1.Mechanism of Yizhi Qingxin Prescription in Regulating PKA/CaN Pathway to Improve Cognitive Function in Alzheimer's Disease Model Mice
Xiaochen GUO ; Jiangang LIU ; Dandan SHI ; Ziqi NING ; Yaoyao ZHANG ; Fang LIU ; Meixia LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):97-108
ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease (AD) through regulating mitochondrial Ca2+ homeostasis and kinetic balance based on the protein kinase A (PKA)/calcineurin (CaN) signaling pathway. MethodsSixty three-month-old amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice were randomly divided into a model group, a donepezil group(0.65 mg·kg-1), a low-dose Yizhi Qingxin prescription group (YQF-L,2.6 g·kg-1), a medium-dose Yizhi Qingxin prescription group (YQF-M,5.2 g·kg-1), and a high-dose Yizhi Qingxin prescription group (YQF-H,10.4 g·kg-1), with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily, with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition (NOR) and Morris water maze (MWM) tests. Hematoxylin-eosin (HE)/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy (TEM) was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester (Fluo-4 AM) Ca2+ probe was used to measure intracellular Ca2+ concentration in brain tissue. Western blot was used to determine the protein expression of PKA, CaN, sodium/calcium/lithium exchanger (NCLX), mitochondrial calcium uniporter (MCU), calmodulin (CaM), dynamin-related protein 1 (Drp1), and phosphorylated dynamin-related protein 1 (serine 637 site) [p-Drp1(S637)] in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the expression of PKA, CaN, CaM, NCLX, MCU, and Drp1 mRNAs. ResultsCompared with those in the normal group, the recognition index (RI) of the model group decreased (P0.01), and the number of crossings through the original platform area, the duration of stay in the target quadrant, and the distance were reduced (P0.01). The protein expression of PKA, NCLX, and p-DRP1 (ser637) significantly decreased (P0.05), and the mRNA expression of PKA and NCLX significantly decreased (P0.05). The escape latency (EL) was prolonged (P0.05), and the intracellular Ca2+ level significantly increased (P0.01). The protein expression of CaN, CaM, MCU, and Drp1, as well as the mRNA expression of CaN, MCU, and Drp1, significantly increased (P0.05). After intervention with Donepezil and Yizhi Qingxin prescription, compared with that in the model group, the RI of the treatment group significantly increased (P0.05), and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased (P0.05). The protein expression of PKA, NCLX, and p-Drp1 (ser637) and the mRNA expression of PKA and NCLX significantly increased (P0.05). On the 4th and 5th days, the EL was shortened (P0.05), and the intracellular Ca2+ level decreased (P0.05). The protein expression of CaN, CaM, MCU, and Drp1 and the mRNA expression of CaN, MCU, and Drp1 significantly decreased (P0.05). ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway, upregulates the expression of PKA, NCLX, and p-Drp1 (ser637) proteins, reduces the expression of CaN, CaM, MCU, and Drp1 proteins, and regulates Ca2+ homeostasis and mitochondrial dynamic balance, thereby enhancing the spatial learning and memory abilities of AD mice.
2.Mechanism of Yizhi Qingxin Prescription in Regulating PKA/CaN Pathway to Improve Cognitive Function in Alzheimer's Disease Model Mice
Xiaochen GUO ; Jiangang LIU ; Dandan SHI ; Ziqi NING ; Yaoyao ZHANG ; Fang LIU ; Meixia LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):97-108
ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease (AD) through regulating mitochondrial Ca2+ homeostasis and kinetic balance based on the protein kinase A (PKA)/calcineurin (CaN) signaling pathway. MethodsSixty three-month-old amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice were randomly divided into a model group, a donepezil group(0.65 mg·kg-1), a low-dose Yizhi Qingxin prescription group (YQF-L,2.6 g·kg-1), a medium-dose Yizhi Qingxin prescription group (YQF-M,5.2 g·kg-1), and a high-dose Yizhi Qingxin prescription group (YQF-H,10.4 g·kg-1), with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily, with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition (NOR) and Morris water maze (MWM) tests. Hematoxylin-eosin (HE)/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy (TEM) was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester (Fluo-4 AM) Ca2+ probe was used to measure intracellular Ca2+ concentration in brain tissue. Western blot was used to determine the protein expression of PKA, CaN, sodium/calcium/lithium exchanger (NCLX), mitochondrial calcium uniporter (MCU), calmodulin (CaM), dynamin-related protein 1 (Drp1), and phosphorylated dynamin-related protein 1 (serine 637 site) [p-Drp1(S637)] in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the expression of PKA, CaN, CaM, NCLX, MCU, and Drp1 mRNAs. ResultsCompared with those in the normal group, the recognition index (RI) of the model group decreased (P0.01), and the number of crossings through the original platform area, the duration of stay in the target quadrant, and the distance were reduced (P0.01). The protein expression of PKA, NCLX, and p-DRP1 (ser637) significantly decreased (P0.05), and the mRNA expression of PKA and NCLX significantly decreased (P0.05). The escape latency (EL) was prolonged (P0.05), and the intracellular Ca2+ level significantly increased (P0.01). The protein expression of CaN, CaM, MCU, and Drp1, as well as the mRNA expression of CaN, MCU, and Drp1, significantly increased (P0.05). After intervention with Donepezil and Yizhi Qingxin prescription, compared with that in the model group, the RI of the treatment group significantly increased (P0.05), and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased (P0.05). The protein expression of PKA, NCLX, and p-Drp1 (ser637) and the mRNA expression of PKA and NCLX significantly increased (P0.05). On the 4th and 5th days, the EL was shortened (P0.05), and the intracellular Ca2+ level decreased (P0.05). The protein expression of CaN, CaM, MCU, and Drp1 and the mRNA expression of CaN, MCU, and Drp1 significantly decreased (P0.05). ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway, upregulates the expression of PKA, NCLX, and p-Drp1 (ser637) proteins, reduces the expression of CaN, CaM, MCU, and Drp1 proteins, and regulates Ca2+ homeostasis and mitochondrial dynamic balance, thereby enhancing the spatial learning and memory abilities of AD mice.
3.The roles of eosinophils in different liver diseases
Guojing XING ; Yuan DENG ; Lifei WANG ; Longlong LUO ; Zhen WANG ; Zhaojie ZHANG ; Meixia YANG ; Ting ZHANG ; Xiaohui YU ; Jiucong ZHANG
Journal of Clinical Hepatology 2025;41(7):1456-1460
Liver diseases have a high prevalence rate worldwide with relatively poor long-term clinical outcomes and have become one of the leading causes of disease burden and death around the world,which poses significant challenges to public health.Eosinophils(Eos)are a class of highly conserved multifunctional immune cells that play critical effector roles in allergic diseases.In recent years,an increasing amount of evidence has shown that Eos plays an important role in the pathogenesis of liver diseases,exerting a protective or harmful effect in different liver diseases,which has become a research hotspot in this field.This article elaborates on the role and potential mechanism of action of Eos in liver diseases,in order to provide a new perspective for in-depth research on the pathogenesis of liver diseases and lay the foundation for developing therapeutic strategies targeting Eos.
4.Disinfection effect of periodic hypochlorous acid on water supply pipeline and metagenomic next-generation sequencing for water specimens
Hong ZHOU ; Xiaodong GAO ; Meixia WANG ; Mengzhu ZHANG ; Jun YANG ; Jing ZHUANG ; Hua XU ; Wei SUN ; Qingfeng SHI
Chinese Journal of Infection Control 2025;24(9):1244-1249
Objective To explore the disinfection effect of periodic hypochlorous acid infusion on water supply pipelines.Methods Water specimens from 6 water outlets of central sterile supply department were collected at baseline for microbial culture.After introducing a slightly acidic hypochlorous acid water generator,water speci-mens were collected every 10 days.Continuous disinfection with hypochlorous acid was carried out on the 1st-3rd day,and discontinued on the 4th-10th day.Water specimens of 6 water outlets were collected on the 1st,4th,7th,and 10th day of each cycle,in total 3 cycles.Microbial culture and metagenomic next-generation sequencing(mNGS)analysis were conducted simultaneously on all water specimens from the outlets of the endoscope cleaning tank.Results Before disinfection of the pipeline,a total of 18 bottles of water specimens were collected.Bacterial count of water specimens from 10 bottles(55.56%)was between 102 and 104 CFU/mL,mainly Sphingomonas ad-hesins and Bacillus cereus.After disinfection,only 2 out of 72 water specimens(2.78%)exceeded the bacterial lim-it.The mNGS results showed that three most dominant bacterial genera in the pre-disinfection water specimens were Sphingomonas,Methylobacterium,and Ralstonia,with stringent mapped reads number(SMRN)ranging from 10 000 to 100 000;while the most dominant bacterial genera in post-disinfection water specimens were Lacto-baci-llus,Ralstonia,Acinetobacter,and Bradyrhizobium.PCoA analysis showed that there was a statistically sig-nificant difference in β-diversity of water specimens before and after disinfection(P<0.05).Conclusion Periodic hypochlorous acid infusion disinfection can effectively remove bacterial biofilms in water pipelines,but there is a risk of bacterial biofilm recovery during disinfection suspension.In the future,monitoring and management of medical water should be strengthened.
5.Application effect of combination treatment of laparoscope and resectoscope for bladder diverticula(report of 9 cases)
Chao WANG ; Meixia ZHENG ; Rongyuan ZHANG ; Shiqing ZHANG ; Dapeng YU ; Lei XING ; Kuan JIA ; Chuan LÜ ; Yuehai YU
China Journal of Endoscopy 2025;31(5):84-88
Objective To evaluate the surgical technique and clinical value of laparoscopic bladder diverticulectomy guided by inserting ureteral catheters into the diverticulum under plasmakinetic resectoscope.Methods From December 2018 to May 2024,9 patients underwent laparoscopic bladder diverticulectomy in combination with resectoscope.Each patient had a solitary bladder diverticulum with a median maximum diameter of 6.40(5.70,7.40)cm(range:5.0~8.5 cm).Among the 9 patients,3 patients had concurrent benign prostatic hyperplasia(BPH)and simultaneously underwent transurethral plasmakinetic resection of the prostate;1 patient had concurrent both BPH and bladder calculi,requiring simultaneously underwent plasmakinetic resection of the prostate and bladder calculi removal;2 patients required ureteral reimplantation as the diverticulum was directly involving the ureteral orifice;1 case underwent ureteroscopic double-J stent implantation because the opening of the ipsilateral ureter was adjacent to the entrance of the diverticulum.Results Bladder diverticulectomy was successfully performed in the all patients.Median operative time was 160.00(120.00,317.50)min(range:85~345 min).Median estimated blood loss was 20.00(10.00,150.00)mL(range:10~300 mL).No iatrogenic injuries to adjacent organs were observed.Pelvic drains were removed 1~3 d postoperatively,with no urine leakage.Urinary catheters were maintained for 7~10 d after operation.Follow-up at 3~12 months showed no recurrence or hydronephrosis in any of the patients.Conclusion Laparoscopic resection of bladder diverticula guided by ureteral catheter placed into bladder diverticula by means of resectoscope has the advantages of less trauma,less bleeding and faster recovery,and is an effective measure for the treatment of bladder diverticula.
6.The roles of eosinophils in different liver diseases
Guojing XING ; Yuan DENG ; Lifei WANG ; Longlong LUO ; Zhen WANG ; Zhaojie ZHANG ; Meixia YANG ; Ting ZHANG ; Xiaohui YU ; Jiucong ZHANG
Journal of Clinical Hepatology 2025;41(7):1456-1460
Liver diseases have a high prevalence rate worldwide with relatively poor long-term clinical outcomes and have become one of the leading causes of disease burden and death around the world,which poses significant challenges to public health.Eosinophils(Eos)are a class of highly conserved multifunctional immune cells that play critical effector roles in allergic diseases.In recent years,an increasing amount of evidence has shown that Eos plays an important role in the pathogenesis of liver diseases,exerting a protective or harmful effect in different liver diseases,which has become a research hotspot in this field.This article elaborates on the role and potential mechanism of action of Eos in liver diseases,in order to provide a new perspective for in-depth research on the pathogenesis of liver diseases and lay the foundation for developing therapeutic strategies targeting Eos.
7.Research on the effect of home-based pulmonary rehabilitation in patients with moderate chronic obstruc-tive pulmonary disease
Bin ZHANG ; Yi LI ; Meixia LIU
Chinese Journal of Rehabilitation Medicine 2025;40(2):217-222
Objective:To explore the effect of supervised home-based pulmonary rehabilitation by wearable devices on moderate chronic obstructive pulmonary disease(COPD).Method:A total of 70 patients with moderate COPD in the stable stage who visited the Respiratory Rehabilita-tion Center of Beijing Rehabilitation Hospital of Capital Medical University from January 2020 to October 2021 were randomly divided into a control group and a study group,with 35 cases in each group.The inter-vention lasted for 10 weeks.Cardiopulmonary exercise tests(FEV1,FEV1/FVC%,FEV1%pred,VO2max,VO2AT,maximum power),COPD Assessment Test(CAT),St.George's Respiratory Questionnaire(SGRQ)and modified Medical Research Council dyspnea scale(mMRC)were compared between the two groups before and after rehabilitation.After the study was completed,the compliance of the two groups was compared.Result:A total of 15 subjects dropped out of 70 cases,and finally 27 cases were included in the control group and 28 cases in the study group.There was no significant improvement in FEV1,FEV1/FVC%,and FEV1%pred after rehabilitation in the two groups(P>0.05).After rehabilitation,VO2max,VO2AT,maximum power,SGRQ,CAT and mMRC[(14.2±2.2vs.18.4±1.6)and(13.9±2.4vs.17.7±1.9),(10.6±1.3vs.11.9±1.6)and(10.3±1.3vs.11.9±1.4),(69.9±7.5vs.88.3±8.4)and(68.6±9.0vs.86.4±9.7),(45.4±9.9vs.35.4±7.5)and(45.3±12.1vs.36.3±8.4),(19.2±3.4vs.12.8±3.5)and(19.5±3.7vs.13.3±3.7),(2.5±0.9vs.1.5±0.6)and(2.6±1.0vs.1.8±0.7)]were significantly improved(P<0.01),but there were no significant differences between the groups(P>0.05).The stop training rate of the control group was significantly higher than that of the study group(37%vs.11%,P<0.05).However,there was no significant difference between the two groups in the proportion of peo-ple who did not reach the target time and target intensity[(15%vs.21%)and(15%vs.29%)](P>0.05).Conclusion:There is no significant difference between home-based pulmonary rehabilitation and traditional out-patient pulmonary rehabilitation in improving exercise capacity,symptoms and quality of life,but the compli-ance is better.
8.Study on the Mechanism of miR-93 Targeting MFN2 to Regulate Mitochondrial-associated Endoplasmic Reticulum Membrane Homeostasis and Affect ARDS-induced Pulmonary Fibrosis
Ning AN ; Meixia XU ; Xiaoxia ZHANG
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2025;54(4):491-497
Objective To investigate the regulatory role of miR-93/MFN2 axis in pulmonary fibrosis associated with acute respiratory distress syndrome(ARDS)through endoplasmic reticulum stress(ERS)and mitochondrial function.Methods An in v itro model of ARDS-induced pulmonary fibrosis was established by treating human embryonic lung fibroblasts(HFL-1)with li-popolysaccharide(LPS).Four experimental groups were employed in functional validation:negative control inhibitor(inhibitor NC),miR-93 inhibitor,miR-93 inhibitor+scrambled control siRNA(si-NC),and miR-93 inhibitor+MFN2-targeting siRNA(si-MFN2).Collagen Ⅰ(COLⅠ)secretion was assesed by ELISA and Western blotting;MFN2 and miR-93 expressions were detec-ted by qRT-PCR;Cell proliferation was assessed by CCK-8 assay;Apoptosis was evaluated by flow cytometry;ERS marker(Bip/GRP78,IRE1)levels and mitophagy protein Beclin-1 were detecetd by Western blotting.The miR-93-MFN2 interaction was confirmed via dual-luciferase assays.Results Compared with control group,COL Ⅰ secretion in HFL-1 cells was signifi-cantly increased in LPS group(P<0.01 vs.control),validating the in vitro pulmonary fibrosis model.Compared to the inhibitor NC group,the miR-93 inhibitor group exhibited significantly upregulated MFN2 expression,decreased HFL-1 cell proliferation,increased apoptosis,and reduced COLⅠ secretion(all P<0.01).MFN2 was confirmed as a direct target of miR-93 by dual-lu-ciferase assays.Compared with inhibitor NC group,levels of ERS markers(Bip/GRP78,IRE1)were downregulated,and the mi-tophagy marker Beclin-1 was upregulated in miR-93 inhibitor group(P<0.01).These effects were rescued after co-transfection with miR-93 inhibitor and si-MFN2.Compared to the miR-93 inhibitor group alone,the miR-93 inhibitor+si-MFN2 group showed attenuated suppression of cell proliferation,increased COLⅠ secretion,upregulated ERS markers(Bip/GRP78,IRE1),and downregulated Beclin-1 expression.Conclusion miR-93 exacerbates ARDS-associated pulmonary fibrosis by directly targe-ting and suppressing MFN2.This disruption likely compromised mitochondria-associated ER membrane(MAM)homeosta-sis.Targeting themiR-93/MFN2 axis alleviates fibrosis by attenuating ERS and promoting mitophagy,highlighting its potential as a therapeutic strategy.
9.Application effect of combination treatment of laparoscope and resectoscope for bladder diverticula(report of 9 cases)
Chao WANG ; Meixia ZHENG ; Rongyuan ZHANG ; Shiqing ZHANG ; Dapeng YU ; Lei XING ; Kuan JIA ; Chuan LÜ ; Yuehai YU
China Journal of Endoscopy 2025;31(5):84-88
Objective To evaluate the surgical technique and clinical value of laparoscopic bladder diverticulectomy guided by inserting ureteral catheters into the diverticulum under plasmakinetic resectoscope.Methods From December 2018 to May 2024,9 patients underwent laparoscopic bladder diverticulectomy in combination with resectoscope.Each patient had a solitary bladder diverticulum with a median maximum diameter of 6.40(5.70,7.40)cm(range:5.0~8.5 cm).Among the 9 patients,3 patients had concurrent benign prostatic hyperplasia(BPH)and simultaneously underwent transurethral plasmakinetic resection of the prostate;1 patient had concurrent both BPH and bladder calculi,requiring simultaneously underwent plasmakinetic resection of the prostate and bladder calculi removal;2 patients required ureteral reimplantation as the diverticulum was directly involving the ureteral orifice;1 case underwent ureteroscopic double-J stent implantation because the opening of the ipsilateral ureter was adjacent to the entrance of the diverticulum.Results Bladder diverticulectomy was successfully performed in the all patients.Median operative time was 160.00(120.00,317.50)min(range:85~345 min).Median estimated blood loss was 20.00(10.00,150.00)mL(range:10~300 mL).No iatrogenic injuries to adjacent organs were observed.Pelvic drains were removed 1~3 d postoperatively,with no urine leakage.Urinary catheters were maintained for 7~10 d after operation.Follow-up at 3~12 months showed no recurrence or hydronephrosis in any of the patients.Conclusion Laparoscopic resection of bladder diverticula guided by ureteral catheter placed into bladder diverticula by means of resectoscope has the advantages of less trauma,less bleeding and faster recovery,and is an effective measure for the treatment of bladder diverticula.
10.Disinfection effect of periodic hypochlorous acid on water supply pipeline and metagenomic next-generation sequencing for water specimens
Hong ZHOU ; Xiaodong GAO ; Meixia WANG ; Mengzhu ZHANG ; Jun YANG ; Jing ZHUANG ; Hua XU ; Wei SUN ; Qingfeng SHI
Chinese Journal of Infection Control 2025;24(9):1244-1249
Objective To explore the disinfection effect of periodic hypochlorous acid infusion on water supply pipelines.Methods Water specimens from 6 water outlets of central sterile supply department were collected at baseline for microbial culture.After introducing a slightly acidic hypochlorous acid water generator,water speci-mens were collected every 10 days.Continuous disinfection with hypochlorous acid was carried out on the 1st-3rd day,and discontinued on the 4th-10th day.Water specimens of 6 water outlets were collected on the 1st,4th,7th,and 10th day of each cycle,in total 3 cycles.Microbial culture and metagenomic next-generation sequencing(mNGS)analysis were conducted simultaneously on all water specimens from the outlets of the endoscope cleaning tank.Results Before disinfection of the pipeline,a total of 18 bottles of water specimens were collected.Bacterial count of water specimens from 10 bottles(55.56%)was between 102 and 104 CFU/mL,mainly Sphingomonas ad-hesins and Bacillus cereus.After disinfection,only 2 out of 72 water specimens(2.78%)exceeded the bacterial lim-it.The mNGS results showed that three most dominant bacterial genera in the pre-disinfection water specimens were Sphingomonas,Methylobacterium,and Ralstonia,with stringent mapped reads number(SMRN)ranging from 10 000 to 100 000;while the most dominant bacterial genera in post-disinfection water specimens were Lacto-baci-llus,Ralstonia,Acinetobacter,and Bradyrhizobium.PCoA analysis showed that there was a statistically sig-nificant difference in β-diversity of water specimens before and after disinfection(P<0.05).Conclusion Periodic hypochlorous acid infusion disinfection can effectively remove bacterial biofilms in water pipelines,but there is a risk of bacterial biofilm recovery during disinfection suspension.In the future,monitoring and management of medical water should be strengthened.

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