Objective:To analyze the clinical characteristics and outcomes of Haemophilus influenzae (Hi) meningitis in children. Methods:This is a retrospective case series study. This study included 34 Hi meningitis patients who admitted to Beijing Children′s Hospital, Capital Medical University, from January 1, 2010, to December 31, 2023. Data on clinical presentations, laboratory tests, hearing assessment and outcomes at discharge were collected. Patients were divided into 2 groups according to the outcome at discharge: favorable outcome group and unfavorable outcome group. Mann-Whitney U test and Fisher exact test was used to estimate the risk factors for an unfavorable outcome at discharge. Results:Thirty-four patients were enrolled. There were 16 males and 18 females. The age at onset ranged from 3 months to 12 years. Fever (34 patients (100%)), convulsions (17 patients (50%)), and coma (21 patients (62%)) were the common clinical presentations. Twenty-four patients (71%) developed complications. There were 15 patients (44%) needed treatment in the intensive care unit, 5 patients (15%) received intubation, and 4 patients (12%) had developed shock. The favorable outcome group included 23 patients, and the unfavorable outcome group included 11 patients. Female, patients with limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L were risk factors of unfavorable outcome at discharge (all P<0.05). Among the 23 patients (68%) in favorable outcomes group, 13 patients (57%) had data available on their long-term follow-up results, including 12 patients with favorable long-term outcomes and 1 patient with unfavorable long-term outcome. Among the 11 patients (32%) in unfavorable outcomegroup, 1 patient died, the other 10 patients (91%) had data available on their long-term outcomes. Eight patients had unfavorable long-term outcomes and 2 patients with favorable long-term outcomes. Patients who had unfavorable outcomes at discharge were at a greater risk of experiencing unfavorable long-term outcomes ( P=0.001). Conclusions:It is common for patients with Hi meningitis to have intracranial complications or develop into critical conditions. Patients who have limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and who exhibit a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L tend to have unfavorable outcomes; they need to be assessed for sequelae.

OBJECTIVES: Rheumatoid arthritis (RA) imposes a heavy burden on individuals, families, and society. This study analyzed the incidence and mortality trends of RA in China from 1990 to 2023 to provide epidemiological evidence for precise prevention and control. METHODS: Data on RA incidence, age-standardized incidence rate (ASIR), deaths, and age-standardized mortality rate (ASMR) in China by sex and age group from 1900 to 2021 were extracted from the Global Burden of Disease (GBD) 2021 database. Joinpoint regression was used to analyze trends in ASIR and ASMR. An age-period-cohort model was constructed using R4.3.1 to evaluate longitudinal age trends and estimate relative risk (RR) values for period and cohort effects. RESULTS: In 2021, the number of RA cases, ASIR, deaths, and ASMR in China were 247 300, 13.70 per 100 000, 10 300, and 0.54 per 100 000, respectively. From 1990 to 2021, the ASIR of RA increased annually among both females and males, with average annual percentage changes (AAPCs) of 0.44% and 0.72%, respectively. Over the same period, ASMR declined in the total population and among females, with AAPCs of -0.78% and -1.19%, while the change in males was not statistically significant. Age-period-cohort analysis showed that the peak incidence occurred in women aged 60-64 years and men aged 75-79 years, and mortality increased with age. The period effect for incidence rose in both sexes, reaching 1.10 [95% confidence interval (CI) 0.94 to 1.27] for females and 1.14 (95% CI 1.02 to 1.27) for males during 2017 to 2021, compared with 2002 to 2006. The mortality period effect RR exhibited a downward-upward-downward pattern, decreasing to 0.56 (95% CI 0.52 to 0.61) in females and 0.75 (95% CI 0.68 to 0.82) in males in 2017 to 2021. Cohort analysis indicated that the highest incidence risk occurred in individuals born during 2012 to 2016, while the cohort effect RR for female RA mortality showed a continuous decline beginning with the 1922 to 1926 birth cohort. CONCLUSIONS The incidence and mortality risks of RA in China have continued to decline. However, with the aging of the population, the incidence and mortality risks among the elderly have increased. Middle-aged women and elderly men should receive focused attention. Health authorities should strengthen education, prevention, and screening among middle-aged women and enhance disease monitoring in elderly populations to reduce the national burden of RA.
Humans ; China/epidemiology* ; Arthritis, Rheumatoid/epidemiology* ; Incidence ; Male ; Female ; Middle Aged ; Adult ; Aged ; Cohort Studies ; Mortality/trends* ; Age Distribution ; Age Factors ; Aged, 80 and over ; Adolescent

Objective:To evaluate the role and molecular mechanism of laminin β1(LAMB1)in cortical neurons in regulation of glutamate receptors.Methods:Recombinant lentivirus(LV-shLamb1)-mediated knockdown of LAMB1 expression in mouse primary cortical neurons was performed,followed by immunofluorescence staining and Western blot to detect changes in F-actin,glutamate receptor subtypes(AMPA receptors GluR1/GluR2,NMDA receptors NR1/NR2A),and ERK-related protein expression in cortical neurons.Results:LV-shLamb1 significantly inhibited LAMB1 expression in mouse cortical neurons.Concurrently,LV-shLamb1 markedly increased F-actin polymerization,as well as the expression of AMPA receptor subunits GluR1 and GluR2,and NMDA receptor subunits NR1 and NR2A.Further,Western blot detection showed that the phosphorylation level of ERK was significantly increased after LV-shLamb1 infec-tion.Conclusion:LAMB1 is expressed in cortical neurons.Suppression of LAMB1 expression in mouse cortical neu-rons activates the ERK pathway,which in turn promotes the polymerization of the cytoskeletal protein F-actin and the expression of glutamate receptors.This suggests that LAMB1 may regulate F-actin homeostasis and glutamate receptor levels through the ERK pathway,thereby playing a potentially important role in neuronal function.

Objective:To evaluate the role and molecular mechanism of laminin β1(LAMB1)in cortical neurons in regulation of glutamate receptors.Methods:Recombinant lentivirus(LV-shLamb1)-mediated knockdown of LAMB1 expression in mouse primary cortical neurons was performed,followed by immunofluorescence staining and Western blot to detect changes in F-actin,glutamate receptor subtypes(AMPA receptors GluR1/GluR2,NMDA receptors NR1/NR2A),and ERK-related protein expression in cortical neurons.Results:LV-shLamb1 significantly inhibited LAMB1 expression in mouse cortical neurons.Concurrently,LV-shLamb1 markedly increased F-actin polymerization,as well as the expression of AMPA receptor subunits GluR1 and GluR2,and NMDA receptor subunits NR1 and NR2A.Further,Western blot detection showed that the phosphorylation level of ERK was significantly increased after LV-shLamb1 infec-tion.Conclusion:LAMB1 is expressed in cortical neurons.Suppression of LAMB1 expression in mouse cortical neu-rons activates the ERK pathway,which in turn promotes the polymerization of the cytoskeletal protein F-actin and the expression of glutamate receptors.This suggests that LAMB1 may regulate F-actin homeostasis and glutamate receptor levels through the ERK pathway,thereby playing a potentially important role in neuronal function.

Objective:To analyze the clinical characteristics and outcomes of Haemophilus influenzae (Hi) meningitis in children. Methods:This is a retrospective case series study. This study included 34 Hi meningitis patients who admitted to Beijing Children′s Hospital, Capital Medical University, from January 1, 2010, to December 31, 2023. Data on clinical presentations, laboratory tests, hearing assessment and outcomes at discharge were collected. Patients were divided into 2 groups according to the outcome at discharge: favorable outcome group and unfavorable outcome group. Mann-Whitney U test and Fisher exact test was used to estimate the risk factors for an unfavorable outcome at discharge. Results:Thirty-four patients were enrolled. There were 16 males and 18 females. The age at onset ranged from 3 months to 12 years. Fever (34 patients (100%)), convulsions (17 patients (50%)), and coma (21 patients (62%)) were the common clinical presentations. Twenty-four patients (71%) developed complications. There were 15 patients (44%) needed treatment in the intensive care unit, 5 patients (15%) received intubation, and 4 patients (12%) had developed shock. The favorable outcome group included 23 patients, and the unfavorable outcome group included 11 patients. Female, patients with limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L were risk factors of unfavorable outcome at discharge (all P<0.05). Among the 23 patients (68%) in favorable outcomes group, 13 patients (57%) had data available on their long-term follow-up results, including 12 patients with favorable long-term outcomes and 1 patient with unfavorable long-term outcome. Among the 11 patients (32%) in unfavorable outcomegroup, 1 patient died, the other 10 patients (91%) had data available on their long-term outcomes. Eight patients had unfavorable long-term outcomes and 2 patients with favorable long-term outcomes. Patients who had unfavorable outcomes at discharge were at a greater risk of experiencing unfavorable long-term outcomes ( P=0.001). Conclusions:It is common for patients with Hi meningitis to have intracranial complications or develop into critical conditions. Patients who have limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and who exhibit a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L tend to have unfavorable outcomes; they need to be assessed for sequelae.

Objective:To explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge.Methods:This study was a retrospective cohort study that included 268 children with bacterial meningitis who were discharged from the infectious medicine ward of Beijing Children′s Hospital from September 2018 to September 2023. The children were managed with a multidisciplinary collaborative comprehensive healthcare management model after discharge. Outpatient data at 1 month and 6, 12 and 24 months after discharge were collected, including (height, weight, body mass index, nutritional feeding status, hearing and vision screening results, Gesell developmental assessment results and intervention guidance services. The follow-up interval or frequency was dynamically adjusted or increased according to the child′s situation. The paired sample t-test and chi square test were applied to compare the differences in Gesell developmental quotient (DQ) and developmental delay rate between the first and last assessments to preliminarily explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge. Results:All the 268 children completed their first assessment one month after discharge, and 37 children were found to have abnormal physical growth, mainly obesity (28 children), and another 9 children were malnutrition. Nutritional intervention and feeding guidance services were provided to all the 37 children, and as of the last follow-up, 20 children′s physical growth evaluations had turned normal. A total of 188 children completed at least 2 developmental assessments, with an interval of (14.2±9.4) months between the first and last assessments (range: 3.1-49.5 months). The DQ values of in the energy region of adaptability, gross motor skills, fine motor skills, language, and personal social skills at the last assessment were significantly higher than those at the first assessment [(91.93±13.28) vs (80.73±15.96) points, (91.69±12.96) vs (78.31±16.58) points, (89.32±16.11) vs (80.68±15.63) points, (90.10±16.65) vs (82.04±18.43) points, (92.01±14.05) vs (77.82±17.42) points]; moreover, the rates of developmental delay in each energy region were significantly lower than those at the initial assessment (9.6% vs 35.1%, 9.6% vs 42.0%, 18.1% vs 33.0%, 13.3% vs 31.9%, 9.6% vs 42.0%) (all P<0.05). Among the 200 children who completed the hearing screening, 18 were found with hearing abnormalities, and 2 were diagnosed with hearing loss in the Otolaryngology Department. Among 217 children who completed vision screening, 23 had abnormalities, and 5 were diagnosed with ophthalmic abnormalities in Ophthalmology Department (2 with strabismus, 2 with refractive errors, and 1 with optic nerve injury). Two children were found to have autism-like behavior during monitoring, and were referred to a developmental behavior clinic to be diagnosed with autism spectrum disorder and were given early diagnosis and intervention guidance. Conclusion:The comprehensive healthcare management model for children with bacterial meningitis after discharge can integrate clinical and healthcare resources, which is beneficial for improving the prognosis and enhancing the quality of life for children with special health status.

Objective:To investigate the changes of melanin concentration hormone receptor 1(MCHR1)in dorsal root ganglion(DRG)of mice with neuropathic pain.Methods:The expression profile of MCHR1 in the DRG of mice were observed by immunofluorescent staining.Neuropathic pain model was established by spared nerve injury(SNI)in mice.Male mice(C57BL/6)were randomly divided into 2 groups:Sham-operated group and SNI group.The paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)were observed by von Frey fibers and thermal radiation stimulation.The mRNA and protein levels of MCHR1 in DRG were detected by real time RT-PCR and West-ern Blot,respectively.Results:MCHR1 was widely distributed in mouse DRG and co-labeled with small and medium-sized neuronal markers calcitonin gene-related peptide(CGRP)and isolectin B4(IB4),as well as large diameter neu-ronal marker NF200.Stable mechanical hyperalgesia and heat hyperalgesia were observed in the ipsilateral hindpaw of mice at 7 days post-SNI.Real time RT-PCR and Western Blot experiments showed that mRNA and protein expression levels in DRG were both significantly up-regulated in SNI-treated mice,as compared with Sham group.Conclusion:MCHR1 was widely distributed in large,medium and small neurons of DRG.After the SNI model mice presented a sta-ble phenomenon of hyperalgesia,the transcription and protein level of MCHR1 in DRG were significantly elevated in SNI mice.These data suggest that MCHR1 in DRG may be involved in the occurrence and development of neuropathic pain.

Objective:To investigate the changes of melanin concentration hormone receptor 1(MCHR1)in dorsal root ganglion(DRG)of mice with neuropathic pain.Methods:The expression profile of MCHR1 in the DRG of mice were observed by immunofluorescent staining.Neuropathic pain model was established by spared nerve injury(SNI)in mice.Male mice(C57BL/6)were randomly divided into 2 groups:Sham-operated group and SNI group.The paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)were observed by von Frey fibers and thermal radiation stimulation.The mRNA and protein levels of MCHR1 in DRG were detected by real time RT-PCR and West-ern Blot,respectively.Results:MCHR1 was widely distributed in mouse DRG and co-labeled with small and medium-sized neuronal markers calcitonin gene-related peptide(CGRP)and isolectin B4(IB4),as well as large diameter neu-ronal marker NF200.Stable mechanical hyperalgesia and heat hyperalgesia were observed in the ipsilateral hindpaw of mice at 7 days post-SNI.Real time RT-PCR and Western Blot experiments showed that mRNA and protein expression levels in DRG were both significantly up-regulated in SNI-treated mice,as compared with Sham group.Conclusion:MCHR1 was widely distributed in large,medium and small neurons of DRG.After the SNI model mice presented a sta-ble phenomenon of hyperalgesia,the transcription and protein level of MCHR1 in DRG were significantly elevated in SNI mice.These data suggest that MCHR1 in DRG may be involved in the occurrence and development of neuropathic pain.

Objective:To analyze the characteristics and prognosis of hearing loss in children with bacterial meningitis.Methods:This was a single-center retrospective cohort study. Patients diagnosed with bacterial meningitis who were hospitalized in Beijing Children′s Hospital between 2010 and 2016 and older than 28 days and younger than 18 years at symptom onset were included in this study ( n=573). All clinical information including hearing assessment results during hospitalization were reviewed. All patients with hearing loss were followed up to repeat their hearing test and assess their hearing condition with parents′ evaluation of aural and (or) oral performance of children (PEACH). Patients were grouped according to their hearing assessment results, and Logistic regression analysis was used to analyze the risk factors for hearing loss in patients with bacterial meningitis. Results:Five hundred and seventy-three patients were enrolled in this study, including 347 males and 226 females. The onset age ranged from 29 days to 15.8 years. Two hundred and forty-six patients had identified causative pathogens, among whom 92 cases (37.4%) were pneumococcal meningitis cases. Hearing loss was found in 160 cases (27.9%) during hospitalization, involving 240 ears. Permanent hearing loss was found in 20 cases (16.9%), involving 32 ears. In the patients with permanent hearing loss, 87.5% (28/32) of ears were identified as severe or profound hearing loss during hospitalization. Logistic regression analysis showed that dystonia, the protein concentration level in cerebrospinal fluid>1 g/L, glucose concentration level lower than 1 mmol/L and subdural effusion were independent risk factors for hearing loss ( OR=2.426 (1.450-4.059), 1.865 (1.186-2.932), 1.544 (1.002-2.381) and 1.904 (1.291-2.809)). Conclusions:Hearing loss is a common sequela of bacterial meningitis in children. Most patients have transient hearing loss, but patients with severe or profound hearing impairment have a higher risk of developing permanent hearing loss.

[Abstract] Objective: To investigate the mechanisms of carnitine palmitoyltransferase 1c (CPT1c) expression to affect the proliferation and apoptosis of human thyroid papillary cancer B-CPAP cells through the AMP-dependent/activated protein kinase (AMPK) pathway in the low glucose and hypoxic conditions. Methods: Firstly,humanthyroidpapillarycarcinomaB-CPAP cells were cultured under normal condition or low glucose and hypoxic condition respectively, followed with the treatment of AMPK inhibitor compound C. Western blotting was used to detect the expressions of AMPK, p-AMPK, peroxisome proliferator-activated receptor α (PPARα) and CPT1c; the proliferation and apoptosis were detected by CCK-8 and Flow cytometry, respectively. Then PPARα-siRNA was synthesized and transfected into B-CPAP cells to knock down PPARα, and then the cells were cultured under normal or low glucose and hypoxic condition respectively.Above indicators were also detected to verify the regulation of PPARα on CPT1c. Finally, the human luciferase reporter plasmid containing CPT1c gene promoter was constructed, and the effect of PPARα on the activity of CPT1c promoter luciferase activity was observed by immunofluorescence. Results: The expressions ofAMPK, p-AMPK, PPARα and CPT1c were significantly increased in B-CPAP cells under low glucose and hypoxia condition (P<0.05 or P<0.01), while cell proliferation and apoptosis rate did not change significantly (P>0.05). After the treatment of AMPK inhibitor compound C, the expressions of p-AMPK, PPARα and CPT1c in low glucose and hypoxia group were significantly decreased (P<0.05 or P<0.01), the inhibitory rate on cell proliferation and apoptosis rate were significantly increased (P<0.05). However, the change range was smaller than that in the normal culture + compound C group (P<0.05).After PPARα knockdown, the expressions ofAMPK, p-AMPK, PPARα and CPT1c in cancer cells cultured under normal conditions were significantly decreased (P<0.05 or P<0.01), and the inhibitory rate on cell proliferation and apoptosis rate were significantly increased (P<0.05). While under low glucose and hypoxia condition, the expression of CPT1c in cells after transfection was significantly decreased (P<0.05), and the inhibition rate on cell proliferation and the apoptosis rate were significantly increased (P<0.05); However, the change range was still lower than that of normal condition group after transfection (P<0.05).After PPARα overexpression, the ratio of fluorescence in the empty vector group was not significantly different from that of the blank group (P>0.05), and the ratio of fluorescence was significantly increased in PPARα over-expression group (P<0.05). Conclusions: AMPK can increase the expression of PPARα to promote the expression of CPT1c in thyroid cancer B-CPAP cells under low glucose and hypoxia conditions, thereby inhibiting cell apoptosis and maintaining cell proliferation ability.