A metal-poor star with abundances from a pair-instability supernova.

The most massive and shortest-lived stars dominate the chemical evolution of the pre-galactic era. On the basis of numerical simulations, it has long been speculated that the mass of such first-generation stars was up to several hundred solar masses1-4. The very massive first-generation stars with a mass range from 140 to 260 solar masses are predicted to enrich the early interstellar medium through pair-instability supernovae (PISNe)5. Decades of observational efforts, however, have not been able to uniquely identify the imprints of such very massive stars on the most metal-poor stars in the Milky Way6,7. Here we report the chemical composition of a very metal-poor (VMP) star with extremely low sodium and cobalt abundances. The sodium with respect to iron in this star is more than two orders of magnitude lower than that of the Sun. This star exhibits very large abundance variance between the odd- and even-charge-number elements, such as sodium/magnesium and cobalt/nickel. Such peculiar odd-even effect, along with deficiencies of sodium and α elements, are consistent with the prediction of primordial pair-instability supernova (PISN) from stars more massive than 140 solar masses. This provides a clear chemical signature indicating the existence of very massive stars in the early universe.

Total Syntheses of Polycyclic Diterpenes Phomopsene, Methyl Phomopsenonate, and iso-Phomopsene via Reorganization of C-C Single Bonds.

The first total syntheses of polycyclic diterpenes phomopsene (1), methyl phomopsenonate (2), and iso-phomopsene (3) have been accomplished through the unusual cascade reorganization of C-C single bonds. This approach features: (i) a synergistic Nazarov cyclization/double ring expansions in one-step, developed by authors, to rapid and stereospecific construction of the 5/5/5/5 tetraquinane scaffold bearing contiguous quaternary centers and (ii) a one-pot strategic ring expansion through Beckmann fragmentation/recombination to efficiently assemble the requisite 5/5/6/5 tetracyclic skeleton of the target molecules 1-3. This work enables us to determine that the correct structure of iso-phomopsene is, in fact, the C7 epimer of the originally assigned structure. Finally, the absolute configurations of three target molecules were confirmed through enantioselective synthesis.

Gorham-Stout disease affecting the spine with cerebrospinal fluid leakage and Chiari-like tonsillar herniation: a rare case report and review of literature.

BACKGROUND: Gorham-Stout disease (GSD) is a very rare disorder characterized by massive osteolysis of poorly understood aetiology. The association between GSD involving the skull base and cerebrospinal fluid (CSF) leakage has been reported in the literature. However, few cases of CSF leakage and Chiari-like tonsillar herniation in GSD involving the spine have been reported. CASE PRESENTATION: We present the case of a 20-year-old man with GSD involving the thoracic and lumbar spine, which caused CSF leakage and Chiari-like tonsillar herniation. The patient underwent four spinal surgeries for osteolytic lesions of the spine over a 10-year period. Here, we discuss the possible aetiology of the development of CSF leakage. Epidural blood patch (EBP) was performed at the T11-T12 level to repair the CSF leakage. After EBP treatment, rebound intracranial hypertension (RIH) developed, and tonsillar herniation disappeared 2 months later. CONCLUSIONS: GSD involving the spine with CSF leakage and Chiari-like tonsillar herniation is relatively rare. For patients who have undergone multiple spinal surgeries, minimally invasive treatment is an alternative treatment for CSF leakage. EBP can repair CSF leakage secondary to GSD and improve chronic brain sagging, with reversibility of Chiari-like malformations.

Supine transfer test-induced changes in cardiac index predict fluid responsiveness in patients without intra-abdominal hypertension.

BACKGROUND: The reversible maneuver that mimics the fluid challenge is a widely used test for evaluating volume responsiveness. However, passive leg raising (PLR) does have certain limitations. The aim of the study is to determine whether the supine transfer test could predict fluid responsiveness in adult patients with acute circulatory failure who do not have intra-abdominal hypertension, by measuring changes in cardiac index (CI). METHODS: Single-center, prospective clinical study in a 25-bed surgery intensive care unit at the Fudan University Shanghai Cancer Center. Thirty-four patients who presented with acute circulatory failure and were scheduled for fluid therapy. Every patient underwent supine transfer test and fluid challenge with 500 mL saline for 15-30 min. There were four sequential steps in the protocol: (1) baseline-1: a semi-recumbent position with the head of the bed raised to 45°; (2) supine transfer test: patients were transferred from the 45° semi-recumbent position to the strict supine position; (3) baseline-2: return to baseline-1 position; and (4) fluid challenge: administration of 500 mL saline for 15-30 min. Hemodynamic parameters were recorded at each step with arterial pulse contour analysis (ProAQT/Pulsioflex). A fluid responder was defined as an increase in CI ≥ 15% after fluid challenge. The receiver operating characteristic curve and gray zone were defined for CI. RESULTS: Seventeen patients were fluid challenge. The r value of the linear correlations was 0.73 between the supine transfer test- and fluid challenge-induced relative CI changes. The relative changes in CI induced by supine transfer in predicting fluid responsiveness had an area under the receiver operating characteristic curve of 0.88 (95% confidence interval 0.72-0.97) and predicted a fluid responder with 76.5% (95% confidence interval 50.1-93.2) sensitivity and 88.2% (95% confidence interval 63.6-98.5) specificity, at a best threshold of 5.5%. Nineteen (55%) patients were in the gray zone (CI ranging from -3 and 8 L/min/m2). CONCLUSION: The supine transfer test can potentially assist in detecting fluid responsiveness in patients with acute circulatory failure without intra-abdominal hypertension. Nevertheless, the small threshold and the 55% gray zone were noteworthy limitation. TRIAL REGISTRATION: Predicting fluid responsiveness with supine transition test (ChiCTR2200058264). Registered 2022-04-04 and last refreshed on 2023-03-26, https://www.chictr.org.cn/showproj.html?proj=166175 .

Expression of the Populus Orthologues of AtYY1, YIN and YANG Activates the Floral Identity Genes AGAMOUS and SEPALLATA3 Accelerating Floral Transition in Arabidopsis thaliana.

YIN YANG 1 (YY1) encodes a dual-function transcription factor, evolutionary conserved between the animal and plant kingdom. In Arabidopsis thaliana, AtYY1 is a negative regulator of ABA responses and floral transition. Here, we report the cloning and functional characterization of the two AtYY1 paralogs, YIN and YANG (also named PtYY1a and PtYY1b) from Populus (Populus trichocarpa). Although the duplication of YY1 occurred early during the evolution of the Salicaceae, YIN and YANG are highly conserved in the willow tree family. In the majority of Populus tissues, YIN was more strongly expressed than YANG. Subcellular analysis showed that YIN-GFP and YANG-GFP are mainly localized in the nuclei of Arabidopsis. Stable and constitutive expression of YIN and YANG resulted in curled leaves and accelerated floral transition of Arabidopsis plants, which was accompanied by high expression of the floral identity genes AGAMOUS (AG) and SEPELLATA3 (SEP3) known to promote leaf curling and early flowering. Furthermore, the expression of YIN and YANG had similar effects as AtYY1 overexpression to seed germination and root growth in Arabidopsis. Our results suggest that YIN and YANG are functional orthologues of the dual-function transcription factor AtYY1 with similar roles in plant development conserved between Arabidopsis and Populus.

Polycomb proteins control floral determinacy by H3K27me3-mediated repression of pluripotency genes in Arabidopsis thaliana.

Polycomb group (PcG) protein-mediated histone methylation (H3K27me3) controls the correct spatiotemporal expression of numerous developmental regulators in Arabidopsis. Epigenetic silencing of the stem cell factor gene WUSCHEL (WUS) in floral meristems (FMs) depends on H3K27me3 deposition by PcG proteins. However, the role of H3K27me3 in silencing of other meristematic regulator and pluripotency genes during FM determinacy has not yet been studied. To this end, we report the genome-wide dynamics of H3K27me3 levels during FM arrest and the consequences of strongly depleted PcG activity on early flower morphogenesis including enlarged and indeterminate FMs. Strong depletion of H3K27me3 levels results in misexpression of the FM identity gene AGL24, which partially causes floral reversion leading to ap1-like flowers and indeterminate FMs ectopically expressing WUS and SHOOT MERISTEMLESS (STM). Loss of STM can rescue supernumerary floral organs and FM indeterminacy in H3K27me3-deficient flowers, indicating that the hyperactivity of the FMs is at least partially a result of ectopic STM expression. Nonetheless, WUS remained essential for the FM activity. Our results demonstrate that PcG proteins promote FM determinacy at multiple levels of the floral gene regulatory network, silencing initially floral regulators such as AGL24 that promotes FM indeterminacy and, subsequently, meristematic pluripotency genes such as WUS and STM during FM arrest.

MicroRNA-30a Targets Notch1 to Alleviate Podocyte Injury in Lupus Nephritis.

The microRNA miR-30a has been reported to mitigate podocyte damage and resist injurious factors in lupus nephritis (LN), but the precise molecular mechanisms underlying these effects remain elusive. We hypothesized that miR-30a can ameliorate podocyte injury by downregulating the Notch1 signaling pathway and investigated the role of miR-30a in the pathogenesis of podocyte-treated with Immunoglobulin G from patients with LN (IgG-LN). The study enrolled 30 patients from new-onset systemic lupus erythematosus and 28 healthy individuals, then evaluated the levels of their serum miR-30a using RT-qPCR. Additionally, MPC5 cells were transfected with NICD-vector to overexpress Notch1, then with miR-30a mimics or inhibitors to determine miR-30a effects on Notch1. Analysis of function and regulatory mechanisms were performed with RT-qPCR, Western blotting, and CCK8 assays. Furthermore, we verified the candidate sequence targeted by miR-30a using a luciferase reporter gene assay. We observed a significant decrease in the serum miR-30a levels in patients with LN. Also, in IgG-LN-treated podocytes, miR-30a decreased and Notch1 expression was elevated. Bioinformatic analysis and transfection experiments revealed that Notch1 is a direct target of miR-30a. Further supporting this finding, miR-30a upregulation appeared to alleviate IgG-LN-treated podocyte injury, and Notch1 overexpression reversed this effect. To conclude, miR-30a can ameliorate podocyte injury via suppression of the Notch1 signaling pathway.

Subacute thyroiditis during early pregnancy: a case report and literature review.

BACKGROUND: Subacute thyroiditis (SAT) is rarely diagnosed in pregnant women, and only 7 cases have been reported to date. Thyroid dysfunction, especially hyperthyroidism, during pregnancy has been associated with both maternal and neonatal complications. Thus, the early diagnosis and treatment of SAT during pregnancy may be beneficial. We present a case report and literature review to complement the diagnostic evaluation and management of SAT during pregnancy. CASE PRESENTATION: A 27-year-old woman presented in gestational week 17 of her first pregnancy and had a negative prior medical history. She presented to the Endocrinology Department complaining of neck pain for one month that had intensified in the last five days. Physical examination revealed a diffusely enlarged thyroid gland that was firm and tender on palpation. The patient also had an elevated temperature and heart rate. The increasing and long-lasting pain coupled with a decreased level of thyroid-stimulating hormone indicated hyperthyroidism. Ultrasound findings were indicative of SAT. Importantly, the pain was so severe that 10 mg of oral prednisone per day was administered in gestational week 18, which was increased to 15 mg/d after 10 days that was discontinued in week 28. Levothyroxine was started in gestational week 24 and administered throughout the pregnancy. The patient responded well to the treatments, and her neck pain disappeared in gestational week 21. She gave birth to a healthy male in gestational week 41. CONCLUSION: SAT can be diagnosed and effectively managed during pregnancy, thus benefiting mothers and infants.

APOD: accurate sequence-based predictor of disordered flexible linkers.

MOTIVATION: Disordered flexible linkers (DFLs) are abundant and functionally important intrinsically disordered regions that connect protein domains and structural elements within domains and which facilitate disorder-based allosteric regulation. Although computational estimates suggest that thousands of proteins have DFLs, they were annotated experimentally in <200 proteins. This substantial annotation gap can be reduced with the help of accurate computational predictors. The sole predictor of DFLs, DFLpred, trade-off accuracy for shorter runtime by excluding relevant but computationally costly predictive inputs. Moreover, it relies on the local/window-based information while lacking to consider useful protein-level characteristics. RESULTS: We conceptualize, design and test APOD (Accurate Predictor Of DFLs), the first highly accurate predictor that utilizes both local- and protein-level inputs that quantify propensity for disorder, sequence composition, sequence conservation and selected putative structural properties. Consequently, APOD offers significantly more accurate predictions when compared with its faster predecessor, DFLpred, and several other alternative ways to predict DFLs. These improvements stem from the use of a more comprehensive set of inputs that cover the protein-level information and the application of a more sophisticated predictive model, a well-parametrized support vector machine. APOD achieves area under the curve = 0.82 (28% improvement over DFLpred) and Matthews correlation coefficient = 0.42 (180% increase over DFLpred) when tested on an independent/low-similarity test dataset. Consequently, APOD is a suitable choice for accurate and small-scale prediction of DFLs. AVAILABILITY AND IMPLEMENTATION: https://yanglab.nankai.edu.cn/APOD/.

Predictive and prognostic value of v-set and transmembrane domain-containing 1 expression in monocytes for coronary artery disease.

The aim of this study was to investigate the correlation between v-set and transmembrane domain-containing 1 (VSTM1) expression and incidence of major adverse cardiac events (MACE) in patients with coronary heart disease (CHD). A total of 310 patients were divided into a non-acute coronary syndrome (non-ACS) group (containing the stable angina group, and the asymptomatic coronary artery diseaseand other patients group) and an ACS group (containing unstable angina and acute myocardial infarction patients). Monocytic VSTM1 expression levels (assessed via average fluorescence intensity derived from antibody binding to VSTM1) in each group were detected and analyzed. The cut-off value of monocytic VSTM1 expression to predict the onset of ACS and MACE was confirmed. VSTM1 expression in monocytes from the ACS group was lower than that of the non-ACS group. The incidence of MACEs in the high VSTM1-expression group was much less than that of those in the low VSTM1 expression group at the 1 year follow-up stage. VSTM1 expression had an independent-inversed association with increased incidence of MACE and ACS. VSTM1 expression in monocytes may help to predict the occurrence of ACS in patients with CHD, and moreover it may provide the means to evaluate MACE prognosis during CHD patient follow-up.

Differential diagnostic value of bilateral inferior Petrosal sinus sampling (BIPSS) in ACTH-dependent Cushing syndrome: a systematic review and Meta-analysis.

BACKGROUND: Previous studies have shown inconsistent results about the usefulness of bilateral inferior petrosal sinus sampling (BIPSS) in differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome. This meta-analysis evaluated the diagnostic value of BIPSS via the published literature. METHODS: This study searched PubMed, Embase, Web of Science, Cochrane library, and Wanfang database for published data on the use of BIPSS in Cushing syndrome differential diagnosis as of October 2019. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curves were calculated based on the relevant data. RESULTS: This meta-analysis included a total of 23 studies with 1642 patients. The calculated sensitivity, specificity, PLR, and NLR were 0.94 (95% confidence interval, CI: 0.91-0.96), 0.89 (95% CI: 0.79-0.95), 8.8 (95% CI: 4.3-17.9), and 0.07 (95% CI: 0.04-0.11), respectively. The pooled DOR and area under the ROC curve were 129 (95% CI: 48-345) and 0.97 (95% CI: 0.95-0.98), respectively. CONCLUSION: This meta-analysis indicated that BIPSS had high diagnostic value for detecting ACTH in patients with ACTH-dependent Cushing syndrome, and BIPSS should be used as an effective method to identify ACTH-secretion sources.

Impacts of urbanization on the temperature-cardiovascular mortality relationship in Beijing, China.

The effect of temperature on cardiovascular disease (CVD) mortality has been extensively studied. However, it remains largely unknown over whether there is any difference between urban and suburban areas within the same city and how urbanization modifies the relationship between temperature and CVD mortality. In order to examine whether the association between temperature and CVD mortality existed difference in urban and suburban areas, and how urbanization modified this association, we used a distributed lag nonlinear model and a generalized additive model to investigate temperature-related CVD mortality in urban and suburban areas in Beijing, China, from 2006 to 2011. The age, gender, and educational attainment of the population were stratified to explore the modifying effect. We observed that the impacts of heat and cold temperature on CVD mortality were higher in suburban areas than in urban areas. In addition, the elderly and illiterate subjects in suburban areas were more vulnerable to both heat and cold than their counterparts in urban areas. Moreover, higher urbanization levels were significantly associated with districts having lower the excess risks for temperature- CVD mortality. Our findings provide evidence that populations in suburban Beijing have higher risk of temperature-related CVD mortality than those in urban areas. Therefore, greater attention should be paid to vulnerable groups in suburban areas to reduce temperature-related health burden.

Genetic association of polymorphism rs2230054 in CXCR2 gene with gout in Chinese Han male population.

Neutrophils are crucial in the process of gout flare and remission. The signal transduction pathway of chemokine plays a vital role in the chemotaxis and activation of neutrophils. CXCR2 gene knocked out can avoid the acute neutrophilic inflammation stimulated by monosodium urate (MSU) crystals in mice. To investigate the relationship among CXCR1 rs2234671, CXCR2 rs1126579, and rs2230054 polymorphisms with gout arthritis flare in the Chinese Han male population, a case-control study was carried out in 412 gout patients and 508 gout-free individuals. TaqMan probes fluorescence real-time polymerase chain reaction (PCR) was used to genotype CXCR1 rs2234671, CXCR2 rs1126579, and rs2230054 SNPs. There was a clear link between CXCR2 rs2230054 T included genotypic and T allelic frequencies and gout cases (c2 = 9.286, p = 0.002 by genotype, c2 = 8.639, p = 0.003 by allele), while no significant differences were observed between the gouty arthritis group and the control group in CXCR1 rs2234671 and CXCR2 rs1126579 genotypic and allelic frequencies. Multivariate logistic regression analysis showed that the T genotype included in rs2230054 can decrease the risk of gouty arthritis (adjusted OR = 0.47; 95% CI: 0.31-0.74) compared with the CC genotype. Our study might suggest that rs2230054 in CXCR2 is associated with susceptibility to gout in Chinese males.

Selenoprotein S protects against high glucose-induced vascular endothelial apoptosis through the PKCßII/JNK/Bcl-2 pathway.

Vascular endothelial apoptosis is closely associated with the pathogenesis and progression of diabetic macrovascular diseases. Selenoprotein S (SelS) participates in the protection of vascular endothelial and smooth muscle cells from oxidative and endoplasmic reticulum stress-induced injury. However, whether SelS can protect vascular endothelium from high glucose (HG)-induced apoptosis and the underlying mechanism remains unclear. The present study preliminarily analyzed aortic endothelial apoptosis and SelS expression in diabetic rats in vivo and the effects of HG on human umbilical vein endothelial cell (HUVEC) apoptosis and SelS expression in vitro. Subsequently, SelS expression was up- or downregulated in HUVECs using the pcDNA3.1-SelS recombinant plasmid and SelS-specific small interfering RNAs, and the effects of high/low SelS expression on HG-induced HUVEC apoptosis and a possible molecular mechanism were analyzed. As expected, HG induced vascular endothelial apoptosis and upregulated endothelial SelS expression in vivo and in vitro. SelS overexpression in HUVECs suppressed HG-induced increase in apoptosis and cleaved caspase3 level, accompanied by reduced protein kinase CßII (PKCßII), c-JUN N-terminal kinase (JNK), and B-cell lymphoma/leukemia-2 (Bcl-2) phosphorylation. In contrast, inhibiting SelS expression in HUVECs further aggravated HG-induced increase in apoptosis and cleaved caspase3 level, which was accompanied by increased PKCßII, JNK, and Bcl-2 phosphorylation. Pretreatment with PKC activators blocked the protective effects of SelS and increased the apoptosis and cleaved caspase3 level in HUVECs. In summary, SelS protects vascular endothelium from HG-induced apoptosis, and this was achieved through the inhibition of PKCßII/JNK/Bcl-2 pathway to eventually inhibit caspase3 activation. SelS may be a promising target for the prevention and treatment of diabetic macrovascular complications.

Differential Expression of MicroRNAs and miR-206-Mediated Downregulation of BDNF Expression in the Rat Fetal Brain Following Maternal Hypothyroidism.

To investigate the mechanism responsible for the neurological alterations, miRNA expression profile and brain-derived neurotrophic factor (BDNF) were evaluated in brain tissues of fetal or neonatal rats and from maternal rats with hypothyroidism. Ninety female Wistar rats were divided into a control and a hypothyroid group, which were mated. Brain samples of the offspring were obtained at maternal embryonic day (E) E13 and E17 as well as postnatal day (P) P0 and P7, and the hippocampus and cortex were separated at P7. BDNF mRNA at E13 was tested by real-time PCR and protein expression by Western blot. Luciferase assays were used to confirm that miR-206 targets the 3'-untranslated region (3'-UTR) of BDNF. In the brain tissues of fetal and neonatal rats from maternal rats with hypothyroidism, differentiation miRNAs profile were found at E13, E17, P0, and P7. Compared with the control group, miR-206 levels in the hypothyroidism group were increased by 3.1-fold by micro-array, and were higher as measured by SYBR green real-time qRT-PCR (p<0.01). There was no significant difference in the BDNF mRNA levels at E13 between the hypothyroidism group and the control group (1.767±0.477 vs. 1.798±0.462, respectively; p>0.05), but pro-BDNF and mature BDNF protein levels in the hypothyroid group at E13 were significantly lower than those in the control group (p<0.05). miR-206 targeted 3'-UTR of BDNF. Our data highlight the role of miR-206 as a post-transcriptional inhibitor of BDNF at E13 in pregnant hypothyroid rats.

Predictive modeling of microbial single cells: A review.

In practice, food products tend to be contaminated with food-borne pathogens at a low inoculum level. However, the huge potential risk cannot be ignored because microbes may initiate high-speed growth suitable conditions during the food chain, such as transportation or storage. Thus, it is important to perform predictive modeling of microbial single cells. Several key aspects of microbial single-cell modeling are covered in this review. First, based on previous studies, the techniques of microbial single-cell data acquisition and growth data collection are presented in detail. In addition, the sources of microbial single-cell variability are also summarized. Due to model microbial growth, traditional deterministic mathematical models have been developed. However, most models fail to make accurate predictions at low cell numbers or at the single-cell level due to high cell-to-cell heterogeneity. Stochastic models have been a subject of great interest; and these models take into consideration the variability in microbial single-cell behavior.

miRNA-125b-5p Suppresses Hypothyroidism Development by Targeting Signal Transducer and Activator of Transcription 3.

BACKGROUND A deficiency of maternal thyroid hormones (THs) during pregnancy has severe impacts on fetal brain development. Neural stem cells (NSCs) are major targets of THs and provided a powerful model to explore the underlying mechanism of THs during brain development. Although miRNA-125 might be associated with the NSCs differentiation, the relationship between miR-125 and hypothyroidism (HypoT) development remains unclear. MATERIAL AND METHODS In our study, we screened a differentially expressed gene miR-125b-5p from brain between euthyroid (EuT) and HypoT rats. In vitro, we employed anion exchange resin to remove THs to stimulate HypoT. QRT-PCR and Western blot were used to examine the expression of signal transducer and activator of transcription 3 (Stat3). The relationship between miR-125b-5p and Stat3 was detected via a dual-luciferase assay. RESULTS QRT-PCR results showed that the level of miR-125b-5p in HypoT rat brains was significantly suppressed, suggesting some relationship between miR-125b-5p and HypoT. In C17.2, miR-125b-5p promoted cell differentiation into neurons by regulating the expression of tubulin beta chain 3 (TUBB3) and glial fibrillary acid protein (GFAP). QRT-PCR and Western blot results revealed that miR-125b-5p mimic modulated the contents of total Stat3 and p-Stat3. A dual-luciferase assay showed that miR-125b-5p negatively regulated the expression of Stat3 by binding with the first site in 3' UTR of Stat3. CONCLUSIONS These results revealed Stat3 is a new target of miR-125b-5p and revealed the mechanism of miR-125b-5p suppressing HypoT development. These findings provide a new target for HypoT therapy.

Lower Serum Vitamin D Level Was Associated with Risk of Dry Eye Syndrome.

BACKGROUND To determine the association between serum 25(OH)D and dry eye syndrome (DES) incidence. This study was also designed to determine whether serum 25(OH)D levels were associated with ocular parameter of DES patients. MATERIAL AND METHODS This is a case-control study with 70 DES cases and 70 healthy controls. Clinical data included body mass index (BMI, kg/m²), smoking history, diabetes, and blood pressure. Serum 25(OH)D was chosen as the main parameter and reflected the level of vitamin D. The DES parameters included ocular surface disease index (OSDI) scales, tear film breakup time (TBUT) and Schirmer test I. The differences in each parameter between case and control groups were detected and the association of serum 25(OH)D and DES parameter were detected. RESULTS It was shown that 25(OH)D levels were lower in patients with DES than in healthy controls. When the 25(OH)D levels was stratified, vitamin D deficiency was more common in the DES cases. In advanced studies, it was found that there were statistically significant associations between serum 25(OH) D levels and the Schimer test, TBUT, and OSDI scales. CONCLUSIONS A significant association between serum 25(OH)D level and DES incidence was detected in this study. Considering the relatively small sample size of this study, larger studies are needed in the future.

The Suppression of Kallistatin on High-Glucose-Induced Proliferation of Retinal Endothelial Cells in Diabetic Retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a severe ocular complication of diabetes. Kallistatin has multiple biological functions including anti-inflammation and antiangiogenesis. Our aim was to detect the level of kallistatin in the vitreous of proliferative DR (PDR) and its effect on proliferation, migration, and tube formation of human retinal endothelial cells (HRECs) under high glucose in an in vitro model. METHODS: Vitreous humor samples were obtained through pars plana vitrectomy from 7 nondiabetic patients with idiopathic macular holes or idiopathic preretinal membranes and 10 PDR patients. The vitreous levels of kallistatin were measured by ELISA. HRECs were cultured with different concentrations of glucose and 1,000 nM kallistatin. The proliferation of HRECs was evaluated by a Cell Counting Kit-8 assay. Cell migration was assessed by using Transwell chambers. Cell sprouting was detected by tube formation assay. The RNA interference technique was used to create the knockdown of the kallistatin gene in HRECs for evaluating its effect on the proliferation, migration, and tube formation of HRECs. RESULTS: The vitreous levels of kallistatin were significantly lower in PDR patients in comparison with nondiabetic control patients (p < 0.05). Compared with 5 mM of normal glucose treatment, high glucose (30 mM) in culture significantly increased the proliferation and migration of HRECs, which was attenuated by 1,000 nM kallistatin. In addition, 1,000 nM kallistatin was shown to suppress high-glucose-induced tube formation and the expression of vascular endothelial growth factor of HRECs. Furthermore, the knockdown of kallistatin enhanced the proliferation, migration, and tube formation of HRECs. CONCLUSIONS: Our data indicated that kallistatin might be a potent inhibitory factor for PDR. The molecule plays its role by inhibiting high-glucose-induced proliferation of HRECs. The findings suggest that the upregulation of kallistatin might be an effective strategy for PDR prevention.