Associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage enzymes in patients with knee osteoarthritis.

OBJECTIVE: Animal studies suggest that S100A8/S100A9 may be involved in the pathogenesis of osteoarthritis (OA); however, there has been no clinical study examining the associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage degradation enzymes in knee OA patients so far. Therefore, this study was designed to investigate the cross-sectional associations between serum levels of S100A8/S100A9 and the outcomes in patients with knee OA. DESIGN: A total of 141 subjects with clinical knee OA were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was used to assess joint symptoms. Magnetic resonance imaging (MRI) was used to measure knee structural abnormalities including cartilage defects. Knee radiography was used to assess joint space narrowing (JSN), osteophytes and the radiographic severity of OA. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of S100A8/S100A9, matrix metalloproteinase (MMP)-3, MMP10 and MMP13. RESULTS: In multivariable analyses, serum S100A8/S100A9 were positively associated with total WOMAC score (ß: 0.111 per 10 ng/ml, P = 0.021), WOMAC weight-bearing pain (ß: 0.015 per 10 ng/ml, P = 0.043) and WOMAC physical dysfunction (ß: 0.091 per 10 ng/ml, P = 0.010), and had positive associations with total cartilage defects and cartilage defects at lateral femoral, lateral tibial and medial femoral sites (ORs: 1.006-1.008 per 10 ng/ml, all P < 0.05) and serum levels of MMP3 (ß: 0.002 per 10 ng/ml, P = 0.032) in patients with clinical knee OA. CONCLUSIONS: Serum levels of S100A8/S100A9 were positively associated with increased knee symptoms, cartilage defects and serum cartilage degradation enzymes in patients with knee OA, suggesting that S100A8/S100A9 may have a role to play in knee OA. Future longitudinal studies are required to confirm these findings.

Associations between knee structural measures, circulating inflammatory factors and MMP13 in patients with knee osteoarthritis.

OBJECTIVE: To investigate cross-sectional associations between serum level of Matrix metalloproteinase (MMP)13 and knee structural measures and circulating inflammatory factors in patients with symptomatic knee osteoarthritis (OA). DESIGN: A total of 149 subjects with symptomatic knee OA were included. Magnetic resonance imaging was used to measure infrapatellar fat pad (IPFP) volume, IPFP signal intensity alternation, cartilage volume and cartilage defects. Knee radiography was used to assess radiographic OA using the Kellgren-Lawrence (K-L) grading system. Enzyme-linked immunosorbent assay was used to measure the serum levels of inflammatory factors and MMP13. RESULTS: In multivariable analyses, serum MMP13 was negatively associated with cartilage volume at patellar site (ß: -32.94 mm3 per 10 ng/ml, P < 0.05), and positively associated with cartilage defect at medial femoral site (OR: 1.13 per 10 ng/ml, P < 0.05). Also, MMP13 was positively associated with K-L grading and IPFP signal intensity alteration (OR: 1.14 and 1.15 per 10 ng/ml, respectively, both P < 0.05), and negatively associated with IPFP volume (ß: -0.34 cm3 per 10 ng/ml, P < 0.05). Furthermore, serum level of adiponectin was negatively associated serum MMP13 quartiles (OR: 0.66 per 10 µg/ml, P < 0.05), and serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-8 and IL-18 were positively associated with serum MMP13 quartiles (ORs: 1.01-1.18 per 10 pg/ml, all P < 0.05). CONCLUSIONS: Serum level of MMP13 was associated with knee structural abnormalities as well as serum inflammatory factors. These suggest that systemic MMP13 may play a role in knee OA, and could be regulated by inflammatory factors.

Efficacy and safety of liraglutide versus sitagliptin, both in combination with metformin, in Chinese patients with type 2 diabetes: a 26-week, open-label, randomized, active comparator clinical trial.

AIMS: To compare the efficacy and safety of liraglutide versus sitagliptin as add-on to metformin after 26 weeks of treatment in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: This 26-week open-label, active comparator trial (NCT02008682) randomized patients (aged 18-80 years) with T2DM inadequately controlled with metformin [glycated haemoglobin (HbA1c) 7.0-10.0% (53-86 mmol/mol)] 1 : 1 to once-daily subcutaneously administered liraglutide 1.8 mg (n = 184) or once-daily oral sitagliptin 100 mg (n = 184), both as add-on to metformin. The primary endpoint was change in HbA1c from baseline to week 26. RESULTS: Liraglutide was superior to sitagliptin in reducing HbA1c from baseline [8.1% (65 mmol/mol)] to 26 weeks, as evidenced by estimated mean HbA1c change of -1.65% (-18.07 mmol/mol) versus -0.98% (-10.72 mmol/mol), respectively [estimated treatment difference for liraglutide vs sitagliptin of -0.67% (95% CI -0.86, -0.48) or -7.35 mmol/mol (95% CI -9.43; -5.26); p < 0.0001]. More patients receiving liraglutide (76.5%) than sitagliptin (52.6%) achieved the HbA1c target of <7.0% (53 mmol/mol) at week 26 [odds ratio 3.65 (95% CI 2.18, 6.12); p < 0.0001]. Reductions in fasting plasma glucose, 7-point self-measured plasma glucose and body weight were greater with liraglutide than with sitagliptin (p < 0.0001 for all). More patients experienced nausea (14.8% vs 0.5%), diarrhoea (8.2% vs 2.2%) and decreased appetite (10.9% vs 0.5%) with liraglutide than sitagliptin. Two hypoglycaemic episodes were confirmed for liraglutide and one for sitagliptin; none were severe or nocturnal. CONCLUSIONS: Liraglutide provided better glycaemic control and greater body weight reduction than sitagliptin when administered as add-on to metformin. More patients had nausea, diarrhoea and decreased appetite with liraglutide versus sitagliptin.

Clinical value of fluid bolus contrast flow meter during hysterosalpingography.

The purpose of this study was to investigate the clinical value of the fluid bolus contrast flow meter during hysterosalpingography. Hysterosalpingography information of 342 cases, which included a manual handset group of 213 cases and a bolus instrument group of 129 cases were reviewed. Comparative analysis was used to compare the two groups in order to assess the clinical adverse reactions, contrast agent reflux, and image quality. In the instrument bolus group compared with the manual handset group, the clinical adverse reactions decreased from 75.12 to 31.78% (P < 0.001); the backflow phenomenon of the contrast agent decreased from 13.62 to 3.10% (P < 0.01); and image quality significantly improved, with the A class film rate increasing from 54.46 to 68.99% (P < 0.01) and the C class film rate decreasing from 8.92 to 2.33% (P < 0.05). The use of a contrast bolus through the liquid inlet of the hysterosalpingography instrument can provide fully dynamic observation, reducing the contrast agent reflux and adverse reactions as well as improving the image quality and diagnostic accuracy. In addition, the medical staff is not subjected to radiographic radiation. Therefore, it is a safe and reliable imaging method.

Antidepressant drug, desipramine, alleviates allergic rhinitis by regulating Treg and Th17 cells.

Allergic rhinitis (AR) is characterized by IgE-mediated immediate hypersensitivity and usually progresses to chronic nasal inflammation, with depression as one of its comorbidities. The importance of treating the depression in AR patients has been increasingly recognized. Desipramine is a representative of tricyclic-antidepressant agents. In the present study we investigate whether desipramine has therapeutic effects on AR inflammation. BALB/C mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by repeated challenge with OVA intranasally. Desipramine was administered orally to treat the mice. The nasal symptoms (sneezing, nasal scratching etc.) of AR were evaluated to determine the severity of AR. Cytokines in the nasal lavage fluid (NALF), including interferon-gamma (IFN-gamma), interleukin 4 (IL-4) and serum OVA-specific immunoglobulin E (IgE) antibody were measured by ELISA. The regulatory T cells (Treg) and T helper cells 17 (Th17) were quantified by flow cytometric analysis. As a result, the repeated oral administration of desipramine attenuated the nasal symptoms (sneezing and nasal rubbing) in AR mice. Desipramine also suppressed the serum OVA-specific IgE and IL-4 levels, but had no effect on IFN-gamma level. Moreover, desipramine treatment up regulated CD4+CD25+Foxp3+ Treg cells, which were found down-regulated in established AR mice. Meanwhile, desipramine administration attenuated CD4+IL-17+ Th17 cells, which were significantly increased in AR mice. These results suggest that the antidepressant drug, desipramine, also has anti-allergic action, which was possibly achieved by reducing allergen-specific IgE and Th2 cytokine production and maintaining a balance between Treg and Th17 cells. Thus, this study provide the first evidence that desipramine may be utilized to treat allergic diseases, especially for those allergic patients with depression or depression patients with allergy.

Ultrasmall silver nanopores fabricated by femtosecond laser pulses.

Ultrasmall nanopores in silver thin films with a diameter of about 2 nm have been fabricated using femtosecond laser ablation in liquid. Ultrafast laser pulse ablation generates highly nonequilibrium excitated states, from which silver thin films emerge and progressively grow with the assistance of capping agent molecules. During this growth process, capping agent molecules are enclaved within the film, leaving individual ultrasmall pores in the thin film. Our first-principles calculations show that the pore size is critically determined by the dimension of the confined molecules. Our approach advances the capability of optical methods in making nanoscale structures with potential applications in areas such as near-field aperture probes, imaging masks, magnetic plasmonic resonances, and biosensing with individual nanopores.

Effects of lipopolysaccharides on TLR4 expression in INS-1 rat insulinoma cells.

The aim of the study was to obtain insight into the mechanism of sepsis-induced hyperglycemia, to explore the expression of Toll-like receptor 4 (TLR4) on INS-1 cells, the effects of lipopolysaccharide (LPS) on TLR4 expression and cell viability. The expression of TLR4 on INS-1 was detected by both RT-PCR and Western blot assays. After being intervened by LPS of various concentrations (0.01, 0.1, 1, 5, 10mg/L) for a certain time, the effects of LPS on TLR4 expression and cell viability were detected by quantitative real-time reverse-transcriptase polymerase chain reaction, western blotting and CCK-8 assay. Then INS-1 cells were stimulated by LPS (0.1, 1mg/L) together with anti-TLR4 antibody, cell viability and TLR4 expression were detected again. TLR4 expressed in INS-1 cell line. Its expression was up-regulated by the stimulation of LPS higher than 0.1mg/L for 12h (P<0.05). However, there was a little down-regulation of TLR4 between the LPS treated groups and controls with further LPS treatment for 24 and 48 h (P>0.05). In certain concentrations(0.1~10mg/L), viability of INS-1 cells was inhibited by LPS in a dose dependent manner (P<0.05) These effects could be blocked by anti-TLR4 antibody partially. These results suggest that LPS may act directly on the pancreatic ß cells via TLR4 on the ß-cell membrane. LPS increased TLR4 expression in the early short period of time and caused injury to INS-1 cells after a certain time. It could be one of the mechanisms that hyperglycemia occurs in the early stage of sepsis.

Cavernous transformation of the portal vein in nephrotic syndrome.

We report a 19-year-old man with thrombosis of the portal vein associated with a nephrotic syndrome. A computed tomography showed obstruction of the portal vein with prominent collaterals and cavernous transformation. This case is noteworthy as a report of nephrotic syndrome accompanied by extensive abdominal venous thrombosis and was cured successfully.

[Application of AGREEâ ¡ in evaluating quality of esophageal cancer screening practice guidelines].

High-quality clinical practice guidelines are of great significance for standardizing the clinical diagnosis and treatment process and improving the overall quality of health care. The Appraisal of Guidelines for Research & Evaluation InstrumentⅡ (AGREEⅡ) is one of the recognized tools for the evaluation of the quality of clinical practice guidelines. It has been translated into Chinese and is widely used in guideline formulation and quality evaluation. This article intends to take the comparatively high-quality clinical practice guidelines in the field of esophageal cancer screening in China, i.e. "Expert Consensus on Early Esophageal Cancer and Precancerous Lesion Screening in China (2019, Xinxiang)" as an example, to interpret the use of AGREEⅡ item by item, which might provide a reference for medical and health workers to better understand and use the assessment tool.

[Study on the operation process and construction standard of an esophageal cancer screening cohort study].

One of the most cost-effective measures in cancer prevention on cancer is to advocate to be aware of the disease, consciously changing negative behaviors, and taking the initiative to participate in regular physical checkup programs. Esophageal cancer is one of the malignant tumors accompanied by a heavy disease burden in China. Routine screening, early diagnosis, and treatment are the critical points of preventing and treating the disease. Cohort studies help understand the natural history and risk factors of esophageal cancer and identify high-risk groups of the disease. This paper intends to discuss the construction specifications of the multi-dimensional dynamic follow-up shared cohort for esophageal cancer by studying the risk factors, monitoring, and collecting biological sample information, providing references for developing a standardized and unified screening cohort research procedure, and necessary standards on esophageal cancer in the future.

[Data standard and data sharing in clinical cohort studies].

Data standard plays an important role in the process of data collection, Integration and sharing in clinical cohort studies, and more attention have been paid to it. This paper summarizes the 5 international proven data standard model, analyze their characteristics and development status, and match their data modules with the general data set of the clinical cohorts to evaluate the international data standard models' applicability and provide reference for the development and improvement of the data standard model for clinical cohort studies in China.

Expression of a protein kinase C inhibitor in Purkinje cells blocks cerebellar LTD and adaptation of the vestibulo-ocular reflex.

Cerebellar long-term depression (LTD) is a model system for neuronal information storage that has an absolute requirement for activation of protein kinase C (PKC). It has been claimed to underlie several forms of cerebellar motor learning. Previous studies using various knockout mice (mGluR1, GluRdelta2, glial fibrillary acidic protein) have supported this claim; however, this work has suffered from the limitations that the knockout technique lacks anatomical specificity and that functional compensation can occur via similar gene family members. To overcome these limitations, a transgenic mouse (called L7-PKCI) has been produced in which the pseudosubstrate PKC inhibitor, PKC[19-31], was selectively expressed in Purkinje cells under the control of the pcp-2(L7) gene promoter. Cultured Purkinje cells prepared from heterozygous or homozygous L7-PKCI embryos showed a complete blockade of LTD induction. In addition, the compensatory eye movements of L7-PKCI mice were recorded during vestibular and visual stimulation. Whereas the absolute gain, phase, and latency values of the vestibulo-ocular reflex and optokinetic reflex of the L7-PKCI mice were normal, their ability to adapt their vestibulo-ocular reflex gain during visuo-vestibular training was absent. These data strongly support the hypothesis that activation of PKC in the Purkinje cell is necessary for cerebellar LTD induction, and that cerebellar LTD is required for a particular form of motor learning, adaptation of the vestibulo-ocular reflex.

[Current status on prevalence, treatment and management of hypertension among Chinese adults in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

Objective: To investigate the current status of prevalence, treatment, and management on hypertension among Chinese adults from the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases. Methods: We selected a total of 4 000 residents aged ≥18 years for this questionnaire-based survey by multi-stage clustering sampling in 10 National Demonstration Areas between November and December, 2016. Results: There were 3 891 effective questionnaires. The self-reported prevalence of hypertension among aged ≥35 years was 31.47% (1 011/3 213). For the past two weeks, the self-reported treatment of hypertension was 86.75%(877/1 011), with the rates of guidance as 56.87% (575/1 011) on physical activity, 40.95% (414/1 011) on diet, 38.33% (385/1 011) on weight management, and 22.75% (228/1 011) on smoking cessation. For the past 12 months, 74.68% (755/1 011) of the residents aged ≥35 years were under the proper management and 62.12% (628/1 011) of them were under the standardized management programs. The follow-up program lasted for 4 (P(25)-P(75): 4-12) times per year, with 15 (P(25)-P(75): 10-20) minutes per each visit. Hypertensive patients would mainly visit the outpatient clinics (53.51%), followed by home visits (22.91%) and telephone calls (13.64%). Rate of satisfaction on management services was 94.83% (716/755) from the hypertensive patients. Multivariate analysis showed that the rate of self-reported treatment (OR=1.986, 95%CI: 1.222-3.228) and self-reported standardized management (OR=2.204, 95%CI: 1.519-3.199) on hypertension were higher in the Demonstration Areas with higher implementation scores of self-reported non-communicable diseases management. Conclusions: Prevention and management on hypertension in the Demonstration Areas had met the requirement set for the Demonstration Areas during the "12th Five-Year Plan" . Projects on setting up the National Non-communicable Diseases Demonstration Areas had played an active role in promoting the standardized management program on hypertension.

[Management programs on diabetes among Chinese adults in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

Objective: To understand the current situation on management of diabetes mellitus patients aged 35 and above in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases, in China. Methods: Local residents, aged 18 years and above were randomly selected by a complex, multistage, probability sampling method. Face-to-face questionnaire survey was carried out between November and December 2016. Rates regarding prevalence, treatment and management of diabetes were calculated, and influencing factors of diabetes were analyzed by using the non-conditional logistic regression model. Results: A total of 3 213 residents aged ≥35 years were included in this study, of which 11.48% (369/3 213) reported that they had ever been informed by a doctor or other health worker that their blood sugar level was high or being diabetic. The rate of self-reported treatment among the diabetic patients was 83.20% (307/369). Rates on overall management and standardized management were 69.92% (258/369) and 53.66% (198/369), respectively. Higher rates were seen in residents aged 55 to 64 years, 76.32% for overall management and 59.65% for standardized management. Through multiple logistic regression analysis, we found that standardized management for diabetes was much higher in the Demonstration Areas located in the eastern areas (OR=2.942, 95%CI: 1.547-5.594), or patients with characteristics including high implementation score (OR=3.499, 95%CI: 1.865-6.563), already signed family doctors (OR=5.661, 95%CI: 3.237-9.899), or without hypertension (OR=1.717, 95%CI: 1.010- 2.920). Residents who were living in the first and second batch areas of implementation or responding to the NCDs with positive attitude were more likely to accept standardized management. Conclusion: Prevention and management programs on diabetes had met the requirements set for the Demonstration Areas which had promoted the specific implementation and further development of standardized management on diabetes.

[Study on consumption of vegetables and fruits and related influencing factors among residents from the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

Objective: To investigate the consumption of vegetables and fruits and related influencing factors among residents from the National Demonstration Areas of Comprehensive Prevention and Control of Non-communicable Diseases. Methods: From November to December, 2016, a total of 4 000 residents, aged 18 or above, from ten Demonstration Areas, were selected as participants for this study by multi-stage cluster random sampling method. Information on vegetables, fruits consumption and related influencing factors was collected via questionnaire. Results: A total of 3 891 residents were involved in the final analysis. Daily consumption of vegetables and fruits accounted for 72.1% and 53.6% of the residents under study. The residents who were aware of the National Demonstration Areas activities were more willing to have adequate intake of vegetables (OR=3.017, 95%CI: 2.426-3.753) and fruits (OR=1.261, 95%CI: 1.007-1.580). Residents with higher degree of participation activities of the demonstration areas were more likely to have adequate fruits intake (high degree: OR=1.431, 95%CI: 1.210-1.694; medium degree: OR=1.573, 95%CI: 1.315- 1.882). Conclusions: The implementation of the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases has improved the adequate vegetables and fruits intake among residents. Relevant activities carried out in the Demonstration Areas appeared conducive to the healthy lifestyle of the residents.

[Study on the overall implementation status of the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

Objective: To understand the current overall status of implementation on the National Demonstration Areas of Comprehensive Prevention and Control of Non-communicable Diseases. Methods: According to the scheme design of the questionnaires, all the National Demonstration Areas were involved in this study. For each National Demonstration Areas, eight departments were selected to complete a total of 12 questionnaires. Results: Scores related to the implementation of the National Demonstration Areas accounted for 71.8% of the total 170 points. Based on the scores gathered from this study, the 23-items-index-system that represented the status of project implementation was classified into seven categories. Categories with higher percentile scores would include: monitoring (88.0%), safeguard measures (75.0%), health education and health promotion (75.0%). Categories with lower percentile scores would include: the national health lifestyle actions (67.7%), community diagnosis (66.7%), discovery and intervention of high-risk groups (64.7%), and patient management (60.9%). There were significant differences noticed among the eastern, central and western areas on items as safeguard measures, health education/promotion, discovery and intervention of high-risk groups. In all, the implementation programs in the eastern Demonstration Areas seemed better than in the central or western regions. As for the 23 items, five of the highest scores appeared on policy support, mortality surveillance, tumor registration, reporting system on cardiovascular/cerebrovascular events, and on tobacco control, respectively. However, the lowest five scores fell on healthy diet, patient self-management program, oral hygiene, setting up the demonstration units and promotion on basic public health services, respectively. The overall scores in the eastern region was higher than that in the central or the western regions. The scores in the central and western regions showed basically the same. Conclusions: The overall status of implementation on the National Demonstration Areas was satisfactory. Future attention should be focusing on patient management as well as discovery and intervention of high-risk groups, which also presented the lowest scores, in this survey.

[Study on the effectiveness of implementation: the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

Objective: To assess the implementation and impact of programs carried out by the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases. Methods: Both sociological and epidemiological methods were used to collect qualitative and quantitative data in November and December, 2016 in order to conduct on process and outcome evaluation of the above mentioned objective. In the meantime, case study was also conducted. Results: All the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases were found well implemented across the country, with health education and health promotion, surveillance and safeguard measures in particular. A government-led and inter-sector coordination and communication mechanism had been well established, with more than 16 non-health departments actively involved. 28.7% of the residents living in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases were aware of the key messages related to chronic diseases. Among the residents, 72.1% of them consumed vegetables and 53.6% consumed fruits daily, with another 86.9% walked at least 10 minutes per day. Over 70% of the patients with hypertension or diabetes reported that they were taken care of by the Community Health Centers, and above 50% of them were under standardized management. Residents, living in the National Demonstration Areas under higher ranking of implementation scores, were more likely to be aware of relevant knowledge on chronic disease control and prevention (OR=6.591, 95%CI: 5.188-8.373), salt reduction (OR=1.352, 95%CI: 1.151-1.589), oil reduction (OR=1.477, 95%CI: 1.249-1.746) and recommendation on physical activities (OR=1.975, 95%CI: 1.623- 2.403). Conclusion: The implementation of programs carried out by the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases had served a local platform for the control and prevention of non-communicable diseases, and thus become an important 'carrier' for chronic disease prevention and control programs in China.

Age-related spontaneous lacrimal keratoconjunctivitis is accompanied by dysfunctional T regulatory cells.

In both humans and animal models, the development of Sjögren syndrome (SS) and non-SS keratoconjunctivitis sicca (KCS) increases with age. Here, we investigated the ocular surface and lacrimal gland (LG) phenotype of NOD.B10.H2b mice at 7-14, 45-50, and 96-100 weeks. Aged mice develop increased corneal permeability, CD4+ T-cell infiltration, and conjunctival goblet cell loss. Aged mice have LG atrophy with increased lymphocyte infiltration and inflammatory cytokine levels. An increase in the frequency of CD4+Foxp3+ T regulatory cells (Tregs) was observed with age in the cervical lymph node (CLN), spleen, and LG. These CD4+CD25+ cells lose suppressive ability, while maintaining expression of Foxp3 (forkhead box P3) and producing interleukin-17 (IL-17) and interferon-γ (IFN-γ). An increase of Foxp3+IL-17+ or Foxp3+IFN-γ+ cells was observed in the LG and LG-draining CLN. In adoptive transfer experiments, recipients of either purified Tregs or purified T effector cells from aged donors developed lacrimal keratoconjunctivitis, whereas recipients of young Tregs or young T effector cells failed to develop disease. Overall, these results suggest inflammatory cytokine-producing CD4+Foxp3+ cells participate in the pathogenesis of age-related ocular surface disease.

Mechanisms of uterine estrogen signaling during early pregnancy in mice: an update.

Adherence of an embryo to the uterus represents the most critical step of the reproductive process. Implantation is a synchronized event between the blastocyst and the uterine luminal epithelium, leading to structural and functional changes for further embryonic growth and development. The milieu comprising the complex process of implantation is mediated by estrogen through diverse but interdependent signaling pathways. Mouse models have demonstrated the relevance of the expression of estrogen-modulated paracrine factors to uterine receptivity and implantation window. More importantly, some factors seem to serve as molecular links between different estrogen pathways, promoting cell growth, acting as molecular chaperones, or amplifying estrogenic effects. Abnormal expression of these factors can lead to implantation failure and infertility. This review provides an overview of several well-characterized signaling pathways that elucidates the molecular cross talk involved in the uterus during early pregnancy.