Abundant binary promoter switches in lineage-determining transcription factors indicate a digital component of cell fate determination.

Previous studies of the murine Ly49 and human KIR gene clusters implicated competing sense and antisense promoters in the control of variegated gene expression. In the current study, an examination of transcription factor genes defines an abundance of convergent and divergent sense/antisense promoter pairs, suggesting that competing promoters may control cell fate determination. Differentiation of CD34+ hematopoietic progenitors in vitro shows that cells with GATA1 antisense transcription have enhanced GATA2 transcription and a mast cell phenotype, whereas cells with GATA2 antisense transcription have increased GATA1 transcripts and an erythroblast phenotype. Detailed analyses of the AHR and RORC genes demonstrate the ability of competing promoters to act as binary switches and the association of antisense transcription with an immature/progenitor cell phenotype. These data indicate that alternative cell fates generated by promoter competition in lineage-determining transcription factors contribute to the programming of cell differentiation.

The KIR2DL1 intermediate upstream element participates in gene activation.

The human KIR genes encode a family of class I MHC receptors that are expressed on subsets of NK cells. The expression of KIR proteins is controlled by a stochastic process, and competition between sense and antisense promoter elements has been suggested to program the variegated expression of these genes. Previous studies have demonstrated distinct roles of distal, intermediate, and proximal sense promoter/enhancer elements in gene activation and expression. Conversely, proximal and intronic antisense promoter transcripts have been associated with gene silencing at different stages of NK cell development. In the current study, we examine the effect of intermediate promoter deletion on KIR2DL1 expression in the YTS cell line. Homozygous deletion of the KIR2DL1 intermediate element did not affect proximal promoter activity but resulted in increased detection of upstream transcripts. No significant changes in alternative mRNA splicing or expression levels of KIR2DL1 protein were observed. However, intermediate element deletion was associated with a reduced frequency of gene activation by 5-azacytidine. Taken together, these results indicate that the intermediate element is not an enhancer required for KIR expression; however, it is required for the efficient activation of the gene.

Role of aspirin in the prevention of heterotopic ossification following total hip replacement: a systematic review and meta-analysis.

BACKGROUND: To systematically investigate if aspirin (ASA), used as venous thromboembolism (VTE) prophylaxis, plays a role in the prevention of heterotopic ossification (HO) following total hip arthroplasty (THA) and if ASA dosage impacted the rate of HO. METHODS: Eligible studies published from January 2000 to July 2022 were identified from the computerized searching of PubMed, Scopus and Web of Science. HO was defined according to Brooker Classification. Pooled risk ratios (OR) and 95% confidence interval (CI) were estimated under a random-effect model. Additionally, combined HO incidences were compared according to ASA dosage (a regular dose of 325 bid vs. a low dose of 81 mg bid/162 mg qd). RESULTS: Thirteen studies were included. ASA administered for VTE prophylaxis was significantly associated with a reduced risk of all-grade HO following THA (univariate, OR: 0.50, 95% CI: 0.34-0.74, P < 0.001; multivariate, OR: 0.60, 95% CI: 0.49-0.73, P < 0.001). Similar results could be observed for high-grade HO (univariate, OR: 0.57, 95% CI: 0.36-0.89, P = 0.015; multivariate, OR: 0.50, 95% CI: 0.27-0.92, P = 0.026). There was a non-significant trend towards a higher incidence of HO formation for low-dose ASA (31%, 95% CI: 29-34%), compared with regular-dose ASA (21%, 95% CI: 11-33%) (P = 0.069 under test of interaction). CONCLUSIONS: ASA can be an effective option for HO prophylaxis. More well-designed trials with long-term follow-ups are encouraged to confirm the current findings and to investigate the effect of ASA dosage on HO reduction.

Survival of lateral unicompartmental knee arthroplasty at short-, mid-, and long-term follow-up: a systematic review and meta-analysis.

BACKGROUND: The infrequency of lateral unicompartmental knee arthroplasty (UKA) has led to a lack of understanding of its survival. This study aimed to systematically evaluate the survivorship results of lateral UKA at different follow-ups based on available literature. METHODS: Five databases were searched for eligible studies. Pooled survivorships with 95% confidence intervals (CIs) at 3, 5, 10, 15, and 20 years after lateral UKA were estimated using a random-effect model. Subgroup and sensitivity analyses were performed. RESULTS: A total of 26 studies involving 5470 lateral UKAs were included. Survivorships of lateral UKA at 3-, 5-, 10-, 15-, and 20-year follow-ups were 96% (95% CI: 95-98%, I2 : 77.5%), 94% (95% CI: 93-96%, I2 : 70.8%), 88% (95% CI: 84-91%, I2 : 70.8%), 85% (95% CI: 79-91%, I2 : 70.8%), and 78% (95% CI: 71-85%, I2 : 54.2%), respectively. Subgroup analyses found that bearing type, the number of surgeons, and year of publication might be associated with implant survival outcomes. CONCLUSION: Lateral UKA is an effective procedure with excellent survivorships at short-, mid-, and long-term follow-ups. Results suggest a single-surgeon lateral UKA using fixed-bearing. Additional well-designed studies are needed to elucidate the current findings.

Intraday Changes and Clinical Applications of Thyroid Function Biomarkers in Healthy Subjects.

OBJECTIVE: We evaluated the intraday changes of thyroid function biomarkers in healthy subjects to help clinicians diagnose thyroid diseases in appropriate timing. METHODS: Blood samples were collected from 31 subjects at 0:00, 4:00, 8:00, 12:00, 16:00 and 20:00 on the sampling day and analyzed for thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free T3 (FT3), and free T4 (FT4). The intraday concentration changes were analyzed using Friedman's 2-way analysis of variance by ranks. RESULTS: The concentrations of TSH, T3, T4, FT3, and FT4 in males were significantly higher than those in females (P < .01). The obvious peak circadian rhythm of TSH was observed at 0:00 AM with gradual decline thereafter, whereas other biomarkers showed no rhythmic changes. CONCLUSION: Sex differences should be considered in interpreting thyroid function tests. It is important to select the sampling time according to the clinician's diagnostic needs, especially at night when TSH secretion peaks.

Application of chelate GLDA for remediating Cd-contaminated farmlands using Tagetes patula L.

In the present study, via a 180-day field trial, the indicators of soil total cadmium, DTPA-Cd, organic matter, and plant cadmium extraction were tested after the application of chelate tetrasodium glutamate diacetate (GLDA) to investigate the potential of GLDA combined with Tagetes patula L. to remediate cadmium-contaminated soil. To do so, five GLDA treatments (e.g., 0, 292.5, 585, 1170, and 2340 kg hm-2) were practiced. For each treatment, the total GLDA was divided into two applications with 15-day intervals (0.25, 0.47, and 0.61 mg·kg-1) under T. patula plantation. Compared with the control, our results showed that GLDA application significantly increased the biomass of aerial parts of T. patula by 21.9% (p < 0.05). Likewise, Cd content in aboveground and underground parts of T. patula increased by 94.7% and 60.5%, respectively, compared with the control (p < 0.05). GLDA application caused significant increases in Cd accumulations in cell soluble fraction and cell wall by 290% and 123%, respectively (p < 0.05); soil pH and DTPA-Cd content increased with the increase of total application of GLDA. Co-application of GLDA (2340 kg hm-2) and T. patula reduced the total soil Cd content by 12.87% compared with the soil background. Altogether, our findings conclude on the efficacy of GLDA application for the remediation of Cd-contaminated farmlands under T. patula cultivation.

HPV16 E7 Nucleotide Variants Found in Cancer-Free Subjects Affect E7 Protein Expression and Transformation.

The human papillomavirus (HPV) type 16 E7 oncogene is critical to carcinogenesis and highly conserved. Previous studies identified a preponderance of non-synonymous E7 variants amongst HPV16-positive cancer-free controls compared to those with cervical cancer. To investigate the function of E7 variants, we constructed full-length HPV16 E7 genes and tested variants at positions H9R, D21N, N29S, E33K, T56I, D62N, S63F, S63P, T64M, E80K, D81N, P92L, and P92S (found only in controls); D14E, N29H cervical intraepithelial neoplasia (CIN2), and P6L, H51N, R77S (CIN3). We determined the steady-state level of cytoplasmic and nuclear HPV16 E7 protein. All variants from controls showed a reduced level of E7 protein, with 7/13 variants having lower protein levels. In contrast, 2/3 variants from the CIN3 precancer group had near-wild type E7 levels. We assayed the activity of representative variants in stably transfected NIH3T3 cells. The H9R, E33K, P92L, and P92S variants found in control subjects had lower transforming activity than D14E and N29H variants (CIN2), and the R77S (CIN3) had activity only slightly reduced from wild-type E7. In addition, R77S and WT E7 caused increased migration of NIH3T3 cells in a wound-healing assay compared with H9R, E33K, P92L, and P92S (controls) and D14E (CIN2). These data provide evidence that the E7 variants found in HPV16-positive cancer-free women are partially defective for transformation and cell migration, further demonstrating the importance of fully active E7 in cancer development.

Chemical forms of cadmium in soil and its distribution in French marigold sub-cells in response to chelator GLDA.

The use of degradable chelating agents to facilitate phytoextraction is a promising low-cost method for the remediation of heavy metal-contaminated soils. However, there are few studies on how plants and soils respond to the chelating agents. In this study, the responses of French marigold (Tagetes patula L.) and soil cadmium (Cd) to the chelator tetrasodium glutamate (GLDA) was investigated in a 180 d field trial. Five GLDA treatments (0, 292.5, 585, 1170, and 2340 kg hm-2) were carried out in a Cd-contaminated soil (0.47 mg kg-1) under French marigold plantation. The results showed that the application of GLDA promoted the transformation of other forms of Cd in soil to exchangeable state, and the exchangeable Cd and Fe-Mn oxide bound state increased by 42.13% and 32.97% (p < 0.05), respectively. The cell wall Cd accumulations significantly increased 9.39% (p < 0.05) and the percentages of soluble fractions increased by 460.33% (p < 0.05). Furthermore, increases occurred in soil pH, as well as DOC and DTPA-Cd contents with increasing the total amount of GLDA. The composite application of GLDA (2340 kg hm-2) with French marigold reduced the total soil Cd content by 7.59% compared with the soil background. Altogether, results of this study suggested that the application of GLDA can effectively activate soil Cd and enhance the capability of French marigold for the remediation of Cd-contaminated soils.

Genetic variation that determines TAPBP expression levels associates with the course of malaria in an HLA allotype-dependent manner.

HLA class I (HLA-I) allotypes vary widely in their dependence on tapasin (TAPBP), an integral component of the peptide-loading complex, to present peptides on the cell surface. We identified two single-nucleotide polymorphisms that regulate TAPBP messenger RNA (mRNA) expression in Africans, rs111686073 (G/C) and rs59097151 (A/G), located in an AP-2α transcription factor binding site and a microRNA (miR)-4486 binding site, respectively. rs111686073G and rs59097151A induced significantly higher TAPBP mRNA expression relative to the alternative alleles due to higher affinity for AP-2α and abrogation of miR-4486 binding, respectively. These variants associated with lower Plasmodium falciparum parasite prevalence and lower incidence of clinical malaria specifically among individuals carrying tapasin-dependent HLA-I allotypes, presumably by augmenting peptide loading, whereas tapasin-independent allotypes associated with relative protection, regardless of imputed TAPBP mRNA expression levels. Thus, an attenuated course of malaria may occur through enhanced breadth and/or magnitude of antigen presentation, an important consideration when evaluating vaccine efficacy.

Biological variation in the serum and urine kidney injury markers of a healthy population measured within 24 hours.

BACKGROUND AND AIMS: To explore the biological variation (BV) of kidney injury markers in serum and urine of healthy subjects within 24 hours to assist with interpretation of future studies using these biomarkers in the context of known BV. MATERIALS AND METHODS: Serum and urine samples were collected every 4 hours (0, 4, 8, 12, 16 and 20 hours) from 31 healthy subjects within 24 hours and serum creatinine (s-Crea), serum ß2-microglobin (s-ß2MG), serum cystatin C (s-CYSC), serum neutrophil gelatinase-associated lipoprotein (s-NGAL), urine creatinine (u-Crea), urine ß2-microglobin (u-ß2MG), urine cystatin C (u-CYSC), urine neutrophil gelatinase-associated lipoprotein (u-NGAL) were measured. Outlier and variance homogeneity analyses were performed, followed by CV-ANOVA analysis on trend-corrected data (if relevant), and analytical (CVA), within-subject (CVI), and between-subject (CVG) biological variation were calculated. RESULTS: The concentration of kidney injury markers in male was higher than that in female, except for u-CYSC and u-NGAL. There were no significant difference in serum and urine kidney injury markers concentration at different time points. Serum CVI was lower than urine CVI, serum CVG was higher than CVI, and urine CVG was lower than CVI. The individual index (II) of serum kidney injury markers was less than 0.6, while the II of urinary kidney injury markers was more than 1.0. CONCLUSIONS: This study provides new short-term BV data for kidney injury markers in healthy subjects within 24 hours, which are of great significance in explaining other AKI / CKD studies.

Comparative efficacy of 5 suture configurations for arthroscopic rotator cuff tear repair: a network meta-analysis.

BACKGROUND: Rotator cuff tear is one of the most common complaint with shoulder pain, disability, or dysfunction. So far, different arthroscopic techniques including single row (SR), double row (DR), modified Mason-Allen (MMA), suture bridge (SB) and transosseous (TO) have been identified to repair rotator cuff. However, no study has reported the comparative efficacy of these 5 suture configurations. The overall aim of this network meta-analysis was to analyze the clinical outcomes and healing rate with arthroscopy among SR, DR, MMA, SB and TO. METHODS: A systematic literature was searched from PubMed, EBSCO-MEDLINE, Web of Science, google scholar and www.dayi100.com , and checked for the inclusion and exclusion standards. The network meta-analysis was conducted using Review Manager 5.3 and SATA 15.0 software. RESULTS: Thirty-four studies were eligible for inclusion, including 15 randomized controlled trials, 17 retrospective and 2 prospective cohort studies, with total 3250 shoulders. Two individual reviewers evaluated the quality of the 34 studies, the score form 5 and 9 of 10 were attained according to the Newcastle-Ottawa Scale for the 17 retrospective and 2 prospective studies. There was no significant distinction for the Constant score among 5 groups in the 16 studies with 1381 shoulders. The treatment strategies were ranked as MMA, DR, SB, SR and TO. In ASES score, 14 studies included 1464 shoulders showed that no significant differences was showed among all 5 groups after surgery. Whereas the efficacy probability was TO, MMA, DR, SB and SR according to the cumulative ranking curve. The healing rate in 25 studies include 2023 shoulders was significant in both SR versus DR [risk ratio 0.45 with 95% credible interval (0.31, 0.65)], and SR versus SB [risk ratio 0.45 (95% credible interval 0.29, 0.69)], and no significant in the other comparison, the ranking probability was MMA, SB, DR, TO and SR. CONCLUSION: Based on the clinical results, this network meta-analysis revealed that these 5 suture configurations shows no significant difference. Meanwhile, suture bridge may be the optimum treatment strategy which may improve the healing rate postoperatively, whereas the DR is a suboptimal option for arthroscopic rotator cuff repairs.

Adsorption of As(III), Pb(II), and Zn(II) from Wastewater by Sodium Alginate Modified Materials.

Sodium alginate (SA), polyvinyl oxide (PEO), and ceramic nanomaterials were used to prepare alginate composite gel. The present study examined the removal rate and adsorption capacity of alginate composite gel for removal of wastewater As(III), Pb(II), and Zn(II). Batch experiments were conducted to study the influence of experimental parameters such as pH and temperature, as well as the mechanism of As(III), Pb(II), and Zn(II) adsorption with the new adsorbent. The results showed the high efficiency of sodium alginate composite gel for removal of wastewater As(III), Pb(II), and Zn(II). Under the condition of the best liquid-solid ratio and the contact time, the removal rates of As(III), Pb(II), and Zn(II) were 67.42%, 95.31%, and 93.96%, respectively. The pseudo-second-order kinetic equation was superior to fit the adsorption kinetics process. The isothermal adsorption models of As(III) and Pb(II) fitted well with the Freundlich model, and Zn(II) fitted well with the Langmuir model. The results of SEM, EDS, XPS, and FTIR analyses revealed that the adsorption process occurred mainly via chemisorption. The results of the present study suggest that new adsorbents can be effectively utilized for As(III), Pb(II), and Zn(II) removal from water.

[Sustained Effects of Remediation Materials on Soil Copper Remediation Under Oil-Rice Rotation].

In this study, a continuous rape-rice rotation plot experiment was conducted over three years. Repair materials were continuously applied in the first two years, and no repair materials were applied in the second year. The repair effects of hydroxyapatite, lime, biochar, bio-organic fertilizer, and nano-materials on copper contaminated soil and the enrichment of copper in different parts of rape and rice were investigated. The results show that hydroxyapatite, lime, and nanomaterials can significantly increase soil pH, and different restoration materials can effectively inhibit the movement of soil copper. The effective copper treatment with lime restoration soil had the largest decrease. The four seasons of continuous application of restoration materials were 38.9%, 34.9%, 27.88%, and 29.04%, respectively, and the subsequent effect of lime passivation of effective copper was better than other restoration materials. The application of the repair material significantly reduced the copper content in edible parts of rape and rice. In the four seasons of application of the repair material, the maximum copper content in edible parts of different crops decreased by 46.03%, 22.2%, 29.44%, and 31.71%, respectively. Due to the application effect of the repair material, the copper content in the edible part of the two season crops, without the repair material, did not exceed the national food safety limit. With the use of different repair materials, the yields of rapeseed and rice were improved. This test can provide some theoretical basis and technical support for soil improvement in copper-contaminated areas.

Genetic and Epigenetic Regulation of the Smoothened Gene (SMO) in Cancer Cells.

(1) Background: The hedgehog (HH) signaling pathway is a key regulator of embryonic patterning, tissue regeneration, stem cell renewal, and cancer growth. The smoothened (SMO) protein regulates the HH signaling pathway and has demonstrated oncogenic activity. (2) Methods: To clarify the role of the HH signaling pathway in tumorigenesis, the expression profile of key HH signaling molecules, including SMO, PTCH1, GLI1, GLI2, and GLI3, were determined in 33 cancer cell lines and normal prostate cells and tissues. We performed a computational analysis of the upstream region of the SMO gene to identify the regulatory elements. (3) Results: Three potential CpG islands and several putative SMO promoter elements were identified. Luciferase reporter assays mapped key SMO promoter elements, and functional binding sites for SP1, AP1, CREB, and AP-2α transcription factors in the core SMO promoter region were confirmed. A hypermethylated SMO promoter was identified in several cancer cell lines suggesting an important role for epigenetic silencing of SMO expression in certain cancer cells. (4) Discussion: These results have important implications for our understanding of regulatory mechanisms controlling HH pathway activity and the molecular basis of SMO gene function. Moreover, this study may prove valuable for future research aimed at producing therapeutic downregulation of SMO expression in cancer cells.

Differential Activation of the Transcription Factor IRF1 Underlies the Distinct Immune Responses Elicited by Type I and Type III Interferons.

Type I and III interferons (IFNs) activate similar downstream signaling cascades, but unlike type I IFNs, type III IFNs (IFNλ) do not elicit strong inflammatory responses in vivo. Here, we examined the molecular mechanisms underlying this disparity. Type I and III IFNs displayed kinetic differences in expression of IFN-stimulated genes and proinflammatory responses, with type I IFNs preferentially stimulating expression of the transcription factor IRF1. Type III IFNs failed to induce IRF1 expression because of low IFNλ receptor abundance and insufficient STAT1 activation on epithelial cells and thus did not activate the IRF1 proinflammatory gene program. Rather, IFNλ stimulation preferentially induced factors implicated in tissue repair. Our findings suggest that IFN receptor compartmentalization and abundance confer a spatiotemporal division of labor where type III IFNs control viral spread at the site of the infection while restricting tissue damage; the transient induction of inflammatory responses by type I IFNs recruits immune effectors to promote protective immunity.

The Human TET2 Gene Contains Three Distinct Promoter Regions With Differing Tissue and Developmental Specificities.

Tet methylcytosine dioxygenase 2 (TET2) is a tumor suppressor gene that is inactivated in a wide range of hematological cancers. TET2 enzymatic activity converts 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC), an essential step in DNA demethylation. Human TET2 is highly expressed in pluripotent cells and down-regulated in differentiated cells: however, transcriptional regulation of the human TET2 gene has not been investigated in detail. Here we define three promoters within a 2.5 kb region located ∼ 87 kb upstream of the first TET2 coding exon. The three promoters, designated as Pro1, Pro2, and Pro3, generate three alternative first exons, and their presence in TET2 mRNAs varies with cell type and developmental stage. In general, all three TET2 transcripts are more highly expressed in human tissues rich in hematopoietic stem cells, such as spleen and bone marrow, compared to other tissues, such as brain and kidney. Transcripts from Pro2 are expressed by a broad range of tissues and at a significantly higher level than Pro1 or Pro3 transcripts. Pro3 transcripts were highly expressed by embryoid bodies generated from the H9 ES cell line, and the major Pro3 transcript is an alternatively spliced mRNA isoform that produces a truncated TET2 protein lacking the catalytic domain. Our study demonstrates distinct tissue-specific mechanisms of TET2 transcriptional regulation during early pluripotent states and in differentiated cell types.

Tuning of NK-Specific HLA-C Expression by Alternative mRNA Splicing.

A complex system regulating HLA-C expression in NK cells, driven by an NK-specific promoter that produces alternatively spliced variants of the 5'-UTR has been recently identified. Exon content of the NK-specific 5'-UTR varies strikingly across HLA-C alleles, with some exons being allele specific. In order to investigate the possibility that allelic variation in the 5'-UTR modulates HLA-C expression levels, cDNAs containing several distinct classes of 5'-UTR were compared. Subtle changes in 5'-UTR content had a significant effect on the expression of HLA-C*03 and HLA-C*12 cDNA clones, suggesting that alternative splicing can fine-tune the level of protein expression. The HLA-C*06 allele was found to be highly expressed in relation to the other alleles studied. However, its increased expression was primarily associated with differences in the peptide-binding groove. Although the impact of allele-specific alternative splicing of NK-Pro transcripts on protein levels can be modest when compared with the effect of changes in peptide-loading, alternative splicing may represent an additional regulatory mechanism to fine-tune HLA-C levels within NK cells in distinct tissue environments or at different stages of maturation in order to achieve optimal levels of missing-self recognition.

Identification of trophoblast-specific elements in the HLA-C core promoter.

There are several aspects of HLA-C gene expression that distinguish it from the HLA-A and HLA-B genes. First, HLA-C is expressed by extravillous trophoblasts, whereas HLA-A and HLA-B are not. Second, its cell-surface expression is much lower, which has been linked to changes in transcription and efficiency of peptide loading and export. Third, HLA-C possesses a NK cell-specific promoter and a complex alternative splicing system that regulates expression during NK cell development. In this study, we investigate the contribution of the HLA-C core promoter to trophoblast-specific expression. Analysis of transcription start sites showed the presence of a trophoblast-associated start site and additional upstream TATA and CCAAT-box elements in the HLA-C promoter, suggesting the presence of an overlapping trophoblast-specific promoter. A comparison of in vitro promoter activity showed that the HLA-C promoter was more active in trophoblast cell lines than either the HLA-A or HLA-B promoters. Enhanced trophoblast activity was mapped to the central enhanceosome region of the promoter, and mutational analysis identified changes in the RFX-binding region that generated a trophoblast-specific enhancer.

Fixation versus Excision of Osteochondral Fractures after Patellar Dislocations in Adolescent Patients: A Retrospective Cohort Study.

BACKGROUND: Patellar dislocation is one of the most common knee injuries in the adolescent population. It is often combined with osteochondral fracture. The purpose of this study was to compare the outcomes between fixation and excision of osteochondral fractures not involving the bearing surface in adolescent patients with patellar dislocations. METHODS: Patients who underwent surgery for osteochondral fracture following patellar dislocation in our institution from 2007 to 2014 were retrospectively evaluated. Visual analog scale (VAS) of pain and the International Knee Documentation Committee (IKDC) form were used to assess knee pain and function at follow-up. Patient satisfaction was evaluated. Differences in the values of variables among groups were assessed using t-test if equal variance or Mann-Whitney U-test if not equal variance. The Pearson's Chi-square test was applied for dichotomous variables if expected frequency was >5 or Fisher's exact test was applied if not. A value of P < 0.05 was considered statistically significant. RESULTS: Forty-three patients were included, with the average age of 14.1 ± 2.3 (range, 9.0-17.0) years. Nineteen underwent fixation of osteochondral fractures and 24 did not. The average follow-up time was 28 ± 10 months. There was no significant difference in age, gender, follow-up time, causes of injury, times of dislocation, and location of osteochondral fracture between fixation and excision groups. The fixation group had a significantly longer surgery time (82 ± 14 min) and larger size of osteochondral fracture (2.30 ± 0.70 cm2) than the excision group (43 ± 10 min, 1.88 ± 0.62 cm2, respectively, t = 10.77, P < 0.01 and t = 0.84, P < 0.05). At the last follow-up, the average IKDC score in the fixation group (82.52 ± 8.71) was significantly lower than that in the excision group (89.51 ± 7.19, t = 2.65, P < 0.01). There was no significant difference in VAS of pain and patients' satisfaction. There were 7 (16%) patients with recurrent dislocation. CONCLUSION: Excision of osteochondral fractures has equivalent or better outcomes compared to fixation in adolescent patients with patellar dislocations when these fractures do not involve the bearing surface.

Association of TNFRSF1B Promoter Polymorphisms with Human Disease: Further Studies Examining T-Regulatory Cells Are Required.

The TNFR2 receptor is expressed by highly active regulatory T cells, and thus constitutes an important therapeutic target for the treatment of autoimmune disease and cancer. Disease susceptibility as well as the potential response to therapies directed at TNFR2 could be significantly impacted by genetic variation in the promoter of the TNFRSF1B gene that codes for the TNFR2 protein. To date, only a few studies have examined the association of TNFRSF1B promoter variation with disease, and the potential impact on T-regulatory cell (Treg) number and function has not been examined. We propose that copy number variation of a key transcription factor binding site has a significant effect on TNFRSF1B promoter activity, and should be considered in studies of disease susceptibility and especially with regard to variation in the level of TNFR2 expression on Tregs.