Perfluorocarbon liquid-assisted subretinal fluid drainage via the choroid as a treatment for bullous central serous chorioretinopathy in a nanophthalmic eye.

PURPOSE: The report presents a modified surgical technique wherein the perfluorocarbon liquid (PFCL)-assisted drainage of subretinal fluid (SRF) through the choroid was combined with partial-thickness sclerectomy (PTS) and punch sclerostomy as a treatment for bullous central serous chorioretinopathy (bCSCR) in a nanophthalmic eye. METHODS: The developed surgical approach is herein discussed together with a corresponding surgical video. Briefly, two 5 × 4 mm half-thickness sclerectomies and a punch sclerostomy (diameter: 2 mm) to the choroid were performed in the inferior quadrants. Following vitrectomy, SRF was drained through the exposed choroid in the region where the punch sclerostomy was performed, whereafter PFCL was instilled into the vitreous cavity. RESULTS: The complete resolution of SRF accumulation was evident at one-week post-surgery, with no evidence of recurrence over an 18-month follow-up period. No abnormal fluorescent leakage or choroidal vasodilation were evident via fundus fluorescein angiography and indocyanine green angiography examination at the patient's final follow-up visit. CONCLUSION: PFCL-assisted SRF drainage through the choroid combined with PTS and punch sclerostomy may represent a viable approach to treating patients with bCSCR and nanophthalmic eyes, providing a rapid and long-lasting means of eliminating SRF accumulation.

Cultivation, cryopreservation, and transcriptomic studies of host-adapted Cryptosporidium parvum and Cryptosporidium hominis using enteroids.

Cryptosporidium hominis and Cryptosporidium parvum are major causes of severe diarrhea. Comparative studies of them are hampered by the lack of effective cultivation and cryopreservation methods, especially for C. hominis. Here, we describe adapted murine enteroids for the cultivation and complete development of host-adapted C. parvum and C. hominis subtypes, producing oocysts infectious to mice. Using the system, we developed a cryopreservation method for Cryptosporidium isolates. In comparative RNA-seq analyses of C. hominis cultures, the enteroid system generated significantly more host and pathogen responses than the conventional HCT-8 cell system. In particular, the infection was shown to upregulate PI3K-Akt, Ras, TNF, NF-κB, IL-17, MAPK, and innate immunity signaling pathways and downregulate host cell metabolism, and had significantly higher expression of parasite genes involved in oocyst formation. Therefore, the enteroid system provides a valuable tool for comparative studies of the biology of divergent Cryptosporidium species and isolates.

PRETREATED LYOPHILIZED HUMAN AMNIOTIC MEMBRANE GRAFT COVERING FOR RETINAL DETACHMENT WITH POSTERIOR RETINAL BREAKS ABOVE CHORIORETINAL ATROPHY IN PATHOLOGIC MYOPIA.

PURPOSE: To compare the surgical results of vitrectomy with untreated or pretreated lyophilized human amniotic membrane grafts covering in treating retinal detachment related to posterior retinal breaks above chorioretinal atrophy in pathologic myopia. METHODS: Nineteen patients with retinal detachment related to macular hole (MH) located above macular atrophy and/or posterior paravascular retinal breaks (PRBs) located above patchy chorioretinal atrophy in pathologic myopia were included. The eyes of these patients underwent vitrectomy with untreated lyophilized human amniotic membrane covering (n = 10) or perfluorocarbon liquid (PFCL)-assisted pretreated lyophilized human amniotic membrane covering (n = 9; grafts were pretreated in 0.125% indocyanine green and 50% hypertonic glucose solution for 15-20 minutes). The closure of the MH or PRBs, reattachment of the retina, and best-corrected visual acuity were measured postoperatively. RESULTS: Postoperatively, graft dislocation or shift was only found in two eyes (20%) in the untreated group. The closure rate of the MH or PRBs was 80% (8/10) and 100% (9/9) in the untreated group and the pretreated group, respectively. The occurrence rate of excessive gliosis was 40% and 11% in the untreated group and the pretreated group, respectively. In both groups, best-corrected visual acuity was improved and the retinal reattachment rate was 100% at the final visit. CONCLUSION: Perfluorocarbon liquid-assisted pretreated lyophilized human amniotic membrane graft covering was effective in treating retinal detachment related to MH and/or PRBs situated above macular atrophy or patchy chorioretinal atrophy in pathologic myopia. This technique appeared to reduce graft dislocation or shift, promote the closures of MHs/PRBs, and reduce the occurrence of gliosis.

Analysis of the decoupling effect and driving factors of carbon emissions from the transportation sector in Guangdong Province.

To propel the green transformation of the transportation industry in Guangdong Province. Against the backdrop of the five-year plan, this study employs the Tapio decoupling model and the Logarithmic Mean Divisia Index decomposition method to analyze the decoupling status and driving factors of carbon emissions from transportation and economic growth in Guangdong Province from 2001 to 2020. The results show that:(1) Both the total volume of carbon emissions from transportation and per capita emissions exhibit an overall upward trend, with petroleum-based emissions accounting for an overwhelming 96%, with diesel emissions register the highest proportion and most substantial increase. (2) The decoupling status predominantly manifests as weak decoupling, with intermittent years expansive coupling,, expansive negative decoupling, strong decoupling, and recessive coupling, thus indicating a persistent state of decoupling instability. (3) The study introduces the urbanization effect, wherein the effects of income urbanization, as well as spatial urbanization, predominantly exert positive driving influences. Conversely, the effects of energy intensity, population urbanization, industry scale, and energy structure collectively exert negative driving influences. Notably, the effect of income urbanization emerges as the primary factor propelling the augmentation of carbon emissions, while the energy intensity effect serves as the primary factor curbing such escalation. Finally, pertinent policy recommendations are put forth.

High zoonotic potential and heavy environmental burden of Cryptosporidium spp. and Enterocytozoon bieneusi in farmed and pet African pygmy hedgehogs (Atelerix albiventris).

African pygmy hedgehogs (Atelerix albiventris) are widely farmed in southern China and Japan for medicinal materials and as pets. However, little is known about the prevalence, zoonotic potential, and environmental burden of Cryptosporidium spp., Enterocytozoon bieneusi and Giardia duodenalis in these animals. In this study, 380 fecal samples were collected from farmed and pet African pygmy hedgehogs in Guangdong of China, and analyzed for these pathogens by PCR and DNA sequencing. Overall, the detection rates of Cryptosporidium spp., E. bieneusi and G. duodenalis were 35.5%, 70.0% and 0, respectively. By living condition, the highest detection rates of Cryptosporidium spp. (61.5%) and E. bieneusi (100.0%) were both obtained from animals kept in the cave, which could be due to the overcrowding and poor hygiene conditions. Two Cryptosporidium species were identified, including C. erinacei (n = 22) and Cryptosporidium horse genotype (n = 113). The C. erinacei isolates belonged to a new subtype family (XIIIb), which has been identified in a patient with cryptosporidiosis recently. The horse genotype isolates are of a known subtype VIbA13, which was previously identified in a pet store employee in care of hedgehogs with diarrhea. Eleven genotypes of the zoonotic Group 1 were identified in E. bieneusi, with the known genotype SCR05 previously detected in pet rabbits being dominant (235/266, 88.3%). In longitudinal monitoring of Cryptosporidium infection in 11 naturally infected African pygmy hedgehogs, the oocyst shedding intensity decreased gradually from the mean oocysts per gram of feces of ∼6 logs to ∼2 logs over 42 days. The high intensity and long duration of oocyst shedding could lead to heavy environmental contamination and increase the potential for zoonotic transmission of the pathogens. Results of the study suggest that zoonotic Cryptosporidium spp. and E. bieneusi are common in farmed and pet African pygmy hedgehogs. Hygiene and One Health measures should be implemented by pet owners and farmers to prevent zoonotic transmission and environmental contamination of Cryptosporidium spp. and E. bieneusi.

THE LONG-TERM FOLLOW-UP OF AUTOLOGOUS BLOOD CLOT-ASSISTED LYOPHILIZED HUMAN AMNIOTIC MEMBRANE COVERING TREATMENT UNCLOSED MACULAR HOLE.

PURPOSE: The objectives were to assess the long-term morphologic and functional outcome of eyes with unclosed macular hole (MH) in which the internal limiting membrane has been peeled in previous vitrectomy with autologous blood clot-assisted lyophilized human amniotic membrane (LhAM) graft covering. METHODS: Twelve eyes with MH unclosed in previous surgery were selected and studied. Autologous blood clot-assisted LhAM graft was used to cover the MH in vitrectomy. The main clinical outcomes including best-corrected visual acuity, closure of MH, and the outcome of LhAM graft were recorded. RESULTS: The mean minimum diameter of the MH was 641.7 ± 245.9 µ m and the mean axial length was 27.3 ± 3.50 mm. The LhAM graft was maintained in the former position and all the MH closed in 10 eyes, whereas the graft slipped and the MH unclosed in two eyes. The MH closure rate was 83.3% and the mean best-corrected visual acuity improved significantly from 1.47 ± 0.58 logMAR (Snellen 20/590) preoperatively to 1.17 ± 0.60 logMAR (Snellen 20/296) postoperatively. During 18 to 36 months follow-up, LhAM grafts were attached to the retinal surface in nine eyes, detached from the retinal surface in one eye, dislocated from the fovea in one eye, and inserted into the retina in one eye; and macular atrophy occurred in one eye. CONCLUSION: Autologous blood clot-assisted LhAM graft covering provided a simple and effective treatment option for unclosed MH and reduce surgical trauma. Although the graft remained on the macular surface for a long time, it did not affect the recovery of MH and postoperative vision.

Maxillary transverse deficiency diagnosed by 3 methods and its relationship with molar angulation in patients with skeletal Class III malocclusion.

INTRODUCTION: The objective of this study was to evaluate the relationship between maxillary transverse deficiency (MTD) diagnosed by 3 methods and molar angulation measured in 3-dimensions in patients with skeletal Class III malocclusion, which could give reference to the selection of diagnostic methods in MTD patients. METHODS: Cone-beam computed tomography data of 65 patients with skeletal Class III malocclusion (mean age 17.35 ± 4.45 years) were selected and imported into MIMICS software. Transverse deficiencies were evaluated by 3 methods, and molar angulations were measured after reconstructing 3-dimensional planes. Two examiners performed repeated measurements to assess the intraexaminer and interexaminer reliability. Pearson correlation coefficient analyses and linear regressions were performed to determine the relationship between a transverse deficiency and molar angulations. One-way analysis of variance was used to compare the diagnostic results of 3 methods. RESULTS: The novel molar angulation measurement method and 3 MTD diagnostic methods have the interexaminer and intraexaminer intraclass correlation coefficient values >0.6. The transverse deficiency diagnosed by 3 methods was significantly and positively correlated with the sum of molar angulation. There was a statistically significant difference for the transverse deficiencies diagnosed by the 3 methods. The transverse deficiency was significantly higher in Boston University's analysis than in Yonsei's analysis. CONCLUSIONS: Clinicians ought to choose the diagnostic methods properly, considering the feature of the 3 methods and the individual difference of each patient.

Vitreous metabolomic signatures of pathological myopia with complications.

BACKGROUND: Pathological myopia (PM) is closely associated with blinding ocular morbidities. Identifying biomarkers can provide clues on pathogeneses. This study aimed to identify metabolic biomarkers and underlying mechanisms in the vitreous humour (VH) of PM patients with complications. METHODS: VH samples were collected from 39 PM patients with rhegmatogenous retinal detachment (RRD) (n = 23) or macular hole (MH)/myopic retinoschisis (MRS) (n = 16) and 23 controls (MH with axial length < 26 mm) who underwent surgical treatment. VH metabolomic profiles were investigated using ultra-performance liquid chromatography‒mass spectrometry. The area under the receiver operating characteristic curve (AUC) was computed to identify potential biomarkers for PM diagnosis. RESULTS: Bioinformatics analysis identified nineteen and four metabolites altered in positive and negative modes, respectively, and these metabolites were involved in tryptophan metabolism. Receiver operating characteristic analysis showed that seventeen metabolites (AUC > 0.6) in the positive mode and uric acid in the negative mode represent potential biomarkers for PM with complications (AUC = 0.894). Pairwise and pathway analyses among the RRD-PM, MH/MRS-PM and control groups showed that tryptophan metabolism and uric acid were closely correlated with PM. Altered metabolites and pathways in our study were characterized by increased oxidative stress and altered energy metabolism. These results contribute to a better understanding of myopia progression with or without related complications. CONCLUSIONS: Our study provides metabolomic signatures and related immunopathological features in the VH of PM patients, revealing new insight into the prevention and treatment of PM and related complications.

FOXM1 is regulated by DEPDC1 to facilitate development and metastasis of oral squamous cell carcinoma.

The Disheveled, EGL-10, Pleckstrin domain containing 1 (DEPDC1) is a new oncogene that has recently been described. The mechanisms and functions of its expression are yet to be determined in oral squamous cell carcinoma (OSCC). In the present study, the impact of DEPDC1 on the growth and development of OSCC was investigated using animal models, cell lines and human tissue samples. Elevated DEPDC1 expression within cancer cell lines and human OSCC has been identified. Mechanistic examination showed that restored DEPDC1 expression in vivo and in vitro stimulated OSCC tumour development. In addition, FOXM1 interacts with DEPDC1 as indicated by co-immunoprecipitation and immunofluorescence testing. Functionally, DEPDC1 facilitated Wnt/ß-catenin signal transduction and ß-catenin protein nuclear expression. In summary, the DEPDC1, interacting with FOXM1 via Wnt/ß-catenin signaling, the closely regulated OSCC pathogenesis, suggesting that targeting the novel DEPDC1/FOXM1/ß-catenin complex is an essential OSCC therapeutic approach.

Outcomes of 25-gauge pars plana vitrectomy alone with air tamponade for the management of rhegmatogenous retinal detachment with inferior breaks.

BACKGROUND: This study was investigated the surgical outcomes of primary rhegmatogenous retinal detachment (RRD) with inferior retinal breaks (IRBs) that were repaired by 25-gauge pars plana vitrectomy (PPV) with air tamponade. METHODS: This retrospective review included 81 consecutive patients who had RRD with IRBs and underwent PPV with air tamponade in our hospital from January 2017 to January 2020. The main outcomes were single surgery anatomical success (SSAS) rate, postoperative best-corrected visual acuity (BCVA), and complications. RESULTS: The patient population consisted of 29 women and 52 men (mean age, 52.12 years); the mean follow-up interval was 8.88 months. The mean number of affected quadrants was 1.65 (range, 1-4 quadrants) and the mean number of breaks was 3.25. A single break was present in 20 cases (24.7%); two to 10 breaks were present in 61 (75.3%) cases. The SSAS rate was 91.36% (74/81) and the final anatomical success rate was 96.30% (78/81). More than half of the patients had BCVA < 0.3 logarithm of the minimum angle of resolution at the last follow-up. Axial length and patient age were candidate risk factors for redetachment (axial length, p = 0.03; age, p = 0.002). Postoperative complications included macular epiretinal membrane formation in one patient, lens opacity in three patients, and clinically significant macular edema in one patient. CONCLUSIONS: PPV with air tamponade may be effective for the treatment of primary RRD with IRBs. Extensive preoperative discussion may be necessary for young patients and patients with particularly long axial length.

New technique for removal of perfluorocarbon liquid related sticky silicone oil and literature review.

AIM: To investigate the safety and efficacy of sticky silicone oil (SSO) removal using a 22-gauge vein detained needle and inner limiting membrane (ILM) wrap-and-peel technique. METHODS: This retrospective consecutive case series reviewed the records of patients with a history of retinal detachment who had received silicone oil and perfluorocarbon liquid (PFCL) as intraocular tamponades. Patients were included in the analysis if they exhibited SSO remnants during silicone oil removal. The aspiration of most of the SSO remnants was performed by a 22-gauge vein detained needle. The small amounts of droplets adhered to the macula and epi-macular membrane were subsequently removed by the ILM warp-and-peel technique. The anatomical and functional outcomes, and postoperative complications were recorded. In vitro experiments were performed to simulate the formation of SSO remnants in four groups. RESULTS: Of 711 patients who underwent silicone oil removal during the study period, 9 patients exhibited SSO remnants and underwent follow-up for at least 3mo. Seven eyes (78%) underwent the ILM wrap-and-peel technique to completely remove small droplets of SSO that were glued to the macula and epi-macular membrane. No obvious complications occurred. Postoperative optical coherence tomography revealed normal retinal structure in all patients. In vitro analyses showed that balanced salt solution and prolonged vibration (for 1wk) had the strongest effects on silicone oil and PFCL compound opacities. CONCLUSION: SSO remnants could be removed in an intact manner and without complications, using a vein detained needle-assisted and ILM wrap-and-peel technique. The findings suggest that PFCL and infusion fluid should be completely removed before silicone oil injection to prevent SSO formation.

Transscleral Removal of Subretinal Strand without Vitrectomy: A Case Report.

Recurrence of inferior retinal detachment, after vitreoretinal surgery and silicone oil tamponade, along with a subretinal strand, presents a challenge for surgeons. Vitrectomy and retinotomy are the usual treatment in such cases. Here, we present a new transscleral method for addressing this problem. A 13-year-old boy with recurrent retinal detachment after silicone oil tamponade underwent scleral buckling surgery and had a transscleral subretinal strand removed without retinotomy. The retina reattached, and silicone oil was removed 3 months later. The best-corrected visual acuity was 0.4 in decimal vision at 1 year after silicone oil removal. Scleral buckling surgery combined with subretinal strand removal may be used as an alternative to retinotomy, especially for patients with an inferior retinal detachment and local subretinal strand formation.

Geographic Variation Did Not Affect the Predictive Power of Salivary Microbiota for Caries in Children With Mixed Dentition.

Dental caries is one of the most prevalent chronic oral diseases, affecting approximately half of children worldwide. The microbial composition of dental caries may depend on age, oral health, diet, and geography, yet the effect of geography on these microbiomes is largely underexplored. Here, we profiled and compared saliva microbiota from 130 individuals aged 6 to 8 years old, representing both healthy children (H group) and children with caries-affected (C group) from two geographical regions of China: a northern city (Qingdao group) and a southern city (Guangzhou group). First, the saliva microbiota exhibited profound differences in diversity and composition between the C and H groups. The caries microbiota featured a lower alpha diversity and more variable community structure than the healthy microbiota. Furthermore, the relative abundance of several genera (e.g., Lactobacillus, Gemella, Cryptobacterium and Mitsuokella) was significantly higher in the C group than in the H group (p<0.05). Next, geography dominated over disease status in shaping salivary microbiota, and a wide array of salivary bacteria was highly predictive of the individuals' city of origin. Finally, we built a universal diagnostic model based on 14 bacterial species, which can diagnose caries with 87% (AUC=86.00%) and 85% (AUC=91.02%) accuracy within each city and 83% accuracy across cities (AUC=92.17%). Although the detection rate of Streptococcus mutans in populations is not very high, it could be regarded as a single biomarker to diagnose caries with decent accuracy. These findings demonstrated that despite the large effect size of geography, a universal model based on salivary microbiota has the potential to diagnose caries across the Chinese child population.

Rectangular loop suture to correct iris capture of the posterior chamber intraocular lens.

BACKGROUND: To report a new technique for iris capture of the posterior chamber intraocular lens (IOL) implanted in patients with a posterior capsule defect. METHODS: In this retrospective case series, a rectangular loop ciliary body suture technique was performed to rectify iris capture. The suture passes between the IOL and iris in a direction perpendicular to the iris edge capturing the IOL. RESULTS: A total of three IOLs with iris capture underwent a rectangular loop suture technique. No recapture was observed postoperatively. In one case, large astigmatism appeared after the surgery but recovered at 1 month post operation. No further complications were found. CONCLUSIONS: The rectangular loop suture technique is an effective, convenient, and minimally invasive method for iris capture of the IOL.

[Salivary microbial communities associated with severe early childhood caries].

OBJECTIVE: To compare the salivary microbial profiles of healthy subjects and those with severe early childhood caries (S-ECC) by using high-throughput sequencing. METHODS: Salivary samples were obtained from children with S-ECC (group C, n=24) and healthy children (group H, n=24). Total metagenomic DNA was extracted, and DNA amplicons of the V1-V3 hypervariable region of the 16S rRNA gene were generated and subjected to 454 sequencing. The characteristics of oral microbial communities from the two groups were compared based on microbial diversity and taxonomy assignment. RESULTS: First, the microbial richness was significantly higher in group C than group H (P<0.05). Second, the microbial community structure was significantly different for the groups H and C (P<0.01). In addition, caries microbiota was significantly conserved in group C (P<0.001). High expression of suspected cariogenic microorganisms in group C (P<0.1) and health related microorganisms in group H (P<0.1) were identified. Finally, models of caries risk assessment were proposed to distinguish caries from healthy subjects with over 70% accuracy. CONCLUSIONS: Salivary microbiota and certain taxa, such as caries-associated taxa (Prevotella), may be useful to screen/assess the children's risk of developing caries.

Characterization of the complete mitochondrial genome of the lung fluke, Paragonimus kellicotti.

In this study, the complete mitochondrial genome of human lung fluke, Paragonimus kellicotti, was recovered through Illumina sequencing data. This complete mitochondrial genome of P. kellicotti is 13,927 bp in length and has a base composition of A (16.6%), T (41.8%), C (13.%), and G (28.4%), demonstrating an obvious bias of high AT content (58.4%). The mitochondrial genome contains a typically conserved structure, encoding 12 protein-coding genes (PCGs), 22 transfer RNA genes (tRNA), 2 ribosomal RNA genes (12S rRNA and 16S rRNA), and a control region (D-loop region). All PCGs were located on the H-strand. ND4 gene and ND4L gene were overlapped by 39 bp. The nucleotide sequence of 12 PCGs of P. heterotremus and other 10 parasite species were used for phylogenetic analysis. The result indicated P. heterotremus a relative close relationship with species P. westermani (AF219379.2).

Generation and Screening of T-DNA Insertion Mutants Mediated by Agrobacterium tumefaciens in the Garden Asparagus Stem Blight Pathogen Phomopsis asparagi.

The garden asparagus stem blight caused by filamentous fungus Phomopsis asparagi exposes a serious threat on asparagus production globally. However, to present, we understand poorly about the molecular mechanisms of fungal pathogenicity. To facilitate functional genomics research of P. asparagi, here we developed a highly efficient and stable Agrobacterium tumefaciens-mediated transformation approach which yielded 150-200 transformants per 1 × 106 conidia. Our results indicated that 25 °C, acetosyringone concentration of 150 µmol/L, and 72 h were recommended as optimal co-cultivation conditions for the transformation. Using this transformation approach, we constructed a T-DNA insertion mutant library containing 1253 strains. Twenty randomly selected T-DNA insertion mutants were able to grow on 0.2 × PDA selective media after five successive subcultures without selective pressure, indicating that the exogenous T-DNA was stably integrated into the P. asparagi genome. We confirmed several randomly selected mutants using PCR with primers specific to the hph gene. Southern blots suggested that three out of the five selected mutants have a single T-DNA insertion. Interestingly, multiple mutant candidates with growth defects were obtained from the growth assay. Moreover, several mutants were selected for further analysis on the T-DNA flanking sequences through TAIL-PCR analysis. A sequence comparison of total junction fragments implied that the insertion of T-DNA within P. asparagi genome appeared to be a random event. The transformation technology and genetic resources developed here will facilitate studies of pathogenic mechanisms in this devastating filamentous fungal pathogen of garden asparagus.

[Effects of RhoA gene silencing by RNA interference on invasion of tongue carcinoma].

OBJECTIVE: To study the effects of RhoA down-regulation by RNA interference on the invasion of tongue carcinoma Tca8113 and SCC-4. METHODS: Determination of the human RhoA sequence as well as the design and constructionof a short specific small interfering RNAs (siRNA) were performed. The siRNA of RhoA gene was transfected into humantongue squamous cell carcinoma Tca8113 and SCC-4 cells line by Lipofectamine 2000. Quantitative real-time polymerasechain reaction was used to examine the mRNA expressionlevels of RhoA. Protein expressions of mRNA, galectin-3,and matrix metalloproteinase (MMP)-9 were evaluated byWestern blot. Transwell invasion assay was performed toassess the invasion ability of tongue carcinoma. RESULTS: RhoA expressions in Tca8113 and SCC-4 cells were reducedsignificantly after transfection of RhoA-siRNA. Protein levels f galectin-3 and MVP-9 were also down-regulated significantly. Invasion ability was inhibited as well. CONCLUSION: RhoA-siRNA can effectively inhibit RhoA expression in Tca8113 and SCC-4 cells. The invasion ability of tongue carcinoma cells decreased with down-regulation of the protein expressions of galectin-3 and MMP-9, indicating that RhoA-siRNA can inhibit invasion of tongue carcinoma. Results show that RhoA may play an important role in the processes of invasion and metastasis of tongue carcinoma.

[Effect of altitude chronic hypoxia on liver enzymes and its correlation with ACE/ACE2 in yak and migrated cattle].

OBJECTIVE: To investigate the difference of liver enzyme levels and its correlation with serum ACE/ACE2 among yak and cattle on Qinghai-Tibetan plateau, and to further explore the biochemical mechanism of their liver of altitude adaptation. METHODS: The serum samples of yak were collected at 3,000 m, 3,500 m, 4,000 m and 4,300 m respectively, meanwhile the serum samples of migrated cattle on plateau (2,500 m) and lowland cattle (1,300 m) were also collected. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (CHE), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), serum lipase (LPS), angiotensin converting enzyme(ACE), angiotensin converting enzyme-2 (ACE2) in serum were measured by using fully automatic blood biochemcal analyzer. We analysed the differences of the above enzymes and its correlation with ACE/ACE2. We used one way analysis of variance (ANOVA). RESULTS: The levels of ALT in 4,000 m group and 4,300 m group of yak increased significantly compared with other groups, there were no statistically significant differences in AST, CHE, GGT, ACE/ACE2 levels of yaks at different altitudes. As compared to lowland cattle, the serum levels of AST and CHE were increased, the level of LPS and ACE was decreased significantly, respectively, and especially, the ratio of ACE/ACE2 of migranted cattle reduced nearly two times. The levels of LPS were significantly correlated to the ratio of ACE/ACE2 in yak (r = 0.357, P < 0.01), and a high correlation between ALP and ACE/ACE2 in lowland cattle( r = 0.418, P < 0.05), But the biggest contribution rate of the ratio of ACE/ACE2 was only 17.5% for the changes of the levels of liver enzyme. CONCLUSION: The results indicated that with the altitude increased did not significantly influence the changes of liver enzymes' activities in mountainous yaks but not in cattle. However, all above these changes weren't actually correlated to the ratio of ACE/ACE2.

Neuroprotective effect of memantine on the retinal ganglion cells of APPswe/PS1ΔE9 mice and its immunomodulatory mechanisms.

Besides the cognitive impairment and degeneration in the brain, vision dysfunction and retina damage are always prevalent in patients with Alzheimer's disease (AD). The uncompetitive antagonist of the N-methyl-d-aspartate receptor, memantine (MEM), has been proven to improve the cognition of patients with AD. However, limited information exists regarding the mechanism of neurodegeneration and the possible neuroprotective mechanisms of MEM on the retinas of patients with AD. In the present study, by using APPswe/PS1ΔE9 double transgenic (dtg) mice, we found that MEM rescued the loss of retinal ganglion cells (RGCs), as well as improved visual impairments, including improving the P50 component in pattern electroretinograms and the latency delay of the P2 component in flash visual evoked potentials of APPswe/PS1ΔE9 dtg mice. The activated microglia in the retinas of APPswe/PS1ΔE9 dtg mice were also inhibited by MEM. Additionally, the level of glutamine synthetase expressed by Müller cells within the RGC layer was upregulated in APPswe/PS1ΔE9 dtg mice, which was inhibited by MEM. Simultaneously, MEM also reduced the apoptosis of choline acetyl transferase-immunoreactive cholinergic amacrine cells within the RGC layer of AD mice. Moreover, the phosphorylation level of extracellular regulated protein kinases 1 and 2 was increased in APPswe/PS1ΔE9 dtg mice, which was blocked by MEM treatment. These findings suggest that MEM protects RGCs in the retinas of APPswe/PS1ΔE9 dtg mice by modulating the immune response of microglia and the adapted response of Müller cells, making MEM a potential ophthalmic treatment alternative in patients with AD.