Laminar organization is a hallmark of the mammalian neocortex, where the orderly arrangement of diverse neurons stereotypically forms into six distinct layers. The laminar structure provides a basis for the formation of precise neural circuits responsible for high-level cognitive functions. A deeper understanding of the mechanisms underlying neocortical layer formation and cell assembly in the brain will provide a more comprehensive insight into mammalian and even human physiology and behavior. It will also enable the development of novel diagnostic and therapeutic strategies for neurological disorders. To achieve this, it is imperative to elucidate the molecular regulatory networks that determine the fate of neurons in the neocortex. MicroRNAs (miRNAs) are small non-coding RNAs of 18-25 nucleotides in length that play important roles in the gene expression network. A large number of studies have reported that miRNAs are involved in various developmental processes within the nervous system. This review summarizes the progress of research on miRNAs that have been identified in recent years with regard to neocortical layer formation. We start with a comparative analysis of different Cre-line mediated conditional knockout mice for Dicer, a gene indispensable for the synthesis of almost all miRNAs. The results indicate that miRNAs are essential for the formation of neocortical layers, including the determination of the fate of projection neurons and the migration of these cells. Next, we summarize the regulatory roles of miRNAs in the coordinated execution of a series of developmental events that contribute to neocortical layer formation. First, the temporal patterning of neocortical neural progenitors is regulated by miRNAs. Two types of temporally opposite expression gradients and functionally antagonistic miRNAs modulate the competence of neural progenitors by changing their relative expression levels during neurogenesis, thereby shifting the progressive generation of neocortical neurons. Second, it is described that miRNAs influence lamination by regulating the fate of intermediate progenitor cells (IPCs). In particular, several miRNAs that are specifically expressed in multiple gyrencephalic species have been identified in recent years and are involved in regulating the generation of IPCs as well as the generation of upper layer neurons. Third, the regulatory roles of miRNAs in the migration of cortical projection neurons, including the multipolar to bipolar transition and other processes, were presented. Fourth, we described miRNAs that are expressed in postmitotic neurons but play roles in the further specification of different cortical projection neuron subtype identities, in particular the role of several miRNAs in the Mirg cluster in establishing different subtype identities of projection neurons in layer V, promoting corticospinal motor neuron (CSMN) identity but inhibiting callosal projection neuron (CPN) identity. Finally, we discussed current challenges in the study of miRNAs in neocortical layer formation and looked forward to future directions that deserve further exploration, such as the functions of a large number of newly discovered miRNAs, or whether miRNAs regulate the layer-dependent pattern of other neuronal cells with layer distribution features; the contribution of miRNAs in the rapid evolution of the neocortex, especially in the formation of characteristic structures in the primate neocortex; and the use of miRNAs as an entry point to explore finer regulatory networks.

This study followed up the immune memory after 3-dose revaccination among infants with non-and low-response following primary hepatitis B (HepB) vaccination. About 120 children without self-booster doses were finally included who had anti-HBs<10 mIU/ml (anti-HBs negative) at the time of follow-up, of whom 86 children completed blood sampling and anti-HBs testing. Before the challenge dose, all 86 children were negative for anti-HBs, and the GMC of anti-HBs was<10 mIU/ml. The seropositive conversion rate of anti-HBs was 100% and the GMC of anti-HBs was 886.11 (95%CI: 678.15-1 157.84) mIU/ml after the challenge dose. Compared with those with GMC<7 mIU/ml before the challenge dose, infants with GMC>7 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.82 (0.18-1.46) (P=0.012). Compared with those with GMC<1 000 mIU/ml at primary vaccination, infants with GMC≥1 000 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.78 (0.18-1.38)(P=0.012). The results showed a stronger immune memory was found at 9 years after revaccination among infants with non-and low-response to HepB.
Child ; Humans ; Infant ; Hepatitis B Vaccines ; Immunization, Secondary ; Hepatitis B Surface Antigens ; Immunologic Memory ; Follow-Up Studies ; Vaccination ; Hepatitis B/prevention & control* ; Hepatitis B Antibodies

Objective:Assess the 10-year Immune persistence and the predictors after primary vaccination hepatitis B vaccine (HepB) among normal and high-responder infants.Methods:A total of 1 838 Infants of 7-12 months old located in Jinan, Weifang, Yantai and Weihai of Shandong Province who were induced normal or high antibody response (anti-HBs titer ≥ 100 mIU/ml) after primary vaccination (three dose with 0-1-6 procedure) with 5 μg recombinant HepB among newborns were included in the study, in 2009. 3 ml of venous blood samples were collected at baseline survey (T 0) and antibodies against hepatitis B surface antigen (anti-HBs), antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected using chemiluminescence microparticle immunoassay (CMIA) method. A self-designed questionnaire was used to collect information including the infant′s age, sex, birth weight, premature birth, birth number, delivery location and mother′s HBV infection status. In 2014 (followed up for 5 years) and in 2019 (followed up for 10 years) (T 1), 2 ml of venous blood samples were collected. Anti HBS and anti HBC were detected by CMIA method. Those with anti HBS<10 mIU/ml were detected by CMIA method. Multivariate unconditional logistic and linear regression models were used to analyze the influencing factors of anti-HBs positive rate and geometric mean concentration (GMC) at T 1. Results:After 10 years follow-up, 73.94% of the subjects (1 359/1 835) finished the follow-up. 51.15% of the subjects, a total of 625 were boys. The positive rate of anti-HBs was 100% at T 0 and decreased to 53.44% (95% CI: 50.59%-56.26%) at T 1. The average annual decline rate of anti-HBs positive rate from T 0 to T 1 was 6.07%. The GMC of anti-HBs decreased from 607.89 (95% CI: 579.01-642.62) mIU/ml to 16.44 (95% CI: 15.06-18.00) mIU/ml. The average annual decline rate of anti-HBs GMC in 10-year follow-up was 30.30%. Multivariate logistic analysis showed that the positive rate of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time ( OR=0.25, 95% CI:0.07-0.71). Compared with those with GMC<1 000 mIU/ml at T 0, those with GMC ≥ 1 000 mIU/ml had a higher positive rate of anti-HBs at T 1 ( OR=2.29, 95% CI:1.76-2.97). Multivariate regression analysis showed that the GMC of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time (β=-0.50, 95% CI:-1.24-0.24). Compared with those with GMC<1 000 mIU/ml at T 0, those with GMC ≥ 1 000 mIU/ml had a higher GMC of anti-HBs at T 1 (β=0.81, 95% CI: 0.62-1.05). Conclusion:Anti-HBs GMC decreased in 10 years after primary vaccination of 5 μg recombinant hepatitis B vaccine among normal and high-responders. The anti-HBs persistence was mainly associated with whether the first dose was vaccinated in time and the level of anti-HBs at the end of primary vaccination.

Objective:Assess the 10-year Immune persistence and the predictors after primary vaccination hepatitis B vaccine (HepB) among normal and high-responder infants.Methods:A total of 1 838 Infants of 7-12 months old located in Jinan, Weifang, Yantai and Weihai of Shandong Province who were induced normal or high antibody response (anti-HBs titer ≥ 100 mIU/ml) after primary vaccination (three dose with 0-1-6 procedure) with 5 μg recombinant HepB among newborns were included in the study, in 2009. 3 ml of venous blood samples were collected at baseline survey (T 0) and antibodies against hepatitis B surface antigen (anti-HBs), antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected using chemiluminescence microparticle immunoassay (CMIA) method. A self-designed questionnaire was used to collect information including the infant′s age, sex, birth weight, premature birth, birth number, delivery location and mother′s HBV infection status. In 2014 (followed up for 5 years) and in 2019 (followed up for 10 years) (T 1), 2 ml of venous blood samples were collected. Anti HBS and anti HBC were detected by CMIA method. Those with anti HBS<10 mIU/ml were detected by CMIA method. Multivariate unconditional logistic and linear regression models were used to analyze the influencing factors of anti-HBs positive rate and geometric mean concentration (GMC) at T 1. Results:After 10 years follow-up, 73.94% of the subjects (1 359/1 835) finished the follow-up. 51.15% of the subjects, a total of 625 were boys. The positive rate of anti-HBs was 100% at T 0 and decreased to 53.44% (95% CI: 50.59%-56.26%) at T 1. The average annual decline rate of anti-HBs positive rate from T 0 to T 1 was 6.07%. The GMC of anti-HBs decreased from 607.89 (95% CI: 579.01-642.62) mIU/ml to 16.44 (95% CI: 15.06-18.00) mIU/ml. The average annual decline rate of anti-HBs GMC in 10-year follow-up was 30.30%. Multivariate logistic analysis showed that the positive rate of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time ( OR=0.25, 95% CI:0.07-0.71). Compared with those with GMC<1 000 mIU/ml at T 0, those with GMC ≥ 1 000 mIU/ml had a higher positive rate of anti-HBs at T 1 ( OR=2.29, 95% CI:1.76-2.97). Multivariate regression analysis showed that the GMC of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time (β=-0.50, 95% CI:-1.24-0.24). Compared with those with GMC<1 000 mIU/ml at T 0, those with GMC ≥ 1 000 mIU/ml had a higher GMC of anti-HBs at T 1 (β=0.81, 95% CI: 0.62-1.05). Conclusion:Anti-HBs GMC decreased in 10 years after primary vaccination of 5 μg recombinant hepatitis B vaccine among normal and high-responders. The anti-HBs persistence was mainly associated with whether the first dose was vaccinated in time and the level of anti-HBs at the end of primary vaccination.

OBJECTIVE：To study the pharmacokinetics and tissue distribution characteristics of Hydroxycamptothecin （HCPT） nanoparticles in rats ，and to investigate their targeting. METHODS ：Male SD rats were randomly divided into 2 groups，with 6 rats in each group. They were given HCPT nanoparticles and HCPT injection （4 mg/kg based on HCPT ）via tail vein respectively. 500 μL fundus venous plexus blood were sampled at 5，30，60，120，240，360，480，600 and 720 min after administration. The plasma concentration of HCPT in rats were measured by HPLC at different time points. The pharmacokinetic parameters were calculated by DAS 3.0 software. Male SD rats were randomly divided into two groups ，with 24 rats in each group. They were given HCPT nanoparticles and HCPT injection （0.6 mg/kg based on HCPT ）via tail vein ，respectively. Blood was immediately taken from the abdominal aorta ，and heart ，liver，spleen，lung，kidney and brain were removed at 30，60，120，240 min after administration. The plasma and tissue concentration of HCPT in rats were measured by HPLC. The distribution of HCPT ineach tissue and targeting were investigated. RESULTS ：HCPT nanoparticles and its injection conformed to a two-compartment model in rats. Compared with HCPT injection ，AUC0-720 min andAUC0- ∞ increased by 1.89 and 1.87 times respectively ， MRT0-720 min and MRT 0- ∞ increased by 2.74 and 3.00 times respectively， t1/2 β increased by 2.75 times，with statistical significance（P＜0.05）. At 30 min after administration ，HCPT nanoparticles and HCPT injection had the highest concentration in lung；with the passage of time ，the drug gradually accumulated in the liver and reached the highest concentration at 60 min. The relative liver uptake rate of HCPT nanoparticles was the highest （6.28）. Taking liver ad target organ ，and the targeting efficiencies of it in heart ，spleen，lung，kindey，brain and plasma were higher than those of HCPT injection. The selectivity index of HCPT nanoparticles in heart ，lung（except for 30 min after administration ），kidney，brain and plasma were significantly higher than those of HCPT injection at 30-120 min after administration. CONCLUSIONS ：HCPT nanoparticles extend the half-life of the drug ， increase its plasma concentration ，and prolong its action time in vivo ，with significant liver targeting.

OBJECTIVE: To analyze the preoperative influencing factors of varus after Oxford unicompartmental knee arthroplasty. METHODS: A total of 660 patients (767 knees) undergoing Oxford unicompartmental knee arthroplasty in adult joint reconstruction surgery department of Beijing Jishuitan Hospital from January 2018 to December 2019 were retrospectively analyzed. Inclusive criteria: diagnosis was osteoarthritis, single compartment lesions in the medial side of the knee; preoperative flexion deformity was less than 10°, active range of motion was greater than 90°; preoperative X-ray full-length images of both lower limbs showed less than 15° varus (Noyes method); anterior cruciate ligament was well functioned, The cartilage of lateral compartment of knee joint was intact. EXCLUSION CRITERIA: combined with other inflammatory arthropathy; combined with extraarticular deformity; previous knee surgery history. The average age of the patients was (64.4±8.1) years, including 153 males and 497 females. The degree of post-operative varus was measured with Noyes method. The total patients were divided into varus group (Noyes≥3 °) and normal group (Noyes < 3 °). Gender, age, body mass index (BMI), range of motion (ROM), preoperative flexion deformity (FD), American Knee Society pain score (AKS) and American Knee Society function score (AKS function) were recorded. The standard anteroposterior and lateral X-ray films of knee joint and full-length lower extremity kinematic line films were taken by Sonialvision Safine Ⅱ (Shimadzu, Japan) multi-function digital tomography system. The image was measured by picture archiving and communication system (PACS). The following angles were measured preoperative Noyes angle, lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA) and joint line converge angle (JLCA) were measured and analyzed. RESULTS: Gender(P=0.346), operative side (P=0.619), age (P=0.746), BMI (P=0.142), preoperative ROM (P=0.102), preoperative knee pain score (P=0.131) and functional score (P=0.098) were not risk factors for postoperative varus. The influencing factors of postoperative varus were preoperative MPTA < 84 ° (P= 0.018, OR= 3.712, 95%CI: 1.250-11.027), preoperative Noyes > 5°(P=0.000, OR= 3.105, 95%CI: 1.835-5.254), preoperative FD > 5° (P= 0.001, OR=1.976, 95%CI: 1.326-3.234). Pre-operative LDFA (P=0.146) and preoperative JLCA (P= 0.709) had no significant effect on postoperative kinematic line. CONCLUSION Patients with severe preoperative varus, especially those with varus deformity mainly from the tibial side, and those with preoperative flexion deformity are more prone to get varus lower extremity kinematic line after Oxford unicompartmental knee arthroplasty.
Adult ; Aged ; Arthroplasty, Replacement, Knee ; Female ; Humans ; Knee Joint/surgery* ; Knee Prosthesis ; Male ; Middle Aged ; Multivariate Analysis ; Osteoarthritis, Knee/surgery* ; Range of Motion, Articular ; Retrospective Studies

Arthroplasty, Replacement, Hip ; Female ; Hip Joint/surgery* ; Hip Prosthesis ; Humans ; Male ; Sex Characteristics ; Spondylitis, Ankylosing/surgery* ; Treatment Outcome

Objective:To explore the clinical characteristics and prognostic factors of patients with acute glyphosate poisoning, and to provide reference for the comprehensive treatment and prognosis judgment of acute glyphosate poisoning.Methods:The complete hospitalized medical records data of 40 patients with acute glyphosate poisoning who were treated in the emergency department of Affiliated Hospital of Yangzhou University from 2014 to 2019 were collected in August 2020. According to the outcome during the follow-up period of 90 d after discharge from hospital, patients were divided into survival group ( n=33) and treatment failure group ( n=7) . The clinical characteristics of the two groups were analyzed. The influencing factors of prognosis were analyzed by binary logistic regression, and the receiver operating characteristic (ROC) curve was used to evaluate the value of white blood cell count level at admission to the prognosis of patients with acute glyphosate poisoning. Results:The average age of the 40 glyphosate poisoning patients was (57.70±19.72) years old, the oral dose was 100 (50, 200) ml, the hospital stay was 4.0 (1.0, 5.0) d, and the fatality rate was 17.5% (7/40) . The main clinical manifestations were the symptoms of the digestive tract, respiratory tract, cardiovascular system and nervous system. Logistic regression showed that white blood cell level at admission was an influencing factor for the prognosis of patients with acute glyphosate poisoning ( OR=1.148, 95% CI: 1.124-1.791, P=0.003) . The ROC curve showed that the best diagnostic cut-off value of white blood cell level at admission to the prognosis of acute glyphosate poisoning was 14.65×10 9/L, the area under the curve (AUC) was 0.9351. The sensitivity was 100.00%, and the specificity was 84.85%. Conclusion:High level of white blood cell at admission is a risk factor for the prognosis of acute glyphosate poisoning, and white blood cell level at admission has a certain predictive value for the prognosis of acute glyphosate poisoning.

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.

Objective:To explore the clinical characteristics and prognostic factors of patients with acute glyphosate poisoning, and to provide reference for the comprehensive treatment and prognosis judgment of acute glyphosate poisoning.Methods:The complete hospitalized medical records data of 40 patients with acute glyphosate poisoning who were treated in the emergency department of Affiliated Hospital of Yangzhou University from 2014 to 2019 were collected in August 2020. According to the outcome during the follow-up period of 90 d after discharge from hospital, patients were divided into survival group ( n=33) and treatment failure group ( n=7) . The clinical characteristics of the two groups were analyzed. The influencing factors of prognosis were analyzed by binary logistic regression, and the receiver operating characteristic (ROC) curve was used to evaluate the value of white blood cell count level at admission to the prognosis of patients with acute glyphosate poisoning. Results:The average age of the 40 glyphosate poisoning patients was (57.70±19.72) years old, the oral dose was 100 (50, 200) ml, the hospital stay was 4.0 (1.0, 5.0) d, and the fatality rate was 17.5% (7/40) . The main clinical manifestations were the symptoms of the digestive tract, respiratory tract, cardiovascular system and nervous system. Logistic regression showed that white blood cell level at admission was an influencing factor for the prognosis of patients with acute glyphosate poisoning ( OR=1.148, 95% CI: 1.124-1.791, P=0.003) . The ROC curve showed that the best diagnostic cut-off value of white blood cell level at admission to the prognosis of acute glyphosate poisoning was 14.65×10 9/L, the area under the curve (AUC) was 0.9351. The sensitivity was 100.00%, and the specificity was 84.85%. Conclusion:High level of white blood cell at admission is a risk factor for the prognosis of acute glyphosate poisoning, and white blood cell level at admission has a certain predictive value for the prognosis of acute glyphosate poisoning.