ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion （I/R） injury in rats based on the changes of pericytes mediated by Ras homolog family member A （RHOA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK1） pathway. MethodsNinety rats （15 rats for each group） were randomly divided into a sham operation group， a model group， a positive control group receiving Ginkgo biloba extract （21.6 mg·kg^-1）， and groups receiving Naoxintong capsules at low， medium， and high doses of 55， 110， and 220 mg·kg^-1 （NXT-L， NXT-M， and NXT-H groups）， respectively. Except for those in the sham operation group， all rats were subjected to transient middle cerebral artery occlusion （tMCAO） to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager， and the cerebral infarction rate was calculated using 2，3，5-Triphenyl tetrazolium chloride （TTC） staining. Pathological changes were observed by hematoxylin-eosin （HE） staining and Nissl staining， while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels of RHOA， ROCK1， platelet-derived growth factor receptor β （PDGFRB）， α-smooth muscle actin （α-SMA）， tight junction protein （ZO-1）， matrix metalloproteinase-2 （MMP-2）， and matrix metalloproteinase-9 （MMP-9）. ResultsCompared with the sham operation group， the model group exhibited decreased neurological function scores， higher percentage reduction in blood flow， and increased cerebral infarction rates （P<0.01）. Additionally， cortical neuronal nucleus shrinkage， edema， a decreased number of Nissl bodies， reduced pericyte area， elevated albumin content in the cortex （P<0.05）， and increased ischemic modified albumin levels （P<0.01） were observed. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were increased （P<0.01）， while those of ZO-1 were decreased. Compared with the model group， all treatment groups showed improved neurological function scores， lower percentage reduction in blood flow， reduced cerebral infarction rates （P<0.01）， alleviated cortical histological changes， increased number of Nissl bodies， expanded pericyte area， decreased albumin content in the cortex， and reduced ischemia-modified albumin levels （P<0.01）. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were decreased （P<0.01）， while those of ZO-1 were increased. Among the treatment groups， the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply， reduce microcirculation disturbance， and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.

ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion （I/R） injury in rats based on the changes of pericytes mediated by Ras homolog family member A （RHOA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK1） pathway. MethodsNinety rats （15 rats for each group） were randomly divided into a sham operation group， a model group， a positive control group receiving Ginkgo biloba extract （21.6 mg·kg^-1）， and groups receiving Naoxintong capsules at low， medium， and high doses of 55， 110， and 220 mg·kg^-1 （NXT-L， NXT-M， and NXT-H groups）， respectively. Except for those in the sham operation group， all rats were subjected to transient middle cerebral artery occlusion （tMCAO） to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager， and the cerebral infarction rate was calculated using 2，3，5-Triphenyl tetrazolium chloride （TTC） staining. Pathological changes were observed by hematoxylin-eosin （HE） staining and Nissl staining， while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels of RHOA， ROCK1， platelet-derived growth factor receptor β （PDGFRB）， α-smooth muscle actin （α-SMA）， tight junction protein （ZO-1）， matrix metalloproteinase-2 （MMP-2）， and matrix metalloproteinase-9 （MMP-9）. ResultsCompared with the sham operation group， the model group exhibited decreased neurological function scores， higher percentage reduction in blood flow， and increased cerebral infarction rates （P<0.01）. Additionally， cortical neuronal nucleus shrinkage， edema， a decreased number of Nissl bodies， reduced pericyte area， elevated albumin content in the cortex （P<0.05）， and increased ischemic modified albumin levels （P<0.01） were observed. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were increased （P<0.01）， while those of ZO-1 were decreased. Compared with the model group， all treatment groups showed improved neurological function scores， lower percentage reduction in blood flow， reduced cerebral infarction rates （P<0.01）， alleviated cortical histological changes， increased number of Nissl bodies， expanded pericyte area， decreased albumin content in the cortex， and reduced ischemia-modified albumin levels （P<0.01）. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were decreased （P<0.01）， while those of ZO-1 were increased. Among the treatment groups， the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply， reduce microcirculation disturbance， and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.

BACKGROUND: Parkinson's disease (PD) is a leading cause of death and disability worldwide, and is associated with a significant Global Burden of Disease (GBD). We analyzed the trends in PD incidence, mortality, and disability-adjusted life year (DALY) burden in China, and compared them with global data. METHODS: Estimates and 95% uncertainty intervals (UIs) for incidence, mortality, DALYs, years lived with disability (YLDs), and years of life lost (YLLs) for PD were extracted from the GBD, Injuries, and Risk Factors Study 2021. We describe the epidemiology of PD at global and Chinese levels, analyze trends in incidence and mortality from 1990 to 2021 by joinpoint regression models, and decompose PD burden according to population size, age structure, and epidemiological changes. RESULTS: GBD 2021 estimated 508,378 (95% UI: 430,499-592,748) incident cases of PD, 92,035 (95% UI: 75,908-108,133) deaths, and 2,159,514 (95% UI: 1,826,196-2,521,344) DALYs in China, with the higher age-standardized rate (ASR) in incidence, mortality and DALYs than the global levels. The DALY burden of PD in China increased slightly from 1990 to 2021, consistent with the global upward trend. Joinpoint regression analysis indicated that the ASR of incidence in China increased faster than the global average, while the ASR of mortality decreased, with the fastest decline in 2004-2014. Decomposition analysis revealed that men and the middle sociodemographic index (SDI) quintile (32.82%) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging. CONCLUSIONS The burden of PD showed an overall increasing trend from 1990 to 2021, which was primarily driven by population growth and aging. This study highlights the significant challenges in controlling and managing PD, including the increase in cases and gender differences, which may provide guidance for comprehensive strategies to address the changing profiles of PD in China.
Humans ; Parkinson Disease/mortality* ; China/epidemiology* ; Global Burden of Disease ; Male ; Incidence ; Female ; Disability-Adjusted Life Years ; Middle Aged ; Aged ; Adult ; Quality-Adjusted Life Years ; Aged, 80 and over ; Cost of Illness ; Adolescent ; Pattern Analysis, Machine

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

Objective:To analyze the non-motor symptom characteristics of patients with different subtypes of progressive supranuclear palsy (PSP).Methods:Demographic data were collected from patients diagnosed with probable or possible PSP in the PSP cohort at Qilu Hospital of Shandong University from June 2019 to June 2023. Motor symptoms were evaluated using the Progressive Supranuclear Palsy Rating Scale (PSPRS), Unified Parkinson′s Disease Rating Scale-Ⅲ , and the Freezing of Gait Questionnaire. Non-motor symptoms were assessed using the Non-Motor Symptoms Scale (NMSS), the Montreal Cognitive Assessment, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale. Patients were grouped into PSP with Richardson syndrome (PSP-RS), PSP with Parkinsonism (PSP-P), PSP with progressive gait freezing (PSP-PGF), and other subtypes (PSP-other) based on clinical classification. The study compared the non-motor symptom characteristics among the 4 groups and used linear regression models to evaluate the influencing factors of PSP non-motor symptoms.Results:A total of 153 PSP patients were included in this study, with a male-to-female ratio of 89∶64 and an age of (66.0±6.6) years. Among them, 83 were in the PSP-RS group (54.2%), 32 in the PSP-P group (20.9%), 27 in the PSP-PGF group (17.6%), and 11 in the PSP-other group (7.2%). The total NMSS score for non-motor symptoms in PSP patients was 62.6±38.5, with 8.8±4.7 non-motor symptoms per patient. The most common non-motor symptoms among all PSP patients were sleep/fatigue [130/153 (85.0%)], gastrointestinal symptoms [129/153 (84.3%)], urinary symptoms [113/153 (73.9%)], attention/memory impairment [112/153 (73.2%)], and mood symptoms [108/153 (70.6%)]. The total NMSS score of the PSP-RS group (70.8±36.0) was higher than that of the PSP-PGF group (49.4±40.3; t=2.561, P=0.011). The number of non-motor symptoms in the PSP-RS group (9.9±4.4) was greater than that in the PSP-P group (7.7±5.5; t=2.365, P=0.019) and the PSP-PGF group (6.9±4.3; t=2.978, P=0.003). The incidence of memory decline in the PSP-RS group [52/83 (62.7%)] was higher than that in the PSP-P group [10/32 (31.3%); χ 2=9.165, Bonferroni-corrected P=0.012], and the incidence of constipation in the PSP-RS group [49/83 (59.0%)] was higher than that in the PSP-PGF group [8/27 (29.6%); χ 2=7.056, Bonferroni-corrected P=0.048]. Multivariate regression analysis showed that the bulbar symptom score ( β=5.591, 95% CI 1.792-9.389, P=0.005), limb motor score ( β=1.786, 95% CI 0.398-3.174, P=0.013), and gait/axial score ( β=1.956, 95% CI 0.149-3.763, P=0.036) in PSPRS were all associated with non-motor symptom scores. Conclusions:Different PSP subtypes exhibit distinct non-motor symptom profiles. PSP-RS patients bear a heavier non-motor symptom burden, with higher incidences of memory decline and constipation than other subtypes. These findings may aid in the early recognition and clinical diagnosis of PSP.

Objective:To analyze the non-motor symptom characteristics of patients with different subtypes of progressive supranuclear palsy (PSP).Methods:Demographic data were collected from patients diagnosed with probable or possible PSP in the PSP cohort at Qilu Hospital of Shandong University from June 2019 to June 2023. Motor symptoms were evaluated using the Progressive Supranuclear Palsy Rating Scale (PSPRS), Unified Parkinson′s Disease Rating Scale-Ⅲ , and the Freezing of Gait Questionnaire. Non-motor symptoms were assessed using the Non-Motor Symptoms Scale (NMSS), the Montreal Cognitive Assessment, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale. Patients were grouped into PSP with Richardson syndrome (PSP-RS), PSP with Parkinsonism (PSP-P), PSP with progressive gait freezing (PSP-PGF), and other subtypes (PSP-other) based on clinical classification. The study compared the non-motor symptom characteristics among the 4 groups and used linear regression models to evaluate the influencing factors of PSP non-motor symptoms.Results:A total of 153 PSP patients were included in this study, with a male-to-female ratio of 89∶64 and an age of (66.0±6.6) years. Among them, 83 were in the PSP-RS group (54.2%), 32 in the PSP-P group (20.9%), 27 in the PSP-PGF group (17.6%), and 11 in the PSP-other group (7.2%). The total NMSS score for non-motor symptoms in PSP patients was 62.6±38.5, with 8.8±4.7 non-motor symptoms per patient. The most common non-motor symptoms among all PSP patients were sleep/fatigue [130/153 (85.0%)], gastrointestinal symptoms [129/153 (84.3%)], urinary symptoms [113/153 (73.9%)], attention/memory impairment [112/153 (73.2%)], and mood symptoms [108/153 (70.6%)]. The total NMSS score of the PSP-RS group (70.8±36.0) was higher than that of the PSP-PGF group (49.4±40.3; t=2.561, P=0.011). The number of non-motor symptoms in the PSP-RS group (9.9±4.4) was greater than that in the PSP-P group (7.7±5.5; t=2.365, P=0.019) and the PSP-PGF group (6.9±4.3; t=2.978, P=0.003). The incidence of memory decline in the PSP-RS group [52/83 (62.7%)] was higher than that in the PSP-P group [10/32 (31.3%); χ 2=9.165, Bonferroni-corrected P=0.012], and the incidence of constipation in the PSP-RS group [49/83 (59.0%)] was higher than that in the PSP-PGF group [8/27 (29.6%); χ 2=7.056, Bonferroni-corrected P=0.048]. Multivariate regression analysis showed that the bulbar symptom score ( β=5.591, 95% CI 1.792-9.389, P=0.005), limb motor score ( β=1.786, 95% CI 0.398-3.174, P=0.013), and gait/axial score ( β=1.956, 95% CI 0.149-3.763, P=0.036) in PSPRS were all associated with non-motor symptom scores. Conclusions:Different PSP subtypes exhibit distinct non-motor symptom profiles. PSP-RS patients bear a heavier non-motor symptom burden, with higher incidences of memory decline and constipation than other subtypes. These findings may aid in the early recognition and clinical diagnosis of PSP.

Objective To investigate the effects and mechanism of Zhachong Shisanwei Pills on rats with cerebral ischemia.Methods Totally 75 rats were randomly divided into sham-operation group,model group,positive drug group(Ginaton,21.6 mg/kg),and Zhachong Shisanwei Pills low-,medium-,and high-dosage groups(81,162,324 mg/kg).Each treatment group was given the corresponding drug by gavage for 5 days.On the 6th day,a cerebral ischemia rat model was prepared by suture method.After 24 hours of modeling,the drugs were given in the same manner for 2 days.Neurological function scoring,horizontal beam walking scoring,and grip strength testing were performed on rats.TTC staining was used to detect the cerebral infarction rate,HE staining and Nissl staining were used to observe the morphology of brain tissue.TUNEL staining was used to detect the apoptosis rate of brain tissue cells.Differential genes in the treatment of cerebral ischemia using Zhachong Shisanwei Pills were screened by transcriptomics,and RT-qPCR,immunohistochemistry and Western blot were used to detect differential gene mRNA and protein expression.Results Compared with the sham-operation group,the model group rats showed a decrease in neurological function scores,horizontal beam walking scores,grip strength,an increase in cerebral infarction rate,neuronal nucleus condensation,vacuolar changes,widened intercellular spaces,the number of Nissl bodies reduced,and the apoptosis rate increased(P<0.01,P<0.001);compared with the model group,the Zhachong Shisanwei Pills medium-dosage group showed an increase in neurological function score,horizontal beam walking score,and grip strength in rats,a decrease in cerebral infarction rate,a lower degree of neuronal damage,an increase in the number of Nissl bodies,and a decrease in cell apoptosis rate(P<0.05,P<0.01).Transcriptome and bioinformatics analysis screened the Hippo signaling pathway related to the anti-cerebral ischemia effect of Zhachong Shisanwei Pills.The key genes of this pathway,mammalian sterile line 20 like kinase(MST1)1,Yes related protein(YAP)1,large tumor suppressor kinase(LATS)1,and TEA domain family member(TEAD)1 were detected.The results showed that the expression of MST1 mRNA and protein in brain tissue of model rats significantly increased,while the expressions of YAP1,LATS1,TEAD1 mRNA and protein significantly decreased;Zhachong Shisanwei Pills could down-regulate the expression of MST1 in brain tissue of model rats,and up-regulate the expressions of YAP1,LATS1 and TEAD1.Conclusion Zhachong Shisanwei Pills may exert anti-cerebral ischemia effects through the Hippo signaling pathway.

Parkinson′s disease is a common clinical degenerative disease of the nervous system, and rapid eye movement sleep behavior disorder (RBD) is a common sleep symptom of patients with Parkinson′s disease. This article reviews the pathogenesis, epidemiology, clinical characteristics, imaging manifestations, clinical evaluation and treatment of RBD in patients with Parkinson′s disease, in order to deepen the understanding of RBD in patients with Parkinson′s disease.

Objective To investigate the clinical efficacy of hyperbaric oxygen (HBO) combined with transcranial electrical stimulation (tDCS) and memantine tablets on cognitive impairment in the patients with moderate to severe craniocerebral injury.Methods Forty-nine patients with moderate or severe cognitive impairment induced by trauma brain injury (TBI) who were admitted into the Rehabilitation Department and Neurosurgery Department of Shanxi University Hospital from May 2017 to May 2018 were enrolled for the study.The patients were divided into the HBO group (or group A,n =16),the HBO + tDCS group (or group B,n =16) and the HBO + tDCS + memantine group (or group C,n =17) in accordance with different treatment methods.The total scores of Montreal Cognitive Assessment Scale (MoCA) and the scores of each item before and 4 weeks after treatment,the Simple Mental State Examination Scale (MMSE) and Barthel Index (BI) were analyzed to determine improvement of cognitive impairment in the TBI patients.Results After 3 courses of treatment,MoCA comprehensive scores and sub-item scores were all significantly higher than those before treatment,with statistical significance (P ＜ 0.01).In sub-items,the comprehensive scores of VS-EF,ATT,LANG,D-MEM and MoCA in group B were significantly higher than those in group A after treatment,also with statistical significance (P ＜ 0.05).Following treatment,the scores of VS-EF,ATT,LANG and D-MEM in group C were all significantly higher than those in group B after treatment,also with statistical significance (P ＜0.05).The comprehensive scores of MMSE and ADL in group B and C after treatment were all significantly higher than those in group A,and statistical significance could be seen when comparisons were made between them (P ＜ 0.01).The comprehensive scores of MMSE (21.23 ± 6.53) and ADL(64.38 ±12.80) in group C were all obviously higher than those in group B(17.61 ±6.35,5.39 ± 10.22),also with statistical significance (P ＜ 0.05).Conclusion Comprehensive treatment with HBO + tDCS + memantine could achieve obvious better therapeutic effects on cognitive impairment of the patients with severe TBI.For this reason,it is worth further clinical application.

Objective To investigate the clinical efficacy of hyperbaric oxygen (HBO) combined with transcranial electrical stimulation (tDCS) and memantine tablets on cognitive impairment in the patients with moderate to severe craniocerebral injury.Methods Forty-nine patients with moderate or severe cognitive impairment induced by trauma brain injury (TBI) who were admitted into the Rehabilitation Department and Neurosurgery Department of Shanxi University Hospital from May 2017 to May 2018 were enrolled for the study.The patients were divided into the HBO group (or group A,n =16),the HBO + tDCS group (or group B,n =16) and the HBO + tDCS + memantine group (or group C,n =17) in accordance with different treatment methods.The total scores of Montreal Cognitive Assessment Scale (MoCA) and the scores of each item before and 4 weeks after treatment,the Simple Mental State Examination Scale (MMSE) and Barthel Index (BI) were analyzed to determine improvement of cognitive impairment in the TBI patients.Results After 3 courses of treatment,MoCA comprehensive scores and sub-item scores were all significantly higher than those before treatment,with statistical significance (P ＜ 0.01).In sub-items,the comprehensive scores of VS-EF,ATT,LANG,D-MEM and MoCA in group B were significantly higher than those in group A after treatment,also with statistical significance (P ＜ 0.05).Following treatment,the scores of VS-EF,ATT,LANG and D-MEM in group C were all significantly higher than those in group B after treatment,also with statistical significance (P ＜0.05).The comprehensive scores of MMSE and ADL in group B and C after treatment were all significantly higher than those in group A,and statistical significance could be seen when comparisons were made between them (P ＜ 0.01).The comprehensive scores of MMSE (21.23 ± 6.53) and ADL(64.38 ±12.80) in group C were all obviously higher than those in group B(17.61 ±6.35,5.39 ± 10.22),also with statistical significance (P ＜ 0.05).Conclusion Comprehensive treatment with HBO + tDCS + memantine could achieve obvious better therapeutic effects on cognitive impairment of the patients with severe TBI.For this reason,it is worth further clinical application.