Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; alpha-Synuclein/metabolism* ; Male ; Prefrontal Cortex/drug effects* ; Rats, Sprague-Dawley ; Depression/metabolism* ; MAP Kinase Signaling System/drug effects* ; Rats ; Parkinson Disease/metabolism* ; Receptor, trkB/metabolism* ; Phosphorylation ; Disease Models, Animal ; Signal Transduction

To address the challenges of extracting nonlinear features from motor imagery electroencephalogram(EEG)signals and effectively capturing functional connectivity between EEG channels,a classification and recognition method for motor imagery EEG signals is proposed based on mutual information and adaptive graph convolutional network.The proposed method extracts frequency domain information by sub-frequency banding on the original motor imagery EEG signals,uncovers the nonlinear relationships within EEG signals by an adjacency matrix constructed with mutual information neural estimation method,and finally achieve null-frequency feature extraction by capturing the dynamic correlation strength between channels with an adaptive graph convolutional network incorporating convolutional block attention module.On the BCI Competition Ⅳ 2a and BCI Competition Ⅲ 3a datasets,the proposed method has average accuracies of 83.14％and 88.19％,respectively,demonstrating that it can effectively reveal functional connectivity between EEG channels,providing a new approach for decoding motor imagery EEG signals.

To address the challenges of extracting nonlinear features from motor imagery electroencephalogram(EEG)signals and effectively capturing functional connectivity between EEG channels,a classification and recognition method for motor imagery EEG signals is proposed based on mutual information and adaptive graph convolutional network.The proposed method extracts frequency domain information by sub-frequency banding on the original motor imagery EEG signals,uncovers the nonlinear relationships within EEG signals by an adjacency matrix constructed with mutual information neural estimation method,and finally achieve null-frequency feature extraction by capturing the dynamic correlation strength between channels with an adaptive graph convolutional network incorporating convolutional block attention module.On the BCI Competition Ⅳ 2a and BCI Competition Ⅲ 3a datasets,the proposed method has average accuracies of 83.14％and 88.19％,respectively,demonstrating that it can effectively reveal functional connectivity between EEG channels,providing a new approach for decoding motor imagery EEG signals.

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD⁺/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
Mice ; Animals ; Butyric Acid/metabolism* ; Ketone Bodies/metabolism* ; Liver/metabolism* ; Hydroxybutyrates/metabolism* ; Down-Regulation ; Sirtuins/metabolism* ; Hydroxymethylglutaryl-CoA Synthase/metabolism*

Abstract The popularization of the use of electronic has become a global trend, and children are exposed to devices at younger ages. A large proportion of children and adolescents spend on screen time more than 2 h which is recommended in most guidelines. The paper reviews possible effects of screen time on physical and mental health, as well as mental disorders in children and adolescents. It is found that excessive screen time showed negative impacts on mental health, including depression, anxiety, mood disorder, social adaptational problems, behavioral disorders, self injurious behaviors, and health risk behaviors. Much attention has been paid on the association between excessive screen time and mental health of children and adolescents, while possible mechanisms and influencing factors are lacking. Effective intervention studies are needed to provide a basis for child and adolescent health promotion.

To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of symptomatic giant colonic lipomas (≥5 cm). Eight patients with giant colonic lipomas were treated with ESD at the Department of Digestive Endoscopy, Shanghai East Hospital from December 2018 to December 2021. The complete resection rate was 100% with the mean size of the resected lesion of 6.0 cm (ranging from 5.5 cm to 9.0 cm). The mean operation time of ESD was 41 minutes (ranging from 25 minutes to 80 minutes). Minimal bleeding were all successfully stopped with electrocoagulation and 2 small perforations were successfully sutured during the procedures. No abdominal pain, fever, delayed bleeding or perforation occurred after ESD. The mean hospital stay was 3 days (ranging from 3 days to 5 days). No residual or recurrence was found during the follow-up of 8-36 months. Thus, ESD is safe and effective for the treatment of giant colonic lipomas which can avoid surgical resection.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective:To explore the risk factors of linezolid-induced thrombocytopenia (LIT) and evaluate their predictive value.Methods:Medical records of hospital acquired pneumonia (HAP) patients who admitted in Suzhou Municipal Hospital from July 2019 to October 2021 and received linezolid were collected and retrospectively analyzed. Clinical data including general information, comorbidities, linezolid application, laboratory test results, and trough concentration of linezolid was extracted. Patients were divided into LIT group and non-LIT group according to the occurrence of LIT. Clinical characteristics were compared between the 2 groups; risk factors of LIT in patients with HAP were analyzed using a binary logistic regression model, and the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated; the predictive value of the risk factors for LIT were evaluated using receiver operating characteristic (ROC) curve. Results:A total of 74 patients were included in the study, including 55 males and 19 females, aged 82 (73, 88) years. LIT occurred in 25 patients (33.8%). Compared with the non-LIT group, the age and trough concentration of linezolid in patients in the LIT group were higher [88 (81, 92) years vs. 79(70, 86) years, P=0.001; (19.6±10.3) mg/L vs. (9.8±6.4) mg/L, P<0.001], and the baseline platelet count and baseline creatinine clearance rate were lower [181(162, 212) ×10 9/L vs. 229 (169, 289) ×10 9/L, P=0.025; 31(19, 44) ml/(min·1.73 m 2) vs. 46 (27, 65) ml/(min·1.73 m 2), P=0.018]. Binary logistic regression analysis showed that the lower baseline creatinine clearance rate ( OR=0.974, 95 %CI: 0.951-0.998, P=0.035) and higher trough concentration of linezolid ( OR=1.156, 95 %CI: 1.059-1.261, P=0.001) were independent risk factors for LIT in HAP patients. ROC curve analysis showed that the threshold of the age, trough concentration of linezolid, baseline platelet count, and baseline creatinine clearance rate were 87 years (sensitivity 56.0%, specificity 83.7%), 15.4 mg/L (sensitivity 64.0%, specificity 87.8%), 189×10 9/L (sensitivity 67.3%, specificity 68.0%), and 45 ml/(min·1.73 m 2) (sensitivity 53.1%, specificity 80.0%), respectively. Patients were respectively divided into 2 groups according to the thresholds and the incidences of LIT were compared. The results showed that the incidences of LIT in patients with age and trough concentration of linezolid exceeding the thresholds and in patients with baseline plate count and baseline creatinine clearance rate lower than or equal to the thresholds were significantly higher than those in the other patients (all P<0.01). Conclusions:Baseline creatinine clearance rate, trough concentration of linezolid, age, and plate count are risk factors for LIT in HAP patients and their thresholds are 45 ml/(min·1.73 m 2), 15.4 mg/L, 87 years, and 189×10 9/L, respectively. These risk factors have good predictive value for the occurrence of LIT.

Objective:To explore the risk factors of linezolid-induced thrombocytopenia (LIT) and evaluate their predictive value.Methods:Medical records of hospital acquired pneumonia (HAP) patients who admitted in Suzhou Municipal Hospital from July 2019 to October 2021 and received linezolid were collected and retrospectively analyzed. Clinical data including general information, comorbidities, linezolid application, laboratory test results, and trough concentration of linezolid was extracted. Patients were divided into LIT group and non-LIT group according to the occurrence of LIT. Clinical characteristics were compared between the 2 groups; risk factors of LIT in patients with HAP were analyzed using a binary logistic regression model, and the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated; the predictive value of the risk factors for LIT were evaluated using receiver operating characteristic (ROC) curve. Results:A total of 74 patients were included in the study, including 55 males and 19 females, aged 82 (73, 88) years. LIT occurred in 25 patients (33.8%). Compared with the non-LIT group, the age and trough concentration of linezolid in patients in the LIT group were higher [88 (81, 92) years vs. 79(70, 86) years, P=0.001; (19.6±10.3) mg/L vs. (9.8±6.4) mg/L, P<0.001], and the baseline platelet count and baseline creatinine clearance rate were lower [181(162, 212) ×10 9/L vs. 229 (169, 289) ×10 9/L, P=0.025; 31(19, 44) ml/(min·1.73 m 2) vs. 46 (27, 65) ml/(min·1.73 m 2), P=0.018]. Binary logistic regression analysis showed that the lower baseline creatinine clearance rate ( OR=0.974, 95 %CI: 0.951-0.998, P=0.035) and higher trough concentration of linezolid ( OR=1.156, 95 %CI: 1.059-1.261, P=0.001) were independent risk factors for LIT in HAP patients. ROC curve analysis showed that the threshold of the age, trough concentration of linezolid, baseline platelet count, and baseline creatinine clearance rate were 87 years (sensitivity 56.0%, specificity 83.7%), 15.4 mg/L (sensitivity 64.0%, specificity 87.8%), 189×10 9/L (sensitivity 67.3%, specificity 68.0%), and 45 ml/(min·1.73 m 2) (sensitivity 53.1%, specificity 80.0%), respectively. Patients were respectively divided into 2 groups according to the thresholds and the incidences of LIT were compared. The results showed that the incidences of LIT in patients with age and trough concentration of linezolid exceeding the thresholds and in patients with baseline plate count and baseline creatinine clearance rate lower than or equal to the thresholds were significantly higher than those in the other patients (all P<0.01). Conclusions:Baseline creatinine clearance rate, trough concentration of linezolid, age, and plate count are risk factors for LIT in HAP patients and their thresholds are 45 ml/(min·1.73 m 2), 15.4 mg/L, 87 years, and 189×10 9/L, respectively. These risk factors have good predictive value for the occurrence of LIT.

Objective:To explore the incidence, clinical characteristics and prognosis of invasive pulmonary fungal infection(IPFI)in recipients of lung transplantation(LT)in southern China.Methods:From January 2003 to August 2019, retrospective analysis was performed for 300 recipients of lung transplantation at three hospitals in southern China. There were 254 males and 46 females with an average age of (54.98±14.2)years. Clinical data were collected from medical records, including symptoms and signs, imaging studies, bronchoscopy examination, pathogen separation and culture from deep sputum and bronchoalveolar lavage fluid(BALF), fungal-related laboratory tests and tissue pathology.Results:Among 300 cases, 93(31.0%)had at least one episode of IPFI. The most common pathogen was aspergillosis(60.2%), followed by candida(15 cases, 16.1%)and Pneumocystis jeroveci (13 cases, 14.0%). Kaplan Meier analysis indicated that all-cause mortality was significantly higher in IPFI group than that in non-IPFI(nIPFI)group with one-year mortality of 45.2% vs. 26.7% in IPFI and nIPFI groups respectively( P<0.05). Conclusions:IPFI is prevalent after LT in southern China. And aspergillosis is the most common pathogen and Candida comes the next. The median occurring time for aspergillosis is 6 months after LT. Candida infection occurs earlier at airway anastomosis. A higher incidence of invasive fungal disease(IFD)associated with a lower survival indicates that IPFI has a substantial mortality among recipients after LT. Prophylactic agents should be optimized based upon an epidemiologically likely pathogen.