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Ischemic brain injury is a severe medical condition with high incidences in elderly people without effective treatment for the resulting neural damages. Using a unilateral mouse stroke model, we analyze single-cell transcriptomes of ipsilateral and contralateral cortical penumbra regions to objectively reveal molecular events with single-cell resolution at 4 h and 1, 3, and 7 days post-injury. Here, we report that neurons are among the first cells that sense the lack of blood supplies by elevated expression of CCAAT/enhancer-binding protein β (C/EBPβ). To our surprise, the canonical inflammatory cytokine gene targets for C/EBPβ, including interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α), are subsequently induced also in neuronal cells. Neuronal-specific silencing of C/EBPβ or IL-1β and TNF-α substantially alleviates downstream inflammatory injury responses and is profoundly neural protective. Taken together, our findings reveal a neuronal inflammatory mechanism underlying early pathological triggers of ischemic brain injury., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The aim of this study was to explore a new total tongue reconstruction strategy based on the five-point eight-line segment (FIPELS) technique and a palatal speech appliance, and to evaluate the functional and aesthetic outcomes. Twenty patients with tongue squamous cell carcinoma were included in this study. All patients underwent total tongue resection followed by tongue reconstruction with an anterolateral thigh flap. The patients were divided randomly into two groups according to the reconstruction strategy: FIPELS group (10 patients) and traditional flap design group (10 patients). All 10 patients in the FIPELS group received a palatal speech appliance 1 month after the surgery. A Likert scale was used to assess swallowing function, speech articulation, and the aesthetic outcome of the reconstructed tongue in the traditional and FIPELS (with and without the palatal speech appliance) groups. Compared with the traditional group, swallowing function (1 month, P = 0.016; 3 months, P = 0.021) and the aesthetic outcome (1 month, P = 0.016; 3 months, P = 0.020) were significantly better in the FIPELS group (without the palatal speech appliance); however, there was no significant difference in speech articulation (1 month, P = 0.549; 3 months, P = 0.513). Within the FIPELS group, significantly better speech articulation was obtained with the palatal speech appliance than without it (1 month, P = 0.031; 3 months, P = 0.015)., (Copyright © 2022 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background Deep learning (DL) algorithms could improve the classification of ovarian tumors assessed with multimodal US. Purpose To develop DL algorithms for the automated classification of benign versus malignant ovarian tumors assessed with US and to compare algorithm performance to Ovarian-Adnexal Reporting and Data System (O-RADS) and subjective expert assessment for malignancy. Materials and Methods This retrospective study included consecutive women with ovarian tumors undergoing gray scale and color Doppler US from January 2019 to November 2019. Histopathologic analysis was the reference standard. The data set was divided into training (70%), validation (10%), and test (20%) sets. Algorithms modified from residual network (ResNet) with two fusion strategies (feature fusion [hereafter, DL feature ] or decision fusion [hereafter, DL decision ]) were developed. DL prediction of malignancy was compared with O-RADS risk categorization and expert assessment by area under the receiver operating characteristic curve (AUC) analysis in the test set. Results A total of 422 women (mean age, 46.4 years ± 14.8 [SD]) with 304 benign and 118 malignant tumors were included; there were 337 women in the training and validation data set and 85 women in the test data set. DL feature had an AUC of 0.93 (95% CI: 0.85, 0.97) for classifying malignant from benign ovarian tumors, comparable with O-RADS (AUC, 0.92; 95% CI: 0.85, 0.97; P = .88) and expert assessment (AUC, 0.97; 95% CI: 0.91, 0.99; P = .07), and similar to DL decision (AUC, 0.90; 95% CI: 0.82, 0.96; P = .29). DL decision , DL feature , O-RADS, and expert assessment achieved sensitivities of 92%, 92%, 92%, and 96%, respectively, and specificities of 80%, 85%, 89%, and 87%, respectively, for malignancy. Conclusion Deep learning algorithms developed by using multimodal US images may distinguish malignant from benign ovarian tumors with diagnostic performance comparable to expert subjective and Ovarian-Adnexal Reporting and Data System assessment. © RSNA, 2022 Online supplemental material is available for this article .

Objective: The aim of the study was to analyze the characteristics of renal function in patients diagnosed with COVID-19. Methods: In this retrospective, single-center study, we included all confirmed cases of COVID-19 in a tertiary hospital in Guangdong, China from January 20, 2020 to March 20, 2020. Blood and urine laboratory findings related to renal function were summarized, and the estimated glomerular filtration rate (eGFR) and endogenous creatinine clearance (Ccr) were also calculated to assess the renal function. Results: A total of 12 admitted hospital patients were diagnosed with COVID-19, included 3 severe cases, and 9 common cases. Serum creatinine (Scr) was not abnormally elevated in all of the patients, and blood urea nitrogen (BUN) was abnormally elevated in only 25.0% of the patients. However, compared with the recovery period, the patient's Scr and BUN increased significantly in peak of disease (p-scr = 0.002 & p-bun < 0.001). By observing the fluctuations in Scr and BUN from admission to recovery, it was found that the peak of Scr and BUN appeared within the first 14 day of the course of the disease. Urinary microprotein detection indicated that the abnormally elevated rates of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), and urine transferring (TRU) standardized by urinary creatinine in peak of disease were 41.7, 41.7, 50.0, and 16.7%, respectively. The abnormal rates of the calculated eGFR and Ccr were 66.7 and 41.7%. Conclusion: Scr and BUN were generally increased during the course of COVID-19. Detection of urinary microproteins and application of multiple indicators assessment could be helpful for discovering abnormal renal function in patients with COVID-19. However, the evidence is limited due to the small sample size and observational nature. Additional studies, especially large prospective cohort studies, are required to confirm these findings., (Copyright © 2020 Hong, Chi, Liu, Huang, Guo, Fan, Lin, Qu, Chen, Wu, Wang, Zhang, Wu, Pan, Lin, Zhou and Zhang.)

Long non-coding RNAs (lncRNAs) are an emerging class of RNA species that may play a critical regulatory role in gene expression. However, the association between lncRNAs and atrial fibrillation (AF) is still not fully understood. In this study, we used RNA sequencing data to identify and quantify the both protein coding genes (PCGs) and lncRNAs. The high enrichment of these up-regulated genes in biological functions concerning response to virus and inflammatory response suggested that chronic viral infection may lead to activated inflammatory pathways, thereby alter the electrophysiology, structure, and autonomic remodeling of the atria. In contrast, the downregulated GO terms were related to the response to saccharides. To identify key lncRNAs involved in AF, we predicted lncRNAs regulating expression of the adjacent PCGs, and characterized biological function of the dysregulated lncRNAs. We found that two lncRNAs, ETF1P2, and AP001053.11, could interact with protein-coding genes (PCGs), which were implicated in AF. In conclusion, we identified key PCGs and lncRNAs, which may be implicated in AF, which not only improves our understanding of the roles of lncRNAs in AF, but also provides potentially functional lncRNAs for AF researchers., (Copyright © 2019 Wu, Zhou, Fan, Zheng, Wen, Han, Wang, Wang, Zhang, Shan, Li, Hu, Lu, Chen, Hong and Zheng.)

Background: It is known that organ transplant recipients have a significantly higher risk for developing cancers, but the association between immunosuppression in organ transplantation and the risk for prostate cancer (PCa) remains unclear. We aimed to assess the evidence regarding the association of solid organ transplantation with PCa risk., Methods: A literature search of the PubMed, Embase, and Web of Science databases was performed up to March 2019. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using a fixed-effect or random-effect model., Results: In total, 26 articles including 33 independent population-based cohort studies with 556,812 recipients and 2,438 PCa cases were identified and included in this meta-analysis. PCa risk in the solid organ transplant recipients did not increase compared with the general population (RR=1.04; 95% CI: 0.90-1.18). Independent analysis of different kinds of organ replacements further indicated immune inhibition in the transplantation of kidney, liver, heart, and lung, and was not associated with elevated PCa risk (RR=0.89; 95% CI: 0.83-0.95; RR=0.61, 95% CI: 0.21-1.02; RR=1.70, 95% CI: 0.88-2.52; RR=0.87, 95% CI: 0.57-1.16, respectively)., Conclusions: This study demonstrated that immunosuppression in solid organ transplant recipients was not associated with higher PCa risk., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.06.03). The authors have no conflicts of interest to declare., (2019 Translational Cancer Research. All rights reserved.)

Glioma is known to be the most prevalent primary brain tumor. In recent years, there has been evidence indicating myeloid cell leukemia-1 (MCL1) plays a role in brain glioblastoma. Therefore, the present study was conducted with aims of exploring the ability of MCL1 silencing to influence glioma cell senescence and apoptosis through the mediation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Glioma and tumor-adjacent tissues were collected in order to detect the presence of higher levels of MCL1 protein expression. Next, the mRNA and protein expression of MCL1, PI3K, Akt, B cell lymphoma 2 (Bcl2), Bcl2-associated X (Bax), B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1), and phosphatase and tensin homolog (PTEN) were determined. Cell counting kit-8 assay was applied to detect cell proliferation, β-galactosidase staining for cell senescence, and flow cytometry for cell cycle entry and apoptosis. Initially, the results revealed higher positive expression rate of MCL1 protein, increased mRNA and protein expression of MCL1, PI3K, Akt, Bmi-1, and Bcl-2 and decreased that of Bax and PTEN in human glioma tissues. The silencing of MCL1 resulted in a decrease in mRNA and protein expression of PI3K, Akt, Bmi-1, and Bcl-2 and an increase in Bax and PTEN expressions in glioma cells. Moreover, silencing of MCL1 also inhibited cell proliferation and cell cycle entry in glioma cells, and promoted glioma cell senescence and apoptosis. In conclusion, the aforementioned results collectively suggested that the silencing of MCL1 promotes senescence and apoptosis in glioma cells through inhibiting the PI3K/Akt signaling pathway. Thus, decreasing the expression of MCL1 might have therapeutic functions in glioma. © 2018 IUBMB Life, 71(1):81-92, 2019., (© 2018 International Union of Biochemistry and Molecular Biology.)

Objective: To investigate the ideal animal models for attention deficit hyperactivity disorder (ADHD) subtypes and the effect of glucocorticoid receptor (GR) function on the behavior of ADHD rats by comparing behavioral differences between spontaneously hypertensive rats (SHRs), Wistar Kyoto (WKY) rats, and Sprague-Dawley (SD) rats., Methods: A total of 24 male SHRs aged 21 days were randomly divided into GR agonist group, GR inhibitor group, and SHR group, with 8 rats in each group. Eight male WKY rats and 8 male SD rats, also aged 21 days, were enrolled as WKY group and SD group respectively. The GR agonist group was treated with intraperitoneal injection of dexamethasone (0.5 mg/kg daily); the GR inhibitor group was treated with intraperitoneal injection of mifepristone (RU486) (54 mg/kg daily); the SHR, WKY, and SD groups were treated with intraperitoneal injection of normal saline (0.5 mL/kg daily). The course of treatment was 14 days for all groups. The open field test and Lat maze test were used to evaluate spontaneous activity and non-selective attention., Results: The open field test showed that before drug intervention the SHR group had significantly higher numbers of line crossings and rearings than the WKY and SD groups (P<0.05); the WKY group had a significantly higher number of line crossings than the SD group (P<0.05); the SD group had a significantly higher number of groomings than the WKY group (P<0.05). After drug intervention, the GR agonist group had significantly lower numbers of line crossings and groomings than the SHR group (P<0.05). The Lat maze test indicated that before drug intervention the SHR group had significantly higher numbers of corner crossings and rearings than the WKY and SD groups (P<0.05); the WKY group had significantly higher numbers of rearings and leanings than the SD group (P<0.05). After drug intervention, the GR agonist group had significantly lower numbers of corner crossings and rearings than the SHR group (P<0.05); the GR inhibitor group had a significantly higher number of rearings than the SHR group (P<0.05); the WKY group had significantly higher numbers of rearings and leanings than the SD group (P<0.05)., Conclusions: SHR is an ideal animal model for mixed subtype ADHD, and further studies are needed to determine whether WKY rats can be used as an animal model for attention-deficit subtype ADHD. GR agonist can effectively improve spontaneous activity and non-selective attention in SHRs.

MicroRNAs (miRNAs), a novel class of important gene-regulatory molecules, correlates with tumor growth, invasion, metastasis, and chemo resistance in gastric cancer (GC). Microarray analysis revealed that aberrant expressed microRNA-17 (miR-17) and DEDD were identified in GC. DEDD has been found to act as an endogenous suppressor of tumor growth and metastasis through epithelial-mesenchymal transition (EMT) process. However, the role of miRNA-17 (miR-17) has not been clearly evaluated in GC, thereby a series of in vitro experiments were performed in this study. The levels of miR-17 and DEDD in GC tissues from patients diagnosed with GC and in five GC cell lines (SGC-7901, MKN-45, HGC-27, BGC823, and AGS) were detected. It was found that miR-17 up-regulated and DEDD down-regulated in GC, and SGC-7901 and AGS cells were adopted for the in vitro cell experiments, in which the expression of miR-17 or DEDD was regulated by transfection. DEDD was validated to be a target gene of miR-17. Inhibition of miR-17 impaired EMT in GC cells. In addition, transwell assay and scratch test results revealed that inhibition of miR-17 hindered GC cell invasion and migration. Moreover, inhibition of miR-17 reduced resistance to cisplatin- or 5-Fu in GC cells and induced cisplatin- or 5-Fu-treated GC cell apoptosis, which evaluated by using CCK-8 and flow cytometry assays. From the short review above, the key findings emerge that inhibition of miR-17 may have tumor suppressive effects on GC and enhance its chemosensitivity by promoting DEDD, highlighting a novel target for GC therapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Congenital muscular dystrophy type 1C (MDC1C) is caused by the homozygous or compound heterozygous mutations of the FKRP gene. This article reported the clinical and mutation features of a child with MDC1C. The boy aged 8 months visited the hospital due to delayed development. As for clinical manifestations, the boy could not turn over or sit stably by himself, and there was a significant reduction in muscle tension; biceps reflex in both upper extremities and patellar tendon reflex and Achilles tendon reflex in both lower extremities could not be induced. The boy also had a stereotyped facial expression and strabismus. Gene detection revealed c.350C>G and c.1303C>T compound heterozygous mutations in the FKRP gene. The c.350C>G mutation came from the mother and had been reported as a pathogenic missense mutation. The c.1303C>T mutation came from the father and was a new missense mutation, and a bioinformatics analysis showed that it might be a pathogenic mutation. The boy was diagnosed with MDC1C with reference to the clinical features of hypotonia and motor developmental delay and FKRP gene mutation sequencing.

Inflammation plays a crucial role in the pathogenesis of stroke. This study aims to determine lipoprotein (a) [Lp(a)] levels in serum and to investigate their associations with stroke recurrence events in a 3-month follow-up study in patients with acute ischemic stroke (AIS). Serum Lp(a) levels were determined in 203 ischemic stroke patients and 120 normal controls at admission. The severity and clinical outcome of ischemic stroke patients were evaluated by the National Institutes of Health Stroke Scale (NIHSS). We followed the participants for a median of 3 months using a standard questionnaire to determine the stroke recurrence events. The correlation analysis and multiple linear regression analysis were performed. Compared with controls, serum Lp(a) levels were significantly increased in ischemic stroke patients than in controls. NIHSS scores and infarct volume were positively correlated with Lp(a) (P < 0.001). Finally, 34 patients (16.7%; 95% CI, 11.6-21.9%) had a stroke recurrence. Serum Lp(a) levels in patients with recurrent stroke were significantly higher as compared with those in patients without recurrent stroke (P < 0.001). In multivariate analysis, there was an increased risk of stroke recurrence associated with Lp(a) levels ≥300 mg/l (OR, 2.87; 95% CI, 1.98-4.32; P = 0.009) after adjusting for possible confounders. With an AUC of 0.872 (95% CI, 0.816-0.927), Lp(a) showed a significantly greater discriminatory ability to predict stroke recurrence as compared with NIHSS score (AUC, 0.782; 95% CI, 0.704-0.859; P < 0.01). Our findings suggest that elevated serum Lp(a) levels can predict the risk of early stroke recurrence in patients with first-ever ischemic stroke. Further research is needed to replicate these findings.

This case-control study investigated the association of transforming growth factor-β (TGF-β) receptor type I and II ( TGFBR1 and TGFBR2 ) gene polymorphisms with the risk of hypospadias in a Chinese population. One hundred and sixty two patients suffering from hypospadias were enrolled as case group and 165 children who underwent circumcision were recruited as control group. Single nucleotide polymorphisms (SNPs) in TGFBR1 and TGFBR2 genes were selected on the basis of genetic data obtained from HapMap. PCR-restriction fragment length polymorphism (PCR-RFLP) was performed to identify TGFBR1 and TGFBR2 gene polymorphisms and analyze genotype distribution and allele frequency. Logistic regression analysis was conducted to estimate the risk factors for hypospadias. No significant difference was found concerning the genotype and allele frequencies of TGFBR1 rs4743325 polymorphism between the case and control groups. However, genotype and allele frequencies of TGFBR2 rs6785358 in the case group were significantly different in contrast with those in the control group. Patients carrying the G allele of TGFBR2 rs6785358 polymorphism exhibited a higher risk of hypospadias compared with the patients carrying the A allele ( P <0.05). The TGFBR2 rs6785358 genotype was found to be significantly related to abnormal pregnancy and preterm birth (both P <0.05). The frequency of TGFBR2 rs6785358 GG genotype exhibited significant differences amongst patients suffering from four different pathological types of hypospadias. Logistic regression analysis revealed that preterm birth, abnormal pregnancy, and TGFBR2 rs6785358 were the independent risk factors for hypospadias. Our study provides evidence that TGFBR2 rs6785358 polymorphism might be associated with the risk of hypospadias., (© 2017 The Author(s).)

Background: To evaluate the suitability of a modified lateral upper arm free flap (LAFF) for reconstruction of soft tissue defects after resection of oral cancer., Methods: Eighteen cases of soft tissue defect repair performed between January 2011 and December 2013 using a modified LAFF after resection of oral cancer were reviewed. The design and harvest of the LAFF, the reconstruction procedure, and postoperative morbidity were reviewed and evaluated over a follow-up period of at least 12 months., Results: The overall flap survival was 94.4 % (17/18 patients). A broad scar at the donor site was the most common morbidity, but patients did not report dissatisfaction with the scar because they could easily cover it. All wounds at the donor site achieved primary recovery. One case of flap loss was repaired with a radial forearm free flap. One case complicated by diabetes mellitus involved infection of the flap with one-third of the flap becoming necrotic. This flap survived after removal of the necrotic tissue. In one other case, fat liquefactive necrosis (1.5 × 1.0 cm) occurred in the flap on the tip of the tongue, and this flap survived after debridement. Overall, the shape and function of the reconstructed tissues were well restored, and there was no severe morbidity at the donor site in any case., Conclusion: The modified LAFF was safe and reliable for the reconstruction of soft tissue defects after resection of oral cancer.

Background: Gelsolin (GSN) is one of the most abundant actin-binding proteins, and is involved in cancer development and progression., Patients and Methods: A hospital-based case-control study including 201 patients with OSCC and 199 healthy controls was conducted. Seventeen single-nucleotide polymorphisms (SNPs) of GSN were investigated by Sequenom Mass ARRAY and iPLEX-MALDI-TOF technology., Results: Through comparison of the 17 SNPs on GSN gene between the two groups, SNP rs1078305 and rs10818524 were verified to be significantly associated with an increased risk of OSCC. For GSN rs1078305, the TT genotype was associated with increased risk for OSCC (OR = 1.92, 95% CI = 1.11-3.32, p = 0.028). CT/TT variants were also associated with increased risk for OSCC compared to the CC genotype (OR = 1.83, 95% CI = 1.25-3.84, p = 0.032)., Conclusion: The rs1078305 and rs10818524 SNPs of GSN were associated with increased risk for OSCC development in a Chinese Han population.

The tumor suppressor gene phosphatase and tensin homologue (PTEN) plays a significant role in regulating cell growth, proliferation, and apoptosis. However, there are no data regarding the role of PTEN polymorphisms in the development of oral squamous cell carcinoma (OSCC). A hospital-based case-control study was conducted to investigate the potential association between PTEN polymorphisms and the risk of OSCC in a Chinese Han population. The study population comprised 201 patients with OSCC and 199 healthy controls. Seventeen single-nucleotide polymorphisms (SNPs) of PTEN were investigated and genotyped using Sequenom Mass ARRAY and iPLEX-MALDI-TOF technology. The observed genotype frequencies of these polymorphisms were in agreement with Hardy-Weinberg equilibrium in the control group (P > 0.05 for all). The heterozygous CT genotype was not associated with significantly increased risk for OSCC (OR = 0.89, 95 % CI = (0.55-1.42), P = 0.83), the TT genotype was not associated with increased risk for OSCC (OR = 1.01, 95 % CI = (0.58-1.74), P = 0.74) compared to the PTEN SNP rs1234224 homozygous CC genotype. Meanwhile, CT/TT variants were not associated with increased risk for OSCC compared with the CC genotype (OR = 0.93, 95 % CI = 0.60-1.44, P = 0.73). The T allele was not associated with significantly increased risk compared to the C allele (OR = 0.99, 95 % CI = 0.72-1.58, P = 0.69). Similar associations with the risk of OSCC were observed for the other genotypes of PTEN gene polymorphisms. There were no significant differences in the distribution of the genotype and allele frequencies of polymorphisms of the PTEN gene between the OSCC patients and controls in a Chinese Han population. Further studies are needed to clarify the specific roles of PTEN polymorphisms in the etiology of OSCC.

Purpose: To investigate the clinical outcomes of composite lateral arm free flap to reconstruct soft tissue defect after oral cancer ablation., Methods: Fifteen cases of soft-tissue defects were reconstructed using composite lateral arm free flap from January 2011 to December 2013. Color Doppler ultrasound blood flow detector was used to avoid variation of posterior radial collateral artery (PRCA). Composite flaps were designed according to the direction of PRCA, shape and area of the soft-tissue defect, which were over condylus lateralis humeri, with areas ranged from 4 cｍ×5 cm-11 cm×5 cm and an average vascular pedicle length of 10cm. Primary closure was achieved on all donor sites., Results: Fourteen flaps survived while vascular crisis was found in one flap 1 day post operation. The flap was replaced after an invalid salvation. All patients were followed up over 12 months, no recurrence was found. All patients achieved good recovery of morphology and functions with only 2 reporting local numbness of donor sites, which were relieved after 6 months., Conclusions: Composite lateral arm free flap, with consistent anatomy, suitable thickness and reliable blood supply, is a proper method to reconstruct postoperative soft tissue defect of patients with oral carcinoma.

An efficient multi-component reaction to synthesize multi-substituted 1,3-oxazolidine compounds of high optical purity was described. All the products were well-characterized and the absolute configuration of one chiral center was determined. The plausible mechanism was proposed and a kinetic resolution of epoxides process was confirmed.

Background: This study evaluated the safety and effectiveness of the extended lateral arm free flap (ELAFF) for repair of partial tongue defects after radical resection of tongue cancer., Methods: The study included nine consecutive patients who underwent repair of a partial tongue defect with an ELAFF after radical resection of tongue cancer from November 2010 to December 2013. Lesions were at the tip or margin of the tongue. Details of the reconstructive surgery, donor-site and recipient-site morbidity, and functional and esthetic outcomes were evaluated during a minimum of 12 months follow-up. Patient-reported Visual Analog Scale (VAS) scores on a scale of 0 (minimum satisfaction) to 10 (maximum satisfaction) were used to evaluate esthetic outcomes., Results: All patients were followed up for 12 months (median 24 months). The overall survival rate was 88 % (8/9). The donor site was closed primarily in all patients. The most frequent donor-site morbidity was a broad scar. Poor functional outcomes were associated with postoperative adjuvant radiotherapy. The shape and function of the reconstructed tongue were satisfactory. VAS scores (mean ± SD) for patient satisfaction with recipient-site and donor-site esthetics were 6.92 ± 1.70 and 7.33 ± 2.01, respectively., Conclusion: The ELAFF is a safe and effective option for repair of partial tongue defects after radical resection of tongue cancer., Level of Evidence V: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

CD8+ T cells are critical in the balance between fetal tolerance and antiviral immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) are important negative immune regulatory molecules involved in viral persistence and tumor metastasis. Here, we demonstrate that Tim-3+PD-1+CD8+ T cells from decidua greatly outnumbered those from peripheral blood during human early pregnancy. Co-culture of trophoblasts with CD8+ T cells upregulated PD-1+ and/or Tim-3+ immune cells. Furthermore, the population of CD8+ T cells co-expressing PD-1 and Tim-3 was enriched within the intermediate memory subset in decidua. This population exhibited high proliferative activity and Th2-type cytokine producing capacity. Blockade of Tim-3 and PD-1 resulted in decreased in vitro proliferation and Th2-type cytokine production while increased trophoblast killing and IFN-γ producing capacities of CD8+ T cells. Pregnant CBA/J females challenged with Tim-3 and/or PD-1 blocking antibodies were more susceptible to fetal loss, which was associated with CD8+ T-cell dysfunction. Importantly, the number and function of Tim-3+PD-1+CD8+ T cells in decidua were significantly impaired in miscarriage. These findings underline the important roles of Tim-3 and PD-1 pathways in regulating decidual CD8+ T-cell function and maintaining normal pregnancy.

A synthetic approach to stable enols was introduced and series of acyclic aliphatic solid enols were obtained and characterized. Relationship between the structure and the stability of these enols was discussed. Gaussian 09 calculations had been carried out to rationalize the stability of the enols. These enol structures were confirmed by (1)H NMR, (13)C NMR, MS, IR, partly by single crystal X-ray structure analysis and the protons exchange experiments. This work showed that very stable acyclic aliphatic enols can be synthesized efficiently without any purification.

Objective: To construct a recombinant plasmid pIRES-GM-CSF-IL-21, and to investigate its antitumor effect on tumors in the mice., Methods: Fifty Bal b/c mice were included in this study. Cultured hepatoma H22 cells were inoculated in the left lobe of the liver to develop orthotopically transplanted liver tumor models. The mice with orthotopically transplanted liver tumor were randomly divided into 5 groups (n = 10): (1) Each mouse received injection of recombinant plasmid pIRES-GM-CSF-IL-21; (2) Received injection of plasmid pIRES-GM-CSF; (3) pIRES-IL-21; (4) Received injection of ampty plasmid pIRES (H22/neo group); (5) Received injection of PBS (H22 group) via the tail vein, respectively. Therefore, the anti-tumor effect was induced by both GM-CSF and IL-21, or by either of them alone. The serum levels of IFN-γ and IL-2 were detected by ELISA, and the cytotoxicity of spleen NK and CTL cells were tested by MTT colorimetry., Results: Comparing with the H22 and H22/Neo groups, the tumor weight in the mice of H22/GM-CSF group was (0.603 ± 0.223) g, H22/IL21-treated group (0.583 ± 0.290) g and H22/GM-CSF-IL21-treated group (0.303 ± 0.323) g, significantly lower than that in the H22 group [(1.591 ± 0.280) g] and H22/Neo group [(1.489 ± 0.155) g]. Among them the tumor growth was most significantly inhibited in the H22/GM-CSF-IL-21 group (0.303 ± 0.323) g, compared with that of H22 and H22/neo groups (P < 0.01). But there was no significant difference between the tumor weights of the H22/GM-CSF group and H22/IL-21 group, and between the tumor weights of the H22 and H22/Neo groups (P > 0.05). The levels of IFN-γ and IL-2 in peripheral blood of mouse models treated with H22/GM-CSF-IL-21 were significantly increased than that in the H22/GM-CSF group and H22/IL-21 group (all P < 0.01), but significantly decreased in the H22group and H22/Neo group (P < 0.01). The anti-tumor activity of splenic NK cells and CTLs in the H22/GM-CSF-IL21 group was significantly enhanced (P < 0.01), compared with the significantly decreased in the H22 and H22/Neo groups., Conclusions: Our results demonstrate apparent antitumor effect of the plasmid pIRES-GM-CSF-IL-21 on the orthotopically transplanted liver tumor in mice. The combination of both pIRES-GM-CSF and IL-21 is more effective than that of pIRES/IL21 or pIRES/GM-CSF treatment alone. In addition, the plasmid pIRES-GM-CSF-IL-21 can also promote the secretion of IFN-γ and IL-2 in vivo, and enhance the cytotoxic activity of splenic NK and CTLs against the transplanted liver tumor.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome which is caused by germline mutations of the tumor suppressor gene MEN1. This study aimed to identify mutations in a Chinese pedigree with MEN1., Methods: A large Chinese family with MEN1 was collected. All of the coded regions and their adjacent sequences of the MEN1 gene were amplified and sequenced., Results: In this family, a heterozygous cytosine insertion in exon 10 (c.1546&#95;1547insC) inducing a frame shift mutation of MEN1 was found in the proband and the other two suffering members of his family. This mutation was linked to a novel single nucleotide polymorphism (SNP) in intron 3 (IVS3 + 18C > T)., Conclusions: The mutation in exon 10 of MEN1 gene might induce development of parathyroid hyperplasia and pituitary adenoma and cosegregate with MEN1 syndrome. The significance of the new found IVS3 + 18C > T of MEN1 needs a further investigation.

In the title compound, C(23)H(16)BrN, the three benzene rings show a disrotatory counter-rotating arrangement around the central pyridine ring and are twisted with respect to the pyridine ring with dihedral angles of 19.56 (13), 27.54 (13) and 30.51 (13)°.

To obtain full-length FKN nucleotide sequences of homonids including human, chimpanzee, gorilla, orangutan and gibbon, and Old World Monkeys including macaque and leaf monkey and make phylogenetic analysis, three exons of FKN were amplified by degenerated PCR using obtained peripheral blood cells DNA as template which was extracted from homonids and Old World Monkeys. After extracting and purifying from agarose gels, PCR products were sequenced and then spliced by using BioEdit. All the FKN sequences were aligned and compared the percent identity by using DNAStar. The phylogenetic tree was constructed using maximum evolution approach in Mega. The negative selection sites were analyzed by using Datamonkey. There is an apparent 30 bp nucleotides deletion mutation in homonids FKN comparing to that of Old World Monkeys besides other point mutations. Homology of nucleotide sequence between human and chimpanzee, gorilla, orangutan, gibbon, macaque and leaf monkey is 99.2%, 98.4%, 98.1%, 96.5%, 95.9% and 93.8%, respectively. Homology of amino acid sequence of them is 98.5%, 98.0%, 97.7%, 94.7%, 93.7% and 90.5%, respectively. In the same time, the genealogical relationship of human is a lot closer to chimpanzee than it is to gorilla and other apes. It is generally agreed that the evolution rule of FKN gene is in accord with that of the higher primates. In addition, Datamonkey shows that there are 3 negative selection sites 53Q, 84D and 239N in FKN. The full-length FKN gene of human, chimpanzee, gorilla, orangutan, gibbon, macaque and leaf monkey were sequenced successfully, and the FKN sequences analysis lays the foundation for further studying its evolution in immunological function in higher primates and the relation between its structure and function.

Objective: Dendritic cells play an important role in the pathogenesis of atherosclerosis. To explore the effects of hyperglycemia on the maturation and immune function of human monocyte derived dendritic cells (MDCs)., Methods: Immature MDCs were cultured in RPMI1640 medium with either 5.5 mmol/L D-glucose (NG), 25 mmol/L D-glucose (HG) or 5.5 mmol/L D-glucose + 19.5 mmol/L mannitol (HM) in the absence or presence of 30 mmol/L N-acetylcysteine [NAC, a reactive oxygen species inhibitor (ROS)] for 48 hours. FACS was used to investigate the MDCs immunophenotypic expression. Immune function was evaluated by allogeneic mixed T lymphocyte reaction and measurement of cytokine levels from culture supernatants. Intracellular ROS production in MDCs was also measured by 2', 7'-dichlorodihydrofluorescein (DCF, 10 micromol/L) fluorescence using confocal laser-scanning microscopy techniques., Results: Compared with NG and HM treated MDCs, the expression of maturation markers such as CD1a, HLA-DR, CD83, CD86 were significantly upregulated, allogeneic T cells proliferation as well as the cytokines secretions (IL-2, IL-12, IL-10 and IFN-gamma) significantly increased in HG treated MDCs. Intracellular ROS production in MDCs was also significantly increased and all these stimulatory effects of HG could be partially attenuated by NAC., Conclusion: High glucose promote the maturation of MDCs and augment their capacity to stimulate T-cell proliferation and cytokine secretions at least in part through enhancing intracellular ROS generation. These stimulating effects of high glucose on MDCs maturation may be one of the mechanisms of accelerated atherosclerosis found in patients with diabetes.

Aim: To clone mouse interleukin 21(mIL-21) gene and construct its eukaryotic expression vector., Methods: mIL-21 cDNA was amplified from ConA-activated mouse T cells by RT-PCR. And then the cDNA was cloned into eukaryotic expression plasmid pcDNA3.1 to construct recombinant plasmid pcDNA3.1/mIL-21 which was introduced into Sp2/0 cells by lipofectin. Expression of mIL-21 gene was detected by RT-PCR and NK cytotoxicity assay., Results: Recombinant plasmid pcDNA3.1/mIL-21 was constructed correctly and mIL-21 gene was expressed in transfected Sp2/0 cells., Conclusion: mIL-21 gene was cloned and expressed successfully, which lays the foundation for further studying anti-tumor effect of mIL-21 gene therapy in animal models.