shorten hospitalization time.

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