Clinical characteristics of cystic encephalomalacia in children.

Purpose: To investigate the primary causes and clinical characteristics of cystic encephalomalacia (CE) in children. Methods: The clinical data of 50 children who were admitted to our hospital due to CE between January 2008 and December 2020 were retrospectively reviewed. Their primary causes, clinical manifestations and cranial magnetic resonance imaging features were analyzed. Results: Among all patients, 5 had prematurity, 19 had hypoxic-ischemic encephalopathy (HIE), 13 had intracranial infection, 14 had traumatic brain injury and hemorrhage, 4 had cerebral infarction, 2 had congenital genetic diseases, and 1 had hypoglycemia. The average time from primary disease onset to CE diagnosis was 70.1 ± 61.0 days. The clinical manifestations included speech or motor developmental delay (n = 33), epilepsy (n = 31), dystonia (n = 27), limb paralysis (n = 16), and visual or auditory impairment (n = 5). Patients with HIE as the primary cause of CE had a significantly higher occurrence of dystonia, while a significantly higher incidence of paralysis was observed in those with cerebral infarction as the primary cause. Conclusion: CE in children is mainly caused by HIE, intracranial infection, and cerebral hemorrhage. The major clinical manifestations included speech or motor developmental delay, epilepsy, and dystonia. Magnetic resonance imaging is an important tool for the diagnosis of CE.

WRKY22 Transcription Factor from Iris laevigata Regulates Flowering Time and Resistance to Salt and Drought.

Iris laevigata Fisch. is an excellent ornamental plant in cold regions due to its unique ornamental ability and strong cold resistance. However, the flowering period of the population is only about 20 days, greatly limiting its potential uses in landscaping and the cutting flower industry. In addition, I. laevigata is often challenged with various abiotic stresses including high salinity and drought in its native habitats. Thus, breeding novel cultivars with delayed flowering time and higher resistance to abiotic stress is of high importance. In this study, we utilized sequencing data from the I. laevigata transcriptome to identify WRKYs and characterized IlWRKY22, a key transcription factor that modulates flowering time and abiotic stress responses. IlWRKY22 is induced by salt and drought stress. We cloned IlWRKY22 and found that it is a Group IIe WRKY localized in the nucleus. Overexpressing IlWRKY22 in Arabidopsis thaliana (L.) Heynh. and Nicotiana tabacum L. resulted in a delayed flowering time in the transgenic plants. We created transgenic N. tabacum overexpressing IlWRKY22, which showed significantly improved resistance to both salt and drought compared to the control plants. Thus, our study revealed a unique dual function of IlWRKY22, an excellent candidate gene for breeding novel Iris cultivars of desirable traits.

Bilateral versus unilateral orchidopexy: IVF/ICSI-ET outcomes.

Introduction: Cryptorchidism is a common genital disorder. Approximately 20% of azoospermic or infertile men reported having histories of cryptorchidism. Bilateral cryptorchidism may have been more condemned than unilateral cryptorchidism. Early treatment by orchidopexy is the definitive procedure for cryptorchid patients with cryptorchidism. However, fertility potency after orchidopexy may be adversely affected and assisted reproduction techniques will be required for infertile patients. Objective: To compare the reproductive outcomes between unilateral and bilateral orchidopexy groups. Methods: A retrospective cohort study at a tertiary hospital, including a total of 99 infertile men who underwent orchidopexy to treat cryptorchidism and subsequently underwent their first IVF/ICSI-ET cycle. Men were grouped according to the laterality of their cryptorchidism and orchidopexy surgeries they received. Fertilization rate and live birth rate were chosen as parameters for evaluating outcomes. Results: The sperm concentration and viability were significantly higher in unilateral orchidopexy group than in bilateral orchidopexy group (28.09 ± 27.99 vs 7.99 ± 14.68, P=0.001; 33.34 ± 22.52 vs 11.95 ± 17.85, P=0.001). Unilateral orchidopexy group showed lower demand for ICSI (66.07% vs 95.35%, P<0.001). Interestingly, both groups exhibited similar rates of fertilization, clinical pregnancy, live birth and birth defect. Boy birth ratio was lower in bilateral orchidopexy group as compared to unilateral orchidopexy group (27.27% vs 58.62%, P=0.026). Conclusion: A history of bilateral orchidopexy surgery correlates with a worsened sperm parameter and a higher demand for ICSI as compared to patients with history of unilateral orchidopexy. However, this does not influence the final live birth rate.

Gut microbiota regulates host melatonin production through epithelial cell MyD88.

Melatonin has various physiological effects, such as the maintenance of circadian rhythms, anti-inflammatory functions, and regulation of intestinal barriers. The regulatory functions of melatonin in gut microbiota remodeling have also been well clarified; however, the role of gut microbiota in regulating host melatonin production remains poorly understood. To address this, we studied the contribution of gut microbiota to host melatonin production using gut microbiota-perturbed models. We demonstrated that antibiotic-treated and germ-free mice possessed diminished melatonin levels in the serum and elevated melatonin levels in the colon. The influence of the intestinal microbiota on host melatonin production was further confirmed by fecal microbiota transplantation. Notably, Lactobacillus reuteri (L. R) and Escherichia coli (E. coli) recapitulated the effects of gut microbiota on host melatonin production. Mechanistically, L. R and E. coli activated the TLR2/4/MyD88/NF-κB signaling pathway to promote expression of arylalkylamine N-acetyltransferase (AANAT, a rate-limiting enzyme for melatonin production), and MyD88 deficiency in colonic epithelial cells abolished the influence of intestinal microbiota on colonic melatonin production. Collectively, we revealed a specific underlying mechanism of gut microbiota to modulate host melatonin production, which might provide novel therapeutic ideas for melatonin-related diseases.

Relationship between peri-coronary inflammation and coronary vascular function in patients with suspected coronary artery disease.

Background: In this study, we aim to investigate the relationship between the attenuation of peri-coronary adipose tissue (PCAT) in patients with suspected coronary artery disease (CAD) and the assessment of coronary vascular functions using coronary flow reserve (CFR). Methods: We included 364 patients who underwent 13N-NH3 positron emission tomography/computed tomography and coronary computed tomography angiography (CCTA). We determined the relationship between fat attenuation index (FAI), PCAT volume, and other qualitative CT-derived anatomic parameters with CFR. Results: We detected a decrease in CFR (<2.5) in 206 (57%) patients. At the patient level, those with reduced CFR showed a significantly higher prevalence of diffused atherosclerosis (41% vs. 23%; P < 0.001) and higher FAI (-75.5 HU vs. -77.1 HU; P = 0.014). In patients without obstructive CAD, FAI was significantly higher in those with reduced CFR (-75.5 HU vs. -77.7 HU, P = 0.026). On the vessel level, 1,092 vessels were analyzed, and 642 (59%) exhibited reduced CFR. The vessels with reduced CFR presented a significantly higher prevalence of obstructive CAD (37% vs. 26%; P < 0.001), diffused atherosclerosis (22% vs. 11%; P < 0.001), low-attenuation plaque (6% vs. 3%; P = 0.030), and positive remodeling (7% vs. 2%; P = 0.001). FAI was higher in vessels with reduced CFR (-80.8 HU vs. -81.8 HU; P = 0.045) than in normal CFR. In the patient-level analysis, obstructive CAD, diffused atherosclerosis, and FAI were independently linked with CFR. FAI was still associated with global CFR after adjusting for traditional risk factors (age, hypertension, diabetes, hyperlipidemia, and smoking). FAI remained independently associated with reduced CFR in patients without obstructive CAD. Conclusions: Coronary perivascular inflammation evaluated by CCTA was independently associated with coronary vascular function. In patients without obstructive CAD, FAI was higher in the presence of reduced CFR. Altogether, FAI can help reveal microcirculatory damage in patients who do not exhibit epicardial artery stenosis.

Determination of viable myocardium through delayed enhancement cardiac magnetic resonance imaging combined with 18F-FDG PET myocardial perfusion/metabolic imaging before CABG.

PURPOSE: Study aims to investigate the consistency of delayed enhancement cardiac magnetic resonance imaging (DE-CMR) and 18F-FDG PET myocardial imaging in evaluating myocardial viability before CABG. METHODS: The study analyzed data from 100 patients who were examined with DE-CMR, PET imaging, and echocardiography before and after CABG. All subjects were followed up for 6-12 month post- CABG. RESULTS: DE-CMR and PET imaging have high consistency (90.1%; Kappa value = 0.71, p < 0.01) in determining myocardial viability. The degree of delayed enhancement was negatively correlated with the improvement in myocardial contractile function in this segment after revascularization (P < 0.001). The ratio of scarred myocardial segments and total DE score was significantly lower in the improvement group than non-improvement group. Multivariate regression identified that hibernating myocardium (OR = 1.229, 95%CI: 1.053-1.433, p = 0.009) was influencing factor of LVEF improvement after CABG. CONCLUSION: Both imaging techniques are consistent in evaluating myocardial viability. Detecting the number of hibernating myocardium by PET is also important to predict the left heart function improvement after CABG.

Luteal phase support of intramuscular progesterone associated with lower hypertensive disorders of pregnancy as compared to vaginal progesterone: A cohort study.

OBJECTIVE: To compare the hypertensive disorders of pregnancy (HDP) risk between vaginal and intramuscular (IM) progesterone in programmed frozen-thawed embryo transfer (FET) cycles. METHODS: This was a retrospective cohort study at a tertiary hospital, and only women who achieved ongoing pregnancy after programmed FET between January 2018 and June 2022 were included. Women with chronic hypertension before pregnancy or with history of gestational hypertension or pre-eclampsia in previous pregnancies were excluded. All women were divided into IM progesterone or vaginal progesterone groups according to the route of progesterone supplementation. Follow-up information on obstetric complications and neonatal outcomes were obtained by telephonic interviews. The primary outcome was HDP. Association between routes of progesterone supplementation and HDP was assessed by subgroup analysis and multivariable logistic regression. RESULTS: A total of 5891 programmed FET cycles (3196 IM progesterone cycles and 2695 vaginal progesterone cycles) were included in the analysis. The prevalence of HDP in the IM progesterone group was significantly lower than that of the vaginal progesterone group (6.54% vs 9.17%, P < 0.001). Therein, the prevalence of gestational hypertension (3.57% vs 4.94%, P = 0.009) and pre-eclampsia (2.97% vs 4.23%, P = 0.009) in the IM progesterone group were all significantly lower as compared to the vaginal progesterone group. According to subgroup analysis, IM progesterone was associated with lower HDP risk in all subgroups. The logistic regression analysis showed that the IM progesterone cycles were associated with lower risk of HDP compared to vaginal progesterone cycles (adjusted odds ratio 0.66, 95% CI: 0.54-0.80, P < 0.001). CONCLUSION: Among women undergoing programmed FET cycles, progesterone supplementation with IM progesterone was associated with reduced HDP risk compared to vaginal progesterone.

Serine synthesis sustains macrophage IL-1ß production via NAD+-dependent protein acetylation.

Serine metabolism is involved in the fate decisions of immune cells; however, whether and how de novo serine synthesis shapes innate immune cell function remain unknown. Here, we first demonstrated that inflammatory macrophages have high expression of phosphoglycerate dehydrogenase (PHGDH, the rate-limiting enzyme of de novo serine synthesis) via nuclear factor κB signaling. Notably, the pharmacological inhibition or genetic modulation of PHGDH limits macrophage interleukin (IL)-1ß production through NAD+ accumulation and subsequent NAD+-dependent SIRT1 and SIRT3 expression and activity. Mechanistically, PHGDH not only sustains IL-1ß expression through H3K9/27 acetylation-mediated transcriptional activation of Toll-like receptor 4 but also supports IL-1ß maturation via NLRP3-K21/22/24/ASC-K21/22/24 acetylation-mediated activation of the NLRP3 inflammasome. Moreover, mice with myeloid-specific depletion of Phgdh show alleviated inflammatory responses in lipopolysaccharide-induced systemic inflammation. This study reveals a network by which a metabolic enzyme, involved in de novo serine synthesis, mediates post-translational modifications and epigenetic regulation to orchestrate IL-1ß production, providing a potential inflammatory disease target.

Prognostic significance of PD-L1 expression in pancreatic cancer: evidence from an updated meta-analysis.

Recent studies revealed that programmed cell death ligand 1 (PD-L1) expression was associated with unfavorable prognosis in various solid tumors, but its clinical relevance for pancreatic cancer has not yet been well established. This meta-analysis summarizes the potential prognostic value of PD-L1 in pancreatic cancer. A quantitative meta-analysis was performed by a systematic search of databases including PubMed, EMBASE, Web of Science, Cochrane library, Scopus and Ovid for eligible studies on the prognostic significance of PD-L1 in pancreatic cancer patients. Pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated to evaluate the strength of the link between PD-L1 expression and clinical prognosis of patients. Seventeen eligible studies with 2669 patients were included in our study. A significant association was observed between PD-L1 abundance and poor overall survival (OS) of patients with pancreatic cancers, with a pooled hazard ratio (HR) of 1.902, 95% CI: 1.657-2.184. Sensitivity analysis confirmed the reliability of our results. Subgroup analysis shows that differences in regions and detection methods of PD-L1 did not change the overall predictive value of PD-L1 for poor prognosis in pancreatic cancer patients. This meta-analysis indicated that the expression of PD-L1 is associated with a worse OS in pancreatic cancer patients. Additionally, PD-L1 may act as a potential parameter for predicting poor prognosis and thus providing a promising target for anticancer therapy in pancreatic cancer.

The time interval between laparoscopic tubal ligation and frozen-thawed embryo transfer does not affect the reproductive outcomes.

BACKGROUND: Hydrosalpinx may decrease implantation and pregnancy rates after embryo transfer. Laparoscopic tubal ligation after embryo freeze and before frozen-thawed embryo transfer (FET) is effective at improving reproductive outcomes for hydrosalpinx patients. This study is to find out the optimal interval between laparoscopic tubal ligation and FET. METHODS: We retrospectively analyzed 259 infertile women who performed laparoscopic tubal ligation for embryo freeze and FET. Participants were divided into three groups, based on the interval between laparoscopic tubal ligation and FET. Group I: <30 days; Group II: 31- 60 days; Group III: >60 days. Outcomes of cleavage-stage and blastocyst-stage embryo FET were analyzed respectively. RESULTS: There was no significant difference in clinical pregnancy rate, live birth rate, implantation rate, biochemical pregnancy rate, ectopic pregnancy rate, miscarriage rate and preterm birth rate among the three groups, in both cleavage-stage and blastocyst-stage embryo FET cycles. In cleavage-stage embryo FET cycle, singleton gestational age was significantly younger in group III (38.11 ± 2.28 weeks) compared with group I (39.29 ± 1.06 weeks, P = 0.001) and group II (38.96 ± 1.05, P = 0.026). Singleton birth weight was significantly heavier in group II (3.65 ± 0.32 Kg) compared with group I (3.38 ± 0.29 Kg, P = 0.001) and group III (3.35 ± 0.60 Kg, P = 0.004). Twin birth weight was significantly heavier in group III (2.72 ± 0.43 Kg) compared to group I (2.23 ± 0.67 Kg, P = 0.002). In blastocyst-stage embryo FET cycles, twin gestational age was significantly younger in group II (34.07 ± 3.18 weeks) compared with group I (35.56 ± 2.27 weeks, P = 0.049) and group III (36.50 ± 1.47 weeks, P = 0.005). Twin birth weight was significantly heavier in group III (2.71 ± 0.39 Kg) compared to group II (2.39 ± 0.67 Kg, P = 0.009). CONCLUSIONS: The duration of the interval between laparoscopic tubal ligation and FET does not affect the reproductive outcomes; however, it may affect the neonate outcomes to some extent.

Scutellarin attenuates oxidative stress and neuroinflammation in cerebral ischemia/reperfusion injury through PI3K/Akt-mediated Nrf2 signaling pathways.

Cerebral ischemia/reperfusion injury (CIRI) seriously threatens human life and health. Scutellarin (Scu) exhibits neuroprotective effects, but little is known about its underlying mechanism. Therefore, we explored its protective effect on CIRI and the underlying mechanism. Our results demonstrated that Scu rescued HT22 cells from cytotoxicity induced by oxygen and glucose deprivation/reoxygenation (OGD/R). Scu also showed antioxidant activity by promoting nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, upregulating heme oxygenase-1 (HO-1) expression, increasing superoxide dismutase (SOD) activity, and inhibiting reactive oxygen species (ROS) generation in vitro. Additionally, Scu reduced nuclear factor-kappa B (NF-κB) activity and the levels of pro-inflammatory factors. Interestingly, these effects were abolished by Nrf2 inhibition. Furthermore, Scu reduced infarct volume and blood-brain barrier (BBB) permeability, improved sensorimotor functions and depressive behaviors, and alleviated oxidative stress and neuroinflammation in rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Mechanistically, Scu-induced Nrf2 nuclear accumulation and inactivation of NF-κB were accompanied by an enhanced level of phosphorylated protein kinase B (p-AKT) both in vitro and in vivo. Pharmacologically inhibiting the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway blocked Scu-induced Nrf2 nuclear translocation and inactivation of NF-κB, as well as its antioxidant and anti-inflammatory activities. In summary, these results suggest that Scu exhibits antioxidant, anti-inflammatory, and neuroprotective effects in CIRI through Nrf2 activation mediated by the PI3K/Akt pathway.

Brain edema after oocyte retrieval: a case report.

BACKGROUND: Brain edema is a rare and serious complication of assisted reproductive technology (ART). The increased intracranial pressure and injured brain parenchyma are life-threatening and may even result in death. The pathogenesis may involve increased vascular permeability mediated by vascular endothelial growth factor and other vasoactive substances, including interleukin 6, interleukin 1ß, angiotensin II, insulin-like growth factor 1, transforming growth factor ß, and the renin-angiotensin system. CASE PRESENTATION: We presented a unique case report of a 29-year-old woman developed sudden irritability, blurred consciousness, and vomiting 8 h after oocyte retrieval. Blood examinations showed hyponatremia and cranial computed tomography showed swelling of the brain parenchyma. After therapeutic use of hypertonic saline and mannitol infusion, the patient's consciousness recovered and her neurological state improved. CONCLUSIONS: Brain edema is a rare and serious complication of ART. Quick infusion of hypertonic salt solution and mannitol is a key treatment. A good prognosis can be achieved after prompt treatment.

A Protective Role of Phenylalanine Ammonia-Lyase from Astragalus membranaceus against Saline-Alkali Stress.

Phenylalanine ammonia-lyase (PAL, E.C.4.3.1.5) catalyzes the benzene propane metabolism and is the most extensively studied enzyme of the phenylpropanoid pathway. However, the role of PAL genes in Astragalus membranaceus, a non-model plant showing high capability toward abiotic stress, is less studied. Here, we cloned AmPAL and found that it encodes a protein that resides in the cytoplasmic membrane. The mRNA of AmPAL was strongly induced by NaCl or NaHCO3 treatment, especially in the root. Overexpressing AmPAL in Nicotiana tabacum resulted in higher PAL enzyme activities, lower levels of malondialdehyde (MDA), and better root elongation in the seedlings under stress treatment compared to the control plants. The protective role of AmPAL under saline-alkali stress was also observed in 30-day soil-grown plants, which showed higher levels of superoxide dismutase (SOD), proline, and chlorophyll compared to wild-type N. Tabacum. Collectively, we provide evidence that AmPAL is responsive to multiple abiotic stresses and that manipulating the expression of AmPAL can be used to increase the tolerance to adverse environmental factors in plants.

Non-coding RNAs as potential biomarkers in osteosarcoma.

Osteosarcoma (OS) is a primary solid malignant tumor that occurs most frequently in the metaphysis of long bones. More likely to happen to children and adolescents. OS has high mortality and disability rate. However, the etiology and pathogenesis of OS have not been fully understood till now. Due to the lack of effective biomarkers, OS cannot be precisely detected in the early stage. With the application of next-generation and high-throughput sequencing, more and more abnormally expressed non-coding RNAs(ncRNAs) have been identified in OS. Growing evidences have suggested the ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), have played an important role in the tumorigenesis and progression of OS. Thus, they can be served as novel biomarkers for diagnosis, treatment and prognosis. This review summarized the application of ncRNA as biomarkers in OS in detail, and discussed the limitation and future improvement of the potential biomarkers.

De Novo Assembly of a Sarcocarp Transcriptome Set Identifies AaMYB1 as a Regulator of Anthocyanin Biosynthesis in Actinidia arguta var. purpurea.

The kiwifruit (Actinidia arguta var. purpurea) produces oval shaped fruits containing a slightly green or mauve outer exocarp and a purple-flesh endocarp with rows of tiny black seeds. The flesh color of the fruit results from a range of anthocyanin compounds, and is an important trait for kiwifruit consumers. To elucidate the molecular mechanisms involved in anthocyanin biosynthesis of the sarcocarp during A. arguta fruit development, de novo assembly and transcriptomic profile analyses were performed. Based on significant Gene Ontology (GO) biological terms, differentially expressed genes were identified in flavonoid biosynthetic and metabolic processes, pigment biosynthesis, carbohydrate metabolic processes, and amino acid metabolic processes. The genes closely related to anthocyanin biosynthesis, such as phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), and anthocyanidin synthase (ANS), displayed significant up-regulation during fruit development according to the transcriptomic data, which was further confirmed by qRT-PCR. Meanwhile, a series of transcription factor genes were identified among the DEGs. Through a correlation analysis. AaMYB1 was found to be significantly correlated with key genes of anthocyanin biosynthesis, especially with CHS. Through a transient expression assay, AaMYB1 induced anthocyanin accumulation in tobacco leaves. These data provide an important basis for exploring the related mechanisms of sarcocarp anthocyanin biosynthesis in A. arguta. This study will provide a strong foundation for functional studies on A. arguta and will facilitate improved breeding of A. arguta fruit.

The Efficacy of Integrated Rehabilitation for Post-Stroke Anxiety: Study Protocol for a Prospective, Multicenter, Randomized Controlled Trial.

Background: Post-stroke anxiety (PSA) remains a challenging medical problem. Integrated rehabilitation involves a combination of traditional Chinese medicine (TCM) and Western conventional rehabilitation techniques. Theoretically, integrated rehabilitation is likely to have significant advantages in treating PSA. Nevertheless, the therapeutic effect of integrated rehabilitation needs to be verified based on large-scale trials with sound methodology. Thus, the aim of this trial is to assess the efficacy and safety of integrated rehabilitation on PSA. Methods: The study is a prospective, multicenter, randomized, controlled trial involving 188 PSA patients from four clinical centers in China. Eligible participants will be randomly divided into the integrated rehabilitation group or the standard care group. Participants in the integrated rehabilitation group will receive a combination of TCM and Western conventional rehabilitation methods, including acupuncture, repeated transcranial magnetic stimulation, traditional Chinese herbal medicine, and standard care. The primary outcome will be the Hamilton Anxiety Rating Scale (HAM-A). The secondary outcomes will include the Self-Rating Anxiety Scale (SAS), the Activities of Daily Living (ADL) scale, the Montreal Cognitive Assessment (MoCA) scale, the simplified Fugl-Meyer Assessment of motor function (FMA) scale, and the Pittsburgh Sleep Quality Index (PSQI). Outcome measurements will be performed at baseline, at the end of the 4-week treatment and the 8-week follow-up. Conclusion: Results of this trial will ascertain the efficacy and safety of integrated rehabilitation on PSA, thereby providing evidence regarding integrated rehabilitation strategies for treating PSA. It will also promote up-to-date evidence for patients, clinicians, and policy-makers. Trial Registration: ClinicalTrials.gov NCT05147077.

Evaluating a Panel of Autoantibodies Against Tumor-Associated Antigens in Human Osteosarcoma.

Background: The aim of this study was to identify a panel of candidate autoantibodies against tumor-associated antigens in the detection of osteosarcoma (OS) so as to provide a theoretical basis for constructing a non-invasive serological diagnosis method in early immunodiagnosis of OS. Methods: The serological proteome analysis (SERPA) approach was used to select candidate anti-TAA autoantibodies. Then, indirect enzyme-linked immunosorbent assay (ELISA) was used to verify the expression levels of eight candidate autoantibodies in the serum of 51 OS cases, 28 osteochondroma (OC), and 51 normal human sera (NHS). The rank-sum test was used to compare the content of eight autoantibodies in the sera of three groups. The diagnostic value of each indicator for OS was analyzed by an ROC curve. Differential autoantibodies between OS and NHS were screened. Then, a binary logistic regression model was used to establish a prediction logistical regression model. Results: Through ELISA, the expression levels of seven autoantibodies (ENO1, GAPDH, HSP27, HSP60, PDLIM1, STMN1, and TPI1) in OS patients were identified higher than those in healthy patients (p < 0.05). By establishing a binary logistic regression predictive model, the optimal panel including three anti-TAAs (ENO1, GAPDH, and TPI1) autoantibodies was screened out. The sensitivity, specificity, Youden index, accuracy, and AUC of diagnosis of OS were 70.59%, 86.27%, 0.5686, 78.43%, and 0.798, respectively. Conclusion: The results proved that through establishing a predictive model, an optimal panel of autoantibodies could help detect OS from OC or NHS at an early stage, which could be used as a promising and powerful tool in clinical practice.

Glycinergic Signaling in Macrophages and Its Application in Macrophage-Associated Diseases.

Accumulating evidences support that amino acids direct the fate decision of immune cells. Glycine is a simple structural amino acid acting as an inhibitory neurotransmitter. Besides, glycine receptors as well as glycine transporters are found in macrophages, indicating that glycine alters the functions of macrophages besides as an inhibitory neurotransmitter. Mechanistically, glycine shapes macrophage polarization via cellular signaling pathways (e.g., NF-κB, NRF2, and Akt) and microRNAs. Moreover, glycine has beneficial effects in preventing and/or treating macrophage-associated diseases such as colitis, NAFLD and ischemia-reperfusion injury. Collectively, this review highlights the conceivable role of glycinergic signaling for macrophage polarization and indicates the potential application of glycine supplementation as an adjuvant therapy in macrophage-associated diseases.

Thalidomide Reduces Activation of Murine Pancreatic Stellate Cells by Inhibiting the TGF-ß/Smad Pathway.

OBJECTIVE: The aim of this study was to investigate the effects and mechanism of thalidomide on pancreatic stellate cell (PSC) activation in mice and to find the optimal timing of thalidomide administration. METHODS: PSCs, isolated from mouse pancreas tissue, were divided into five groups with specific treatments: (A) control PSCs (PSC), (B) PSCs induced by TGF-ß1 (PSC+TGF-ß1), (C) PSCs induced by TGF-ß1 followed by thalidomide (PSC+TGF-ß1+Thalidomide), (D) PSCs receiving TGF-ß1 and thalidomide simultaneously (PSC+(TGF-ß1+Thalidomide)), and (E) PSCs treated with thalidomide only (PSC+Thalidomide). We measured the effects of thalidomide on PSC activation by detecting the expression of α-SMA, collagen type I, and the TGF-ß/Smad pathway through quantitative real-time PCR and Western blot analysis. RESULTS: Compared with TGF-ß1 alone, thalidomide significantly inhibited PSC activation by reducing α-SMA expression (P<0.05) and decreasing collagen type I deposition (P<0.05). PSCs treated with thalidomide alone showed lower expression of α-SMA and collagen type I than those treated with thalidomide and TGF-ß1 at random order (P<0.01). Thalidomide downregulated TGF-ß1 and Smad3 and upregulated Smad7 (P<0.05). CONCLUSION: Thalidomide could repress PSC activation and alleviate fibrosis by regulating the TGF-ß/Smad pathway. Preventive use of thalidomide had maximum effect, and there was no evidence for the reversal of the activation of quiescent PSCs.