Comprehensive Bibliometric Analysis of Stem Cell Research in Alzheimer's Disease from 2004 to 2022.

INTRODUCTION: Stem cell-based regenerative medicine has provided an excellent opportunity to investigate therapeutic strategies and innovative treatments for Alzheimer's disease (AD). However, there is an absence of visual overviews to assess the published literature systematically. METHODS: In this review, the bibliometric approach was used to estimate the searched data on stem cell research in AD from 2004 to 2022, and we also utilized CiteSpace and VOSviewer software to evaluate the contributions and co-occurrence relationships of different countries/regions, institutes, journals, and authors as well as to discover research hot spots and encouraging future trends in this field. RESULTS: From 2004 to 2022, a total of 3,428 publications were retrieved. The number of publications and citations on stem cell research in AD has increased dramatically in the last nearly 20 years, especially since 2016. North America and Asia were the top 2 highest output regions. The leading country in terms of publications and access to collaborative networks was the USA. Centrality analysis revealed that the UCL (0.05) was at the core of the network. The Journal of Alzheimer's Disease (n = 102, 2.98%) was the most productive academic journal. The analyses of keyword burst detection indicated that exosomes, risk factors, and drug delivery only had burst recently. Citations and co-citation achievements clarified that cluster #0 induced pluripotent stem cells, #2 mesenchymal stem cells, #3 microglia, and #6 adult hippocampal neurogenesis persisted to recent time. CONCLUSION: This bibliometric analysis provides a comprehensive guide for clinicians and scholars working in this field. These analysis and results hope to provide useful information and references for future understanding of the challenges behind translating underlying stem cell biology into novel clinical therapeutic potential in AD.

Association analysis for SNPs of LIPE and ITGB4 genes with cashmere production performance, body measurement traits and milk production traits in Liaoning cashmere goats.

Liaoning cashmere goat (LCG) is one of the excellent cashmere goat breeds in China. Because of its larger size, better cashmere, and better cashmere production performance, people pay special attention to it. This article mainly studied the relationship between SNP loci of LIPE gene and ITGB4 gene and milk production, cashmere production and body measurement traits of LCGs. We further identified potential SNP loci by PCR-Seq polymorphism detection and gene sequence comparison of LIPE and ITGB4 genes. Further, we use SPSS and SHEsis software to analyze their relationship to production performance. The consequence indicated that CC genotype of LIPE gene T16409C locus was dominant genotype in milk production and cashmere production, while CT genotype of LIPE gene T16409C locus was dominant in body size. The CT genotype of C168T locus of ITGB4 gene is the dominant genotype of body type and cashmere production, while the dominant genotype of milk production is TT genotype. Through joint analysis, in haploid combinations, H1H2:CCCT is the dominant haplotype combination in cashmere fineness. H3H4:TTCT is a dominant haplotype combination of milk production traits and body measurement traits. These dominant genotypes can provide a reliable basis for the study of production performance of LCG.

Loss of serine/threonine protein kinase 25 in retinal ganglion cells ameliorates high glucose-elicited damage through regulation of the AKT-GSK-3ß/Nrf2 pathway.

Serine/threonine protein kinase 25 (STK25) has critical importance for diabetic complications. However, whether STK25 has a link with diabetic retinopathy is not clearly understood. The damages of retinal ganglion cells (RGCs) caused by high glucose (HG) is a critical determinant for the onset of diabetic retinopathy. Herein, this work focused on assessing the possible role of STK25 in HG-evoked damage to RGCs. An expression abundance of STK25 was occurred in RGCs challenged with HG. STK25 loss lowered the deleterious effects on RGCs, including apoptosis, oxidative stress and inflammation. SKT25 silencing strengthened the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway in HG-challenged RGCs. Moreover, the inhibition of STK25 restored the phosphorylation of AKT and glycogen synthase kinase-3ß (GSK-3ß) in HG-challenged RGCs, whereas limiting AKT decreased the motivating effects of STK25 inhibition on the Nrf2 pathway. Additionally, the beneficial effects of STK25 inhibition on HG injuries were also reversed via the inhibition of Nrf2. Based on these observations, our work suggests that the inhibition of STK25 is protective for RGCs suffering HG injuries, which is achieved by effects on the AKT-GSK-3ß/Nrf2 pathway. STK25 may participate in the onset of diabetic retinopathy by affecting HG-evoked damages of RGCs.

High-throughput analysis of CircRNA in cows with naturally infected Staphylococcus aureus mammary gland.

Circular RNAs (CircRNA) are a special type of non-coding RNA molecule with a closed ring structure and are not affected by RNA exonucases. It has stable expression, is not easy to degrade, and exists in most eukaryotes. However, circRNA regulation of cow mastitis has not been widely recognized. Mammary epithelial tissues were collected from healthy Holstein cows (HCN) and mastitis Holstein cows (HCU). RNA sequencing (RNA SEQ) was performed for the differentially expressed circRNAs, and analysis results showed that 19 differentially expressed circRNAs were identified in HCN and HCU, among which 6 circRNAs were up-regulated and 13 circRNAs were down-regulated. We randomly selected nine circRNAs for Q-PCR verification, and the results showed consistent expression. Three circRNAs: circRNA2860, circRNA5323 and circRNA4027 were confirmed to be significantly differentially expressed circRNAs in cow mastitis. Also, their host genes TRPS1, SLC12A2 and MYH11 might be directly or indirectly play a role in cow mastitis. Furthermore, RNA polymerase transcription factor binding and tight junction are most enriched in GO and KEGG pathways, respectively. In addition, the regulatory network of circRNA-miRNA has been inferred from a bioinformatics perspective, which may help to understand the underlying molecular mechanism of circRNAs involved in regulating mastitis in cows.

Association between the cashmere production performance, milk production performance, and body size traits and polymorphism of COL6A5 and LOC102181374 genes in Liaoning cashmere goats.

The purpose of this study was to analyze the relationship between COL6A5 (collagen type VI alpha 5 chain) and LOC102181374 (alcohol dehydrogenase 1) genes and the production performance of Liaoning cashmere goats by single nucleotide polymorphism (SNP). We have searched for SNP loci of COL6A5 and LOC102181374 genes through sequence alignment and PCR experiments, and have used SPSS and SHEsis software to analyze production data. We obtained five SNP loci in total, including three SNP loci (G50985A, G51140T, G51175A) in COL6A5 gene and two SNP loci (A10067G, T10108C) in LOC102181374 gene. The genotypes G50985A (AG), G51140T (GT), G51175A (AA), A10067G (AA), and T10108C (CC) of these loci have certain advantages in improving the production performance of Liaoning cashmere goats. The haplotype combinations that can improve production performance in COL6A5 gene were H1H5:AGGGAG, H4H4:GGGGAA, and H4H4:GGGGAA. H3H3:GGCC and H2H4:AGTT were the dominant combinations in LOC102181374 gene. At G51175A and A10067G loci, we found that H1H2:AAAG and H1H3:AGAA have dominant effects. These results may provide some support for the molecular breeding of production traits in Liaoning cashmere goats.

Performances of the beam monitoring system and quality assurance equipment for the HIMM of carbon-ion therapy.

PURPOSE: The heavy-ion medical machine (HIMM), which is the first commercial medical accelerator designed and built independently by the institute of modern physics (IMP) in Wuwei, Gansu Province, China, had officially completed clinical trials at the time of this article's writing. Three types of detector systems were developed based on the ionization-chamber principle to monitor the beam parameters during treatment in real time, quickly verify the beam performance during a routine checkup, and ensure patient safety. METHODS AND MATERIALS: The above-mentioned detector systems were used for beam monitoring and quality assurance in the treatment system. The beam-monitoring system is composed of three integral ionization chambers (ICs) and two multistrip ionization chambers (MSICs) as a redundant design. The irradiation dose, beam position, and homogeneity of a lateral profile are monitored online by the beam-monitoring system, and safety interlocks are established to keep the test results under the predefined tolerance limitation. The quality-assurance equipment was composed of one MSIC and one IC stack. The IC stack was used for energy verification. RESULTS: The off-axis response of ICs is within a tolerance of 2%, and the dose interlock system (DIS) response time is less than 7 ms during the treatment process. The positioning resolution of MSICs reached 73 µm. The IC stack can verify the beam range within one spill and the measurement resolution is less than 0.2 mm. CONCLUSIONS: The beam-monitoring system (BMS) and quality-assurance equipment (QAE) have been installed and run successfully within HIMM for two years and are associated with the HIMM treatment system to deliver the right dose to the correct position precisely. Furthermore, the daily QA task is simplified by it. Above all, the system has passed the performance test of the China Food and Drug Administration (CFDA).

Alendronate for the Treatment of Osteoporosis in Men: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Alendronate has been widely used in the treatment of osteoporosis. However, the effect of alendronate in the male osteoporosis remains controversial. STUDY QUESTION: We conducted a meta-analysis to assess the efficacy of alendronate in the treatment of men with osteoporosis. STUDY DESIGN: PubMed, Embase, and Web of Science were searched from their inception to October 25, 2015. Eligible studies were randomized controlled trials that evaluated the effect of alendronate in the male osteoporosis. MEASURES AND OUTCOMES: The outcomes included mean percentage changes in bone mineral density (BMD) of lumbar spine, femoral neck, total hip, trochanter, and total body, and the incidence of new vertebral fractures. Results were expressed with weighted mean difference (WMD), and risk ratio with 95% CIs. A fixed-effects model or random-effects model was used for the meta-analysis according to heterogeneity. RESULTS: Eight studies involving 988 patients met the inclusion criteria. Alendronate significantly increased the mean percentage BMD at the lumbar spine (WMD = 4.95, 95% CI, 2.40-7.49; P < 0.001), femoral neck (WMD = 2.59, 95% CI, 1.52-3.66; P < 0.001), and total hip (WMD = 2.39, 95% CI, 1.05-3.27; P < 0.001), but not at the trochanter (WMD = 1.76, 95% CI, -0.69 to 4.21; P = 0.158) and total body (WMD = 3.29, 95% CI, -0.04 to 6.62; P = 0.053). Moreover, alendronate was also decreased the incidence of vertebral fractures (risk ratio = 0.46, 95% CI, 0.28-0.77; P = 0.003). Subgroup analysis showed that among the male osteoporosis, greater increase in the lumbar spine BMD (WMD = 5.99, 95% CI, 3.42-8.56; P < 0.001) and femoral neck BMD (WMD = 3.66, 95% CI, 2.57-4.76; P = 0.023) was observed when the alendronate was administrated with a dose of 10 mg. CONCLUSION: Based on current evidence, alendronate shows beneficial effect on the lumbar spine, femoral neck, and total hip BMD, and the incidence of new vertebral fractures.

Immobilization of Acidithiobacillus ferrooxidans on cotton gauze for biological oxidation of ferrous ions in a batch bioreactor.

The ability of Acidithiobacillus ferrooxidans to oxidize ferrous iron has been extensively studied in bioleaching to recover metal resources. Although immobilization of A. ferrooxidans is of great importance to achieve high bioleaching performance in practical application, the reported approaches of immobilization of A. ferrooxidans are still limited. This paper is attempting to develop a novel method to immobilize A. ferrooxidans by a less-costly effective carrier from zeolite, activated carbon, and cotton gauze. The results showed that cotton gauze was the most suitable carrier to immobilize A. ferrooxidans cells in comparison with zeolite and activated carbon. Acidithiobacillus ferrooxidans immobilized on the cotton gauze by gravity dehydration could achieve an average ferrous iron oxidation rate of 0.73 g/(L·h). Furthermore, the ferrous iron oxidation ratio attained in the bioreactor under batch operation was maintained above 97.83%. All results indicated that cotton gauze could be an efficient carrier for immobilizing A. ferrooxidans cells for the biooxidation of ferrous ions.

Crocin Upregulates CX3CR1 Expression by Suppressing NF-κB/YY1 Signaling and Inhibiting Lipopolysaccharide-Induced Microglial Activation.

Glaucoma is a group of neurodegenerative diseases characterized by the progressive loss of retinal ganglion cells (RGCs) and optic nerve fibers. Microglial activation has been shown to be deleterious to RGCs and may participate in the progression of glaucoma. Crocin, one of the major active ingredients in saffron, has been found to inhibit microglial activation. However, the mechanism remains unclear. The aim of this study was to investigate whether crocin can inhibit lipopolysaccharide (LPS)-induced microglial activation and to clarify the mechanisms involved. The influence of crocin on primary RGCs and LPS-stimulated BV2 microglial cells survival was determined by the MTT and lactate dehydrogenase assays, or by flow cytometry. BV2 cells were pretreated with various concentrations of crocin for 2 h followed by 1 µg/mL LPS stimulation. Microglial markers and pro-inflammatory mediators were assessed by real-time PCR, western blot and ELISA. Furthermore, CX3CR1 expression was detected and the underlying mechanism was examined. The concentrations of crocin ranged from 0.1 to 1 µM, and did not show any cytotoxicity in RGC and BV2 cells. After crocin pretreatment, the expression of microglial markers (CD11b and Iba-1) and pro-inflammatory mediators (iNOS, COX-2, IL-1ß, and TNF-α) induced by LPS were significantly decreased in a dose-dependent manner. Additionally, CX3CR1 expression was remarkably increased by crocin via the suppression of NF-κB/Yin Yang 1 (YY1) signaling in BV2 cells. In conclusion, crocin effectively suppresses microglial activation and upregulates CX3CR1 expression by suppressing NF-κB/YY1 signaling.

Deterioration mechanisms of tuff with surface fractures under freeze-thaw cycles.

In practical engineering, the development of surface cracks is one of the most important reasons for the destruction of the rock mass, and the development of complex morphology fractures on the rock mass surface significantly influences rock mass mechanics. This paper addresses the freeze-thaw damage issue in rock mass containing surface fractures in cold regions. Tuffs and a control group are selected as research samples, with the control group being prefabricated surface jointed specimens with an inclination angle of 70° and a fracture depth ratio d (crack depth) /t (sample width) of 0.26. The study analyzes the mass, wave velocity loss, macro-microcosmic fracture damage morphology, and mechanical properties of the two specimen groups through laboratory freeze-thaw cycle tests, uniaxial compression tests, and scanning electron microscopy examinations. The results show an overall decrease in mass, wave velocity, and uniaxial compressive strength as the cycle number increases, with the prefabricated jointed group samples showing more significant changes. However, the two specimen groups exhibit different macroscopic failure fracture states. In addition, scanning electron microscopy images illustrate that after freeze-thaw cycles, the large rock mass particles break into smaller fragments, resulting in looser particle arrangements and a transition from initial surface cementation to point contact., which weakens the compressive strength of the rock mass. The paper also explains the mechanism of the diminishing impact of freeze-thaw cycles on the strength of the rock mass after a certain number of cycles. The research outcomes hold significant reference value for engineering construction in cold regions.

Preliminary study of low-pressure ionization chamber for online dose monitoring in FLASH carbon ion radiotherapy.

The FLASH effect of carbon ion therapy has recently attracted significant attention from the scientific community. However, the radiobiological mechanism of the effect and the exact therapeutic conditions are still under investigation. Therefore, the dosimetry accuracy is critical for testing hypotheses about the effect and quantifying FLASH Radiotherapy. In this paper, the FLASH ionization chamber at low-pressure was designed, and its dose rate dependence was verified with the Faraday cup. In addition, the dose response was tested under the air pressure of the ionization chamber of 10 mbar, 80 mbar and 845 mbar, respectively. The results showed that when the pressure was 10 mbar, the dose linearity was verified and calibrated at the dose rate of ∼50 Gy s-1, and the residuals were less than 2%. In conclusion, the FLASH ionization chamber is a promising instrument for online dose monitoring.

Bibliometric Analysis of Psychological Distress in Stroke: Research Trends, Hot Spots, and Prospects- An Emphasis on China.

Background: Currently, the psychological problems of stroke patients are of great concern. It is a hot topic of clinical care research to analyze and discuss the current status and hot spots, frontiers and development trends of research on psychological distress of stroke patients, and to develop and implement psycho-social care programs to improve the quality of life of patients.However, there is an absence of visual overviews to assess the published literature systematically. Methods: The Web of Science (WOS) database was used to search the relevant literature in this field, spanning the period 2009-2023, and the countries, institutions, and research keywords in this field were visualized and analyzed by CiteSpace analysis software. Results: An analysis of 416 papers found that the overall trend of psychological distress in stroke patients was increasing, and the research hotspots were mainly focusing on the relationship between different risk factors and psychological distress in stroke patients, psychological distress in stroke caregivers, positive psychology in stroke patients, and interventions on psychological distress in stroke patients. In the future, the research population may gradually shift to stroke caregivers, and the research focus will be on developing and studying scales. Conclusion: Visual analysis of psychological distress studies in stroke patients can provide strategies for clinical interventions and broaden thinking about clinical care.

Palmitic acid-induced microRNA-143-5p expression promotes the epithelial-mesenchymal transition of retinal pigment epithelium via negatively regulating JDP2.

BACKGROUND: The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is the most crucial step in the etiopathogenesis of proliferative vitreoretinopathy. This study aimed to investigate the role of miR-143-5p in the EMT of RPE cells induced by palmitic acid (PA). METHODS: ARPE-19 cells were treated with PA to induce EMT, followed by E-cadherin and α-smooth muscle actin (α-SMA) expression and the microRNA expression profile analyses. Subsequently, miR-143-5p mimics/inhibitors, and plasmids expressing its predicted target gene c-JUN-dimerization protein 2 (JDP2), were transfected in ARPE-19 cells using lipofectamine 3000, and followed by PA treatment. Their impacts on EMT were explored using wound healing and Western blot assays. Additionally, miR-143-5p mimics and JDP2-expressing plasmid were co-transfected into ARPE-19 cells and treated with PA to explore whether PA induced EMT of ARPE-19 cells via the miR-143-5p/JDP2 axis. RESULTS: PA decreased E-cadherin expression and increased those of α-SMA and miR-143-5p. Inhibiting miR-143-5p suppressed the migration of ARPE-19 cells and altered the expressions of E-cadherin and α-SMA. However, additional PA treatment attenuated these alterations. JDP2 was a target of miR-143-5p. Overexpression of JDP2 inhibited the EMT of ARPE-19 cells, resulting in α-SMA downregulation and E-cadherin upregulation, which were reversed by additional PA treatment via inhibiting JDP2 expression. Overexpression of miR-143-5p reversed the effect of JDP2 on the EMT of ARPE-19 cells and additional PA treatment markedly enhanced the effect of miR-143-5p mimics. CONCLUSION: PA promotes EMT of ARPE-19 cells via regulating the miR-143-5p/JDP2 axis, and these findings provide significant insights into the potential targeting of this axis to treat proliferative vitreoretinopathy.

G-wire-based self-quenched fluorescence probe combining with target-activated isothermal cascade amplification for ultrasensitive microRNA detection.

Herein, we reported the G-wire-based self-quenched fluorescence probe and its application in ultrasensitive microRNA (miRNA) detection by combining with target-activated isothermal cascade amplification. The terminal-single-fluorescein (FAM)-labeled G-rich oligonucletides self-assembled into G-wire nanostructures (G-wires) with K+ and Mg2+. Thereafter, the G-wires brought terminal-labeled FAM into close proximity, as a result, the self-quenched signal probe formed. Besides, when there was the target miRNA, target-activated isothermal cascade amplification converted miRNA into the copious trigger DNA. After hybridization between trigger DNA and the self-quenched probe, the G-wires were splited and forced the apart of proximate FAM, and then the self-quenched probe displayed an "on" mechanism. Therefore, the approach gave a limit of detection (LOM) of 0.82 aM to miRNA-21 and could be implemented within a wide linear range of 2 aM to 2 nM. This approach was able to distinguish the single-mismatched miRNA-21, which was selective and sensitive in detecting human spiked serum samples.

Effects of collagen peptides from Micropterus salmoides skin on oxidative damage induced by cyclophosphamide in mice.

To investigate the protective effect of collagen peptide from Micropterus salmoides skin (CPMs) on oxidative damage induced by cyclophosphamide in mice. Balb/c female mice were divided into blank, model (cyclophosphamide, CTX), positive control (levamisole hydrochloride), and collagen peptide low-, medium-, and high-dose groups. The results showed that CPMs increase the body mass and immune-related organ indexes, such as liver and kidneys of immunosuppressed mice. The activities of ALT, AST, UA, BUN, and MDA in the liver and kidney tissues decreased significantly, while those of SOD and GSH-Px increased significantly. CPMs can relieve the pathological damage to immune organs. CPMs significantly increase the activities of IL-2, IgG, and TNF-α in serum and SOD activity, while the MDA content was decreased compared to the model group. CPMs can exert a protective effect on cyclophosphamide-induced oxidative damage and have application prospects in the field of health food.

Direct conversion of human umbilical cord mesenchymal stem cells into retinal pigment epithelial cells for treatment of retinal degeneration.

Age-related macular degeneration (AMD) is a major vision-threatening disease. Although mesenchymal stem cells (MSCs) exhibit beneficial neural protective effects, their limited differentiation capacity in vivo attenuates their therapeutic function. Therefore, the differentiation of MSCs into retinal pigment epithelial (RPE) cells in vitro and their subsequent transplantation into the subretinal space is expected to improve the outcome of cell therapy. Here, we transdifferentiated human umbilical cord MSCs (hUCMSCs) into induced RPE (iRPE) cells using a cocktail of five transcription factors (TFs): CRX, NR2E1, C-MYC, LHX2, and SIX6. iRPE cells exhibited RPE specific properties, including phagocytic ability, epithelial polarity, and gene expression profile. In addition, high expression of PTPN13 in iRPE cells endows them with an epithelial-to-mesenchymal transition (EMT)-resistant capacity through dephosphorylating syntenin1, and subsequently promoting the internalization and degradation of transforming growth factor-ß receptors. After grafting into the subretinal space of the sodium iodate-induced rat AMD model, iRPE cells demonstrated a better therapeutic function than hUCMSCs. These results suggest that hUCMSC-derived iRPE cells may be promising candidates to reverse AMD pathophysiology.

Sulfiredoxin-1 protects retinal ganglion cells from high glucose-induced oxidative stress and inflammatory injury by potentiating Nrf2 signaling via the Akt/GSK-3ß pathway.

Sulfiredoxin-1 (Srxn1) has been acknowledged as a remarkable pro-survival factor in the protection of cells against stress-induced damage. The persistent exposure of retinal ganglion cells (RGCs) to high glucose (HG) in diabetes induces cellular damage, which contributes to the onset of diabetic retinopathy, a severe complication of diabetes. So far, little is known about the role of Srxn1 in regulating HG-induced injury of RGCs. The goals of this work were to evaluate the possible relevance of Srxn1 in the modulation of HG-induced apoptosis, oxidative stress and inflammation of RGCs in vitro. Our data showed that HG exposure caused a marked decrease in Srxn1 expression in RGCs. The up-regulation of Srxn1 markedly decreased HG-evoked apoptosis, reactive oxygen species (ROS) generation and pro-inflammatory cytokine release in RGCs. On the contrary, the depletion of Srxn1 rendered RGCs more susceptible to HG-induced injury. Further data demonstrated that Srnx1 enhanced the activation of nuclear factor erythroid-2 (E2)-related factor 2 (Nrf2) signaling in HG-exposed RGCs associated with up-regulating the phosphorylation of Akt and glucogen synthase kinase-3ß (GSK-3ß). Notably, the inhibition of Akt abolished Srnx1-overexpression-mediated Nrf2 activation, while GSK-3ß inhibition reversed Srnx1-depletion-mediated inactivation of Nrf2. In addition, Nrf2 inhibition partially abrogated Srnx1-mediated protective effects against HG-induced injury of RGCs. In summary, these data demonstrate that the overexpression of Srxn1 protects RGCs from the HG-induced injury of RGCs by enhancing Nrf2 signaling via modulation of Akt/GSK-3ß axis. Our work highlights that the Srxn1-mediated Akt/GSK-3ß/Nrf2 axis may exert a possible role in regulating RGC injury of diabetic retinopathy.

A combination of lycopene and human amniotic epithelial cells can ameliorate cognitive deficits and suppress neuroinflammatory signaling by choroid plexus in Alzheimer's disease rat.

Neuroinflammation characterized by glial activation and release of proinflammatory mediators is considered to be correlated with cognitive deficits in Alzheimer's disease (AD). Previously, some studies have demonstrated that lycopene (LYCO) or human amniotic epithelial cells (HAECs) could attenuate inflammation in AD. Specifically, the choroid plexus (CP), an epithelial layer that forms the blood-cerebrospinal fluid barrier, is able to modulate the cognitive function, through changes in the neuroinflammatory response and in brain immune surveillance. However, it is unclear if LYCO can interact with HAECs to improve neuroinflammation at the CP. Thus, this study chose the region of interest, considered the feasibility of using a combination of LYCO and HAECs, as a therapeutic agent for immunomodulatory effects at the CP in an acutely induced AD rat model. Results showed that oral administration of LYCO, HAECs transplantation, and their combination significantly improved cognitive deficits in water maze test, decreased the level of proinflammatory mediators (TNF-α and IL-1ß), increased the level of anti-inflammatory mediators (IL-10 and TGF-ß1) in the cerebro-spinal fluid, and hippocampal tissue. Interestingly, LYCO administration, HAECs transplantation and their combination reversed the Aß1-42 induced up-regulation of Toll like receptor 4 and nuclear factor-κB p65 mRNA and protein expressions at the CP. This study provided the novel experimental evidence for the influence of co-treatment with LYCO and HAECs on immunomodulatory capabilities of CP. It could also warrant therapeutic window for the pathophysiology of AD and the associated underlying mechanisms at the CP.

Clinical manifestations and treatment outcomes of syphilitic uveitis in HIV-negative patients in China: A retrospective case study.

Syphilitic chorioretinitis should be included in differential diagnosis of any form of ocular inflammation. A significantly higher proportion of human immunodeficiency virus (HIV)-positive patients with ocular syphilis as compared to HIV-negative cases have been reported in published studies. However, the clinical signs and symptoms are more insidious in HIV-negative patients who are easily misdiagnosed. We report a series of cases of ocular syphilis and describe the clinical manifestations and treatment outcomes of syphilitic chorioretinitis in HIV-negative patients in China.This was a retrospective case series study. The clinical records of patients with syphilis chorioretinitis were reviewed. Demographic information and findings of fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and spectral domain optical coherence tomography (SD-OCT) were analyzed. All patients received the standard treatment. Ophthalmology examination and laboratory evaluation were repeated every 3 months. All changes were recorded. The treatment was considered successful if the patients had no inflammation in both eyes and rapid plasma reagin titer was negative after therapy.The study examined 41 eyes of 28 HIV-negative patients. The main complaints were blurry vision, floaters, and visual field defect. Twenty-seven eyes presented with panuveitis, and all had posterior involvement, including uveitis, vasculitis, chorioretinitis, and optic neuritis. The most common manifestations were uveitis and retinal vasculitis. Disc hyperfluorescence and persistent dark spots were the most common findings on FFA and ICGA. The ill-defined inner segment/outer segment junction was the most frequent manifestation on SD-OCT. Patients were diagnosed with syphilitic uveitis based on positive serological tests. Best-corrected visual acuity (BCVA) was improved in 34 eyes after treatment. Eleven patients were misdiagnosed before serological tests were performed. The delay in treatment led to long-standing cystoid macular edema and optic neuropathy, which were associated with poor BCVA (P = .037).The common manifestations of syphilitic chorioretinitis were uveitis, retinal vasculitis, and optic neuritis. Further diagnosis should be prompted by FFA, ICGA, and SD-OCT when ocular manifestation is suspected. The standard treatment for neurosyphilis was effective. If patients are presumed to be in low-risk groups such as HIV-negative, delays in diagnosis, and therapy may be likely. It is necessary to reiterate the importance of including syphilis uveitis as a differential diagnosis for any form of ocular inflammations, especially posterior uveitis and optic neuropathy.