1.Exploring Mechanism of Chaihu Jia Longgu Mulitang in Depressive-like Rats via AMPK/SIRT1/NF-κB/NLRP3 Signaling Pathway
Guang WANG ; Xinhua SONG ; Jie YANG ; Jinyao XU ; Junhua MEI ; Chao CHEN ; Guohua CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):144-152
ObjectiveTo investigate the effects of Chaihu Jia Longgu Mulitang(CJLM) on depression-like behaviors and neuroinflammation in rats subjected to social isolation combined with chronic unpredictable mild stress(CUMS), and to explore the potential underlying mechanisms. MethodsSixty male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose CJLM groups(2.89, 5.78, 11.56 g·kg-1), as well as a fluoxetine group(10 mg·kg-1). Except for the normal group, all other groups were subjected to social isolation combined with CUMS for 63 d. During the first 35 d, depression models were established only, and from day 36 onward, modeling and drug administration were conducted simultaneously for a total intervention period of 28 d. Depression-like behaviors were evaluated using the sucrose preference test, open-field test, and forced swimming test. Hematoxylin-eosin(HE) staining was performed to observe hippocampal histomorphology. Immunohistochemistry(IHC) was used to detect the expression levels of ionized calcium-binding adapter molecule 1(Iba1) and gasdermin D(GSDMD) proteins in the hippocampus. Western blot analysis was employed to determine the protein expression levels of adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK) and phosphorylated(p)-AMPK, silent information regulator 1(SIRT1), nuclear factor-κB(NF-κB) and p-NF-κB, NOD-like receptor protein 3(NLRP3), and Caspase-1 in the hippocampus. Real-time quantitative polymerase chain reaction(Real-time PCR) was used to detect the mRNA expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, and IL-1β in the hippocampus. ResultsCompared with the normal group, the model group showed a decreased sucrose preference rate(P<0.01), reduced total movement distance(P<0.01), prolonged immobility time(P<0.01), and decreased central zone residence time(P<0.01) in the open-field test, and increased immobility time in the forced swimming test(P<0.01). Hippocampal neuronal structure was damaged. The contents of Iba1 and GSDMD in the hippocampus were significantly increased(P<0.01). The protein expression levels of p-AMPK and SIRT1 in the hippocampus were significantly decreased(P<0.01), whereas the protein expression levels of p-NF-κB, NLRP3, and Caspase-1 were significantly increased(P<0.01). The mRNA expression levels of IL-1β, IL-6, and TNF-α in the hippocampus were significantly upregulated(P<0.01). Compared with the model group, the low-, medium-, and high-dose CJLM groups and the fluoxetine group all were able to reverse depression-like behavioral changes, as evidenced by increased sucrose preference rate, increased total movement distance with shortened immobility time in the open-field test, prolonged central zone residence time, and reduced immobility time in the forced swimming test(P<0.05, P<0.01). Meanwhile, hippocampal neuronal structural damage was alleviated. In the hippocampus, the expression levels of Iba1 and GSDMD were downregulated, the expression levels of p-AMPK and SIRT1 were upregulated, and the abnormal elevations of p-NF-κB, NLRP3, Caspase-1, as well as IL-1β, IL-6, and TNF-α mRNA were suppressed(P<0.05, P<0.01). ConclusionCJLM can ameliorate depression-like behaviors in rats subjected to social isolation combined with CUMS and attenuate hippocampal neuroinflammation and pyroptosis, suggesting that its effects may be associated with the regulation of AMPK/SIRT1/NF-κB/NLRP3 signaling pathway.
2.Effect of Drug Therapy Combined with Multi-dimensional Psychological Intervention on Insomnia Medical Staff in Shift Based on the"Sunshine Hospital"Mode
Junhua MEI ; Jinzhen JIANG ; Junli WANG ; Jing WANG ; Xue GONG ; Lei CHEN ; Yixuan SUN ; Guohua CHEN ; Ying ZHANG
Herald of Medicine 2024;43(7):1089-1095
Objective To explore the effects of drug therapy combined with multi-dimensional psychological intervention on the insomnia of shift medical staff in"sunshine hospital"mode,and to provide a reference for improving the physical and mental health of shift medical staff.Methods A total of 140 cases of medical staff with insomnia in shifts in Wuhan were included and divided into study group and control group by random number table method,70 cases in each group.The control group was given drug treatment,and the study group was treated combined with multi-dimensional psychological intervention.based on"sunshine hospital"model.The scale and questionnaire of PSQI,ISI,ESS and FAS were used to evaluate sleep status and HAMD,HAMA,PHQ-9 and SAS were used to evaluate psychological status,at baseline,visit 1(baseline+intervention for 1 month)and visit 2(baseline+intervention for 3 months),respectively.Results(1)Sleep status:There were differences in 7 dimensions of PSQI score,ISI,ESS,and FAS score between the study group and the control group at different periods(P<0.05);Among them,the PSQI scores of the two groups showed significant difference between the two groups at interview 2(P<0.05);There were significant differences in sleep quality,sleep efficiency scores,ESS and FAS between the two groups at visit 1 and visit 2(P<0.05).(2)Psychological status:HAMD,HAMA,PHQ-9 and SAS scores of the study group and the control group were different in different periods(P<0.05).At interview 2,there were significant differences in HAMA and SAS scores between the two groups(P<0.05).Conclusion Based on the"sunshine hospital"model of drug therapy combined with multi-dimensional psychological intervention,it can significantly improve sleepiness,fatigue symptoms,sleep quality,sleep efficiency,and anxiety and depression of first-line shift medical staff in the short term,and significantly alleviate overall insomnia and anxiety in the long term.
3.Clinical Observation of Supplemented Wendan Decoction Combined with Western Medicine in Treatment of Insomnia Accompanied by Anxiety and Depression in Phlegm-heat Internal Disturbance Syndrome
Jinzhen JIANG ; Guohua CHEN ; Xinhua SONG ; Yihan ZHANG ; Zhiyu LUO ; Guang WANG ; Junhua MEI
Herald of Medicine 2024;43(2):221-227
Objective To explore the clinical effect of clinical observation of supplemented wendan decoction combined with Western medicine in treating insomnia accompanied by anxiety and depression in phlegm-heat internal disturbance syndrome.Methods A total of 120 cases of insomnia with anxiety and depression comorbiditis with phlegm heat disturbance syndrome were randomly divided into control group and treatment group,60 cases in each group.The control group was given escitalopram oxalate tablet combined with dexzopiclonone tablet,and the observation group was given added Wendan decoction on the basis of the control group.Both groups were treated continuously for 6 weeks.Polysomnography monitoring parameters and heart rate variability were compared between the two groups during baseline period and visit 2(baseline period+3 months).Scale scores of the two groups were compared during baseline period,visit 1(baseline period+6 weeks)and visit 2.The content of heart rate variability includes:time domain analysis(standard deviation of normal interval(SDNN),square root of the square sum of the mean of the difference between adjacent normal interval(RMSSD)and frequency domain analysis(LF,HF,LF/HF).The scale scores included the Pittsburgh Sleep Quality Index(PSQI)and Insomnia Severity Index(ISI)to assess sleep status,and the Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Self-assessment Scale for Depression(PHQ-9)and Generalized Anxiety Disorder Scale(GAD-7)to assess anxiety and depression status.Results(1)Polysomnography monitoring:the wake time of observation group was significantly shorter than that of control group,the number of awakenings was significantly less than that of control group,and the percentage of N3 and REM was significantly higher than these of control group(P<0.05).(2)Heart rate variability:RMSSD and HF values in the observation group were significantly higher than those in the control group,and LF/HF values were significantly lower than those in the control group(P<0.05).(3)In terms of sleep:during the interview,PSQI total score,sleep quality,hypnotic drugs and daytime dysfunction in the observation group were significantly lower than those in the control group(P<0.05);At the 3 months,the sleep quality,hypnotic drugs and daytime dysfunction in the observation group were significantly lower than those in the control group(P<0.05).In terms of emotion:HAMA,HAMD and GAD-7 scores were significantly lower than those of control group at 6 weeks(P<0.05);At the 3 months,HAMA and GAD-7 scores were significantly lower than those of control group(P<0.05).Conclusion Supplemented Wendan decoction combined with western medicine can obviously optimize the sleep structure of insomnia patients with anxiety and depressionof phlegm-heat disturbance syndrome,improve sleep continuity and deepen sleep depth,and improve parasympathetic functional activities,contribute to sympathetic parasympathetic balance,can improve insomniaand depression symptoms recently,and significantly improve anxiety symptoms in the short term,with good safety.
4.Polysomnography and Neuropsychological Analysis of Patients With Post-Traumatic Stress Disorder Two Years After the COVID-19 Pandemic in Wuhan
Junhua MEI ; Yanjie XU ; Xue GONG ; Jinmei XU ; Guohua CHEN ; Weiqi CHEN ; Yicong WANG ; Zhaohong KONG ; Yilong WANG ; Qing YANG
Psychiatry Investigation 2024;21(3):219-229
Objective:
We used polysomnography (PSG) monitoring and neuropsychological scales to explore the characteristics of coronavirus disease-2019 (COVID-19) patients diagnosed with post-traumatic stress disorder (PTSD) in Wuhan, two years after the onset of the COVID-19 pandemic.
Methods:
A total of 42 patients in the Sleep Medicine Center were diagnosed with insomnia between December 2021 and May 2022; they were divided into the PTSD group (patients with PTSD diagnosed with insomnia after COVID-19 infection) and the non-PTSD group (patients with insomnia without PTSD). A healthy control group was simultaneously included.
Results:
The PTSD group was more significant than the non-PTSD group in partial manifestations of sleep disorders, neuropsychological clinical symptoms, and partial PSG data. Patients with different COVID-19 subtypes showed significant differences in the course of disease, sleep disorders, neuropsychological clinical symptoms, relevant scale scores, and PSG data analysis.
Conclusion
The emotional anxiety and depression of COVID-19 patients diagnosed with PTSD two years after the COVID-19 pandemic in Wuhan are more significant, and will not be self-alleviated with the passage of time. It is necessary to continue to pay attention to the PTSD symptoms and sleep psychology of COVID-19 infected patients, and take appropriate measures. Patients with severe and critical COVID-19 have more severe sleep and mental disorders, and there is a significant correlation between the duration of the disease and the severity of mental and mental disorders and sleep disorders after recovery.
5.Erjing pills attenuate functional impairment of retinal neurovascular unit in diabetic rats
Xiangduo ZUO ; Junhua DUAN ; Mijia MEI ; Xiaolan LIU ; Xiang XU ; Xuefang LI ; Bin QIU ; Jingping LI
Chinese Journal of Pathophysiology 2024;40(12):2319-2327
AIM:The objective of this study was to investigate the ameliorative effect of Erjing pills(PL)on the functional impairment of the diabetic retinal neurovascular unit(NVU)in rats.METHODS:A diabetic retinopathy(DR)model was established using BN rats,which were then treated with freeze-dried Erjing pills powder.After 12 weeks,various assessments were conducted:retinal thickness was measured using OCT,fundus lesions were evaluated with FFA,and retinal cell structure,arrangement,and layer thickness were analyzed through HE staining.Additionally,transmission electron microscopy was employed to examine ultrastructural changes in retinal ganglion cells(RGCs),and retinal leakage was assessed using EB in vivo perfusion.The expression of ZO-1,a tight junction protein in the retina,was detected via immunohistochemistry,while Western blot analysis quantified the levels of ZO-1,occludin,and claudin-5 proteins in rat retinal tissue.Serum vascular endothelial growth factor(VEGF)levels were measured using an ELISA kit.RESULTS:Results showed that OCT,FFA,HE staining,and transmission electron microscopy indicated a significant reduction in retinal thickness in the MOD group compared to the CON group(P<0.05).In contrast,the retinal thickness increased in the CDC,PLL,and PLH groups compared to the MOD group,with significant improvement observed in the PLH group(P<0.05).Additionally,the number of RGCs increased,and sodium fluorescein leakage from fundus mi-crovessels decreased in the CON group relative to the administered groups.Transmission electron microscopy revealed ir-regular deformation of RGC nuclei,mitochondrial reduction and swelling,and organelle loss in the MOD group compared to the CON group.However,the CDC,PLL,and PLH groups demonstrated varying degrees of improvement in cellular layers.EB leakage assay results indicated a significant increase in retinal EB leakage in the MOD group compared to the CON group(P<0.01).EB leakage was significantly reduced in the CDC group compared to the MOD group(P<0.01),with some reduction also observed in the PLL and PLH groups(P<0.05,P<0.01).Immunohistochemistry and Western blot analyses revealed a significant decrease in the expression of retinal tight junction proteins ZO-1,occludin,and clau-din-5 in the MOD group compared to the CON group(P<0.05).Protein expression was notably higher in the CDC group compared to the MOD group(P<0.01),with increases also observed in the PLL and PLH groups(P<0.05,P<0.01).ELISA results showed that VEGF levels were significantly higher in the MOD group compared to the CON group(P<0.01).The CDC,PLL,and PLH groups exhibited varying degrees of reduction in VEGF levels compared to the MOD group(P<0.05,P<0.01).CONCLUSION:These findings suggest that PL effectively ameliorates retinal NVU damage in DR rats.
6.Erjing pills attenuate functional impairment of retinal neurovascular unit in diabetic rats
Xiangduo ZUO ; Junhua DUAN ; Mijia MEI ; Xiaolan LIU ; Xiang XU ; Xuefang LI ; Bin QIU ; Jingping LI
Chinese Journal of Pathophysiology 2024;40(12):2319-2327
AIM:The objective of this study was to investigate the ameliorative effect of Erjing pills(PL)on the functional impairment of the diabetic retinal neurovascular unit(NVU)in rats.METHODS:A diabetic retinopathy(DR)model was established using BN rats,which were then treated with freeze-dried Erjing pills powder.After 12 weeks,various assessments were conducted:retinal thickness was measured using OCT,fundus lesions were evaluated with FFA,and retinal cell structure,arrangement,and layer thickness were analyzed through HE staining.Additionally,transmission electron microscopy was employed to examine ultrastructural changes in retinal ganglion cells(RGCs),and retinal leakage was assessed using EB in vivo perfusion.The expression of ZO-1,a tight junction protein in the retina,was detected via immunohistochemistry,while Western blot analysis quantified the levels of ZO-1,occludin,and claudin-5 proteins in rat retinal tissue.Serum vascular endothelial growth factor(VEGF)levels were measured using an ELISA kit.RESULTS:Results showed that OCT,FFA,HE staining,and transmission electron microscopy indicated a significant reduction in retinal thickness in the MOD group compared to the CON group(P<0.05).In contrast,the retinal thickness increased in the CDC,PLL,and PLH groups compared to the MOD group,with significant improvement observed in the PLH group(P<0.05).Additionally,the number of RGCs increased,and sodium fluorescein leakage from fundus mi-crovessels decreased in the CON group relative to the administered groups.Transmission electron microscopy revealed ir-regular deformation of RGC nuclei,mitochondrial reduction and swelling,and organelle loss in the MOD group compared to the CON group.However,the CDC,PLL,and PLH groups demonstrated varying degrees of improvement in cellular layers.EB leakage assay results indicated a significant increase in retinal EB leakage in the MOD group compared to the CON group(P<0.01).EB leakage was significantly reduced in the CDC group compared to the MOD group(P<0.01),with some reduction also observed in the PLL and PLH groups(P<0.05,P<0.01).Immunohistochemistry and Western blot analyses revealed a significant decrease in the expression of retinal tight junction proteins ZO-1,occludin,and clau-din-5 in the MOD group compared to the CON group(P<0.05).Protein expression was notably higher in the CDC group compared to the MOD group(P<0.01),with increases also observed in the PLL and PLH groups(P<0.05,P<0.01).ELISA results showed that VEGF levels were significantly higher in the MOD group compared to the CON group(P<0.01).The CDC,PLL,and PLH groups exhibited varying degrees of reduction in VEGF levels compared to the MOD group(P<0.05,P<0.01).CONCLUSION:These findings suggest that PL effectively ameliorates retinal NVU damage in DR rats.
7.Study on event-related potential P300 in patients with chronic insomnia combined with anxiety and depression
Lijuan LI ; Yaqian YIN ; Xue GONG ; Mei WAN ; Xiao WU ; Bingling ZHOU ; Wei SHAO ; Lijun LUO ; Junhua MEI
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(2):148-153
Objective:To explore the clinical significance of event-related potential P300 in the diagnosis and treatment of cognitive function in patients with chronic insomnia combined with anxiety and depression.Methods:Sixty patients with chronic insomnia complicated with anxiety and depression treated in Wuhan First Hospital from October 2020 to March 2021 were selected as the observation group, and 60 healthy volunteers were selected as the control group in the same period.Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) were used to evaluate the anxiety and depression status of patients.Mini mental state examination (MMSE) and Montreal cognitive assessment scale (MoCA) were used to evaluate the cognitive function of the subjects.All subjects were tested for P300 event-related potential, and the latency and amplitude of P300 event-related potential were recorded.SPSS 25.0 software was used for statistical analysis.Independent sample t-test was used for comparison between groups.Pearson correlation analysis was used to analyze the correlation between cognitive function and P300 event-related potential. Results:The scores of HAMA ((16.65±5.10), (9.30±4.42)) and HAMD ((18.07±3.97), (8.48±3.21)) in the observation group were higher than those in the control group ( t=8.438, 14.545, both P<0.05), and the MoCA score (22.35±4.25) was lower than that(25.65±2.29) in the control group ( t=-5.291, P<0.05). In the eight dimensions of MoCA, the scores of visual space and executive ability ((3.38±1.46), (4.63±0.69)), naming ((2.37±0.78), (2.65±0.48)), language ((2.17±0.96), (2.53±0.81)) and delayed recall ((2.58±1.45), (4.17±0.85))in the observation group were lower than those in the control group ( t=-5.991, -2.394, -2.259, -7.292, all P<0.05). Compared with the control group, the latencies of P300 (N1, N2, P3) in the observation group were significantly prolonged ( t=3.281, 4.342, 4.492, all P<0.01). The latencies of P300 (N1, N2, P3) were positively correlated with HAMD score ( r=0.242, 0.301, 0.311, all P<0.05). The latencies of P300 (N2, P3) were positively correlated with HAMA score ( r=0.205, 0.207, both P<0.05). The latencies of P300 (N2, P3) were negatively correlated with the delayed recall score of MoCA ( r=-0.197, -0.236, both P<0.05). Conclusion:There are different degrees of cognitive impairment in patients with chronic insomnia combined with anxiety and depression.P300 in patients with chronic insomnia combined with anxiety and depression shows prolonged latency.P300 latency is related to depression, anxiety and cognition in patients with chronic insomnia combined with anxiety and depression.Event-related potential P300 may be used as a neurophysiological objective evaluation tool for cognitive impairment in patients with chronic insomnia combined with anxiety and depression.
8.Effect of repetitive transcranial magnetic stimulation combined with cognitive behavioral therapy on insomnia in menopausal women
Jinmei XU ; Zhaohui ZHANG ; Xiaoxiang ZHOU ; Xue GONG ; Qing YANG ; Guohua CHEN ; Junhua MEI
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(7):617-622
Objective:To explore the effect of repetitive transcranial magnetic stimulation(rTMS) combined with cognitive behavioral therapy for insomnia(CBT-I)for menopausal women with insomnia.Methods:A total of 76 menopausal women with insomnia who were hospitalized from April 2020 to October 2021 were enrolled.Then they were randomly divided into observation group and control group, with 38 cases in each group.Both observation group and control group were treated with CBT-I. Meanwhile, the patients in observation group were treated with low-frequency repetitive rTMS, on the contrary, the patients in control group were treated with sham rTMS.The intervention lasted for 4 weeks.Insomnia severity index (ISI), Pittsburgh sleep quality index (PSQI) and polysomnography (PSG) were all recorded at baseline and 4 weeks after intervention, as well as adverse events. Data was analyzed by SPSS 22.0 software. Data which was normally distributed, was compared by independent t-test and paired t-test. Results:(1)The scores of ISI (16.39±4.03, 15.66±4.89) and the PSQI(14.97±2.70, 14.11±3.60) in observation group and control group at baseline were not significantly different( t=-0.716, -1.190, both P>0.05). After treatment, the ISI and PSQI scores of the observation group (10.08±3.65, 9.58±1.73)were lower than those of the control group (12.82±4.47, 12.13±2.32), and the differences were statistically significant ( t=2.926, 5.440, both P<0.05). (2) After treatment, all sleep parameters were significantly improved from baseline in observation group (all P<0.05). Sleep efficiency, wake time during sleep, and number of awakenings were significantly improved from baseline in control group(all P<0.05). Compared with control group((70.38±12.99)%, (17.39±11.75)%, (13.98±6.35)%), the observation group reported a greater statistically improvement in sleep efficiency, N3% and REM%((79.52±9.31)%, (22.80±6.05)%, (18.78±6.68)%, respectively)( t=-3.526, -2.524, -3.212, all P<0.05). Neither group had serious adverse effects. Conclusion:The rTMS combined with CBT-I can significantly improve the sleep quality in menopausal women with insomnia. With its high safety rTMS combined with CBT-I may be a recommended non-drug therapy among menopausal women with insomnia.
9.Role and mechanisms of synaptic plasticity decrease mediated by KIBRA in cognitive dysfunction by chronic cerebral hypoperfusion
Jianzhen PAN ; Lijie YANG ; Bingzheng SHEN ; Junhua MEI ; Zhaohui YAO
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(10):910-917
Objective:To explore the role and mechanism of kidney brain protein (KIBRA) down-regulation in cognitive dysfunction caused by chronic cerebral hypoperfusion.Methods:Ninety male SPF grade Sprague Dawley (SD) rats were divided into four groups according to random number table: sham operation group ( n=15), chronic hypoperfusion group (2VO group, n=25), chronic hypoperfusion stereotaxic injection of AAV-KIBRA group (2VO+ AAV-KIBRA group, n=25), chronic hypoperfusion stereotaxic injection of AAV-Vector group (2VO+ AAV-vector group, n=25). Chronic cerebral hypoperfusion model was established by bilateral ligation of common carotid artery, and stereotactic injection of 2 μL AAV-KIBRA or AAV-vector was performed for 30 days.Morris water maze, in vitro electrophysiology, p21-activated kinase 3(PAK3) activity detection, Western blot, immunoprecipitation and Golgi staining were used to detect spatial learning and memory ability, long-term potentiation(LTP), KIBRA level expression, PAK3 activity changes and the distribution of dendritic spines.SPSS 16.0 statistical software was used for statistical data.One-way ANOVA was used to compare the differences between groups.LSD test was used to compare the significance of data differences between the two groups.Welch test was used for uneven variance. Results:After 1 month of chronic cerebral hypoperfusion, the level of KIBRA in the hippocampus of rats was detected by homogenate and Western blot, and it was found that the level of KIBRA in 2VO group was lower than that of sham group(73.49±4.12)% ( P<0.01). AAV-KIBRA injection in hippocampal CA1 region significantly up-regulated the level of KIBRA to (91.91±7.01)% over 2VO group ( P<0.01). Morris water maze test showed that the latency of the 2VO group(3rd-7th day trail data: (48.18±2.82)s, (43.45±2.27)s, (32.27±2.22)s, (26.55±2.37)s, (17.18±2.67)s) were significantly longer than those of the sham group((41.67±2.74)s, (32.58±2.57)s, (22.50±2.94)s, (16.91±2.39)s, (8.75±1.52)s) (all P<0.05), and the latencies of the 2VO+ AAV-KIBRA group 3rd-7th day trail data: (43.83±2.95)s, (35.25±2.15)s, (26.58±2.03)s, (19.92±2.17)s, (17.75±1.35)s) was significantly shorter than that of the 2VO group ((all P<0.01). The Morris water maze test with the platform removed showed that the latency of rats in the 2VO group to reach the platform region was significantly longer than that of the sham group, while the latency of rats in the 2VO+ AAV-KIBRA group to reach the platform region was significantly shorter than that in the 2VO group ( P<0.01). At the same time, the retention time and the crossing times in the platform region of 2VO group were less than those of the sham group ( P<0.01), but the retention time and the crossing times in the platform region of 2VO+ AAV-KIBRA group were significantly higher than those in the 2VO group ( P<0.01). The electrophysiological records of the brain slices showed that the relative excitatory postsynaptic field potential of 2VO group (1.43±7.43) was significantly lower than that of sham group (2.21±6.54) after high frequency stimulation, while the relative excitatory postsynaptic field potential of 2VO+ AAV-KIBRA group (1.90±8.15) was higher than that of 2VO group ( P<0.01). Immunoprecipitation in rat hippocampus revealed that PAK3 could be detected by Western blot assay when KIBRA was precipitated.The results showed that the relative enzyme activity of PAK3 in 2VO hippocampal tissue (0.64±0.04) was significantly lower than that in sham group (1.02±0.07), while the relative enzyme activity of PAK3 in 2VO+ AAV-KIBRA group (0.86±0.03) was significantly higher than that in 2VO group.Golgi staining showed that the density of dendritic spines in 2VO hippocampal neurons((6.85±0.43)/10 μm) was significantly lower than that in sham group((11.83±0.58)/10 μm), while the density of dendritic spines in 2VO+ AAV-KIBRA group((10.22±0.39)/10 μm) was significantly higher than that in 2VO group. Conclusion:The down-regulated of KIBRA after chronic cerebral hypoperfusion plays a key role in cognitive dysfunction and is also involved in the decrease of synaptic functional plasticity.The downregulation of KIBRA is involved in the structural plasticity of dendrites through the regulation of PAK3 activity.Therefore, KIBRA may be an important target for the prevention and treatment of cognitive function of chronic cerebral hypoperfusion.
10.Construction and verification of a new nomogram for predicting stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy at high altitude
Xuepeng MEI ; Xiaobin CHEN ; Shizheng PI ; Yichong CHEN ; Junhua XING ; Haijiu WANG ; Shuai GAO ; Ying ZHOU
Journal of Clinical Hepatology 2021;37(3):648-653
ObjectiveTo investigate related factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and to establish a nomogram model for predicting the risk of stone recurrence after surgery based on independent risk factors. MethodsA retrospective analysis was performed for the clinical data of 144 patients with gallstones who underwent endoscopic minimally invasive gallbladder-preserving cholecystolithotomy in Qinghai University Affiliated Hospital from January 2012 to January 2018, and according to postoperative stone recurrence, the patients were divided into non-recurrence group and recurrence group. The chi-square test was used for comparison of categorical data between two groups. LASSO and logistic regression analyses were used to analyze independent risk factors for postoperative stone recurrence, and the corresponding nomogram prediction model was plotted according to regression coefficient. The calibration curve was plotted to evaluate the reliability of the predictive nomogram; Harrell consistency index was used to quantify the discriminatory performance of the predictive nomogram; the receiver operating characteristic (ROC) curve was used to evaluate the sensitivity, specificity, and area under the ROC curve (AUC) of this predictive nomogram. ResultsAll 144 patients underwent successful endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, among whom 14 patients (9.7%) experienced stone recurrence after surgery. The multivariate analysis showed that family history (odds ratio [OR]= 3.245, 95% confidence interval [CI]: 0.752-13567, P=0.104), regular diet (OR=3.752, 95% CI: 1.067-14.141, P=0.041), stone homogeneity (OR=5.871, 95% CI: 1636-25.390, P=0.010), and medication compliance (OR=0.225, 95% CI: 0.057-0.799, P=0.024) were independent risk factors for recurrence. The nomogram model had an index of concordance (C-index) of 0.835 (95% CI: 0.732-0.938) in the modeling sample and 0.7925 in the verification sample, suggesting that the nomogram model in this study had good accuracy and discrimination. The predictive nomogram had an AUC of 0.835, suggesting that this nomogram had a relatively high predictive value. ConclusionFamily history, regular diet, stone homogeneity, and medication compliance are independent risk factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and the nomogram constructed based on these independent risk factors may help to predict the risk of postoperative stone recurrence.

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