Objective:To investigate the correlation between macular cherry red spot (CS) and severity of neurological manifestations in Chinese children with sialidosis (SD) type I.Methods:A evidence-based medical study. "China", "Sialidosis" and "Sialidoses" were used as Chinese and English search terms. The literature was searched in CNKI, Wanfang and PubMed. The cases were all from China and matched the diagnostic criteria. According to the presence or absence of CS in the fundus, the SD children were divided into a group with CS (+) and a group without CS (-), and the correlation between the occurrence of ocular CS and neurological manifestations was compared with meta-analysis by RevMan 5.3 software.Results:Sixty-eight studies were initially retrieved according to the search strategy, and 17 studies were finally included, and 5 studies with CS+ and CS- were meta-analyzed. Among the 43 patients, 28 were male and 15 were female, with a median age of 12 years. Visual impairment was observed in 37 cases (90.2%, 37/41, 2 cases not recorded), and CS was present in 24 cases (55.8%, 24/43). The most common neurological manifestation was myoclonus (97.7%, 42/43), followed by cerebellar ataxia (95.1%, 39/41, 2 cases not recorded) and seizures (91.4%, 32/35, 8 cases not recorded). Pathogenic NEU1 gene mutations were detected in 42 cases and one case was undocumented. The incidence of seizure in group CS+ (100%, 20/20) was higher than that in group CS- (80%, 12/15). Meta-analysis showed that there was no statistically significant difference between the incidence of myoclonus or ataxia [relative risk ( RR)=1.13, 95% confidence interval ( CI) 0.79-1.63, P=0.49] and seizure ( RR=1.13, 95% CI 0.84-2.06, P=0.24) among the children in the CS+ and CS- groups. Conclusions:The incidence of ocular CS in Chinese children with type I SD was 55.8%. There was no correlation with neurological manifestations, however the incidence of seizure was significantly higher in patients with CS than in others without CS.

Objective:To investigate the cognitive function and its influencing factors among residents in Qingdao city.Methods:The 5 311 research subjects over 65 years old were selected from Qingdao by simple random sampling and stratified sampling. All subjects were investigated by AD8 dementia early screening questionnaire and community screening instrument dementia (CSI-D) to evaluate the prevalence of cognitive decline in this study.The score of AD8 dementia early screening questionnaire ≥2 points or the score of CSI-D ≤7 points was considered to be cognitive decline. Mann-Whitney U test, Chi-square test, Fisher exact probability method, univariate and multivariate Logistic regression analysis and Bootstrap verification were performed using SPSS 26.0 software. Results:Among 5 311 subjects, 1 899 subjects had normal cognitive function (35.76%) and 3 412 subjects had cognitive decline (64.24%). The age of the cognitive decline group was significantly higher than that of the normal group ( P<0.01). There were significant differences in gender, educational level, rural residents, marital status, chronic medical history, hypertension, rheumatoid arthritis, cerebrovascular disease, intervertebral disc disease, ischemic heart disease, monthly household income and alcohol consumption between the two groups (all P<0.05). Univariate Logistic regression analysis showed that female ( β=0.313, OR=1.367, 95% CI=1.221-1.530), age ( β=0.052, OR=1.053, 95% CI=1.043-1.063), rural residents ( β=0.850, OR=2.340, 95% CI=2.042-2.682), widowed ( β=0.557, OR=1.745, 95% CI=1.500-2.029), chronic medical history ( β=0.290, OR=1.336, 95% CI=1.191-1.498), hypertension ( β=0.134, OR=1.143, 95% CI=1.020-1.281), rheumatoid arthritis ( β=0.458, OR=1.581, 95% CI=1.222-2.046), cerebrovascular disease ( β=0.584, OR=1.794, 95% CI=1.352-2.380), intervertebral disc disease ( β=0.578, OR=1.782, 95% CI=1.370-2.319), ischemic heart disease ( β=0.501, OR=1.651, 95% CI=1.272-2.143) were the risk factors for cognitive decline. Higher education level, higher monthly household income and abstinence ( β=-0.244, OR=0.783, 95% CI=0.619-0.992) were protective factors for cognitive decline. Multivariate logistic regression analysis showed that age ( β=0.035, OR=1.036, 95% CI=1.025-1.047), rural residents ( β=0.215, OR=1.239, 95% CI=1.047-1.468), chronic medical history ( β=0.191, OR=1.210, 95% CI=1.067-1.372), cerebrovascular disease ( β=0.480, OR=1.616, 95% CI=1.195-2.187), intervertebral disc disease ( β=0.456, OR=1.578, 95% CI=1.190-2.094) were risk factors for Alzheimer's disease. Higher education level and higher monthly household income were protective factors for Alzheimer's disease. Conclusion:The elderly with chronic diseases, low income and low education level may be at the high risk of cognitive function decline, which should be paid attention to in early screening and intervention.

Cellular force transducer plays a crucial role in normal development of the follicles,which consists of integrin,focal adhesion,signal pathways and cytoskeleton.In follicle development,cellular force transducer converts force stimulation into biochemical signal,and activates the signal pathways to make cytoskeleton respond to stimulation.This process promotes various biological functions of germ cells,such as migration,meiosis and ovulation.This review summarizes the mechanism of follicles'development from two aspects,the role of cellular force transducer in the development of follicles and the related signal pathways,so as to provide a new idea for the further study of follicle development.

Objective:To observe and analyze the clinical characteristics and correlation between the eye and nervous system in children with infantile gangliosideosis.Methods:From November 2018 to January 2021, 3 children with infantile ganglion lipidosis diagnosed by genetic examination in the Department of Ophthalmology and Neurology, Beijing Children's Hospital of Capital Medical University, and through China National Knowledge Infrastructure and Wanfang database and The National Library of Medicine of the United States (PubMed) were searched, and 53 cases of Chinese infantile gangliosideosis diagnosed by gene, enzyme activity or pathological examination were selected and a total of 56 cases were included in the study. The searching time was from the establishment of the database to February 2021, and the search keywords are"gangliosideosis", "cherry-spot" macula and "Chinese". The demographic characteristics of 56 cases of children and other system manifestations were analyzed such as eyes, nervous system, skin, bones. According to the presence or absence of cherry-spot (CS) on the fundus examination, the children were divided into a fundus CS group (group A) and a fundus without CS group (group B), with 20 and 27 cases, respectively. The age of onset, gender, different types and neurological manifestations of the two groups of children were compared and analyzed. The non-parametric rank sum test was used for age comparison between groups; the χ2 test or Fisher's exact test were used for the comparison of gender, disease type and incidence between groups. Results:Among the 56 children, 27 were males and 29 were females; the median age of onset was 7.0 months. There were 33 and 23 cases of GM1 and GM2, respectively. Among 44 children with visual function examination records, 41 cases (93.2%, 41/44) were unable to follow the visual object. Of 47 children who underwent ocular fundus examination, 20 cases (42.6%, 20/47) had CS on the fundus. The main manifestations of the nervous system are neuromotor development regression or retardation (100%, 56/56), convulsions (58.1%, 25/43), and "startle" phenomena (89.7%, 26/29). Among 42 patients with brain magnetic resonance imaging examination records, 39 cases (92.9%) were abnormal. The incidence of "startle" and seizures in group A was higher than that in group B, and the difference was statistically significant ( χ2=5.815, 6.182, P=0.021, 0.013). Conclusios:Chinese infantile gangliosideosis is more common in GM1 type. Ocular visual impairment is the visual object as the main manifestation, the incidence of fundus CS is 42.6%, and the symptoms of neurological damage in children with CS are more severe.

Objective To evaluate the role of mitochondrial ATP sensitive potassium ( mito-KATP ) channel in dexmedetomidine-induced inhibition of subarachnoid hemorrhage ( SAH )-caused programmed cell death ( PCD) in cardiomyocytes of rats. Methods On hundred and twenty clean-grade healthy male Sprague-Dawley rats, aged 9-10 weeks, weighing 350-400 g, were divided into 5 groups ( n=24 each) using a random number table method: sham operation group ( group Sham ) , SAH group, SAH plus dexmedetomidine group ( group SD) , 5-HD plus SAH and dexmedetomidine group ( group HSD) and 5-HD plus SAH group ( group HS) . The rats were subjected to SAH by intracranial vascular puncture after being anesthetized with pentobarbital sodium. Dexmedetomidine 5 μg∕kg was infused for 10 min via the jugular vein starting from the time point after intracranial vascular puncture, followed by a continuous infusion of 5μg·kg-1 ·h-1 for 1 h in SD and HSD groups. 5-HD 30 mg∕kg was intraperitoneally injected at 1 h before intracranial vascular puncture in HSD and HS groups. Blood samples were collected from the abdominal aor-ta at 24 h after intracranial vascular puncture for determination of serum cardiac troponin I ( cTnI) concen-trations. The animals were then sacrificed, and myocardial specimens were collected for determination of PCD rate ( by TUNEL) , reactive oxygen species ( ROS) activity ( by DCFH-DA assay) , and expression of cleaved caspase-3, cleaved caspase-1 and interleukin-1beta ( IL-1β) ( by Western blot) . Results Com-pared with group Sham, the serum concentrations of cTnI, PCD rate and ROS activity were significantly in-creased, and the expression of cleaved caspase-3, cleaved caspase-1 and IL-1βwas up-regulated in SAH, SD, HSD and HS groups ( P<0. 05) . Compared with group SAH, the serum concentrations of cTnI, PCD rate and ROS activity were significantly decreased, and the expression of cleaved caspase-3, cleaved caspase-1 and IL-1βwas down-regulated in group SD, and the serum concentrations of cTnI, PCD rate and ROS activity were significantly increased, and the expression of cleaved caspase-3, cleaved caspase-1 and IL-1βwas up-regulated in group HS ( P<0. 05) . Compared with group SD, the serum concentrations of cT-nI, PCD rate and ROS activity were significantly increased, and the expression of cleaved caspase-3, cleaved caspase-1 and IL-1β was up-regulated in group HSD ( P<0. 05) . Compared with group HSD, the serum concentrations of cTnI, PCD rate and ROS activity were significantly increased, and the expression of cleaved caspase-3, cleaved caspase-1 and IL-1βwas up-regulated in group HS ( P<0. 05) . Conclusion mito-KATP channel is involved in dexmedetomidine-induced inhibition of PCD in cardiomyocytes of rats with SAH.

Objective To evaluate the role of Toll-like receptor 4 (TLR4)-p38 mitogen-assoliated protein kinase (p38MAPK)-nuclear factor kappa B (NF-κB) signaling pathway in sevoflurane-induced decrease in cognitive function of aged rats.Methods Sixty SPF healthy male Sprague-Dawley rats,aged 20 months,weighing 550-750 g,were divided into 5 groups (n =12 each) using a random number table method:control group (C group),sevoflurane group (S group),TAK242 plus sevoflurane group (TS group),SB202190 plus sevoflurane group (SS group),and PDTC plus sevoflurane group (PS group).All the rats were intubated after anesthesia and connected to an animal ventilator.TAK242,SB202190 and PDTC 10 μl were injected into the lateral cerebral ventricle in TS,SS and PS groups,respectively,and normal saline containing the equal volume of DMSO was given in C and S groups.Starting from 10 min after lateral cerebral ventricle injection,4％ sevoflurane was inhaled for 6 h via the tracheal tube,with the inhaled oxygen concentration 30％ and oxygen flow rate 2 L/min.The mixture of air and oxygen was inhaled in C group.The learning and memory ability was assessed by Morris water maze test at 7 days after the end of sevoflurane anesthesia,and the escape latency and swimming distance were recorded.Animals were sacrificed after the end of Morris water maze test,and brains were removed and hippocampi were isolated for determination of neural apoptosis (by TUNEL),contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in hippocampal tissues (by enzyme-linked immunosorbent assay),and expression of caspase-3,phosphorylated p38MAPK (p-p38MAPK),total p38MAPK (t-p38MAPK) and NF-κB in nucleus (by Western blot).The apoptosis rate and p-p38MAPK/t-p38MAPK ratio were calculated.Results Compared with C group,the escape latency and swimming distance were significantly prolonged at each time point,the apoptosis rate and contents of TNF-oα and IL-1β were increased,the expression of caspase-3,p-p38MAPK and NF-κB was up-regulated,and p-p38MAPK/t-p38MAPK ratio was increased in the other four groups (P＜0.05).Compared with S group,the escape latency and swimming distance were significantly shortened at each time point,the apoptosis rate and contents of TNF-α and IL-1β were decreased,and the expression of caspase-3 was down-regulated in TS,SS and PS groups,the expression of NF-κB was significantly down-regulated in TS and SS groups,and the expression of p-p38MAPK was significantly down-regulated,and p-p38MAPK/t-p38MAPK ratio was decreased in TS group (P＜0.05).Compared with TS group,the escape latency and swimming distance were significantly prolonged at each time point,the apoptosis rate and contents of TNF-α and IL-1β were increased,the expression of caspase-3 and p-p38MAPK was up-regulated,and p-p38MAPK/t-p38MAPK ratio was increased in SS and PS groups,and the expression of NF-κB was significantly up-regulated in PS group (P＜0.05).The expression of NF-κB was significantly up-regulated in PS group when compared with SS group (P＜0.05).Conclusion TLR4-p38MAPKNF-κB signaling pathway is involved in sevoflurane-induced decrease in cognitive function of aged rats.

Objective To evaluate the role of Toll-like receptor 4 (TLR4) signaling pathway in sevoflurane anesthesia-induced cognitive dysfunction in aged rats.Methods Twenty-seven SPF healthy male Sprague-Dawley rats,aged 20 months,weighing 550-750 g,were divided into 3 groups (n =9 each) using a random number table:control group (C group),sevoflurane anesthesia group (S group) and TLR4 antagonist plus sevoflurane anesthesia group (TS group).TLR4 monoclonal antibody 30 μl was injected into the lateral cerebral ventricle in group TS,and the equal volume of serum containing no antibody was injected into the lateral cerebral ventricle in C and S groups.At 10 min after completion of injection,S and TS groups inhaled the mixture of 4％ sevoflurane and 30％ oxygen for 6 h,and group C only inhaled the mixture of air and oxygen.Morris water maze test was performed at 24 h after the end of sevoflurane anesthesia.The animals were sacrificed after completion of Morris water maze test,brains were removed and hippocampi were isolated for determination of nerve cell apoptosis (using TUNEL) and expression of activated caspase-3 (using immunofluorescent staining).Nerve cell apoptosis rate was calculated.The expression of high-mobility group box 1 protein (HMGB1) mRNA in hippocampi was measured by Northern blot assay at 6 h after the end of sevoflurane anesthesia.The expression of amyloid precursor protein (APP) and amyloid beta protein (Aβ) in hippocampi was assessed by Western blot at 24 h after the end of sevoflurane anesthesia.Results Compared with C group,the escape latency was significantly prolonged,nerve cell apoptosis rate was increased,the expression of activated caspase-3,HMGB1 mRNA,APP and Aβ was up-regulated in group S,and nerve cell apoptosis rate was increased,the expression of activated caspase-3,HMGB1 mRNA,APP and Aβ was up-regulated (P＜0.05),and no significant change was found in the escape latency in group TS (P＞0.05).Compared with S group,the escape latency was significantly shortened,nerve cell apoptosis rate was decreased,and the expression of activated caspase-3,HMGB1 mRNA,APP and Aβ was down-regulated in group TS (P＜0.05).Conclusion Activation of TLR4 signaling pathway is involved in the mechanism of sevoflurane anesthesia-induced cognitive dysfunction in aged rats.

To confirm the etiology of a dead case for a 6 year-old female Ailurus fulgens,one strain of the predominant bacteria from pathologic tissues(heart,liver,spleen,lung and other samples) of the dead Ailurus fulgens were examined and isolated.The isolate was named R1 and no other bacteria were isolated.The bacterial etiological examination(morphological characteristics,biochemical characteristics and 16S rDNA gene detection)of R1 showed that it was identifed as K.peneumoniae.Artificial infection to mice about R1 was also conducted in this study.R1 had strong pathogenicity to mice and the LD50 is 6.5 × 104 CFU/mL.Moreover,the clinical and pathological features of the dead mice were consistent with that of the Ailurus fulgens.To find effective therapeutic drugs of curing other Ailurus fulgens,antibiotic sensitivity test of R1 was conducted,and the results revealed that R1 was highly sensitive to cefotaxime et al,moderately sensitive to amikacin and resistant to penicillin.These data showed that K.peneumoniae was bacterial pathogen leading to death of the Ailurus fulgens and it had strong resistance to penicillins,macrolides and virginiamycin and it had broad drug resistance spectrum.However,R1 is sensitive to cephalosporins and aminoglycoside antibiotics.

Objective To explore the effect of erythropoietin (EPO) attenuating apoptosis in old rat hippocampal neuronal cells exposed to sevoflurane and the role of toll like receptor 4.Methods Twenty months old SD rats,male,550-750 g,in accordance with the random number table,were divided into 3 groups (n =9):control group (group C),sevoflurane treatment (group S),and sevoflurane plus EPO treatment (group ES).The rats in group S and ES were subjected to inhale 4％ sevoflurane for 6 h,but the rats in group C were inhaled air-oxygen only.The rats in group ES were injected with EPO into caudal vein at 24 h,48 h,and 72 h after sevoflurane exposure.The cognitive ability was assessed by Morris water maze test;the effects of hippocampal apoptosis were assessed by TUNEL assays;the expressions of TLR4 mRNA was measured by RT-PCR assay;mitochondrial membrane potential (MMP) was assessed by JC-1 fluorescence;the expressions of APP and Aβ were assessed by western blot.Results Compared with group C,there were significant increases of escape latency period,neuronal apoptosis,TLR4 mRNA,and APP and Aβ expression,but a decrease of MMP in group S (P＜0.05).Compared with group S,there were significant decreases of escape latency period,neuronal apoptosis,TLR4 mRNA,and APP and Aβ expression,but a increase of MMP in group ES (P＜0.05).Conclusion The attenuation of rat hippocampal neuronal apoptosis induced by EPO could be associated with inhibition of TLR4,improvement of MMP,as well as inhibition of APP and Aβ activity.

Objective To explore the changes of cognitive ability in elderly rats induced by sevoflurane exposure,and their relation with Toll like receptor 4 (TLR4)-MyD88 signal pathway.Methods Forty-eight male SD rats,weighting 550-750 g,in accordance with the random number table,were divided into 4 groups (n=12):control group (C group),sevoflurane treatment group (S group),sevoflurane plus TAK242 treatment group (TS group),and sevoflurane plus ST2825 treatment group (SS group).The rats in S,TS and SS groups were subjected to inhale 4％ sevoflurane for 6 h,but the rats in C group were inhaled by air-oxygen only.The rats in TS and SS group were injected with 20 μL TAK242 (1 g/L) or 20 μL ST2825 (1 g/L) via lateral ventricle 10 min before sevoflurane exposure,respectively.The cognitive ability was assessed by Morris water maze test and open field test;the levels of hippocampal tumor necrosis factor (TNF)-α and interleukin (IL)-1β were assessed by ELISA;the Aβ expressions was assessed by Western blotting.Results As compared with those in the C group,significant increase of escape latency,time of the animals spent in the central square,and TNF-α,IL-1β and Aβ expressions,but decrease of number of crossing the grid,and smaller number of standing on the back legs were noted in the S group (P＜0.05).As compared with S group,TS and SS group had significantly decreased escape latency,time of the animals spent in the central square,and TNF-oα,IL-1β and Aβ expressions,but statistically larger number of crossing the grid and number of standing on the back legs (P＜0.05).Conclusion The cognitive dysfunction of elderly rats induced by sevoflurane exposure could be associated with TLR4-MyD88 signal pathway.