Progressive coronal caudal curve after corrective osteotomies for congenital cervicothoracic scoliosis: incidence and predictors.

OBJECTIVE: Postoperative progressive coronal caudal curve (PCC) was characterized by a postoperative de novo caudal S-curve ≥ 20° following congenital cervicothoracic scoliosis (CTS) corrective osteotomies, and at least 20° greater than the preoperative measurement, while the incidence was uncertain and the pathogenesis was equivocal. The objective of this study was to investigate the morbidity and potential factors contributing to PCC following CTS surgery. METHODS: This study reviewed 72 CTS patients between 2005 and 2021. Patients were categorized into two groups according to the absence or presence of PCC at last follow-up, namely the nonprogressive curve group (NPC-group) and the progressive curve group (PC-group). Demographics, radiographic data and the Scoliosis Research Society-22 (SRS-22) questionnaire results were reviewed. Multivariate linear regression analyses were utilized to determine possible predictors for PCC. RESULTS: PCC was observed in 11 (15%) of the total 72 patients. Compared with the NPC-group, the PC-group exhibited greater postoperative residual local curve (24.0 ± 9.7° vs. 9.1 ± 4.4°, P < 0.001), upper instrumented vertebra (UIV) tilt (16.9 ± 7.4° vs. 6.2 ± 3.7°, P < 0.001), T1 tilt (14.3 ± 9.4° vs. 6.6 ± 3.9°, P = 0.022) and neck tilt (10.1 ± 6.7° vs. 3.7 ± 2.5, P = 0.009). The multivariable linear regression demonstrated that the larger postoperative UIV tilt, residual local curve and neck tilt were associated with PCC. In addition, patients with PCC showed lower SRS-22 scores in terms of pain, mental health, self-image and satisfaction (P < 0.05). CONCLUSIONS: The morbidity of PCC was 15% in CTS patients who underwent corrective osteotomies. Greater residual local curve, postoperative UIV tilt and neck tilt were identified as predictors for PCC.

Active DHEA uptake in the prostate gland correlates with aggressive prostate cancer.

Strategies for patient stratification and early intervention are required to improve clinical benefits for patients with prostate cancer. Here, we found that active DHEA utilization in the prostate gland correlated with tumor aggressiveness at early disease stages, and 3ßHSD1 inhibitors were promising for early intervention. [3H]-labeled DHEA consumption was traced in fresh prostatic biopsies ex vivo. Active DHEA utilization was more frequently found in patients with metastatic disease or therapy-resistant disease. Genetic and transcriptomic features associated with the potency of prostatic DHEA utilization were analyzed to generate clinically accessible approaches for patient stratification. UBE3D, by regulating 3ßHSD1 homeostasis, was discovered to be a regulator of patient metabolic heterogeneity. Equilin suppressed DHEA utilization and inhibited tumor growth as a potent 3ßHSD1 antagonist, providing a promising strategy for the early treatment of aggressive prostate cancer. Overall, our findings indicate that patients with active prostatic DHEA utilization might benefit from 3ßHSD1 inhibitors as early intervention.

Celastrol recruits UBE3A to recognize and degrade the DNA binding domain of steroid receptors.

Strategies to degrade steroid receptors and their alternative splicing isoforms are critical for disease management. Here we report that celastrol recruited the ubiquitin ligase UBE3A and degraded androgen receptor (AR), AR-v7, and glucocorticoid receptor (GR) to suppress prostate cancer development. UBE3A was not an optimal endogenous AR ubiquitin ligase in mice and patients, but celastrol promoted the interaction between UBE3A and AR. Multiple domains of AR, including the DNA binding domain (DBD), were implicated into the UBE3A-AR interaction. Sharing a conserved DBD, GR, AR-v7, and other steroid receptors were recognized and degraded by UBE3A after celastrol treatment. Thus, celastrol suppressed prostate cancer cell proliferation more potently than enzalutamide. Modifying the carboxyl group of celastrol improved its anti-tumor activity. Together, our findings revealed that celastrol might be a potential molecular glue to enhance the interaction between UBE3A and steroid receptors to degrade multiple steroid receptors and splicing isoforms in prostate cancer, paving a way for further drug optimization and disease treatment.

In Situ Silver-Based Electrochemical Oncolytic Bioreactor.

In this study, it is shown for the first time that a reduced graphene oxide (rGO) carrier has a 20-fold higher catalysis rate than graphene oxide in Ag+ reduction. Based on this, a tumor microenvironment-enabled in situ silver-based electrochemical oncolytic bioreactor (SEOB) which switched Ag+ prodrugs into in situ therapeutic silver nanoparticles with and above 95% transition rate is constructed to inhibit the growths of various tumors. In this SEOB-enabled intratumoral nanosynthetic medicine, intratumoral H2 O2 and rGO act as the reductant and the catalyst, respectively. Chelation of aptamers to the SEOB-unlocked prodrugs increases the production of silver nanoparticles in tumor cells, especially in the presence of Vitamin C, which is broken down in tumor cells to supply massive amounts of H2 O2 . Consequently, apoptosis and pyroptosis are induced to cooperatively contribute to the considerably-elevated anti-tumor effects on subcutaneous HepG2 and A549 tumors and orthotopic implanted HepG2 tumors in livers of nude mice. The specific aptamer targeting and intratumoral silver nanoparticle production guarantee excellent biosafety since it fails to elicit tissue damages in monkeys, which greatly increases the clinical translation potential of the SEOB system.

[Bioinformatics Analysis on Key Genes and Immune Infiltration of Osteosarcoma].

Objective To screen the potential key genes of osteosarcoma by bioinformatics methods and analyze their immune infiltration patterns. Methods The gene expression profiles GSE16088 and GSE12865 associated with osteosarcoma were obtained from the Gene Expression Omnibus(GEO),and the differentially expressed genes(DEGs)related to osteosarcoma were screened by bioinformatics tools.Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and analysis of immune cell infiltration were then carried out for the DEGs.The potential Hub genes of osteosarcoma were identified by protein-protein interaction network,and the expression of Hub genes in osteosarcoma and normal tissue samples was verified via the Cancer Genome Atlas(TCGA). Results A total of 108 DEGs were screened out.GO annotation and KEGG pathway enrichment revealed that the DEGs were mainly involved in integrin binding,extracellular matrix (ECM) structural components,ECM receptor interactions,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Macrophages were the predominant infiltrating immune cells in osteosarcoma.Secreted phosphoprotein 1(SPP1),matrix metallopeptidase 2(MMP2),lysyl oxidase(LOX),collagen type V alpha(II)chain(COL5A2),and melanoma cell adhesion molecule(MCAM)presented differential expression between osteosarcoma and normal tissue samples(all P<0.05). Conclusions SPP1,MMP2,LOX,COL5A2,and MCAM are all up-regulated in osteosarcoma,which may serve as potential biomarkers of osteosarcoma.Macrophages are the key infiltrating immune cells in osteosarcoma,which may provide new perspectives for the treatment of osteosarcoma.

Effect of unilateral pulsed jet lavage prior to vertebroplasty on the intravertebral pressure and cement distribution.

BACKGROUND: Percutaneous vertebroplasty is the most common treatment for osteoporotic vertebral compression fracture. However, the morbidity of vertebroplasty-related complications, such as cement leakage, remains high. We tested a new technique of unilateral pulsed jet lavage and investigated its effect on the intravertebral pressure and bone cement distribution. METHODS: Thirty lumbar vertebrae (L1-L5) from six cadaver spines were randomly allocated into two groups (with and without irrigation). Prior to vertebroplasty, pulsed jet lavage was performed through one side of the pedicle by using a novel cannula with two concentric conduits to remove the fat and bone marrow of the vertebral bodies in the group with irrigation. The control group was not irrigated. Then, standardized vertebroplasty was performed in the vertebral bodies in both groups. Changes in the intravertebral pressure during injection were recorded. Computed tomography (CT) was performed to observe the cement distribution and extravasations, and the cement mass volume (CMV) was calculated. RESULTS: During cement injection, the average maximum intravertebral pressure of the unirrigated group was higher than that of the irrigated group (4.92 kPa versus 2.22 kPa, P < 0.05). CT scans showed a more homogeneous cement distribution with less CMV (3832 mm3 vs. 4344 mm3, P < 0.05) and less leakage rate (6.7% vs. 46.7%, P < 0.05) in the irrigated group than in the control group. CONCLUSIONS: Unilateral pulsed jet lavage can reduce intravertebral pressure and lower the incidence of cement leakage during vertebroplasty. An enhanced bone cement distribution can also be achieved through this lavage system.

[Cancer incidence and mortality in Guangzhou City from 2000 to 2002].

BACKGROUND & OBJECTIVE: Population-based cancer registration has never been carried out before in Guangzhou. This study was to analyze the cancer incidence and mortality in Guangzhou and to provide references for prevention and treatment of cancer. METHODS: Data of cancer incidence and mortality during 2000--2002 were collected from Guangzhou Population-based Cancer Registry. Cancer incidence and mortality were calculated and analyzed. RESULTS: The crude cancer incidence during 2000--2002 in Guangzhou was 227.7 per 100,000 (257.0 per 100,000 in males and 196.5 per 100,000 in females)û the crude cancer mortality was 147.9 per 100,000 (183.6 per 100,000 in males and 109.7 per 100,000 in females). The incidence of lung cancer ranked first followed by those of liver cancer, nasopharyngeal cancer, gastric cancer and colon cancer in males. Breast cancer was the leading cancer in females followed by those of lung cancer, liver cancer, colon cancer and nasopharyngeal cancer. The cancer incidence and mortality increased with age. CONCLUSION: Cancer incidence is high in Guangzhou, and the research for prevention and treatment of cancer should be enhanced.