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Background Plasma glial fibrillary acidic protein (GFAP) has emerged as a promising biomarker in neurological disorders, but further evidence is required in relation to its usefulness for diagnosis and prediction of Alzheimer disease (AD). Methods Plasma GFAP was measured in participants with AD, non-AD neurodegenerative disorders, and controls. Its diagnostic and predictive value were analyzed alone or combined with other indicators. Results A total of 818 participants were recruited (210 followed). Plasma GFAP was significantly higher in AD than in non-AD dementia and non-demented individuals. It increased in a stepwise pattern from preclinical AD, through prodromal AD to AD dementia. It effectively distinguished AD from controls [area under the curve (AUC) > 0.97] and non-AD dementia (AUC > 0.80) and distinguished preclinical (AUC > 0.89) and prodromal AD (AUC > 0.85) from Aβ-normal controls. Adjusted or combined with other indicators, higher levels of plasma GFAP displayed predictive value for risk of AD progression (adjusted hazard radio= 4.49, 95%CI, 1.18–16.97, P = 0.027 based on the comparison of those above vs below average at baseline) and cognitive decline (standard-β=0.34, P = 0.002). Additionally, it strongly correlated with AD-related cerebrospinal fluid (CSF)/neuroimaging markers. Conclusions Plasma GFAP effectively distinguished AD dementia from multiple neurodegenerative diseases, gradually increased across the AD continuum, predicted the individual risk of AD progression, and strongly correlated with AD CSF/neuroimaging biomarkers. Plasma GFAP could serve as both a diagnostic and predictive biomarker for AD.

UNSTRUCTURED Aim of the study: Breast milk is the safest and most nutritious food for infants, and breastfeeding has many psychological and physical benefits for infants and mothers, but the problems encountered in the breastfeeding process, such as lack of milk, swelling, and other factors, are that postpartum women reduce their willingness to breastfeed themselves, if they can improve lactation through TCM auxiliary therapy, the treatment is safer than drugs and can also relieve the discomfort of postpartum breastfeeding. There are many different TCM adjuvant therapies for the treatment of milk deficiency, such as acupuncture, tuina, acupressure, moxibustion, cupping, etc., and this study wants to discuss the overall efficacy of various TCM auxiliary therapies, and sort out in detail the relevant meridians and acupuncture points for the common treatment of breast deficiency for reference. Study Design: A systematic review up to October 2022 was conducted using electronic databases such as Embase, Web of Science, CINAHL, Cochrane, CNKI, PubMed, and Airitilibrary. One author extracted data using a pre-designed database that was reviewed by another independent author; All co-authors were included in data assessment and interpretation. These factors were summarized using MATA-Analysis. Through different therapies of traditional Chinese medicine, acupressure point stimulation has achieved clinical remarkable, showing that it can effectively improve lactation and breast fullness, thereby helping patients with milk deficiency to increase their feeding rate. Results: The data results are statistically different. Statistics in TCM-assisted therapies, the most common is acupressure for breast massage, followed by moxibustion and ear burial beans. Through different therapies of traditional Chinese medicine, acupuncture point stimulation has achieved clinical remarkable, showing that it can effectively improve lactation and breast fullness, thereby helping patients with milk deficiency to increase feeding rate. Conclusion: Nowadays, it is still rare for patients with postpartum milk deficiency to see the use of TCM-assisted therapy clinically. The results of this systematic review can be empirically significant. Breast acupressure, ear acupuncture, and moxibustion are non-invasive treatments and can effectively help patients in lactation, and clinical should be considered and widely promoted.

Central immunity components especially microglia in dementia have been well studied and corresponding immunotherapy gradually caught the attention. However, few studies focused on peripheral immunity and dementia. To address the issue, we examined the longitudinal association between incident dementia and peripheral immunity markers encompassing immune cell counts, and their derived ratios including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and lymphocyte-to-monocyte ratio (LMR), utilizing data of 361,653 participants from the UK Biobank (UKB). During a median follow-up of 8.99 years, 4239 participants developed dementia. The results revealed that increased innate immunity markers were associated with higher dementia risk (per SD increment hazard ratio [HR]; 95% confidence interval [CI] 1.14; 1.09-1.19 for neutrophils, 1.16; 1.11-1.20 for NLR and 1.11; 1.07-1.16 for SII), while increased adaptive immunity markers were associated with lower dementia risk (0.93; 0.90-0.97 for lymphocytes and 0.94; 0.90-0.98 for LMR). Our study pinpoints the differential role of innate and adaptive immunity in dementia incidence, which may provide some new perspectives in etiology and therapy of dementia.

Study Objectives This study assessed the associations between sleep behaviors with white matter macro and microstructure. Methods A total of 26 354 participants in the UK Biobank (mean [standard deviation], age, 63.7 [7.5] years, 53.4% female) were included in this study. A healthy sleep score integrated sleep behaviors including chronotype, insomnia, sleep duration, daytime sleepiness, and snoring. Linear and nonlinear relationships were calculated between individual and aggregate sleep behaviors with white matter hyperintensities (WMH) and microstructural injury. Results A “U-shaped” relationship was revealed between sleep duration and WMH, and the lowest WMH was at 7.7 h per night. Four unhealthy sleep behaviors including late chronotype, sleep duration (>8 h or Conclusions Unhealthy sleep behaviors were associated with increased WMH impacts and worse white matter microstructure in specific tracts across middle and older age. These findings provide the potential to improve white matter integrity by reversing unhealthy sleep behaviors.

Objectives Although postpartum rooming-in is encouraged by the World Health Organization, independent separated nursery care is still widely adopted in Eastern countries. Our aim is to evaluate the effect of shared decision making (SDM) assisted by patient decision aids on subjective decisional conflict and regret among women who are required to make choices regarding postpartum infant care. Methods A total of 196 pregnant women who came for routine checkups 1 month before delivery were randomly assigned to the SDM group or the classic group. Before the mothers were discharged after delivery, their decision-making difficulties were evaluated. The primary outcome was the decisional conflict, which was assessed using the SURE (Sure of myself; Understand information; Risk-benefit ratio; Encouragement) scale. The secondary outcome was the decisional regret, which was measured using the Decision Regret scale. Results Compared with the classic group, SDM group had surer feelings about the choice (P＜.001), felt more confident about knowing the benefits and risks of each option (P＜.001), had a clearer understanding of the benefits and risks (P＜.001), and felt sufficiently supported with enough advice to make a suitable choice (P＜.001). No significant difference was noted in the Decision Regret scores between groups. The choice of 24-hour rooming-in, 12-hour rooming-in, and separated nursery care was not significantly different between groups. Conclusions SDM reduced the decisional conflict and uncertainty of the mothers. Available choices of postpartum mother–infant care should be provided to mothers through SDM that includes individual values, health goals, and clear knowledge and transparency.

Background: Excessive oxidative stress may contribute to neurodegeneration by leading to protein aggregation and mitochondrial dysfunction. Uric acid (UA) is an important endogenous antioxidant that protects against oxidative stress, yet its exact role in neurodegeneration remains unclear. Objective: To explore the performance of serum UA in neurodegenerative disorders. Methods: A total of 839 controls and 840 patients, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), motor neuron disease (MND), Creutzfeldt-Jakob disease (CJD), and mixed dementia (MixD) were enrolled. Fasting serum UA levels were measured in all participants and compared between patients and controls. Linear regression models were utilized to explore possible relationships of serum UA with cognition, disease duration, age, and age of onset. Results: Compared to controls (355.48 ± 85.38 μmol/L), serum UA was significantly lower in AD (291.29 ± 83.49 μmol/L, p

The relevance between circulating metabolites and vascular events remains controversial and comprehensive studies are lacking. We sought to investigate the prospective associations of plasma metabolomics with risks of incident stroke, ischemic stroke (IS), hemorrhagic stroke (HS), and myocardial infarction (MI). Within the UK Biobank cohort, 249 circulating metabolites were measured in 90 438 participants without baseline vascular diseases. Cox proportional hazards regressions were applied to estimate adjusted hazard ratios (HRs) for per 1 standard deviation increment in metabolites. The least absolute shrinkage and selection operator algorithm was used for selecting metabolite subsets. During a median of 9.0 years of follow-up, we documented 833 incident stroke and 1256 MI cases. Lipid constituents, comprising cholesterol, cholesteryl esters, free cholesterol, phospholipids, and total lipids, in very low- (VLDL), intermediate- (IDL), and low-density lipoprotein (LDL) particles were positively associated with MI risk (HR = 1.12 to 1.36; 95% CI = 1.06 to 1.44), while in high-density lipoprotein (HDL) particles showed inverse associations (HR = 0.68 to 0.81; 95% CI = 0.63 to 0.87). Similar association pattern with MI was also observed for VLDL, IDL, LDL, and HDL particles themselves. In contrast, triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI risk (HR = 1.14 to 1.28; 95% CI = 1.08 to 1.35) and, to a slightly lesser extent, with stroke and IS. Unsaturation of fatty acids and albumin were inversely associated with risks of stroke, IS, and MI. In contrast, the linear association for HS is absent. When combining multiple metabolites, the metabolite risk score captured a drastically elevated risk of all vascular events, about twice that of any single metabolite. Taken together, circulating metabolites showed remarkably widespread associations with incident MI, but substantially weakened associations with risks of stroke and its subtypes. Exhaustive metabolomics profiling may shed light on vascular risk prediction and, in turn, guide pertinent strategies of intervention and treatment.

Pumpkin seeds (PSs) are common in daily diet, which have diverse biological activities. We characterized the metabolome of PSs and revealed their anti-inflammation mechanism that have not been fully elucidated. The air-dried and powdered PSs were extracted and reconstituted in 600 μl phosphate buffer for NMR analyses, and fatty acid profile was analyzed by GC–MS. The fatty acid esters of hydroxy fatty acids (FAHFAs) were analyzed by HPLC–MS, and anti-inflammatory activity of oleic acid ester of hydroxy oleic acid (OAHOA) was explored in vitro and in vivo. Finally, analysis of variance was performed (statistically significant when P

Objectives Herpes zoster and postherpetic neuralgia (PHN) are often refractory to current standard treatments and can reduce patients' quality of life (QoL). Pulsed radiofrequency (PRF) effectively controls intractable neurological pain. The aim of the study was to conduct a systematic review and meta-analysis to evaluate the efficacy of PRF in PHN management. Materials and methods We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) published up to October 2019. The primary outcomes were pain levels and rescue analgesia at different postintervention time intervals. The secondary outcomes were QoL and sleep quality. Results We reviewed 6 RCTs involving 420 patients. The meta-analysis revealed that the PRF group exhibited significantly lower pain scores in PHN than did the control group at 2 to 3 days (weighted mean differences [WMD]=-2.82; 95% confidence interval [CI]: -5.08 to -0.55), 1 week (WMD=-2.95; 95% CI: -4.53 to -1.37), 2 weeks (WMD=-3.17; 95% CI: -4.11 to -2.23), 4 weeks (WMD=-2.59; 95% CI: -3.40 to -1.79), 8 weeks (WMD=-3.02; 95% CI: -4.17 to -1.88), and 6 months (WMD=-1.94; 95% CI: -2.85 to -1.03). After intervention, QoL was significantly higher in the PRF group than in the control group. No major complications were reported. Discussion PRF safely and effectively reduced pain scores and improved QoL in patients with herpes zoster in the cervical to lumbosacral areas. PRF could be considered during refractory PHN treatment. Future studies require standardized PRF settings and outcome assessment tools, including physical and emotional function assessments.

Objective We aimed to predict population composition, mortality, sociodemographic index (SDI), and cause-specific disability-adjusted life year (DALY) rate in China from 2018 through 2021. Study design Using the time series method autoregressive integrated moving average (ARIMA) models on all available data, mainly Statistics Year Report by the Global Burden of Disease Study 2017, we predicted populations, deaths, DALYs attributable to disease conditions, and injuries (causes) for China from 2018 through 2021 at levels 0, 1, 2, and 3. Methods The time series method ARIMA models was used on history data. Results The predicted total population and SDI in China are increasing from 2018 through 2021. The under-5 mortality is decreasing; from 10.24% to 0.65% in the period 1990–2021. The all-cause DALY rate decreases. The top causes of DALY rate are non-communicable diseases (level 1), cardiovascular diseases (level 2), and stroke (level 3). For the leading 22 level 2 causes in 2018, the trend of ranking in 2021 is as follows: unchanged, 15; increasing, 4; and decreasing, 3. For the leading 169 level 3 causes in 2018, the trend of ranking in 2021 is: as follows: unchanged, 49; increasing, 63; and decreasing 57. Conclusions Cause-specific and time-dependent health policy should be steered to reduce the major burden focuses and to improve population health.

Although sleep, physical activity and sedentary behavior have been found to be associated with dementia risk, findings are inconsistent and their joint relationship remains unclear. This study aimed to investigate independent and joint associations of these three modifiable behaviors with dementia risks. A total of 431,924 participants (median follow-up 9.0 years) without dementia from UK Biobank were included. Multiple Cox regressions were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Models fitted with restricted cubic spline were conducted to test for linear and nonlinear shapes of each association. Sleep duration, leisure-time physical activity (LTPA), and screen-based sedentary behavior individually associated with dementia risks in different non-linear patterns. Sleep duration associated with dementia in a U-shape with a nadir at 7 h/day. LTPA revealed a curvilinear relationship with dementia in diminishing tendency, while sedentary behavior revealed a J-shaped relationship. The dementia risk was 17% lower in the high LTPA group (HR[95%CI]: 0.83[0.76-0.91]) and 22% higher in the high sedentary behavior group (1.22[1.10-1.35]) compared to the corresponding low-level group, respectively. A combination of seven-hour/day sleep, moderate-to-high LTPA, and low-to-moderate sedentary behavior showed the lowest dementia risk (0.59[0.50-0.69]) compared to the referent group (longer or shorter sleep/low LTPA/high sedentary behavior). Notably, each behavior was non-linearly associated with brain structures in a pattern similar to its association with dementia, suggesting they may affect dementia risk by affecting brain structures. Our findings highlight the potential to change these three daily behaviors individually and simultaneously to reduce the risk of dementia.

Background Genome-wide association studies (GWAS) have revealed numerous loci associated with stroke. However, the underlying mechanisms at these loci in the pathogenesis of stroke and effective stroke drug targets are elusive. Therefore, we aimed to identify causal genes in the pathogenesis of stroke and its subtypes. Methods Utilizing multidimensional high-throughput data generated, we integrated proteome-wide association study (PWAS), transcriptome-wide association study (TWAS), Mendelian randomization (MR), and Bayesian colocalization analysis to prioritize genes that contribute to stroke and its subtypes risk via affecting their expression and protein abundance in brain and blood. Results Our integrative analysis revealed that ICA1L was associated with small-vessel stroke (SVS), according to robust evidence at both protein and transcriptional levels based on brain-derived data. We also identified NBEAL1 that was causally related to SVS via its cis-regulated brain expression level. In blood, we identified 5 genes (MMP12, SCARF1, ABO, F11, and CKAP2) that had causal relationships with stroke and stroke subtypes. Conclusions Together, via using an integrative analysis to deal with multidimensional data, we prioritized causal genes in the pathogenesis of SVS, which offered hints for future biological and therapeutic studies.

Mutations in Presenilin-1 (PSEN1) have been found to be associated with very early onset Alzheimer’s disease (VEOAD). Here, we reported two patients with VEOAD caused by de novo PSEN1 mutations. A 33-year-old man with a de novo p.F177S mutation in PSEN1 presented with progressive decline in memory and daily function. A 37-year-old woman with a de novo PSEN1 p.L381V mutation presented with onset memory impairment, developed cerebellar syndrome, rigidity, and spastic paraparesis. The Amyloid/Tau/Neurodegeneration (ATN) biomarker profiles of both patients were A + T + (N)+. Our finding increases the genetic knowledge of VEOAD and extends the ethnic distribution of PSEN1 mutations.

BACKGROUND The incidence of metabolic syndrome (MetS) is increasing, and n-3 polyunsaturated fatty acids (PUFAs) in salmon (Oncorhynchus) phospholipids can effectively reduce the risk of MetS. RESULTS Under the intervention of 4% salmon phospholipid, the levels of fasting blood glucose (FBG), insulin, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly reduced in the plasma of MetS mice, whereas adiponectin was significantly increased. By screening, we found that the 18 differential metabolites, consisting of seven triglycerides (TGs), six diglycerides (DGs), one phosphatidylethanolamine (PE), three sphingomyelins (SMs) and one eicosanoid, could be the key differential metabolites, and two metabolic pathways were significantly affected: glycerolipid metabolism and glycerophospholipid metabolism. CONCLUSION 4% salmon phospholipids could affect MetS by inhibiting insulin resistance, reducing inflammatory factors and promoting the synthesis of PE, yet the mechanism required further study. Our results could help in the treatment of MetS. © 2021 Society of Chemical Industry.

Patients undergoing gynecological surgery commonly receive indwelling transurethral Foley catheters, however duration of catheterization is associated with risk of urinary tract infections and other adverse effects. Early removal of catheters is encouraged, however optimal timing postsurgery remains unclear. This quasi-experimental study compared outcomes for women after removal of a Foley catheter at two different times following benign gynecological surgery. Participants received either early catheter removal, within 6 hours of surgery ( n = 38) or standard catheter removal, within 12 to 24 hours of surgery ( n = 45). There were no significant differences in outcomes for discomfort scores or re-catheterization rates between groups. However, the early removal group had a significantly shorter time to first ambulation and shorter hospital stays. Early removal of Foley catheters in patients who underwent gynecological surgery did not increase adverse events. Early removal of catheters after gynecological surgery may decrease re-catheterization rates and increase patient satisfaction.

Objective: Stress urinary incontinence (SUI) is a common disease in aged women, and some of them need surgical correction. Recently, the mid-urethral sling is an accepted surgical approach for SUI. However, complication may occur in this surgery, and some of them are needle-related. Therefore, the needleless system may diminish this-type complication. Materials and methods: We conducted a retrospective study to evaluate the feasibility of women with SUI undergoing needleless sling surgery in 2017. Assessments were performed by two independent special urogynecologists before, during and post operation periods. We used a category-time-site-pain code following the International Continence Society and International Urogynecological Association (ICS/IUGA) Complication Classification Code (CCC) guidelines. Results: Thirty-eight women were analyzed. The characteristics of the patients were 66.3 ± 12.8 years old (mean ± standard deviation) of age, 2.8 ± 1.2 of parity, and 25.6 ± 4.2 kg/m2 of body mass index. All had history of vaginal delivery for term. The objective cure rate at 2- and 4-week follow-up was 97.4% (n = 37) and 94.7% (n = 36), respectively. The subjective cure rate at 2- and 4-week follow-up was both 89.5% (n = 34). Both objective and subjective cure rates remained constant and similar to the end of 4 weeks. There were 6 patients (15.8%) who had complications according to ICS/IUGA CCC guidelines. Conclusion: This needleless mid-urethral sling procedure seemed to be feasible in the management of women with SUI in this small series and short-term follow-up study, suggesting that a further prospective, randomized, comparative study with other tension-free procedures and mini-sling systems can be conducted. Keywords: Mid-urethral sling, Needleless, Stress urinary incontinence

Health care workers are at a higher risk of psychological distress than ordinary people. Stress affects physical and mental health, and can even produce an intention to leave. The current training for new graduate nurses (NGNs) during this transitional period mostly focuses on the cultivation of professional ability, with less attention to mental health or emotional feelings, and thus there are insufficient structured support strategies. As such, this study explores the effects of intervention through an appropriate education program on the learning, mental health and work intentions of new recruits during the transition period. A pre-test and post-test for a single group was designed for new nursing staff in a large teaching hospital in northern Taiwan. The test period was from May 2017 to December 2018, and a total of 293 cases were accepted. A three-month adaptive education program was provided and evaluated in terms of: care for learning, care for health, improving professional ability, and individualized guidance on satisfaction, mental health disturbance and work intention. The new graduate nurses who received gentle care and counseling showed a downward trend in their BSRS-5 scores and statistical differences over time (p &lt, 0.001). The higher the BSRS-5 score, the easier it is for new graduate nurses in acute and intensive care units. There is a tendency for turnover leave (p = 0.03). After the intervention of the overall plan, the turnover rate of new graduate nurses within three months was 12.6%, and the one-year retention rate was 87.9%. The adaptive education program uses multiple support strategies to improve learning and professional abilities, to reduce psychological emotions, and thereby to increase retention. Today will face new medical challenges, the education programs will become more important across clinical care settings, and it will be important to rigorously validate their performance in helping NGNs.

As the COVID-19 pandemic continues to rage worldwide, Taiwan has achieved outstanding performance in controlling the spread of the outbreak domestically, earning global appreciation. Nurses on the frontlines deserve much of the credit for the ongoing success in fighting against this outbreak in Taiwan. Taiwan's success to date is grounded in proactive preparedness and deployment by the government and effective teamwork among government agencies, medical institutions, enterprises, and the public. Comprehensive containment strategies and preparedness have allowed nurses to effectively perform their duties and combat the pandemic. Nurses safeguard the public's health a myriad of ways, including implementing quarantine measures at air and seaports, conducting fever screenings, delivering inpatient isolation treatments, performing case contact tracing, providing community care services, and operating special chartered-flight services. The Taiwan Nurses Association (TWNA) provides vital lead in this pandemic response, advocating for the safety, health and wellbeing of nurses; highlighting the contributions and value of nurses; and enhancing the professional image and status of nurses. Furthermore, through its global platform, TWNA shares with peer organizations worldwide the content and efficacy of actions taken by the national government, the contributions of healthcare workers, and the support and encouragement received from the public in COVID-19 containment to demonstrate values of Taiwan and nursing.台灣護理人員在COVID-19防疫的關鍵角色.新冠肺炎（COVID-19）肆虐全球，台灣防疫表現全球讚賞，站在防疫第一線的護理人員居功厥偉。透過政府超前部署積極作為與發揮團體力量，使政府、醫療機構、企業，以及民眾上下一心共同應戰，因防疫策略與整備完善，使護理人員能安心堅守崗位，齊心對抗疫情。無論是機場港口檢疫、發燒篩檢、住院隔離治療、社區居家追蹤，甚至防疫接機出勤，護理師秉持專業承諾，無役不與，守護民眾健康。台灣護理學會在此次防疫亦發揮專業領導角色，為護理師的安全、健康與福祉倡議發聲，彰顯護理師的防疫貢獻與價值，提升護理專業形象、地位與影響力；並透過全球平台，將我國政府在COVID-19防疫的積極作為與成果、醫護人員的貢獻，以及民眾的支持與鼓勵分享國際，向全世界彰顯台灣政府的防疫貢獻與護理專業的價值。.

To commemorate the 200th birthday of Florence Nightingale, the World Health Organization announced 2020 as the "International Year of the Nurse and the Midwife." Nursing is in the frontline of transformational care. The actions of nurses help bring positive changes to the world. Taiwan cannot stand outside of the global community. The Taiwan Nurses Association is also involved actively in international affairs. The expertise and enthusiasm of Taiwan's nurses may be highlighted by attending and responding to various meetings, conferences, and global nursing events organized by the International Council of Nurses (ICN) such as the Council of National Nursing Association Representatives (CNR), ICN Congress, and Nursing Now campaign. This article shares important information and insights on the 2019 ICN CNR meeting and the ICN Congress to expand the international perspective of nurses and to inspire and explore the future development of the nursing profession in Taiwan.邁向2020國際護理師與助產師年—台灣護理躍動國際.為紀念護理鼻祖南丁格爾女士即將到來的200歲生日，世界衛生組織（World Health Organization）宣布2020年為「國際護理師與助產師年」。護理正站在轉型照護的第一線，護理師的行動將為世界帶來改變，台灣不能自外於國際社會，台灣護理學會也積極參與各項國際事務。透過參與國際護理協會（International Council of Nurses, ICN）所舉辦的會議、研討會及全球性護理活動，包括ICN國家代表會議、ICN國際護理大會及響應Nursing Now活動，讓國際看見台灣護理人的專業與熱誠。本文分享2019年ICN國家代表會議與ICN國際護理大會重要訊息與見聞，以擴展護理人員國際視野，期能對台灣護理專業未來發展方向有所啟發與助益。.

Background CSF1R-related leukoencephalopathy, also known as hereditary diffuse leukoencephalopathy with spheroids (HDLS), is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor (CSF1R) gene mutation. Few of CSF1R mutations have been functionally testified and the pathogenesis remains unknown. Methods In order to investigate clinical and pathological characteristics of patients with CSF1R-related leukoencephalopathy and explore the potential impact of CSF1R mutations, we analyzed clinical manifestations of 15 patients from 10 unrelated families and performed brain biopsy in 2 cases. Next generation sequencing was conducted for 10 probands to confirm the diagnosis. Sanger sequencing, segregation analysis and phenotypic reevaluation were utilized to substantiate findings. Functional examination of identified mutations was further explored. Results Clinical and neuroimaging characteristics were summarized. The average age at onset was 35.9 ± 6.4 years (range 24–46 years old). Younger age of onset was observed in female than male (34.2 vs. 39.2 years). The most common initial symptoms were speech dysfunction, cognitive decline and parkinsonian symptoms. One patient also had marked peripheral neuropathy. Brain biopsy of two cases showed typical pathological changes, including myelin loss, axonal spheroids, phosphorylated neurofilament and activated macrophages. Electron microscopy disclosed increased mitochondrial vacuolation and disorganized neurofilaments in ballooned axons. A total of 7 pathogenic variants (4 novel, 3 documented) were identified with autophosphorylation deficiency, among which c.2342C > T remained partial function of autophosphorylation. Western blotting disclosed the significantly lower level of c.2026C > T (p.R676*) than wild type. The level of microtubule associated protein 1 light chain 3-II (LC3-II), a classical marker of autophagy, was significantly lower in mutants expressed cells than wild type group by western blotting and immunofluorescence staining. Conclusions Our findings support the loss-of-function and haploinsufficiency hypothesis in pathogenesis. Autophagy abnormality may play a role in the disease. Repairing or promoting the phosphorylation level of mutant CSF1R may shed light on therapeutic targets in the future. However, whether peripheral polyneuropathy potentially belongs to CSF1R-related spectrum deserves further study with longer follow-up and more patients enrolled. Trial registration ChiCTR, ChiCTR1800015295. Registered 21 March 2018.

Acute hepatic injury caused by inflammatory liver disease is associated with high mortality. This study examined the role of caveolin‐1 (Cav‐1) in lipopolysaccharide (LPS) and D‐galactosamine (GalN)‐induced fulminant hepatic injury in wild type and Cav‐1‐null (Cav‐1−/−) mice. Hepatic Cav‐1 expression was induced post‐LPS/GalN treatment in wild‐type mice. LPS/GalN‐treated Cav‐1−/− mice showed reduced lethality and markedly attenuated liver damage, neutrophil infiltration and hepatocyte apoptosis as compared to wild‐type mice. Cav‐1 deletion significantly reduced LPS/GalN‐induced caspase‐3, caspase‐8 and caspase‐9 activation and pro‐inflammatory cytokine and chemokine expression. Additionally, Cav‐1−/− mice showed suppressed expression of Toll‐like receptor 4 (TLR4) and CD14 in Kupffer cells and reduced expression of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 in liver cells. Cav‐1 deletion impeded LPS/GalN‐induced inducible nitric oxide synthase expression and nitric oxide production and hindered nuclear factor‐κB (NF‐κB) activation. Taken together, Cav‐1 regulated the expression of mediators that govern LPS‐induced inflammatory signalling in mouse liver. Thus, deletion of Cav‐1 suppressed the inflammatory response mediated by the LPS‐CD14‐TLR4‐NF‐κb pathway and alleviated acute liver injury in mice.

It was demonstrated that isoflavones can cross the blood-brain barrier, making them desirable candidate agents for the prevention of neurological symptoms. 8-Hydroxydaidzein (8-OHD, 4',7,8-trihydoxyisoflavone) is an isoflavone found only in fermented soy food. Current results showed that 8-OHD inhibited LPS-stimulated production of nitric oxide (NO) and proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, by inhibiting gene expression in BV2 microglial cells. Moreover, 8-OHD markedly quenched reactive oxygen species (ROS) and activated NF-E2-related factor 2 (Nrf2) so as to upregulate expression of Phase II enzymes, including heme oxygenase (HO)-1, NAD(P)H quinone dehydrogenase 1 (NQO1), and the modifier subunit of glutamate cysteine ligase (GCLM). 8-OHD also suppressed LPS-stimulated phosphorylation of Akt and NF-κB-p65. The anti-inflammatory activity of 8-OHD was attenuated by the HO-1 inhibitor zinc protoporphyrin (Znpp) but augmented by the PI3K/Akt inhibitor LY294002. 8-OHD also diminished LPS-induced prostaglandin E