COVID-19 hospitalization increases the risk of developing glioblastoma: a bidirectional Mendelian-randomization study.

Background: As a result of the COVID-19 pandemic, patients with glioblastoma (GBM) are considered a highly vulnerable population. Despite this, the extent of the causative relationship between GBM and COVID-19 infection is uncertain. Methods: Genetic instruments for SARS-CoV-2 infection (38,984 cases and 1,644,784 control individuals), COVID-19 hospitalization (8,316 cases and 1,549,095 control individuals), and COVID-19 severity (4,792 cases and 1,054,664 control individuals) were obtained from a genome-wide association study (GWAS) from European populations. A total of 6,183 GBM cases and 18,169 controls from GWAS were enrolled in our study. Their associations were evaluated by applying Mendelian randomization (MR) including IVW meta-analysis, MR-Egger regression, and weighted-median analysis. To make the conclusions more robust and reliable, sensitivity analyses were performed. Results: Our results showed that genetically predicted COVID-19 hospitalization increases the risk of GBM (OR = 1.202, 95% CI = 1.035-1.395, p = 0.016). In addition, no increased risk of SARS-CoV-2 infection, COVID-19 hospitalization and severity were observed in patients with any type of genetically predicted GBM. Conclusion: Our MR study indicated for the first time that genetically predicted COVID-19 hospitalization was demonstrated as a risk factor for the development of GBM.

A bimetallic metal-organic framework derived MnS/CoS@C heterostructure with enhanced sodium-ion storage.

Manganese sulfide (MnS) has gained significant attention as a high capacity and durable anode material for sodium-ion batteries (SIBs) due to its high theoretical capacity and decent redox reversibility. However, sluggish Na+ diffusion and significant volume variation during charge/discharge cycles limited its rate capability and cycling stability. Here, a new MnS/CoS heterojunction embedded in S-doped carbon (MnS/CoS@C) is designed through sulfurization of a bimetallic metal-organic framework (MOF). The synergistic effect of heterojunction design and carbon framework encapsulation integrates several benefits, including facilitating ion/electron transport, alleviating volume variation, and preventing the agglomeration of metal sulfide nanoparticles. Therefore, the MnS/CoS@C composite manifests remarkable rate capability (526.1 mA h g-1 at 0.1 A g-1 and 273.7 mA h g-1 at 10 A g-1) and stable long-term cycle life (214.8 mA h g-1 after 1000 cycles at 5 A g-1). Meanwhile, the sodium storage mechanism is examined using in situ electrochemical impedance spectroscopy (EIS), ex situ X-ray diffraction (XRD) and ex situ X-ray photoelectron spectroscopy (XPS). Coupled with a carbon nanosheet cathode, a prototype sodium-ion capacitor (SIC) has been fabricated. The SIC can achieve a high energy density of 120.7 W h kg-1 and a maximum power density of 12 250 W kg-1, demonstrating the high application potential of the composite for sodium-ion based energy storage systems.

Arthroscopic treatment of unstable scaphoid fracture and nonunion with two headless compression screws and distal radius bone graft.

BACKGROUND: The treatment of unstable scaphoid fracture and nonunion remains a challenging problem for hand surgeons. Minimally invasive treatment has become the preferred method of treatment. PURPOSE: This study introduces the arthroscopic technique with two headless compression screws (HCS) fixation and distal radius bone grafting for the treatment of unstable scaphoid fracture and nonunion, aiming to evaluate its clinical and radiological outcomes. METHODS: It was a retrospective study. From January 2019 to February 2021, a total of 23 patients were included in the current study. Among them, 13 patients with unstable scaphoid fracture underwent arthroscopic treatment with two HCS; 10 patients with scaphoid nonunion underwent arthroscopic treatment with two HCS and a distal radius bone graft. The range of motion of the wrist, visual analog scale (VAS), grip strength, the Modified Mayo Wrist Score (MMWS), the Patient-Rated Wrist Evaluation (PRWE) score, and the Disability of the Arm, Shoulder and Hand (DASH) score were collected at preoperatively and the final follow-up. A computed tomography scan of the wrist was performed on each patient to analyze for union and postoperative osteoarthritis during the follow-up period. RESULTS: Significant improvement was only observed in wrist extension. Clinical outcomes including grip strength, VAS pain score, MMWS, PRWE score, and DASH score were significantly improved at the final follow-up. In the subgroup analysis, both patients stabilized with either two HCS or a distal radius bone graft and two HCS have improved clinical outcomes after surgery, respectively. All patients achieved union. No screw fixation failure occurred, and no other postoperative complication was observed in any of the patients. CONCLUSIONS: The arthroscopic technique with two-HCS fixation and distal radius bone grafting is a reliable and effective technique for the treatment of unstable scaphoid fracture and nonunion, providing satisfactory union rates and clinical outcomes.

Implication of lncRNA ZBED3-AS1 downregulation in acquired resistance to Temozolomide and glycolysis in glioblastoma.

Temozolomide (TMZ) is the recommended drug for glioblastoma (GBM) treatment, but its clinical effect is restricted due to drug resistance. This research studies the effects of long non-coding RNA (lncRNA) ZBED3-AS1 and its related molecules on acquired TMZ resistance in glioblastoma (GBM). ZBED3-AS1 was identified to be downregulated in TMZ-resistant GBM cells by analyzing GSE113510 and GSE100736 datasets. ZBED3-AS1 downregulation was detected in TMZ-resistant GBM tissues and cell lines (U251/TMZ and U87/TMZ). ZBED3-AS1 knockdown promoted, whereas its overexpression suppressed TMZ resistance, viability and mobility, and glycolytic activity of TMZ-resistant cells. ZBED3-AS1 bound to Spi-1 proto-oncogene (SPI1) but did not affect its expression. Instead, it blocked SPI1-mediated transcriptional activation of thrombomodulin (THBD). SPI1 and THBD increased TMZ resistance and glycolysis in TMZ-resistant cells. Either ZBED3-AS1 overexpression or SPI1 knockdown in U87/TMZ cells blocked the growth of orthotopic and subcutaneous xenograft tumors in nude mice. In conclusion, this study demonstrates that ZBED3-AS1 downregulation and THBD activation is linked to increased TMZ resistance and glycolysis in GBM cells.

Current Status and Prospects of Clinical Treatment of Osteosarcoma.

Osteosarcoma, one of the common malignant tumors in the skeletal system, originates in mesenchymal tissue, and the most susceptible area of occurrence is the metaphysis with its abundant blood supply. Tumors are characterized by highly malignant spindle stromal cells that can produce bone-like tissue. Most of the osteosarcoma are primary, and a few are secondary. Osteosarcoma occurs primarily in children and adolescents undergoing vigorous bone growth and development. Most cases involve rapid tumor development and early blood metastasis. In recent years, research has grown in the areas of molecular biology, imaging medicine, biological materials, applied anatomy, surgical techniques, biomechanics, and comprehensive treatment of tumors. With developments in molecular biology and tissue bioengineering, treatment methods have also made great progress, especially in comprehensive limb salvage treatment, which significantly enhances the quality of life after surgery and improves the 5-year survival rate of patients with malignant tumors. This article provides a review of limb salvage, immunotherapy, gene therapy, and targeted therapy from traditional amputation to neoadjuvant chemotherapy, providing a reference for current clinical treatments for osteosarcoma.

Treatment with b-AP15 to Inhibit UCHL5 and USP14 Deubiquitinating Activity and Enhance p27 and Cyclin E1 for Tumors with p53 Deficiency.

Background: TP53 protein is lost or mutated in about half of all types of human cancers and small molecules to regulate mutant p53 repair, or interrupt ubiquitination degradation of p53 induced by E3-ubiquitin ligase Mdm2 have a potential application in clinical application. Methods: To inhibit the deubiquitinase activity of 19S proteasome and restore the p53 protein level, in this study, we utilized p53 knockout mice to test the anti-cancer effect of a specific USP14 and UCH37 inhibitor b-AP15. Results: Our results show that UCHL5, USP14 and COPS5 are upregulated in p53-related tumors, and higher expression of these genes results in a shorter overall survival in patients with p53 deficiency. Treatment with b-AP15, a UCHL5 and USP14 deubiquitinating activity inhibitor in 19S regulatory subunit, induces tumor regression and prolong the survival period of tumor-loaded mice through down-regulation of COPS5 and its downstream AP-1 and E2F1, and up-regulation of the cell cycle-related proteins p27 and Cyclin E1. Conclusions: Thus, our results suggested that inhibition of UCHL5 and USP14 deubiquitinating activity in 19S proteasome may contribute an extensive approach to preventing tumor progress due to p53 deficiency.

Nonoxid-HMGB1 Attenuates Cognitive Impairment After Traumatic Brain Injury in Rats.

Traumatic brain injury (TBI) is a major global burden of health. As an accepted inflammatory mediator, high mobility group box 1 (HMGB1) is found to be effective in facilitating neurogenesis and axonal regeneration. SH3RF2 (also known as POSHER), an E3 ligase SH3 domain-containing ring finger 2, belongs to the SH3RF family of proteins. Here, we aimed to investigate the role of redox states of HMGB1 on neurite outgrowth and regeneration both in vitro and in vivo. In this study, distinct recombinant HMGB1 redox isoforms were used. Sequencing for RNA-seq and data analysis were performed to find the potential downstream target of nonoxid-HMGB1 (3S-HMGB1). Protein changes and distribution of SH3RF2 were evaluated by western blot assays and immunofluorescence. Lentivirus and adeno-associated virus were used to regulate the expression of genes. Nonoxid-HMGB1-enriched exosomes were constructed and used to treat TBI rats. Neurological function was evaluated by OF test and NOR test. Results demonstrated that nonoxid-HMGB1 and fr-HMGB1, but not ds-HMGB1, promoted neurite outgrowth and axon elongation. RNA-seq and western blot assay indicated a significant increase of SH3RF2 in neurons after treated with nonoxid-HMGB1 or fr-HMGB1. Notably, the beneficial effects of nonoxid-HMGB1 were attenuated by downregulation of SH3RF2. Furthermore, nonoxid-HMGB1 ameliorated cognitive impairment in rats post-TBI via SH3RF2. Altogether, our experimental results suggest that one of the promoting neurite outgrowth and regeneration mechanisms of nonoxid-HMGB1 is mediated through the upregulated expression of SH3RF2. Nonoxid-HMGB1 is an attractive therapeutic candidate for the treatment of TBI.

The effect of a high-quality nursing model employing low-frequency pulse electrical stimulation combined with early systemic functional exercises on the function of the affected limb in brachial plexus injury patients.

OBJECTIVE: To explore the effect of a high-quality nursing model employing low-frequency pulse electrical stimulation combined with early systemic functional exercises on the function of the affected limb in brachial plexus injury patients. METHODS: A total of 98 brachial plexus injury patients admitted to our hospital were recruited as the research cohort. All the patients were treated with surgery to repair, release, and transfer or transplant nerves according to each patient's condition. After the operations, the patients were randomly divided into one of two groups: the control group (n=49) or the research group (n=49). The control group did early systemic functional exercises, while the research group was administered low frequency pulse electrical stimulation in addition to doing the early systemic functional exercises. The clinical efficacy, the visual analogue scale (VAS) scores before and after the treatment, the brachial plexus function scores, the nerve conduction velocities and amplitudes, the SF-36 questionnaires, the incidences of complications, and the nursing satisfaction were compared between the two groups. RESULTS: After the treatment, the overall response rate to the treatment in the research group was significantly higher than it was in the control group (95.92% vs 81.63%, P<0.05). The VAS scores in both groups were decreased, and the scores in the research group were lower than the scores in the control group (P<0.05). The upper limb, lower limb, and the whole brachial plexus scores were increased in both groups, and the scores in the research group were higher than the scores in the control group (P<0.05). The motor conduction velocities, the sensory conduction velocities, and the amplitudes of the ulnar and median nerves in the two groups were increased, and the research group had higher levels than the control group (P<0.05). The emotional function, physical pain, physical health, role function, social function, mental health, energy, and general health scores in the two groups were increased, and the research group was higher than the control group (P<0.05). The incidence of complications in the research group was lower than it was in the control group, but the nursing satisfaction was higher than it was in the control group (all P<0.05). CONCLUSION: The high-quality nursing model based on low-frequency pulse electrical stimulation combined with early systemic functional exercise can effectively promote the functional recovery of the affected limb in brachial plexus injury patients. It can reduce pain and the incidence of complications and it can improve the quality of life and the satisfaction with the nursing at the same time.

Downregulation of miR-223 and miR-19a induces differentiation and promotes recruitment of osteoclast cells in giant-cell tumor of the bone via the Runx2/TWIST-RANK/RANKL pathway.

Giant-cell tumor (GCT) of the bone is an invasiveness and high recurrent bone tumor that is considered borderline or potentially malignant. To explore the molecular mechanism leading to bone destruction and identify novel targets for treatment, we conducted silencing of miR-223 and miR-19a in stromal giant cells and identified TWIST and Runx2 as their target genes. We investigated the impact of these microRNAs and their target genes on stromal giant cells that promote the differentiation of monocyte/macrophages into osteoclast cells and recruitment to the bone microenvironment, which in turn enhances the bone destruction capacity of GCT. MiR-223 and miR-19a were found to regulate the expression of TWIST and Runx2, influence the RANKL-RANK pathway and the expression of MCP-1, and finally regulate the pathophysiological process of osteolytic bone destruction. Our results indicate that re-expression of miR-223 and miR-19a induces an inhibitory effect on the bone destruction capacity of GCT, suggesting that re-expression of miR-223 and miR-19a can be a novel strategy for the treatment of GCT.

[Effectiveness analysis of maintaining the stability between the fourth and the fifth metacarple base during the treatment in the hamate-metacarpal joint injury].

Objective: To explore the effectiveness of maintaining the stability between the fourth and the fifth metacarple base during the treatment in the hamate-metacarpal joint injury. Methods: Between September 2015 and June 2017, 13 cases of hamate-metacarpal joint injury were treated, including 12 males and 1 female, aged from 17 to 55 years (mean, 30.8 years). The injury causes included heavy boxing in 10 cases and falling in 3 cases. There were 2 cases of simple fourth metacarpal basal fracture, 1 basal fracture of the fourth metacarpal bone combined with intermetacarpal ligament fracture, 7 fractures of the fourth and fifth metacarpal base, 2 fourth metacarpal basal fractures combined with the fifth metacarpal basal fracture dislocation, and 1 base fracture of fourth and fifth metacarpal bone combined with hamate bone fracture. The time from injury to operation was 5-11 days (mean, 7.2 days). According to different damage degree and stability change between the fourth and the fifth metacarple base, a preliminary classification was made for different degrees of injury: 2 cases of type Ⅰ, 1 case of type Ⅱ, 7 cases of type Ⅲ, 2 cases of type Ⅳ, and 1 case of type Ⅴ. The patients were treated with corresponding internal fixation methods under the principle of stability recovery between the fourth and fifth metacarple base. Results: All the incisions healed by first intention without infection or skin necrosis. All the 13 patients were followed up 6-18 months with an average of 9.4 months. All fractures healed clinically, and the healing time was 5.5-8.0 weeks with an average of 6.3 weeks. No complication such as plate breakage, fracture dislocation, fracture malunion, and bone nonunion occurred. Hand function was evaluated according to the total active motion (TAM) functional evaluation standard of hand surgery at 6 months after operation, and the results was excellent in 9 cases, good in 3 cases, and fair in 1 case, with an excellent and good rate of 92.3%. Conclusion: Stability between the fourth and fifth metacarple base is of great significance to the classification and the treatment of the hamate-metacarpal joint injury.

[Articular external fixation for chronic dorsal instability of distal radioulnar joint].

OBJECTIVE: To discuss the clinical result of extrinsic radioulnar tether combined with anchoring nail fixation for treating chronic dorsal instability of the distal radioulnar joint (DRUJ). METHODS: Between July 2011 and December 2012, 6 patients with chronic dorsal instability of the DRUJ were treated with extrinsic radioulnar tether combined with anchoring nail fixation. There were 1 male and 5 females with the average age of 27.3 years (range, 22-35 years). All of 6 patients had a wrist trauma history. The average disease duration was 4.8 years (range, 6 months to 15 years). Radiographs were taken postoperatively to observe the anchoring nail loosening. The stress test and forearm rotation test were used to evaluate the function of DRUJ. The complications, the grip power, range of motion, and visual analogue scale (VAS) scores were recorded at last follow-up. And the joint function was evaluated by disability of arm, shoulder, and hand (DASH) score. RESULTS: Primary healing of incision was obtained in all cases, without any complications such as infection and ulnar neck fracture. All 6 patients were followed up 6-24 months (mean, 13.7 months). Stability was achieved in all patients. Radiographs showed that the joint space was widened and dislocation of the ulnar head was improved at 3 and 6 months after operation. The results of the stress test and forearm rotation test were negative. At last follow-up, the grip power, DASH score, VAS score, and range of motion of the wrist were significantly improved when compared with preoperative ones (P < 0.05). CONCLUSION: Extrinsic radioulnar tether combined with anchoring nail fixation is an easy method of surgical revision to treat chronic dorsal instability of DRUJ, which can maintain the stability and protect the blood supply of triangular fibrocartilage complex.

[APPLICATION OF BUTTERFLY SHAPED LOCKING COMPRESSION PLATE IN COMPLEX DISTAL RADIUS FRACTURES].

OBJECTIVE: To investigate the effectiveness of butterfly shaped locking compression plate for the treatment of complex distal radius fractures. METHODS: Between June 2011 and January 2013, 20 cases of complex distal radius fractures were treated with butterfly shaped locking compression plate fixation. There were 11 males and 9 females with an average age of 54 years (range, 25-75 years). Injury was caused by falling in 10 cases, by traffic accident in 7 cases, and by falling from height in 3 cases. All of fractures were closed. According to AO classification system, there were 8 cases of type C1, 8 cases of type C2, and 4 cases of type C3. Of them, 9 cases had radial styloid process fracture, 4 cases had sigmoid notch fracture, and 7 cases had both radial styloid process fracture and sigmoid notch fracture. The mean interval between injury and operation was 5.2 days (range, 3-15 days). RESULTS: All incisions healed by first intention; no complications of infection and necrosis occurred. All cases were followed up 14 months on average (range, 10-22 months). All factures healed after 9.3 weeks on average (range, 6-11 weeks). No complications such as displacement of fracture, joint surface subsidence, shortening of the radius, and carpal tunnel syndrome were found during follow-up. At last follow-up, the mean palmar tilt angle was 10.2° (range, 7-15°), and the mean ulnar deviation angle was 21.8° (range, 17-24°). The mean range of motion of the wrist was 45.3° (range, 35-68°) in dorsal extension, 53.5° (range, 40-78°) in palmar flexion, 19.8° (range, 12-27°) in radial inclination, 26.6° (range, 18-31°) in ulnar inclination, 70.2° (range, 45-90°) in pronation, and 68.4° (range, 25-88°) in supination. According to the Dienst scoring system, the results were excellent in 8 cases, good in 10 cases, and fair in 2 cases, and the excellent and good rate was 90%. CONCLUSION: Treatment of complex distal radius fractures with butterfly shaped locking compression plate can reconstruct normal anatomic structures, especially for radial styloid process and sigmoid notch fractures, and it can get good functional recovery of the wrist and the distal radioulnar joint.