Identification and validation of long noncoding RNA AC083900.1 and RP11-283C24.1 for prediction of progression of osteosarcoma.

BACKGROUND: The role of cuproptosis, an emerging cell death pathway that makes a remarkable contribution to tumor progression, remains elusive in osteosarcoma (OS), in addition to its regulator, including long-no-coding RNAs (lncRNAs) that are also a critical factor for fueling OS. METHODS: Transcriptome and clinical data from 70 normal human bone tissue samples and 84 frozen clinical osteosarcoma samples were included in this study. Cuproptosis-associated lncRNAs (CRlncs) were identified through differential expression and co-expression analyses. Univariate Cox regression was performed to screen for prognostic lncRNAs, then we used least absolute shrinkage and selection operator regression to distinguish prognosis-related CRlncs (AC083900.1 and RP11-283C24.1) for modeling the CRlncs prognostic signature (CLPS) by multivariate Cox regression using the stepwise method. CLPS performance was tested by independent prognostic analyses, survival curve and receiver operating characteristic (ROC) curve. In addition, the molecular and immune mechanisms that underlie the unfavorable prognosis of CLPS-identified high-risk group were elucidated. RESULT: AC083900.1 and RP11-283C24.1 have been identified as the most important CRlncs for OS progression (hazard ratio: 3.498 and 2.724, respectively), and the derived CLPS demonstrated outstanding performance for the prediction of OS prognosis (AUC of 0.799 and 0.778 in the training and test sets, both adj-p < 0.05 in survival curve). As was anticipated, CLPS also outperformed a recent clinical prognostic approach that only achieved an AUC of 0.682 [metastasis]. It is notable that AC083900.1 progressed OS metastasis, evidenced by its high expression in metastatic OS, its high correlation to metastasis-related genes, and its high AUC of 0.683 for the prediction of metastasis. Mechanistically, AC083900.1 and RP11-283C24.1 dysregulated many critical biological processes regarding humoral immune response, immunoglobulin complex, etc.; while reducing the infiltration of many cytotoxic immune cells (B-cells, TIL, neutrophils, etc.). It is encouraging that BMS-509744 and KIN001-135 demonstrated high therapeutic implications for CLPS-identified high-risk OS, and the low-risk counterpart was sensitive to SB-216763. Quantitative RT-PCR analysis showed that both AC083900.1 and RP11-283C24.1 were significantly upregulated in different osteosarcoma cell lines. CONCLUSION: This study elucidated the roles and mechanisms of AC083900.1 and RP11-283C24.1 in the development of OS, fostering a reliable prognostic approach and treatment for OS patients.

Changes in Serum Prealbumin and Incision Complications Following Spinal Tuberculosis Surgery: A Preliminary Study.

OBJECTIVES: To explore the trend of changes in the serum prealbumin (PA) level in patients with spinal tuberculosis during the perioperative period and its relationship with postoperative incision complications. METHODS: A retrospective study was performed by enrolling 162 patients (82 men and 80 women) with spinal tuberculosis who had been admitted to the Tianjin Haihe Hospital from June 2013 to June 2017. The included patients were then assigned to the elderly group (≥65 years of age, n = 35) and the non-elderly group (<65 years of age, n = 127). The chemotherapy regimen was 3HREZ/9HRE, in combination with nutritional support for 3-4 weeks, as well as one-stage debridement and (or) bone graft fusion and internal fixation. The serum PA levels of patients with spinal tuberculosis at admission, prior to surgery, and at 2 and 4 weeks after surgery were collected, and incision healing and sinus formation were observed for 3 months. Changes in serum PA levels of all patients at different time points were observed using one-way analysis of variance. Pairwise comparison at different time points was performed using the least significant difference method and comparison of serum PA levels between different groups at the same time points was subjected to t-test. The χ2 -test was used for comparison of the incidence of incision complications between different groups and between different subgroups based on different PA levels. RESULTS: There was a gradual increased trend in the PA level from admission to 4 weeks after surgery in all patients [(0.14 ± 0.03) g/L < (0.16 ± 0.04)g/L < (0.22 ± 0.04) g/L < (0.25 ± 0.04) g/L]. The increase in the non-elderly group was higher than that in the elderly group (P < 0.01). Furthermore, the incidence of incision complications in the elderly group was higher than in the non-elderly group (14.29% > 1.78%, P < 0.01). The serum PA level was graded in accordance with NRS2002. There were 88 patients with preoperative grade 0-1 serum PA level (≥0.16g/L) who had no incision complications. The incidence of incision complications in patients with grade 3 serum PA level (<0.10 g/L, 9 patients) was higher than in patients with grade 2 (0.100-0.159 g/L, 66 patients) (44.44% > 6.06%, P < 0.01). CONCLUSION: Changes in serum PA level in patients with spinal tuberculosis during the perioperative period are consistent with the trend of inflammation control and nutrition improvement, and are correlated with the incidence of incision complications after surgery. The relationship between the changes and the timing of surgery is worthy of future research.

Identification of CHRNB4 as a Diagnostic/Prognostic Indicator and Therapeutic Target in Human Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors and there is a lack of biomarkers for ESCC diagnosis and prognosis. Family subunits of cholinergic nicotinic receptor genes (CHRNs) are involved in smoking behavior and tumor cell proliferation. Previous researches have shown similar molecular features and pathogenic mechanisms among ESCC, head and neck squamous cell carcinoma (HNSC), and lung squamous cell carcinoma (LUSC). Using edgeR, three mutual differentially expressed genes of CHRNs were found to be significantly upregulated at the mRNA level in ESCC, LUSC, and HNSC compared to matched normal tissues. Kaplan-Meier survival analysis showed that high expression of CHRNB4 was associated with unfavorable prognosis in ESCC and HNSC. The specific expression analysis revealed that CHRNB4 is highly expressed selectively in squamous cell carcinomas compared to adenocarcinoma. Cox proportional hazards regression analysis was performed to find that just the single gene CHRNB4 has enough independent prognostic ability, with the area under curve surpassing the tumor-node-metastasis (TNM) staging-based model, the most commonly used model in clinical application in ESCC. In addition, an effective prognostic nomogram was established combining the TNM stage, gender of patients, and expression of CHRNB4 for ESCC patients, revealing an excellent prognostic ability when compared to the model of CHRNB4 alone or TNM. Gene Set Enrichment Analysis results suggested that the expression of CHRNB4 was associated with cancer-related pathways, such as the mTOR pathway. Cell Counting Kit-8, cloning formation assay, and western blot proved that CHRNB4 knockdown can inhibit the proliferation of ESCC cells via the Akt/mTOR and ERK1/2/mTOR pathways, which might facilitate the prolonged survival of patients. Furthermore, we conducted structure-based molecular docking, and potential modulators against CHRNB4 were screened from FDA approved drugs. These findings suggested that CHRNB4 specifically expressed in SCCs, and may serve as a promising biomarker for diagnosis and prognosis prediction, and it can even become a therapeutic target of ESCC patients.

LncRNA MIR4435-2HG is downregulated in osteoarthritis and regulates chondrocyte cell proliferation and apoptosis.

PURPOSE: MIR4435-2HG is an oncogenic lncRNA in gastric cancer and lung cancer. Our preliminary microarray data showed that MIR4435-2HG was downregulated in osteoarthritis plasma specimen, indicating the possible involvement of MIR4435-2HG in osteoarthritis. RESULTS: MIR4435-2HG was downregulated in plasma of osteoarthritis than in plasma of healthy controls. Reduced levels of MIR4435-2HG expression effectively distinguished osteoarthritis patients from the control group. Expression levels of MIR4435-2HG increased after treatment. Overexpression of MIR4435-2HG promoted, while MIR4435-2HG knockdown inhibited the proliferation of chondrocytes. In contrast, MIR4435-2HG overexpression inhibited, while MIR4435-2HG knockdown promoted the apoptosis of chondrocytes. CONCLUSION: MIR4435-2HG is downregulated in osteoarthritis and regulates chondrocyte cell proliferation and apoptosis.

Time-multiplexed stereoscopic display with a quantum dot-polymer scanning backlight.

We fabricate a time-multiplexed stereoscopic display, which is composed of a quantum dot-polymer (QDP) scanning backlight, 120 Hz liquid crystal display (LCD), and shutter glasses. Blue LEDs, which can excite QDP film to produce white light, are adopted to replace the traditional white LEDs. The QDP scanning backlight, LCD, and shutter glasses can be controlled by the synchronization signal and work together, enabling viewers to obtain parallax views. Crosstalk is about 1%, and luminance through the shutter glasses is higher than 150 nit. The color gamut can be widely extended to 77.98% rather than the traditional 55.75% in the ITU-R Recommendation BT.2020 (Rec.2020) color space, due to the excellent properties of QD material.

A Comparative Study on the Role of Xpert MTB/RIF in Testing Different Types of Spinal Tuberculosis Tissue Specimens.

AIMS: The aim of the present study was to compare the efficacy of the commercial Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF) test for evaluating different types of spinal tuberculosis (TB) tissue specimens. METHODS: Pus, granulation tissue, and caseous necrotic tissue specimens from 223 patients who were diagnosed with spinal TB and who underwent curettage were collected for bacterial culture and the Xpert MTB/RIF assay to calculate the positive rate. Bacterial culture and phenotypic drug sensitivity testing (pDST) were adopted as the gold standards to calculate the sensitivity and specificity of the Xpert bacterial detection and drug resistance (DR) test. RESULTS: The positive rate (68.61% ± 7.35%) from the Xpert MTB/RIF assays of spinal TB patients' tissue specimens was higher compared with bacterial culture (44.39% ± 6.51%, Z = 5.1642, p < 0.01), and the positive rates from Xpert MTB/RIF assays on the three types of specimens were all higher than those of bacterial culture, with statistically significant results for pus and granulation tissue specimens. The positive rates for pus using the two bacteriological tests were higher than those for granulation tissue but were not statistically significant. However, the positive rates obtained from granulation tissue were statistically significantly higher than those obtained from caseous necrotic tissue. With bacterial culture and pDST as the gold standards, the sensitivity of Xpert MTB/RIF assays for MTB was 96.97%, while the sensitivity and specificity of the DR test also remained relatively high. CONCLUSION: For efficient and accurate diagnosis of spinal TB and DR and timely provision of effective treatment, multiple specimens, especially the pus of spinal TB patients, should be collected for Xpert MTB/RIF assays.

Study on the relationship between vitamin D deficiency and susceptibility to spinal tuberculosis.

OBJECTIVE: To investigate the effect of vitamin D deficiency on susceptibility to spinal tuberculosis and its pathological development. METHODS: A case-control design was used in this study. A total of 163 treatment-naïve patients with spinal tuberculosis admitted to this institute for an operation from June 2013 to May 2016 were included in the case group, and 170 subjects who received a health examination in the same hospital were included in the control group. Control group patients were frequency-matched with the case group by age, gender, and season. Serum 25-hydroxyvitamin D levels were detected using an enzyme linked immunosorbent assay (ELISA). Pathological classification of patients in the case group was conducted according to intraoperative findings, and definite diagnosis of spinal tuberculosis was confirmed after operation. RESULTS: The serum level of vitamin D [23.99 (20.55, 29.54) nmol/L] in the case group was lower than that in the control group [42.94 (35.68, 51.04) nmol/L], and the difference was statistically significant (Z = -9.048, P < 0.05). Out of the 163 patients with spinal tuberculosis who underwent pathological classification, 107 cases of caseous necrosis and 56 cases of hyperplasia were identified. Based on the vitamin D levels of the patients in the case group, these patients were further divided into a low-level group (<25 nmol/L) and a high-level group (≥25 nmol/L). The proportion of patients with caseous necrosis in the low-level group (79.17%) was higher than that in the high-level group (46.27%), with a statistically significant difference (χ2 = 18.937, P < 0.05). CONCLUSION: Vitamin D deficiency is associated with susceptibility to spinal tuberculosis and its pathological classification, and vitamin D deficiency affects the occurrence and development of spinal tuberculosis.

Forked osteotomy arthroplasty for elbow tuberculosis: six years of follow-up.

BACKGROUND: Elbow tuberculosis (TB) is not rare in China. Most patients are diagnosed when it is at an advanced stage and with bony ankylosis complications. For a developing country, such as China, it is important for there to be safe and cost-effective procedures. MATERIALS AND METHODS: A retrospective study was designed to assess the effects of improved forked excision arthroplasty for treating elbow TB. There were 20 patients (average age, 48.45 years). For all patients, the preoperative diagnosis was elbow TB at an advanced stage. All patients underwent forked excision arthroplasty. Patients were evaluated preoperatively and postoperatively with the Mayo's elbow performance score (MEPS). Mean follow-up was at 74.4 months. RESULTS: At the last follow-up, the mean postoperative MEPS was 83.7 compared with the preoperative MEPS of 20.25. Results of Mayo's elbow performance index were excellent in seven patients, good in 12 and fair in one, and none were poor. The range of elbow motion also improved significantly. CONCLUSION: This study of forked elbow excision arthroplasty has shown promising results for treating elbow TB. Most patients had ideal postoperative outcomes and exhibited painless elbow joints, with satisfactory functional recovery at medium-term follow-up. Further studies with longer follow-up are warranted. LEVEL OF EVIDENCE: III.