Retinol-binding protein type 1 expression predicts poor prognosis in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide, with high incidence and poor survival rates. RBP1 is highly expressed in several kinds of cancer and plays a potential prognostic factor. However, the relationship between RBP1 and HNSCC were analyzed based on The Cancer Genome Atlas (TCGA) database. MATERIALS AND METHODS: RBP1 expression and clinical information were obtained from the Cancer Genome Atlas (TCGA) database. Tumor tissue and adjacent normal tissue of 6 HNSCC patients were collected to analyze the RBP1 mRNA expression level by quantitative PCR. Cox regression analysis was used to evaluate the prognostic values of RBP1 and clinical data in HNSCC. A nomogram was also established to predict the impact of RBP1 on prognosis based on Cox multivariate results. The methylation level of RBP1 in HNSC and its prognosis were analyzed in UALACN and MethSurv. Finally, the potential biological functions of RBP1 were investigated using gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA). RESULTS: The mRNA expression levels of RBP1 were highly expressed in HNSCC tissue. The Cox analyses demonstrate that highly-expressed RBP1 is an independent prognosis marker(P < 0.05). ROC curve analysis showed that performances of RBP1 (area under the ROC curve: 0.887, sensitivity: 84.1%, specificity: 79.9%). The methylation was increased in HNSCC patients compared with normal subjects(P < 0.05) and was associated with better prognosis at sites cg06208339, cg12298268, cg12497564, cg15288618, cg20532370, cg23448348. Additionally, RBP1 expression is mildly associated with immune cell infiltration and immunological checkpoints. CONCLUSION: RBP1 is overexpressed and associated with poor patient prognosis in head and neck squamous cell carcinoma.

Clinical outcomes of endothelial keratoplasty with an entire recipient's Descemet stripping for iridocorneal endothelial syndrome.

PURPOSE: To investigate whether entire recipient's Descemet stripping reduced endothelial cell loss (ECL) following Descemet membrane endothelial keratoplasty (DMEK) for iridocorneal endothelial (ICE) syndrome DESIGN: Randomized controlled clinical trial SETTING: Zhongshan Ophthalmic Center PATIENT: Forty-eight patients (48 eyes) with ICE syndrome were enrolled between March 10, 2014, and May 11, 2022. The eligible patients were divided into the entire recipient's Descemet stripping group (the entire stripping group, 24 eyes) or the standard technique group (the standard group, 24 eyes). INTERVENTIONS: DMEK was performed in all cases with concomitantly procedures. The entire recipient's Descemet membrane or the central 8.0 or 8.25-mm diameter of the Descemet membrane was removed intraoperatively. MAIN OUTCOMES MEASURES: ECL, corrected distance visual acuity (CDVA), intraocular pressure (IOP), graft survival, and surgical complications were compared 9, 12 and 24 months after surgery. RESULTS: After a 9 months follow-up, ECL was significantly lower in the entire stripping group than in the standard group. At 2 years postoperatively, the ECL rate was 66±5% and 74±4% (95%confidence interval (CI): -0.04 to 0.01; p = 0.040), with a cumulative graft success rate of 83% and 67% (95%CI: -0.07 to 0.39; p = 0.318) in the entire stripping group and the standard group, respectively. Postoperative CDVA level was comparable between the 2 groups throughout the follow-up period. No significant differences were observed in the incidence of main complications between the 2 groups. CONCLUSIONS: Entire recipient's Descemet stripping may delay the pathological progression of ICE syndrome, thereby reducing ECL following DMEK.

Prediction of midpalatal suture maturation stage based on transfer learning and enhanced vision transformer.

BACKGROUND: Maxillary expansion is an important treatment method for maxillary transverse hypoplasia. Different methods of maxillary expansion should be carried out depending on the midpalatal suture maturation levels, and the diagnosis was validated by palatal plane cone beam computed tomography (CBCT) images by orthodontists, while such a method suffered from low efficiency and strong subjectivity. This study develops and evaluates an enhanced vision transformer (ViT) to automatically classify CBCT images of midpalatal sutures with different maturation stages. METHODS: In recent years, the use of convolutional neural network (CNN) to classify images of midpalatal suture with different maturation stages has brought positive significance to the decision of the clinical maxillary expansion method. However, CNN cannot adequately learn the long-distance dependencies between images and features, which are also required for global recognition of midpalatal suture CBCT images. The Self-Attention of ViT has the function of capturing the relationship between long-distance pixels of the image. However, it lacks the inductive bias of CNN and needs more data training. To solve this problem, a CNN-enhanced ViT model based on transfer learning is proposed to classify midpalatal suture CBCT images. In this study, 2518 CBCT images of the palate plane are collected, and the images are divided into 1259 images as the training set, 506 images as the verification set, and 753 images as the test set. After the training set image preprocessing, the CNN-enhanced ViT model is trained and adjusted, and the generalization ability of the model is tested on the test set. RESULTS: The classification accuracy of our proposed ViT model is 95.75%, and its Macro-averaging Area under the receiver operating characteristic Curve (AUC) and Micro-averaging AUC are 97.89% and 98.36% respectively on our data test set. The classification accuracy of the best performing CNN model EfficientnetV2_S was 93.76% on our data test set. The classification accuracy of the clinician is 89.10% on our data test set. CONCLUSIONS: The experimental results show that this method can effectively complete CBCT images classification of midpalatal suture maturation stages, and the performance is better than a clinician. Therefore, the model can provide a valuable reference for orthodontists and assist them in making correct a diagnosis.

Clinical Outcomes of Descemet Membrane Endothelial Keratoplasty for Iridocorneal Endothelial Syndrome With a Glaucoma Drainage Device.

PURPOSE: The purpose of this study was to evaluate the feasibility and clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) for treating iridocorneal endothelial (ICE) syndrome with a glaucoma drainage device (GDD). METHODS: In this retrospective, interventional case series, data of ICE eyes with a GDD treated with DMEK were collected at the Zhongshan Ophthalmic Center. A total of 24 patients (24 eyes) with mild-to-moderate ocular anterior segment anomalies together with good intraocular pressure (IOP) control preoperatively were included between March 10, 2014, and November 11, 2021. Cases were performed DMEK with concomitantly procedures, such as goniosynechialysis, an entire recipient's Descemet stripping, trimming of glaucoma tubes, and an inferiorly peripheral iridotomy. Graft survival, corrected distance visual acuity (CDVA), endothelial cell loss, IOP, and surgical complications were documented. RESULTS: The mean length of follow-up after surgery was 30.8 ± 7.8 months. Postoperative CDVA improved significantly. At 1 and 2 years postoperatively, 10 (50%) of 20 eyes and 7 (47%) of 15 eyes achieved a CDVA of 20/32 or better, cumulative graft success rates by Kaplan-Meier survival analysis were 89% and 67%, and endothelial cell loss were (59 ± 10)% and (71 ± 7)%, respectively. Within the follow-up period, IOP elevation and progressive peripheral anterior synechiae occurred in 7 (29%) and 5 (21%) of 24 eyes, respectively. CONCLUSIONS: With specific technical modifications, DMEK had not increased the risk of postoperative complications and provided comparable clinical outcomes in the treatment of ICE eyes with a GDD with those observed in the treatment of ICE eyes without a GDD.

The Role of 25-OH Vitamin D in Alzheimer's Disease through Mendelian Randomization and MRI.

INTRODUCTION: The mechanism underlying the relationship between Alzheimer's disease (AD) and minerals (serum calcium, copper, iron, magnesium, zinc), vitamins (25-OH vitamin D, vitamin A1 [retinol], B9 [folic acid], B12, C) is unclear. METHODS: In a two-step Mendelian randomization analysis, the association between positive nutritional elements and 3935 MRI phenotypes was examined, and the mediation proportion was calculated. Horizontal pleiotropy and heterogeneity of Mendelian randomisation were assessed using MR-Egger, Cochran's Q test, MR-PRESSO. RESULTS: 25-OH vitamin D (p = 0.0019, OR = 0.6179, 95% CI = 0.4562-0.8368, IVW) is negatively associated with AD among 10 nutrients. The mediation proportion of the effect of vitamin D on AD mediated by IDP_dMRI_TBSS_L3_Superior_fronto-occipital_fasciculus_L was approximately 7.08%. DISCUSSION: Our results support 25-OH vitamin D as a causal protective factor for Alzheimer disease. It was found that the Superior_fronto-occipital_fasciculus_L may play a minimal mediating role.

The role of herpes simplex virus infection in the etiology of head and neck cancer-a Mendelian randomization study.

Introduction: Head and neck cancer (HNC) is a complex disease, and multiple risk factors can lead to its progression. Observational studies indicated that herpes simplex virus (HSV) may be correlated with the risk of HNC. However, the causal effects and direction between them were still unclear. Methods: This study utilized a Mendelian randomization (MR) approach for causality assessment between HSV infection and Head and neck cancer based on the latest public health data and Genome-Wide Association Study (GWAS) data. The causal effects were estimated using IVW, weighted median, and MR-Egger. A reverse MR analysis was subsequently performed. Cochrans Q test, MR-Egger intercept test, leave one out analysis, and the funnel plot were all used in sensitivity analyses. Results: Genetically predicted higher level of HSV-1 IgG was causally related to HNC (OR=1.0019, 95%CI=1.0003-1.0036, p=0.0186, IVW) and oral and oropharyngeal cancer (OR=1.0018, 95%CI=1.0004-1.0033, p=0.0105, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and HNC. However, HSV-2 infection was not causally related to HNC data and oropharyngeal cancer data. Sensitivity analysis was performed and revealed no heterogeneity and horizontal pleiotropy. Conclusion: Collectively, a significant association was noted between HSV infection and increased risk of HNC, providing valuable insights into the etiology of this malignancy. Further in-depth study is needed to validate these findings and elucidate the underpinning mechanisms.

The Differences of Serum Thrombopoietin Levels Between Acquired Aplastic Anemia and Immune Thrombocytopenia in Pediatric Patients.

Thrombopoietin (TPO) is the critical regulator of platelet production. However, the role of TPO in pediatric patients with thrombocytopenic disorders has not been fully elucidated. In the present study, we attempted to investigate serum TPO levels in patients with acquired aplastic anemia (aAA) and immune thrombocytopenia (ITP). We analyzed the endogenous plasma concentration of TPO and platelet count at the time of TPO measurement in 166 patients with aAA and 280 patients with ITP retrospectively. We further observed a correlation between platelet counts and TPO. Serum TPO levels were significantly higher in aAA compared with ITP (1142 vs. 77.99 pg/mL, P <0.001). In patients with aAA, an elevation for TPO levels in very severe AA (VSAA) was seen when compared with non-severe AA (NSAA) (1360 vs. 984.4 pg/mL, P <0.05). In contrast, the circulating TPO levels with chronic ITP (CITP) showed a decrease than newly diagnosed ITP (NITP) and persistent ITP (PITP) (62.28 vs. 81.56 pg/mL, P <0.01, 62.28 vs. 87.82 pg/mL, P <0.05, respectively). There was a negative correlation between platelet counts and TPO levels in aAA (r s =-0.3325, P <0.001) as well as ITP (r s =-0.2570, P <0.001). Especially, TPO levels were inversely correlated with platelet counts in NSAA (r s =-0.3672, P <0.001) and NITP (r s =-0.3316, P <0.001). After grouping by age or sex, there were no statistical differences in aAA or ITP. Serum TPO levels were markedly elevated in pediatric patients with aAA compared with ITP. It was higher in VSAA and lower in CITP, suggesting that serum TPO level could play a role in classifying disease severity or clinical course in aAA and ITP.

Eltrombopag combined with immunosuppressive therapy for pediatric severe aplastic anemia.

BACKGROUND: Severe aplastic anemia (SAA) is caused by immune-mediated destruction. Standard immunosuppressive therapy (IST) is effective but needs to be improved. METHODS: The data of patients with SAA and received IST were analyzed retrospectively to conducted this historical control study. RESULTS: A total of 115 SAA patients (60 males; median age of 5.77 years and median follow-up time of 45 months) were enrolled in this study. The complete response rates (CRR) of the eltrombopag group at 3 and 6 months were higher than the control group (30.3% vs.8.2% at 3 months; 50.0% vs. 10.2% at 6 months). The overall response rates (ORR) showed no differences. There were significant differences in the times from G-CSF, Red blood cell transfusion, and Platelet transfusion between the two groups. No difference in overall survival (OS), event-free survival (EFS), and relapse rate between two groups. There is no variable were associated with prognosis in both groups. CONCLUSION: Addition of eltrombopag to IST confers faster hematological response and higher early hematological response in pediatric SAA patients. IMPACT: Addition of eltrombopag to standard immunosuppressive therapy confers faster hematological response and higher early hematological response in pediatric severe aplastic anemia patients. Eltrombopag showed reliable safety but had no impact on long-term response and prognosis. This article is a historical controlled study consisting of 115 pediatric severe aplastic anemia patients and makes up for the lack of clinical data deficient on pediatric severe aplastic anemia with TPO-RA combined with IST.

A riboflavin transporter deficiency presenting as pure red cell aplasia: a pediatric case report.

Introduction: Riboflavin transporter deficiency (RTD) is a rare genetic disorder that affects riboflavin transport, leading to impaired red blood cell production and resulting in pure red cell aplasia. Recognizing and understanding its clinical manifestations, diagnosis, and management is important. Case presentation: A 2-year-old patient presented with pure red cell aplasia as the primary symptom of RTD. After confirming the diagnosis, rapid reversal of anemia was achieved after high-dose riboflavin treatment. Conclusion: RTD often has an insidious onset, and neurological symptoms appear gradually as the disease progresses, making it prone to misdiagnosis. Genetic testing and bone marrow biopsy can confirm the diagnosis.

Hexafluoropropylene oxide trimer acid (HFPO-TA) exerts cytotoxic effects on leydig cells via the ER stress/JNK/ß-trcp/mcl-1 axis.

Hexafluoropropylene oxide trimer acid (HFPO-TA) is an alternative to perfluorooctanoic acid (PFOA) and is widely used in various industries. The effects of HFPO-TA on the male reproductive system and the underlying mechanisms are still not fully understood. In this study, TM3 mouse Leydig cells were used as the main model to evaluate the cytotoxicity of HFPO-TA in vitro. HFPO-TA inhibited the viability and expression of multiple biomarkers of Leydig cells. HFPO-TA also induced Leydig cell apoptosis in a caspase-dependent manner. Moreover, HFPO-TA induced the ubiquitination and degradation of Mcl-1 in a ß-TrCP-dependent manner. Further investigations showed that HFPO-TA treatment led to the upregulation of ROS, which activated the ER stress/JNK/ß-TrCP axis in Leydig cells. Overall, our study provides novel insights into the cytotoxic effects of HFPO-TA on the male reproductive system.

FOXO1 Single-Nucleotide Polymorphisms Are Associated with Bleeding Severity and Sensitivity of Glucocorticoid Treatment of Pediatric Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune-mediated hemorrhagic disease. Emerging evidence indicates that FOXO1 SNPs are related to the immune dysregulation of several autoimmune diseases suggesting that FOXO1 may be involved in inflammation and pathologic activities in patients with ITP. This study aimed to evaluate whether FOXO1 gene single-nucleotide polymorphisms (SNPs) are associated with susceptibility to ITP and clinical priorities of concern include bleeding severity and sensitivity of glucocorticoid treatment. This study recruited 327 newly diagnosed ITP and 220 healthy controls. Four SNPs (rs17446593, rs17446614, rs2721068, and rs2721068) of the FOXO1 gene were detected using the Sequenom MassArray system. Bleeding severity were classified into the mild and severe groups based on the bleeding scores. ITP patients were classified as sensitive and insensitive to glucocorticoid treatment according to the practice guideline for ITP (2019 version). The frequencies of the four SNPs did not show any significant differences between the ITP and healthy control groups. Patients with AA genotype at rs17446593 (p = 0.009) and GG genotype at rs17446614 (p = 0.009) suffered more severe bleeding than patients without them. Carriers of haplotype Grs17446593Ars17446614Crs2721068Trs2755213 were protective to severe bleeding (p = 0.002). The AA genotype at rs17446593 was significantly higher in ITP patients sensitive to glucocorticoid treatment than in those insensitive to glucocorticoid treatment (p = 0.03). Haplotype Grs17446593Grs17446614Trs2721068Trs2755213 increases the risk of glucocorticoid resistance (p = 0.007). Although FOXO1 gene polymorphisms were not associated with susceptibility to ITP, the AA genotype at rs17446593 and GG genotype at rs17446614 were associated with bleeding severity. Haplotype GACT have a protective effect against severe bleeding. Patients with AA genotype at rs17446593 may tend to have good responds to glucocorticoid treatment. However, the FOXO1 gene haplotype GGTT increases the risk of glucocorticoid-resistant. Trial registration: ChiCTR1900022419.

Gut microbiota and risk of coronary heart disease: a two-sample Mendelian randomization study.

Background: The relationship between gut microbiota composition and coronary heart disease (CHD) has been recently reported in several observational studies. However, the causal effect of gut microbiota on coronary heart disease is uncharted. Objective: This study attempted to investigate the effect of gut microbiota on coronary heart disease by Mendelian randomization (MR) analysis. Methods: Through the two-sample MR method, single-nucleotide polymorphisms relevant to gut microbiota were selected as instrument variables to evaluate the causal association between gut microbiota and the risk of CHD. Results: According to the selection criteria of the inverse variance-weighted average method, Class Actinobacteria, Class Lentisphaeria, Family Clostridiales vadinBB60group, Genus Clostridium innocuum group, Genus Bifidobacterium, Genus Butyricicoccus, Genus Oxalobacter, Genus Turicibacter, and Order Victivallales, presented a suggestive association with coronary heart disease. Conclusion: This two-sample Mendelian randomization study found that gut microbiota was causally associated with coronary heart disease. Further randomized controlled trials are needed to clarify the protective effect of probiotics on coronary heart disease and their specific protective mechanisms.

Clinical characteristics of hepatitis-associated aplastic anemia in children.

To understand the current situation of hepatitis-related aplastic anemia (HAAA) in children, we analyzed the patients with HAAA admitted to our hospital in the past 5 years to understand the disease characteristics and prognosis. The clinical data of patients with HAAA admitted to our hospital from February 2017 to May 2022 were retrospectively analyzed. A total of 81 patients with HAAA, 56 males and 25 females. The median onset age was 5.9 years. The median time from hepatitis to occurrence of hemocytopenia was 30 days, and the median follow-up time was 2.77 years. There were 23 cases (28.5%) of severe aplastic anemia (SAA), 50 cases of very severe aplastic anemia (VSAA), and 8 cases of non-severe aplastic anemia (NSAA). At the beginning of the disease, cytotoxic T lymphocyte (CTL) was higher than normal in 60% of patients, and the median CD4/CD8 ratio was 0.2. As of follow-up, 72 children survived, 4 were lost, and 5 died. Thirty-four cases were treated with immunosuppressive therapy (IST), with a median follow-up time of 0.97 years. The total reaction rate was 73.5% (25/34), the complete reaction rate was 67.6% (23/34), and the nonreaction rate was 26.5% (9/34). Multivariate analysis suggested that co-infection was an independent risk factor affecting the efficacy of IST at 6 months, with an OR value of 16.76, 95% CI (1.23, 227.95), P=0.034. No independent influencing factors were found at the end of follow-up. The proportion of CTL cells in peripheral blood of children with HAAA is relatively increased, and IST is effective in 73.5% of children. Co-infection may prolongs the time to response to IST.

The causal association between COVID-19 and herpes simplex virus: a Mendelian randomization study.

Introduction: The coronavirus disease 2019 (COVID-19) has emerged as a main global public health challenge. Additionally, herpes simplex virus type-1 (HSV-1) and type 2 (HSV-2) are widespread viruses that can cause orolabial herpes and genital herpes. Several clinical case reports have declared a possible association between the two, however, the causal relationship between them has not been clarified. Methods: This study utilized a Mendelian randomization (MR) approach for causality assessment between COVID-19 infection and HSV infection based on the latest public health data and Genome-Wide Association Study (GWAS) data. Multiple causal estimation methods, such as IVW, weighted median, simple mode, and weighted mode, were employed to validate the causal relation between COVID-19 infection and HSV infection, with COVID-19 infection, COVID-19 hospitalization, and severe COVID-19 as exposures, and HSV1/2 infection as the outcome. A reverse MR analysis was subsequently performed. Results: MR analysis exhibited that COVID-19 infection was relevant to a reduced risk of HSV1 infection (p=7.603239e-152, OR=0.5690, 95%CI=0.5455-0.5935, IVW). Regarding the effect of COVID-19 infection on HSV2, MR analysis suggested that COVID-19 infection was correlated with an augmented risk of HSV2 infection (p=6.46735e-11, OR=1.1137, 95%CI=1.0782-1.1502, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and COVID-19. Discussion: Altogether, COVID-19 infection might cause a decreased risk of HSV1 infection and an elevated risk of HSV2 infection.

Application of Ag nanoparticles decorated on graphene nanosheets for electrochemical sensing of CEA as an important cancer biomarker.

In this research, a novel biosensing platform is described based on graphene nano-sheets decorated with Ag nano-particles (GNSs@Ag NPs). The designed electrochemical aptasensor was employed to determine carcinoembryonic antigen (CEA), an important cancer biomarker. Inherently, aptasensing interfaces provide high sensitivity for CEA tumor marker because of the high specific surface area and excellent conductivity of the prepared GNSs@Ag NPs composite. The established assay demonstrated a wide linear range from 0.001 pg/mL to 10 pg/mL with a correlation coefficient of 0.9958 and low detection limit (DL) of 0.5 fg/mL based on S/N = 3 protocol. The derived biosensor illustrated acceptable selectivity towards common interfering species including HER2, VEGF, IgG, MUC1 and CFP10. In addition, the aptsensor showed good reproducibility and fast response time. The applicability of the suggested strategy in human serum samples was also examined and compared to the commercial enzyme-linked immunosorbent assay (ELISA). Based on the experimental data, it was found that the discussed sensing platform can be exerted in the monitoring of CEA in different cancers for early diagnosis.

Correlations between schizophrenia and lichen planus: a two-sample bidirectional Mendelian randomization study.

Background: Several existing studies have shown a correlation between schizophrenia and lichen planus (LP). However, the causality of this relationship remains uncertain. Thus, this study aimed to examine the causal association between schizophrenia and LP. Methods: A two-sample Mendelian randomization (MR) study was carried out to investigate whether schizophrenia is causally related to LP and vice versa, and genetic variants in this study were taken from previous genome-wide association studies. We used the inverse variance weighted (IVW) method as the main analysis. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Results: Our results show that schizophrenia has a protective effect on LP (OR = 0.881, 95%CI = 0.795-0.975, p = 0.015). Conversely, we observed no significant relationship between LP and schizophrenia in reverse MR analysis (OR = 0.934, 95%CI = 0.851-1.026, p = 0.156). Conclusion: Our two-sample Mendelian randomization study supports a significant causal relationship between LP and schizophrenia and finds that schizophrenia can reduce the incidence of LP. This is in contrast to previous findings and provides new insights into the relationship between LP and schizophrenia, but the exact mechanism needs further investigation.

Correlations between gut microbiota and lichen planus: a two-sample Mendelian randomization study.

Purpose: Several existing studies have revealed that the occurrence of lichen planus (LP) is relevant to the gut microbiota, and the causal relationship between gut microbiota and LP was analyzed using the Mendelian randomization (MR) method. Methods: Through the two-sample MR method, single nucleotide polymorphisms (SNPs) relevant to gut microbiota were selected as instrument variables (IVs) to evaluate the causal association between gut microbiota and the risk of LP. Results: According to the selection criteria of inverse-variance weighted (IVW), six bacterial genera were found to be significantly linked to the initiation of LP; The IVW results suggested that Oxalobacteraceae, Victivallaceae, and Actinobacteria could restrain the initiation of LP, showing protective effects against LP. Desulfovibrio, Veillonella, and Ruminococcus gauvreauii groups were demonstrated to have casual correlations with the onset of LP. Conclusion: The relationship between gut microbiota and LP was not a single positive or inverse relationship. Investigation of the causal relationship of these gut microbiota with LP could further provide evidence for the intestine-skin axis theory. However, the specific mechanism of microorganisms affecting the skin remains to be clarified. In this paper, the protective effects and mechanisms of Oxalobacteraceae, Victivallaceae, and Actinobacteria on LP require further exploration.

Endoplasmic Reticulum Stress and Autophagy Are Involved in Hepatotoxicity Induced by Tributyltin.

Tributyltin (TBT), a common contaminant in aquatic ecosystems, has severe toxic effects on multiple tissues and organs, especially the liver. Previous toxicogenomic analysis has indicated that the main mechanism of TBT-induced hepatotoxicity is related to the activation of the apoptotic pathway. However, the mechanism of action occurring before the activation of apoptosis is still unclear. Herein, we applied proteomic technology to explore the protein expression profile of TBT-treated HL7702 normal human liver cells. The ultrastructural changes in cells were observed by transmission electron microscopy. After low dose (2 µΜ) TBT treatment, activation of the unfolded protein response and endoplasmic reticulum stress were observed; the expression levels of PERK, ATF6, BiP, and CHOP were significantly elevated, and splicing of XBP1 mRNA was initiated. When the TBT concentration increased to 4 µΜ, the protein levels of Beclin1, Atg3, Atg5, Atg7, and Atg12-Atg5 were significantly elevated, and the protein level of LC3Ⅰ decreased while that of LC3Ⅱ increased, suggesting the activation of autophagy. As the TBT concentration continued to increase, autophagy could not eliminate the damage, and apoptosis eventually occurred. These results indicate novel pathways of hepatotoxicity induced by TBT and provide insights for future studies.

Elevated TCR-αß+ double-negative T cells in pediatric patients with acquired aplastic anemia.

BACKGROUND AND AIMS: The pathophysiology of acquired aplastic anemia (aAA) is most associated with T cell mediated immune dysfunction, but the role of CD4- CD8- double negative T cells (DNTs) in pediatric patients with aAA is unclear. In this study, we aimed to investigate the proportion of TCR-αß+ DNTs in pediatric patients with aAA and correlation with the response to immunosuppressive therapy (IST). MATERIALS AND METHODS: Assessment of DNTs from peripheral blood was done by sensitive multi-color flow cytometry. The potential clinical value of TCR-αß+ DNTs was then assessed by the receiver operating characteristic (ROC) curves. RESULTS: The retrospective study evaluated 164 pediatric patients with aAA and 105 healthy donors (HD). Our data showed higher proportion of TCR-αß+ DNTs in total lymphocytes [1.04% (0.79%-1.40%) vs 0.69% (0.47%-0.87%), p < 0.001] and CD3+ T cells [1.52% (1.10%-1.96%) vs 1.10% (0.70%-1.40%), p < 0.001] in aAA compared to HD. Patients with SAA/VSAA achieving complete response (CR) after IST had a higher proportion of TCR-αß+ DNTs at initial diagnosis, than those not achieving CR for total (1.21%±0.39 vs 0.78%±0.38, p < 0.05) and CD3+ T cells (1.74%±0.53 vs 1.15%±0.59, p < 0.05). The ROC analysis showed areas under the curves (AUCs) for TCR-αß+ DNT proportion in lymphocytes and CD3+ T cells were 0.756 (cutoff value 1.33, p < 0.05) and 0.758 (cutoff value 1.38, p < 0.05), respectively. And the complete response rate was higher in TCR-αß+ DNT proportion high group than in TCR-αß+ DNT proportion low group at baseline (p < 0.001). CONCLUSION: Our observations suggest that elevated TCR-αß+ DNTs seems to play a role in the pathogenesis of aAA, and it was involve in immune response to IST.

Radiologic Features of Atlas Occipitalization and Its Clinical Implications.

STUDY DESIGN: Retrospective radiographic analysis. OBJECTIVES: Evaluation of the anatomic features of the craniovertebral junction in patients with occipitalization with and without atlantoaxial dislocation (AAD). SUMMARY OF BACKGROUND DATA: Atlas occipitalization is a common feature of congenital AAD and usually requires surgical intervention. However, not all instances of occipitalization necessarily lead to AAD. No study has specifically examined and compared the craniovertebral bony morphology in occipitalization with, and without, AAD. MATERIALS AND METHOD: We reviewed computed tomography (CT) scans of 2500 adult outpatients. Occipitalization cases without AAD (ON) were selected. Meanwhile, a series of 20 inpatient occipitalization cases with AAD (OD) were obtained in parallel. Another 20 control cases without occipitalization were also included. Multi-directional reconstructed CT images of all cases were analyzed. RESULTS: A total of 18 adults with ON were found in all 2500 outpatients (0.7%). Both anterior height and posterior height of C1 lateral mass in the control group were significantly larger than those in both the ON and OD groups, whereas posterior height in the OD group was significantly less than that in the ON group. Three morphologic types of the occipitalized atlas posterior arch were identified: Type I, bilateral sides were unfused with opisthion; Type II, unilateral side was unfused with opisthion, whereas the other side was fused; and Type III, bilateral sides were fused with opisthion. In the ON group, three cases were type I (17%), six cases were type II (33%), and nine cases were type III (50%). In the OD group, all 20 cases were type III (100%). CONCLUSIONS: Atlas occipitalization with, and without, AAD results from a distinctly different bony morphology at the craniovertebral junction. The novel classification system based on reconstructed CT images may be useful in prognosticating AAD in the setting of atlas occipitalization.