ZCCHC4 Promotes Osteosarcoma Progression by Upregulating ITGB1.

Zinc finger CCHC-type containing 4 (ZCCHC4), RNA binding protein, has been reported to mediate rRNA methylation and affect tumor cell proliferation. However, the role of ZCCHC4 in the regulation of osteosarcoma (OS) remains unknown. ZCCHC4 was highly expressed in OS tissues and cell lines. Overexpression or silencing of ZCCHC4 promoted or inhibited cell proliferation, epithelial-mesenchymal transition (EMT), and motility. Additionally, we proved that ZCCHC4 facilitates OS progression through upregulating integrin ß1 (ITGB1). In the animal model, ZCCHC4 knockdown reduced OS tumor growth and metastases in vivo. Our findings showed that ZCCHC4 promoted the progression of OS through upregulating ITGB1 and suggested that inhibition of ZCCHC4 could be a novel therapeutic strategy for OS.

Risk factors for infection in patients undergoing knee arthroscopy: A Systematic Review and Meta-analysis.

PURPOSE: The primary aim was to determine the risk of infection after knee arthroscopy and to evaluate the risk factors for surgical site infection (SSI). METHODS: The PubMed/Medline, Embase and Cochrane Library databases were systematically searched, as were the reference lists of previous systematic reviews and meta-analysis manual studies. A random-effects model was used to calculate the estimated pooled odds ratio (OR). RESULTS: A total of 38,321 potential articles met the initial inclusion criteria. After a review of the titles, abstracts and full texts, the remaining 41 articles were included in the final analysis. We identified 9,089,578 patients who underwent knee arthroscopy in 41 articles. High-quality (class I) evidence showed that autografts (cruciate ligament reconstruction) (OR, 2.66% CI, 1.84-3.86) or high procedure complexity (OR, 2.02;95% CI, 1.69-2.43) had a higher risk of infection, while medium-quality (class II or class III) evidence showed that obesity (BMI ≥ 30 kg/m2) (OR, 1.27; 95% CI, 1.08-1.49) or male (OR, 1.52; 95% CI, 1.32-1.75) or diabetes (OR, 1.71; 95% CI, 1.36-2.14) or tobacco use (OR, 1.65; 95% CI, 1.38-1.97) or preoperative steroid use (OR, 3.41; 95% CI, 2.10-5.54) had a higher risk of infection. The meta-analysis showed that there was no association between age or antibiotic prophylaxis and infection incidence. CONCLUSIONS: The meta-analysis showed that significant risk factors for infection after knee arthroscopy included obesity, male sex, diabetes, tobacco use, high procedure complexity, graft type, and preoperative steroid use. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and Level IV studies.

High CD204+ tumor-associated macrophage density predicts a poor prognosis in patients with clear cell renal cell carcinoma.

Purpose: Tumor-associated macrophages (TAMs) play a crucial role in solid tumors and display varying characteristics depending on the specific tumor microenvironment (TME). The study investigated the presence and characteristics of TAMs in renal clear cell carcinoma (ccRCC) and assessed their influence on patient prognosis. Methods: Immunohistochemistry (IHC) was used to identify CD204+ TAMs in a cohort of 72 patients with ccRCC. Kaplan-Meier survival analysis and log-rank test were used to evaluate the prognostic significance of CD204+ TAMs in each group. The TCGA-KIRC cohort was used to analyze the relationship between CD204 and immunity. The functions of CD204+ TAMs in the TCGA-KIRC cohort were analyzed through GO enrichment analysis. Immunofluorescence (IF) was conducted to confirm the positive effects of CD204 on regulatory T (Treg) cells and exhausted T (Tex) cells. Results: There was a negative relation between high infiltration of CD204+ TAMs and both overall survival (OS) and progression-free survival (PFS) in ccRCC. A positive correlation was found between high-infiltrating CD204+ TAMs and distant organ metastasis, as well as lymph node metastasis. In the TCGA-KIRC cohort, the group with high expression of CD204 exhibited significant up-regulation of 120 genes as well as enrichment in the negative regulation of immunity. CD204 high-expression group showed up-regulation of Treg cells and Tex cells. Conclusion: The presence of CD204+ TAMs in ccRCC is associated with a negative prognosis in patients. The high infiltration of CD204 promotes distant organ metastasis by aggerating Treg cells and Tex cells.

Exosomal miRNA Expression Profiling and the Roles of Exosomal miR-4741, miR-32, miR-3149, and miR-6727 on Gastric Cancer Progression.

Objective: Accumulated evidence highlights the biological implications of exosomes in gastric cancer. Herein, we conducted the exosomal miRNA expression profiling and identified potential diagnostic markers for gastric cancer. Methods: Plasma exosomes were isolated and identified from three gastric cancer patients and three healthy participants. Microarrays of exosomal miRNAs were then analyzed. Differentially expressed exosomal miRNAs were screened with fold - change|≥2.0 and p ≤ 0.05. Among them, miR-4741, miR-32, miR-3149, and miR-6727 expressions were verified in tissues and plasma of patients and healthy subjects. ROC curves were conducted for evaluating the diagnostic performance. The roles of miR-32, miR-3149, miR-6727, and miR-4741 on gastric cancer progression were observed by cellular experiments. Results: Isolated exosomes were well characterized by Western blot and transmission electron microscopy as well as nanoparticle-tracking analyses. According to the microarrays, 142 exosomal miRNAs were upregulated, and 34 were downregulated in gastric cancer than healthy subjects. miR-4741 upregulation and miR-32, miR-3149, and miR-6727 downregulations were found in tissues and plasma of gastric cancer patients. The AUCs of miR-4741, miR-32, miR-3149, and miR-6727 were separately 0.8554, 0.9456, 0.7683, and 0.8923. Upregulated miR-32, miR-3149, and miR-6727 as well as downregulated miR-4741 lowered proliferative, migratory, and invasive capacities as well as elevated apoptotic levels of gastric cancer cells. Conclusion: Our study successfully isolated and verified exosomes from plasma of gastric cancer as well as proposed four exosomal miRNAs that could act as promising diagnostic markers and suppress gastric cancer progression.

The impact of diabetes on postoperative outcomes following spine surgery: A meta-analysis of 40 cohort studies with 2.9 million participants.

OBJECTIVE: Although diabetes mellitus (DM) is considered to be an important prognostic factor in spinal surgery, the relationship between these two factors remains unclear. The purpose of this study was to investigate whether diabetes is associated with an increased risk of postoperative complications in patients undergoing spinal surgery. METHODS: We systematically searched the PubMed, Embase, and Cochrane Library for relevant articles published on or before December 25, 2021. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects meta-analysis. The primary outcome was the risk of postoperative complications following spinal surgery, including postoperative infection and reoperation. Furthermore, we conducted subgroup analyses and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results. RESULTS: A total of 40 cohort studies including 2,998,891 participants met the inclusion criteria. Meta-analysis showed that diabetes was significantly associated with postoperative infection (OR 2.21, 95% CI 1.70-2.88, p < 0.001) and reoperation (OR 1.35, 95% CI 1.12-1.64, p = 0.002). Furthermore, the results also found that diabetes was significantly associated with surgery-related death (OR 1.61, 95% CI 1.13-2.30, p = 0.008) and transfusions (OR 1.39, 95% CI 1.11-1.75, p = 0.005), whereas diabetes failed to account for nervous system complications (OR 1.12, 95% CI 0.82-1.52, p = 0.470) and embolism (OR 1.15, 95% CI 0.83-1.60, p = 0.386) for patients following spine surgery. These results were further confirmed by the trim-and-fill procedure and leave-one-out sensitivity analyses. CONCLUSIONS: Diabetes appears to be a risk factor for postoperative infection and reoperation for patients following spinal surgery. Special attention should be devoted to reducing the occurrence of postoperative complications in diabetic patients undergoing spinal surgery.

Sarcopenia for outcomes in patients undergoing spinal surgery: A protocol for a systematic review and pooled analysis of observational studies.

BACKGROUND: Sarcopenia is a progressive age-related skeletal muscle disorder characterized by decreased muscle mass and loss of muscle function. Recent studies have shown that sarcopenia is able to predict a variety of clinical outcomes after spinal surgery. Controversy still exists among previous reports in terms of the definition and measurement of sarcopenia, these findings are heterogeneous so far. Therefore, the aim of the current study is to assess the up-to-date evidence of sarcopenia for postoperative outcomes among people undergoing spinal surgery. METHODS AND ANALYSIS: This protocol was carried out based on the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement. It has been pre-registered in PROSPERO with the registration number of CRD42021260459. Three databases (including Pubmed, EMBASE, and Cochrane Library) will be searched from inception through May 10, 2021 to determine related cohort studies examining sarcopenia on multidimensional outcomes in patients undergoing spinal surgery. Major outcomes will be involved including mortality, morbidity, length of stay, postoperative complications or adverse events. DerSimonian & Laird random-effects meta-analysis will be used to calculate pooled odds ratio (OR) for binary data and pooled weighted mean differences (WMDs) or standardized mean differences (SMDs) for continuous data. The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias of included studies. Narrative synthesis will be carried out if a pooled analysis is not possible. ETHICS AND DISSEMINATION: Ethical approval is not required for this study as the data involved are from the published literatures. We intend to disseminate or share the results of the study in a peer-reviewed journal or at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42021260459.

CircSCAF8 promotes growth and metastasis of prostate cancer through the circSCAF8-miR-140-3p/miR-335-LIF pathway.

Circular RNAs (circRNAs) have been increasingly linked to cancer progression. However, the detailed biological functions of circRNAs in prostate cancer (PCa) remain unclear. Using high-throughput circRNA sequencing, we previously identified 18 urine extracellular vesicle circRNAs that were increased in patients with PCa compared with those with benign prostatic hyperplasia. Spearman correlation analysis of the expression levels of the 18 circRNAs between the tumor tissue and matched urine extracellular vesicles in 30 PCa patients showed that circSCAF8 had the highest R2 (R2 = 0.635, P < 0.001). The Cox proportional hazards regression model was used to estimate the effect of circSCAF8 on progression-free survival. The in vitro and in vivo functional experiments were implemented to investigate the effects of circSCAF8 on the phenotype of PCa. We found that the knockdown of circSCAF8 in PCa cells suppressed the proliferation, migration, and invasion ability, while overexpression of circSCAF8 had the opposite effects. Similar results were observed in vivo. In a cohort of 85 patients who had undergone radical prostatectomy, circSCAF8 expression in PCa tissues was a powerful predictor of progression-free survival (HR = 2.14, P = 0.022). Mechanistically, circSCAF8 can function by binding to both miR-140-3p and miR-335 to regulate LIF expression and activate the LIF-STAT3 pathway that leads to the growth and metastasis of PCa. Collectively, our findings demonstrate that circSCAF8 contributes to PCa progression through the circSCAF8-miR-140-3p/miR-335-LIF pathway.

CircRAB3IP upregulates twist family BHLH transcription factor (TWIST1) to promote osteosarcoma progression by sponging miR-580-3p.

Circular RNAs (circ RNAs) have been found to play an important role in cancer development. However, the role of circRAB3IP in osteosarcoma (OS) is unclear.In the present study, We found that circRAB3IP was highly expressed in OS tissues and OS cells. High levels of circRAB3IP was correlated with advanced TNM stage, distant metastasis. CircRAB3IP knockdown inhibited cell proliferation, migration, and invasion. Moreover, circRAB3IP directly binds to miR-580-3p. TWIST1 is directly targeted by miR-580-3p. We also demonstrated that circRAB3IP act as the sponge of miR-580-3p to promote TWIST1 expression. CircRAB3IP promotes OS cells proliferation, migration, and invasion through modulating miR-580-3p/TWIST1 axis. Moreover, circRAB3IP facilitated tumor formation in vivo. Our findings suggested that circRAB3IP acts as an oncogene in OS by regulating miR-580-3p/TWIST1 axis.

[Percutaneous endoscopic Key-Hole technology for treatment of paracentral cervical disc herniation].

OBJECTIVE: To investigate the effectiveness of percutaneous endoscopic posterior cervical Key-Hole fenestration decompression and nucleus pulposus extirpation in the treatment of paracentral cervical disc herniation. METHODS: Between December 2015 and October 2018, 29 cases of paracentral cervical disc herniation were treated with percutaneous endoscopic posterior cervical Key-Hole fenestration decompression and nucleus pulposus extirpation. There were 16 males and 13 females, with an average age of 49.7 years (range, 39-78 years). The disease duration was 3.5-15.0 months (mean, 6.2 months). The herniated disc located at C 3, 4 in 2 cases, C 4, 5 in 5 cases, C 5, 6 in 9 cases, C 6, 7 in 12 cases, and C 7, T 1 in 1 case. The main symptoms were radiculopathy symptom. The operation time, intraoperative blood loss, hospital stay, and complications were observed and recorded. Visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, cervical range of motion (ROM), Macnab standard, and cervical segment stability were used to evaluate the efficacy and safety of the operation. RESULTS: All patients were followed up 11-43 months, with an average of 19.4 months. The operation time was 67-89 minutes (mean, 73.3 minutes); the intraoperative blood loss was 18-30 mL (mean, 22.9 mL); the hospital stay was 5-10 days (mean, 7.3 days). All the incisions healed by first intention. There was 1 case of hypodynia and hyperalgesia in the affected limb after operation,1 case of decreased limb muscle strength. The VAS scores and JOA scores at each time point after operation were superior to those before operation ( P<0.05). There was no significant difference between the time points after operation ( P>0.05). At last follow-up, the effectiveness was rated according to the Macnab standard as excellent in 11 cases, good in 15 cases, fair in 2 cases, and bad in 1 case, with an excellent and good rate of 89.7%. The CT and MRI showed the decompression of spinal canal and nerve canal. There was no significant difference in cervical ROM between pre- and post-operation ( t=1.427, P=0.165), and no surgical segment instability occurred by X-ray films of flexion and extension of cervical vertebrae. CONCLUSION: For the paracentral cervical disc herniation with simultaneous compression of nerve roots and spinal cord, percutaneous endoscopic posterior cervical Key-Hole fenestration decompression and nucleus pulposus extirpation has the advantages of small trauma, quick recovery, and satisfactory effectiveness, and can be used as a safe and effective minimally invasive procedure.

E26 transformation (ETS)­specific related transcription factor­3 (ELF3) orchestrates a positive feedback loop that constitutively activates the MAPK/Erk pathway to drive thyroid cancer.

Thyroid cancer is the most commonly diagnosed malignancy of the endocrine system, the incidence of which has increased rapidly in the last 30 years. Genetic alterations in pathways, including the mitogen­activated protein kinase (MAPK)/extracellular signal­regulated kinase (Erk) and phosphatidylinositol­3­kinase (PI3K)/protein kinase B (Akt) pathways, are the driving force behind the development of differentiated thyroid cancer cases into aggressive and undifferentiated forms of thyroid cancer. E26 transformation (ETS)­specific related transcription factor­3 (ELF3) belong to the epithelial­specific subfamily of ETS transcription factors and has recently been reported to be involved in various pathophysiological processes. However, the role of ELF3 in thyroid cancer has not yet been investigated. In the present study, data from The Cancer Genome Atlas (TCGA) were analyzed, and it was revealed that ELF3 was overexpressed in patients with papillary thyroid cancer (PTC). Furthermore, the expression of ELF3 was found to be higher in thyroid cancer tissues with a B­Raf proto­oncogene (BRAF) mutation as determined by western blot analysis and IHC staining. Additionally, ELF3 overexpression predicted a poor prognosis in patients with PTC. The MAPK signaling pathway inhibitor PLX4032 was demonstrated to strongly attenuate ELF3 protein levels in BRAF­mutant thyroid cancer cell lines. Knockdown of ELF3 with small interfering RNA (siRNA) inhibited the growth, clone formation, migration and invasion of BRAF mutant thyroid cancer cells. Mechanistically, ELF3 modulated the activity of the MAPK/Erk pathway via transcriptional regulation of the human epidermal growth factor receptor 2 family of receptors as determined by RT­qPCR. In conclusion, the present study demonstrated ELF3 to be a potential prognostic marker for patients with thyroid cancer. Notably, ELF3 was demonstrated to form a positive feedback loop with MAPK pathways leading to the progression of BRAF­mutant thyroid cancer.

ECRG4 acts as a tumor suppressor gene frequently hypermethylated in human breast cancer.

Human breast cancer is a malignant form of tumor with a relatively high mortality rate. Although esophageal cancer-related gene 4 (ECRG4) is thought to be a possible potent tumor suppressor gene that acts to suppress breast cancer, its precise role in this disease is not understood. Herein, we assess the correlation between ECRG4 expression and DNA methylation, probing the potential epigenetic regulation of ECRG4 in breast cancer. We analyzed ECRG4 promoter methylation via methylation-specific PCR (MSPCR), bisulfite sequencing, and a promoter reporter assay in human breast cancer cell lines and samples. Gene expression was assessed by quantitative real-time PCR (qPCR), while protein levels were assessed by Western blotting. CCK8 assays were used to quantify cell growth; Esophageal cancer-related gene 4 wound healing assays were used to assess cellular migration, while flow cytometry was used to assess apoptosis and cell cycle progression. Apoptosome formation was validated via CO-IP and Western blotting. We found that human breast cancer samples exhibited increased methylation of the ECRG4 promoter and decreased ECRG4 expression. Remarkably, the down-regulation of ECRG4 was highly associated with promoter methylation, and its expression could be re-activated via 5-aza-2'-deoxycytidine treatment to induce demethylation. ECRG4 overexpression impaired breast cancer cell proliferation and migration, and led to G0/G1 cell cycle phase arrest. Moreover, ECRG4 induced the formation of the Cytc/Apaf-1/caspase-9 apoptosome and promoted breast cancer cell apoptosis. ECRG4 is silenced in human breast cancer cells and cell lines, likely owing to promoter hypermethylation. ECRG4 may act as a tumor suppressor, inhibiting proliferation and migration, inducing G0/G1 phase arrest and apoptosis via the mitochondrial apoptotic pathway.

[ANATOMIC STUDY ON ENTRY POINT AND IMPLANT TECHNIQUE FOR C2 PEDICLE SCREW FIXATION].

OBJECTIVE: To determine the entry point and screw implant technique in posterior pedicle screw fixation by anatomical measurement of adult dry samples of the axis so as to provide a accurate anatomic foundation for clinical application. METHODS: A total of 60 dry adult axis specimens were selected for pedicle screws fixation. The entry point was 1-2 mm lateral to the crossing point of two lines: a vertical line through the midpoint of distance from the junction of pedicle medial and lateral border to lateral mass, and a horizontal line through the junction between the lateral border of inferior articular process and the posterior branch of transverse process. The pedicle screw was inserted at the entry point. The measurement of the anatomic parameters included the height and width of pedicle, the maximum length of the screw path, the minimum distance from screw path to spinal canal and transverse foramen, and the angle of pedicle screw. The data above were provided to determine the surgical feasibility and screw safety. RESULTS: The width of upper, middle, and lower parts of the pedicle was (7.35 ± 0.89), (5.50 ± 1.48), and (3.97 ± 1.01) mm respectively. The pedicle height was (9.94 ± 1.16) mm and maximum length of the screw path was (25.91 ± 1.15) mm. The angle between pedicle screw and coronal plane was (26.95 ± 1.88) degrees and the angle between pedicle screw and transverse plane was (22.81 ± 1.61) degrees. The minimum distance from screw path to spinal canal and transverse foramen was (2.72 ± 0.83) mm and (1.98 ± 0.26) mm respectively. CONCLUSION: According to the anatomic research, a safe entry point for C2 pedicle screw fixation is determined according to the midpoint of distance from the junction of pedicle medial and lateral border to lateral mass, as well as the junction between the lateral border of inferior articular process and the posterior branch of transverse process, which is confirmed to be effectively and safely performed using the entry point and screw angle of the present study.