An open-pore MFI zeolite nanosheet-modified separator with Li-ion flux regulation for lithium-metal batteries.

Separator modification has become one of the most facile and promising methods to inhibit Li dendrite formation. Herein, an open-pore MFI zeolite nanosheet-modified polyacrylonitrile (open-pore MFI NSs@PAN) separator was prepared via the combination of vacuum filtration and the electrospinning technique. The straight channels in the MFI NSs, the fluid channels formed by the stacking of the MFI NSs and the interconnected network channels formed by the interweaving of the PAN nanofibers jointly constructed a micro/nano pore structure, which provides sufficient Li+ transport channels and enables uniform Li+ flux. Consequently, the open-pore MFI NSs@PAN separator-based cell delivers a stable and uniform Li deposition, demonstrating a more stable cycle-life and better rate capability. Redistributing Li+ flux through straight channel zeolite nanosheets provides a powerful method for suppressing Li dendrites, presenting enormous potential for promoting the commercial application of lithium metal batteries.

Neuropsychiatric disturbance detecting polycythemia vera myelofibrosis: a case report and literature review.

Background: Neuropsychiatric disturbances and chorea are less recognized consequences of polycythemia vera (PV), and their role in post-PV myelofibrosis (MF) has not been reported. Clinical features that predict post-PV MF lack specificity. Case presentation: We describe an elderly patient with PV who developed acute-onset reversible neuropsychiatric disturbances accompanied by generalized chorea and was finally diagnosed with post-PV MF after a bone marrow examination. We also reviewed four cases of late PV associated with neuropsychiatric symptoms since 1966 and analyzed their clinical characteristics and therapeutic effects. Conclusion: Our case indicates that Janus kinase 2 (JAK2)-related PV is a treatable cause of late-onset chorea and that chorea may herald the deterioration of hematological parameters. Our case provides a clinically specific representation of post-PV MF. Patients with a long course of PV are recommended to undergo bone marrow re-examinations when they present with neuropsychiatric symptoms to achieve an early diagnosis of post-PV MF.

Bcl-xL Promotes the Survival of Motor Neurons Derived from Neural Stem Cells.

Neural stem cell (NSC) transplantation creates new hope for the treatment of neurodegenerative disorders by direct differentiation into neurons. However, this technique is limited by poor survival and functional neuron deficiency. In this research study, we generated pro-survival murine NSCs (mNSCs) via the ectopic expression of Bcl-xL. A doxycycline (Dox)-inducible Ngn2-Isl1-Lhx3 system was also integrated into the mNSC genome. The four gene-modified mNSCs can rapidly and effectively differentiate into motor neurons after Dox treatments. Ectopic Bcl-xL could resist replating-induced stress, glutamate toxicity, neuronal apoptosis and remarkably promote the survival of motor neurons. Taken together, we established genetically modified mNSCs with improved survival, which may be useful for motor neuron degenerative diseases.

Low 25-Hydroxyvitamin D Levels Are Associated With Residual Dizziness After Successful Treatment of Benign Paroxysmal Positional Vertigo.

Objective: Vitamin D (Vit D) regulates calcium and phosphate metabolism and helps to maintain otolith organ function. Residual dizziness (RD) is one of the most common complications after the successful treatment of benign paroxysmal positional vertigo (BPPV). Various theories have been suggested to explain the cause of RD, and otolith organ disorder is the most evident cause of RD. This study aimed to investigate the association between serum levels of Vit D and the occurrence of RD after the successful treatment of BPPV. Methods: A prospective study including patients who were diagnosed with de novo posterior semicircular canal-type BPPV (PC-BPPV) was conducted at our institution from May 2017 to May 2019. All the patients underwent canalith repositioning procedures and were followed up. Univariate and multivariate analyses were performed to investigate the relationship between serum 25-hydroxy vitamin D (25(OH)D) levels and RD occurrence after successful BPPV treatment. Results: In total, 123 patients with PC-BPPV were enrolled, and 41.5% (51/123) experienced RD. The serum level of 25(OH)D was significantly lower in PC-BPPV patients with RD [median 16.2 ng/ml (IQR 12.9-22.1)] than in patients without RD [median 20.5 ng/ml (IQR 16.5-26.5)] (P = 0.001). In multivariate models comparing the prevalence of RD in the insufficient group [25(OH)D ≥ 20 to <30 ng/ml], deficient group [25(OH)D < 20 ng/ml] and normal group [25(OH)D ≥ 30 ng/ml], the 25(OH)D levels in the deficient group were associated with the occurrence of RD (odds ratio = 5.48, 95% confidence interval = 1.08-27.71; P = 0.04). Conclusion: Low 25(OH)D levels are associated with the development of RD in patients with PC-BPPV after successful treatment. Further efforts to validate and elucidate the mechanism are needed.

Eliminating predictable DNA off-target effects of cytosine base editor by using dual guiders including sgRNA and TALE.

Predictable DNA off-target effect is one of the major safety concerns for the application of cytosine base editors (CBEs). To eliminate Cas9-dependent DNA off-target effects, we designed a novel effective CBE system with dual guiders by combining CRISPR with transcription activator-like effector (TALE). In this system, Cas9 nickase (nCas9) and cytosine deaminase are guided to the same target site to conduct base editing by single-guide RNA (sgRNA) and TALE, respectively. However, if nCas9 is guided to a wrong site by sgRNA, it will not generate base editing due to the absence of deaminase. Similarly, when deaminase is guided to a wrong site by TALE, base editing will not occur due to the absence of single-stranded DNA. In this way, Cas9- and TALE-dependent DNA off-target effects could be completely eliminated. Furthermore, by fusing TALE with YE1, a cytidine deaminase with minimal Cas9-independent off-target effect, we established a novel CBE that could induce efficient C-to-T conversion without detectable Cas9- or TALE-dependent DNA off-target mutations.

High Serum Levels of Otolin-1 in Patients With Benign Paroxysmal Positional Vertigo Predict Recurrence.

Background: Otolin-1 is an inner ear-specific protein that is exclusively expressed in otoconia and vestibule and cochlea cells. Recent investigations reported that otolin-1 can cross the blood-labyrinthine barrier and that the levels in serum well-reflected otolith status. Serum otolin-1 levels in patients with benign paroxysmal positional vertigo (BPPV) are significantly elevated compared with healthy controls. We aimed to explore whether otolin-1 can also serve as a biomarker for predicting BPPV recurrence. Method: Patients at our institution with new-onset of idiopathic BPPV between May, 2017 and May, 2018 were recruited and followed up for 2 years. All demographic data of the patients were collected, and serum levels of otolin-1 and other laboratory indicators were measured and compared according to the recurrence status. Results: A total of 74 patients, who met the inclusion criteria were enrolled in this study, of which 27 (36.5%) patients had suffered one or more episodes of recurrence after undergoing canal repositioning treatments during the study. The serum levels of otolin-1 in patients with recurrent BPPV were significantly higher than those in patients without recurrent BPPV (363.9 vs. 309.8 pg/ml, p = 0.001). In multivariate analysis comparing the second to fourth quartiles (Q2-Q4) against the first quartile (Q1) of otolin-1, the level of otolin-1 in Q4 could significantly predict BPPV recurrence, and the odds ratio (OR) was elevated by approximately 812% (OR = 9.12; 95% confidence interval [CI]: 1.44-57.9; p = 0.019). Conclusion: High serum levels of otolin-1 were associated with an increased risk of BPPV recurrence, and further investigation is required to confirm this association and clarify the exact mechanism.

Generation of a homozygous ARHGAP11B knockout hiPSC line by CRISPR/Cas9 system.

The human specific gene ARHGAP11B is preferentially expressed in neural progenitors of fetal neocortex and plays a key role in the evolutionary expansion of the neocortex. Here, we generated a homozygous ARHGAP11B knockout human induced pluripotent stem cell (hiPSC) line through CRISPR/Cas9 gene editing system. ARHGAP11B deficient cell line maintained a normal karyotype (46, XX), expressed pluripotency markers, and showed the capability to spontaneously differentiate into all three germ layers in vivo. The ARHGAP11B knockout cell line can provide a new cell model for studying the evolution of human neocortex.

Association between otolin-1 and benign paroxysmal positional vertigo: A meta-analysis.

Background: There is increasing research on the potential of inner ear proteins as serum biomarkers for the diagnosis and prognosis of various inner ear diseases. Among them, benign paroxysmal positional vertigo (BPPV) is the most common vestibular disease. Notably, otolin-1, an inner ear-specific protein, is detectable in the serum of most patients with BPPV patients. Therefore, we found a need to conduct this meta-analysis to determine the relationship between otolin-1 in serum and BPPV. Methods: This meta-analysis was conducted by searching PubMed, EMBASE, Cochrane Library, Google Scholar, and China Network Knowledge Infrastructure databases for the eligible original studies in Chinese or English published between January 2010 and February 2022. Data were collected and pooled by using the mean differences (MDs) corresponding to 95% confidence intervals (CIs). Heterogeneity among these studies was assessed by using I2 statistics and the adopted fixed or random-effect mode thereafter. Egger's and Begg's tests were also used to assess the publication bias. Results: This meta-analysis included six articles with a total of 585 participants. Serum otolin-1 levels were remarkably increased in patients with BPPV as compared to that in healthy controls (MD: 165.38, 95% CI: 110.13-220.64, p < 0.00001). However, Egger's and Begg's tests have indicated no publication bias, and the results were reliable based on the sensitivity analysis. Conclusion: This meta-analysis indicated that there is a higher serum level of otolin-1 in patients with BPPV than in healthy controls. Therefore, otolin-1 may serve as a biomarker for the onset of BPPV.

Characteristics of bone metabolism in postmenopausal female patients with different types of idiopathic benign paroxysmal positional vertigo: A single-centre retrospective study.

OBJECTIVE: The association between benign paroxysmal positional vertigo (BPPV) and impaired calcium metabolism has attracted widespread interest. Several studies have suggested that decreased bone mineral density (BMD) and serum 25-hydroxyvitamin D (25(OH)D) level are related to the occurrence and/or recurrence of BPPV; however, the characteristics of bone metabolism in patients with BPPV subtypes have not been fully investigated, and conclusions have been controversial. This study aimed to evaluate BMD and serum levels of 25(OH)D and bone turnover markers to clarify the characteristics of bone metabolism in patients with different types of BPPV. METHOD: We retrospectively analysed the data of new-onset idiopathic postmenopausal female patients with BPPV at our institution from January 2016 to January 2020. The patients' demographic data including age, medication history, concomitant diseases, onset time, clinical form, laboratory indicators, such as serum levels of 25(OH)D, bone formation markers, namely, amino-terminal propeptide of type I procollagen (PINP) and osteocalcin (OC), bone resorption marker, namely, ß-isomerized carboxy-terminal telopeptide of type I collagen (ß-CTX), and BMD were collected and analysed. RESULTS: This study included 201 consecutive postmenopausal female patients with BPPV. Among them, 138 were diagnosed with posterior semicircular canal BPPV, 42 were diagnosed with lateral semicircular canal canalolithiasis, and 21 were diagnosed with lateral semicircular canal cupulolithiasis. There were no significant differences in age distribution, body mass index, clinical history, levels of albumin, globulin, uric acid, creatinine, or blood urea nitrogen, lipid profiles (except high-density lipoprotein cholesterol) and routine blood parameters among these groups (P > 0.05). There were no significant differences in the mean T-score and BMD values of different sites or in the serum levels of 25(OH)D and bone turnover markers (PINP, OC and ß-CTX) among the subgroups (P > 0.05). The proportion of reduction in BMD (T-score < -1 SD) and decreased serum vitamin D level (< 20 ng/ml) were not significantly different between the subgroups (P > 0.05). CONCLUSION: There were no significant differences in bone metabolism in postmenopausal female patients with different types of idiopathic BPPV.

Increased Otolin-1 in Serum as a Potential Biomarker for Idiopathic Benign Paroxysmal Positional Vertigo Episodes.

Objective: Otolin-1, a main specific otoconia matrix protein, passes through the labyrinth-blood barrier and is detectable in peripheral blood. Serum otolin-1 levels differ between patients with benign paroxysmal positional vertigo (BPPV) and healthy controls and are significantly age-related, increasing in healthy controls with age, suggesting that serum otolin-1 levels reflect otolith status. The aim of this study was to determine whether otolin-1 levels change during vertigo episodes in patients with BPPV and whether any change is specific and sensitive enough for BPPV episodes. Method: Patients diagnosed with de novo idiopathic BPPV during an acute episode were included in the study from May 2017 to May 2018. Blood samples were drawn before patients were treated with canalith-repositioning maneuvers. Serum otolin-1 levels were compared between 78 patients and 121 age- and sex-matched healthy individuals. Results: There were no significant differences between the groups in the age distribution, sex ratio, body mass index, clinical history, routine blood parameters, or total protein, albumin, uric acid, creatinine, blood urea nitrogen and lipid profiles (P > 0.05). Serum levels of otolin-1 were significantly higher in BPPV patients than in healthy controls (P < 0.001). Receiver operating characteristic analysis revealed that a serum otolin-1 value of 299.45 pg/ml was the optimal cut-off value to discriminate patients with BPPV from healthy controls (area under the curve 0.757, 95% CI 0.687~0.826) with a sensitivity of 67.9% and a specificity of 72.7%. Conclusion: Serum levels of otolin-1 may be a potential biomarker for BPPV episodes.

Decreased 25-Hydroxyvitamin D Levels in Patients With Vestibular Neuritis.

Objective: Vestibular neuritis (VN) is characterized by acute onset of vertigo, nausea, and vomiting, without auditory or other neurological symptoms. Although the pathogenesis of VN is not yet clear, many studies have shown that a pro-inflammatory environment can lead to the induction and progression of the disease. Considering the importance of vitamin D in modulating the activation, proliferation, and differentiation of inflammatory physiological processes, we hypothesized that decreased serum vitamin D may be associated with the development of VN. In this study, we evaluated serum levels of 25-hydroxyvitamin D [25(OH)D] in patients presenting acutely with VN and healthy controls and investigated the possible correlation of serum 25(OH)D levels with VN. Methods: A total of 59 consecutive patients diagnosed with VN within 7 days of symptom onset and 112 age- and sex-matched healthy controls referred to Hwa Mei Hospital, University of Chinese Academy of Science, between March 2017 and March 2019 were recruited. Demographic and clinical data, such as age, sex, height, weight, living habits, ongoing health problems, and medication history, for all subjects were recorded, and levels of 25(OH)D were measured and compared. Results: Serum levels of 25(OH)D were lower in patients with VN than in controls (19.01 ± 6.53 vs. 22.94 ± 6.74 ng/ml, p < 0.001). Patients with VN had a higher frequency of vitamin D deficiency (61.0 vs. 34.8%, P = 0.001) than did controls. Regression analyses demonstrated that vitamin D deficiency was associated with VN, with an odds ratio of 4.53 (95% CI = 1.342-15.279, P = 0.015). Conclusion: This prospective study is the first to evaluate serum 25(OH)D levels in patients with VN and found that decreased serum 25(OH)D may be associated with VN occurrence.

Assessment of Bone Metabolism in Male Patients With Benign Paroxysmal Positional Vertigo.

Objective: Several studies have suggested a probable association between benign paroxysmal positional vertigo (BPPV) and both reduction of bone mineral density (BMD) and serum vitamin D levels, but none of these studies have explored their findings by examining bone turnover markers (BTM) in male idiopathic BPPV patients. This study aimed to evaluate the relationship between BMD and serum 25-hydroxyvitamin D (25(OH) D), with the occurrence of BPPV along with the characteristics of bone metabolism in male idiopathic BPPV patients. Methods: This retrospective study comprised 60 male idiopathic BPPV patients and 92 age-matched healthy controls referred to Ningbo No.2 Hospital during the period of February 2016 to February 2018. All subjects' serum levels of 25(OH) D, bone formation marker amino-terminal propeptide of type I procollagen (PINP), and bone resorption marker ß-isomerized carboxy-terminal telopeptide of type I collagen (ß-CTX) were measured. BMD was determined by dual energy X-ray absorption at the lumbar spine and hip. Results: Among male patients with BPPV, the prevalence of BMD reduction was 35.0%, which was similar to that of 27.2% in healthy controls. There were significant differences in the mean serum 25(OH) D level and prevalence of vitamin D deficiency between the two groups, with p-values of 0.049 and 0.009, respectively. The bone turnover markers of PINP and ß-CTX in BPPV patients were lower than those in healthy controls. Logistic regression showed that vitamin D deficiency were associated with BPPV with an odds ratio of 3.8 (95% confidence interval = 1.25-11.73). Conclusion: Our study found that decreased serum vitamin D may be a risk factor for BPPV in male patients. The level of bone turnover among male patients with BPPV was lower than that among healthy controls.

Correlation between vestibular neuritis and cerebrovascular risk factors.

PURPOSE: To investigate the relationship between cerebrovascular risk factors, including carotid plaques, and vestibular neuritis (VN). MATERIALS AND METHODS: According to the inclusion and exclusion criteria, this retrospective study included 90 VN patients and 74 age- and sex-matched healthy controls from January 2016 to December 2017. All subjects' records of cerebrovascular risk factors, such as age, sex, height, weight, history of hypertension and diabetes mellitus, living habits, serum levels of glucose, lipids, glycosylated haemoglobin (HbA1c), creatinine (CR), albumin (ALB), haemoglobin (HGB); and results of carotid colour Doppler ultrasound, were obtained and compared. RESULTS: No significant differences in age; sex ratio; body mass index; history of hypertension or diabetes mellitus; or mean serum lipids, glucose, creatinine, haemoglobin or HbA1c were found between patients with VN and healthy controls (all P > 0.05). The mean serum ALB level was significantly lower in VN patients than in healthy controls (40.65 ±â€¯3.77 vs 42.84 ±â€¯4.32, P = 0.001).The prevalence of carotid plaques was significantly higher in VN patients than in healthy controls (36.67% vs. 16.22%, P = 0.003). Regression analyses demonstrated that a high frequency of carotid plaques was associated with VN with an odds ratio of 2.252 (95% CI 1.165-5.458, P = 0.019). CONCLUSION: A high frequency of carotid plaques may be a risk factor for VN.

Simvastatin improves intracerebral hemorrhage through NF-κB-mediated apoptosis via the MyD88/TRIF signaling pathway.

The aim was to investigate the neuroprotective effects and potential mechanism mediated by simvastatin in a mouse model of intracerebral hemorrhage. CD-1 mice were subjected to infusion of collagenase type IV into the left striatum in order to induce intracerebral hemorrhage. Western blot analysis, the TUNEL assay and the modified neurological severity score were used in the present study to analyze the efficacy of simvastatin for intracerebral hemorrhage. The results demonstrated that simvastatin treatment improved the cerebral water content and blood-brain barrier disruption in the intracerebral hemorrhage animals. Intracerebral hemorrhage-induced neuronal cell death was downregulated by simvastatin treatment compared with the vehicle-treated model group. In addition, the expression levels of aquaporin-4, matrix metallopeptidase 9 and caspase-3 were downregulated and B-cell lymphoma-2 was upregulated by simvastatin treatment compared with the vehicle-treated model. Simvastatin treatment also significantly reduced the Evans blue leakage into the injured hemispheres and improved motor function. Mechanism analysis further indicated that simvastatin treatment downregulated nuclear factor (NF)-κB expression, and upregulated the myeloid differentiation primary response 88 (MyD88) and TIR domain-containing adaptor protein inducing interferon-ß (TRIF) expression levels in neuronal cells in experimental mice. Furthermore, the results revealed that NF-κB overexpression abolished the simvastatin-downregulated MyD88 and TRIF expression levels, as well as the apoptosis of neuronal cells. In conclusion, these results indicated that simvastatin was able to attenuate brain edema and reduce cellular apoptosis by suppressing the NF-κB-mediated MyD88/TRIF signaling pathway subsequent to the induction of intracerebral hemorrhage in mice.

Low 25-hydroxyvitamin D levels in postmenopausal female patients with benign paroxysmal positional vertigo.

OBJECTIVE: Several studies have reported the association of benign paroxysmal positional vertigo (BPPV) with vitamin D deficiency. This study aimed to evaluate serum 25-hydroxy vitamin D (25 (OH) D) levels in native Chinese postmenopausal women with de novo idiopathic BPPV and to investigate the possible relationship between the occurrence of BPPV and low 25 (OH) D levels. METHODS: This retrospective study comprised of 85 postmenopausal women with de novo idiopathic BPPV and 80 age-matched healthy controls. All subjects had bone mineral density (BMD) and serum 25 (OH) D levels measurements recorded, and the results were compared. RESULTS: The prevalence of reduced BMD (T score <-1.0) was significantly higher in female patients with BPPV than in healthy controls (71.8% vs. 51.2%, p = .004). The mean serum 25 (OH) D levels were also significantly lower in female patients with BPPV than in healthy controls (19.1 ± 5.2 vs. 22.5 ± 5.8, p < .001). The regression analyses demonstrated that vitamin D deficiency was associated with BPPV with an odds ratio of 2.1 (95% confidence interval = 1.1-3.1, p = .031). CONCLUSION: Our study suggests that low 25 (OH) D may be a risk factor for BPPV in postmenopausal women.

Reduction of bone mineral density in native Chinese female idiopathic benign paroxysmal positional vertigo patients.

OBJECTIVE: This study aimed to investigate the clinical association between idiopathic benign paroxysmal positional vertigo (BPPV) and reduction of bone mineral density (BMD). METHODS: BMD was measured in 78 native Chinese female de novo idiopathic BPPV patients and 126 healthy controls using dual-energy X-ray absorptiometry. We compared the mean T-scores and abnormal BMD prevalence between the two groups. RESULTS: The mean T-scores were significantly lower in idiopathic BPPV patients than in healthy controls. The prevalence of osteopenia and osteoporosis were significantly higher in idiopathic BPPV patients than in healthy controls (65.4% vs 48.4%, p=0.013). CONCLUSION: BMD reduction may be associated with idiopathic BPPV occurrence.

Changes of peripheral blood Vδ1 T cells in patients with atherosclerotic cerebral infarction.

To observe the ratio of peripheral blood Vδ1 T cells in patients with atherosclerotic cerebral infarction (ACI) and their function changes, and preliminarily explore the mechanism of change in ratio of peripheral blood Vδ1 T cells in ACI patients. 30 ACI patients enrolled in the neurology department in our hospital from January 2016 to December 2016 were selected, and 30 healthy subjects enrolled in the hospital during the same period were selected as healthy controls. Peripheral blood mononuclear cells (PBMC) were obtained by density gradient centrifugation. The ratio of Vδ1 T cells in peripheral blood of ACI patients was detected by flow cytometry, and the correlations between the ratio of Vδ1 T cells and the neurological deficits and infarction size in ACI patients were analyzed. A high proportion of Vδ1 T cells were obtained by in vitro amplification, and high-purity Vδ1 T cells and Naïve CD4 T cells were obtained by flow cytometry and magnetic bead sorting respectively. The effect of Vδ1 T cells on the proliferation of Naïve CD4 T cells and the secretion of IFN-γ were investigated by CFSE staining method; the correlation between the ratio of Vδ1 T cells in peripheral blood and the Ox-LDL level in peripheral blood of ACI patients was analyzed. The Vδ1 T cells in peripheral blood were treated by Ox-LDL, and the effect of Ox-LDL on Vδ1 T cell apoptosis was determined by apoptosis staining method. Compared with the healthy control group, the ratio of Vδ1 T cells in peripheral blood of ACI patients was significantly decreased (P<0.0001). The ratio of Vδ1 T cells in peripheral blood of ACI patients was not significantly correlated with age, sex, hypertension, diabetes and dyslipidemia (P>0.05). However, with the gradual aggravation of neurological deficit and gradual increase of infarct volume, the ratio of Vδ1 T cells in peripheral blood of ACI patients decreased gradually. Besides, the functional studies showed that the immunosuppressive functions of Vδ1 T cells in peripheral blood of ACI patients were also significantly decreased (P<0.0001). The ratio of Vδ1 T cells in peripheral blood of ACI patients was negatively correlated with the Ox-LDL level in peripheral blood (r2=0.1691; P=0.0240); the Ox-LDL treatment of Vδ1 T cells induced apoptosis of Vδ1 T cells, and with the increased Ox-LDL concentration, the ratio of Vδ1 T cell apoptosis gradually increased. The decreased ratio of Vδ1 T cells in peripheral blood and loss of functions in ACI patients lead to the occurrence of immunoinflammatory reactions, which may be one of the possible causes of ACI. In addition, this study also showed that, Ox-LDL could induce Vδ1 T cell apoptosis and lead to decrease in ratio of Vδ1 T cells in peripheral blood, which may be one of the reasons for decreased ratio of Vδ1 T cells in peripheral blood of ACI patients. In summary, this study can further help the understanding of the pathogenesis of ACI.

[Neurodevelopmental outcomes of extremely low birth weight and very low birth weight infants and related influencing factors].

OBJECTIVE: To investigate the neurodevelopmental outcomes of extremely low birth weight (ELBW) and very low birth weight (VLBW) infants at a corrected age (CA) of 18 months and related factors influencing the outcomes. METHODS: The ELBW and VLBW infants who were admitted to the neonatal intensive care unit, survived, and discharged between January 2013 June 2014 were enrolled. These infants were followed up at CAs of 40 weeks and 1, 3, 6, 12, and 18 months to evaluate the neurodevelopmental outcomes. According to the neurodevelopmental status, the infants were divided into normal and abnormal neurodevelopment groups. The differences in clinical data were compared, and the risk factors for abnormal neurodevelopment in ELBW and VLBW infants were analyzed. RESULTS: A total of 338 ELBW and VLBW infants were enrolled, and 15 died during hospitalization. At the CA of 18 months, 145 infants (44.9%) survived and had complete follow-up data, 75 (23.2%) died, and 103 (31.9%) were lost to follow-up. Of the 145 infants who survived and had complete follow-up data, 71 (49.0%) had neurodevelopmental impairment (NDI), and 3 (2.1%) had cerebral palsy. No infants experienced visual damage with blindness in one or both eyes or hearing loss with a need for hearing aid. The logistic regression analysis showed that bronchopulmonary dysplasia (BDP) (OR=3.530, P<0.001) and sepsis (OR=2.528, P=0.035) were independent risk factors for NDI in ELBW and VLBW infants, and the incidence of NDI increased with the severity of BDP. CONCLUSIONS: Sepsis and BPD, especially severe BPD, are risk factors for NDI in ELBW and VLBW infants.

IL-15 up-regulates the MMP-9 expression levels and induces inflammatory infiltration of macrophages in polymyositis through regulating the NF-kB pathway.

This study was aimed to research the effects of IL-15 on inducing inflammatory infiltration of macrophages in polymyositis (PM) through the NF-kB pathway, and whether IL-15 was able to further regulate MMP-9 expression levels. Prepared PM cells, collected from the patients suffering from PM, were administered to SD rats. Also, a group of healthy SD rats was undergoing the same treatment as the control group. The test animals were treated with either anti-IL-15, IL-15, MMP-9 siRNA or ERK1/2 inhibitor. The blood toxicological parameters creatine kinase (CK) and CD163 were tested by using ELISA and immunohistochemistry assay. In addition, NF-kB expression in macrophages was measured by immunocytochemical assay. To measure the degree of cell infiltration the Transwell assay was performed. Lastly, western blot and zymography were carried out to compare MMP-9 and ERK expression levels between the two groups, both in vivo and in vitro. The results showed that S-CK, IL-15 and IL-15Rα levels increased rapidly after the conventional treatment was introduced to the PM infected SD rats. The PM model establishment and IL-15 treatment significantly increased the expressions of IL-15Rα, MMP-9, p-ERK and p-IKBα. However, the same effect can be suppressed by using anti-IL-15, MMP-9 siRNA or ERK1/2 inhibitor (P < 0.05). In addition, IL-15 is proved to increase cell migration and nucleus expression of NF-kB in the macrophages. IL-15 is able to significantly regulate the inflammatory infiltration of macrophages in PM patients through affecting the NF-kB pathway and MMP-9 expression levels.