Prognostic biomarker replication factor C subunit 5 and its correlation with immune infiltrates in acute myeloid leukemia.

OBJECTIVE: To determine the role of replication factor C subunit 5 (RFC5) in acute myeloid leukemia (AML) from four aspects: expression, prognosis, biological functions, and its effects on the immune system. METHODS: The RFC5 gene expression and survival analyses, biological function analyses including functional enrichment analysis of genes co-expressed with RFC5, RFC5-interacted gene network construction, gene set enrichment analysis (GSEA), and immune infiltration analysis were performed using data based on GDC TCGA and GEO. The CIBERSORT algorithm was employed to quantify immune cell fractions. All the statistical analyses were performed in SPSS software, GraphPad Prism, and R software. RESULTS: RFC5 expression was abnormally expressed in AML (P <0.05). Notably, differential RFC5 expression was observed among different FAB AML subtypes and hematopoietic lineages (all P <0.05). More importantly, high RFC5 expression served as an independent prognostic factor for the poor overall survival of AML patients (P <0.001). Enrichment analyses revealed that RFC5 was involved in cell cycle-related pathways in AML. CIBERSORT analysis showed high proportions of M2 macrophages in the high RFC5 expression group. CONCLUSIONS: RFC5 might serve as an effective and robust biomarker for the diagnosis and prognosis of AML. RFC5 might be involved in the AML progression via cell cycle regulation. Moreover, the correlation between RFC5 and immune cells might provide potential assistance for AML treatment.

[Application of multimodal neuroelectrophysiological monitoring technology in surgical treatment of thoracic tuberculosis].

OBJECTIVE: To explore the value of multimodal neuroelectrophysiological monitoring technology in the evaluation of spinal cord and nerve root function for the treatment of thoracic tuberculosis with debridement and bone grafting and posterior internal fixation by transcostal transverse process approach. METHODS: The clinical data of 25 patients with thoracic tuberculosis underwent debridement and bone grafting and posterior vertebral arch internal fixation by transcostal transverse process approach from December 2018 to September 2019 was retrospectively analyzed. Among these 25 patients, including 14 males and 11 females;aged from 20 to 83 years old, with a mean of (63.45±9.65) years;there were 3 cases of single vertebral body destruction, 13 cases of 2 vertebral bodies destruction, and 9 cases of 3 or more vertebral bodies destruction. All surgical patients underwent intraoperative detection of somatosensory evoked potential(SEP) and transcranial electric stimulation-motor evoked potential(TES-MEP);and electromyography (EMG) was used to monitor the pedicle screw placement and lesion removal. The erythrocyte sedimentation rate(ESR) was used to evaluate the decline of inflammatory indexes, the visual analogue scale (VAS) was used to evaluate the thoracic spine pain, and the Cobb angle and Oswestry Disability Index(ODI) were used to evaluate the improvement of function. RESULTS: All 25 patients were successfully monitored. Five patients had abnormal SEP waveforms during operation, 3 cases were caused by intraoperative clearing of lesions and spinal cord compression during irrigation, timely replacement of instruments and gestures, and adjustment of irrigation water flow rate returned the waveform to normal; one case was caused by a decrease in systolic blood pressure, and the waveform returned to normal after timely treatment of increased blood pressure;after 1 case of SEP waveform abnormality, the operation was suspended for 10 minutes and recovered spontaneously, and the waveform abnormality did not reappear until the end of the operation. Seven patients had abnormal TES-MEP waveforms, 5 cases occurred when the pedicle screw was inserted, the nail path was adjusted in time, and the waveform recovered after nail repositioning;one case was caused by tilting the operation bed during operation, and the waveform gradually recovered after adjusting the tilt angle of operation bed; one case occurred during the correction of the pedicle screw and rod system, and the waveform gradually returned to normal after the contralateral screw and rod correction were completed during operation. In 5 cases, the EMG burst potential was detected at the same time when the TES-MEP waveform was abnormal. After adjustment, the EMG burst potential disappeared. There was no abnormality in the TES-MEP and SEP waveforms at the same time. Postoperative VAS, ESR, Cobb angle, and ODI were improved compared with preoperatively (P<0.05). CONCLUSION: In patients with thoracic tuberculosis, the use of debridement and bone grafting and posterior internal fixation by transcostal transverse process approach combined with intraoperative SEP, TES-MEP and EMG monitoring can timely reflect the spinal cord and nerve root function, avoid intraoperative injuries while achieving good fixation and lesion removal.

Multi-modal Neuroelectrophysiological Monitoring in the Treatment of Thoracic Tuberculosis with Debridement and Bone Grafting and Posterior Pedicle Screw Fixation via Costal Transverse Process Approach.

OBJECTIVE: To explore the value of multi-mode neuroelectrophysiological monitoring (MIOM) in evaluating spinal cord and nerve root function in the treatment of thoracic tuberculosis via costal transverse process approach. METHODS: From December 2017 to September 2019, a retrospective study of thoracic tuberculosis patients in our hospital was conducted. This study included 25 patients (14 men and 11 women). The average age of patients at the time of surgery was 63.3 years (range, 20-83 years). All patients (three cases with the destruction of a single vertebral body, 13 cases with the destruction of two vertebral bodies, and nine cases with the destruction of three or more vertebral bodies) underwent costal transverse process approach with debridement and bone grafting and internal fixation combined with intraoperative multimodal neuroelectrophysiological monitoring. During the operation, somatosensory evoked potential (SEP), transcranial electrical stimulation motor evoked potential (TES-MEP), and spontaneous electromyography (EMG) were used to monitor progress. ESR, visual analogue scale (VAS), Cobb angle, and Oswestry disability index (ODI) were statistically analyzed to evaluate the treatment effects and patient satisfaction. RESULTS: All 25 patients were successfully monitored. The follow-up time ranged from 12 to 21 months, with an average of 15.3 months. SEP waveform abnormalities occurred in five patients during the operation, the incidence rate was 28%. Of these five patients, three patients changed their instruments and postures, and adjusted the flushing water flow in time; one patient received pressure therapy in time; the operation was suspended for 10 min for one patient. There were seven cases with abnormal TES-MEP waveform, the incidence rate was 28%. Among these seven cases, five cases adjusted the nail path during the operation and adjusted the nail position in time. One case adjusted the inclination angle of the operating table in time; one case completed the contralateral nail stick correction in time; five of them had abnormal TES-MEP waveforms, and EMG burst potential was also detected, the incidence rate was 20%. After prompt treatment, the abnormal waveforms of all patients returned to normal; no abnormal waveforms, recurrence of tuberculosis, loosening of internal fixation, nerve and spinal cord dysfunction, etc. The VAS score, erythrocyte sedimentation rate (ESR), Cobb angle, and ODI scores of the patients 1 year after operation were significantly improved compared with 1 week after operation (P < 0.05). CONCLUSION: Multi-mode intraoperative electrophysiological detection combined with costal transverse process approach for the treatment of thoracic tuberculosis could avoid intraoperative nerve and blood vessel damage, reduce surgical risk, improve surgical efficiency, and ensure curative effect.

[Clinical study of movable external fixation for elbow tuberculosis].

OBJECTIVE: To compare clinical effect of movable external fixation and fusion fixation for the treatment of elbow tuberculosis. METHODS: From October 2013 to June 2019, 52 patients with elbow tuberculosis treated with standard antituberculosis therapy were divided into movable external fixation group and fusion fixation group according to treatment methods. In group A, there were 25 patients, including 11 males and 14 females, aged from 24 to 75 years old with an average of (42.81± 9.01) years old; the courses of diseases ranged from 2 to 9 months with an average of (3.96±1.45) months. In group B, there were 27 patients, including 15 males and 12 females, aged from 23 to 77 years old with an averageof (44.08±7.44) years old; the courses of diseases ranged from 2 to 7 months with an average of (3.88±1.67) months. All patients were performed focus debridement. Intraoperative blood loss, operative time were compared between two groups. VAS score before operation, 2 weeks and 12 months after operation were applied to evaluate pain relieve;Mayo elbow performance score (MEPS) before operation, 1 and 12 months after operation were used to evaluate clinical effect;changes of erythrocyte sedimentation rate (ESR) and Creactive protein, CRP) before operation, 3 weeks after antituberculosis therapy, 1 week and 6 months after operation were compared between two groups. RESULTS: All patients were followed up from 12 to 20 months with an average of (13.50±4.85) months. No mixed infection and recurrence of tuberculosis occurred. There were no statistical differences in intraoperative blood loss and operative time(P>0.05). There was difference in postoperative VAS score at 2 weeks between movable external fixation group (5.15±0.95) and fusion fixation group (4.04±0.84)(P<0.01);while no difference in postoperative VAS score at 12 months between two groups (P>0.05). No difference in ESR and CRP level between two groups before and after operation (P>0.05). Postoperative Mayo score at 1 and 12 months in movable external fixation group were (78.15±7.83) and (90.19±7.13);in fusion fixation group were (70.40±7.61) and (82.60±8.38);there were differences in Mayo score at different time points between two groups(P<0.01). CONCLUSION: For elbow tuberculosis, movable external fixation and fusion fixation have equal effect in operative time, amount of bleeding and control of tuberculosis infection indicator. Movable external fixation need earlier functional exercise, not conducive to pain relief at early stage, which may be better than fusion fixation, it is worth clinical promoting.

p24G1 Encoded by Grapevine Leafroll-Associated Virus 1 Suppresses RNA Silencing and Elicits Hypersensitive Response-Like Necrosis in Nicotiana Species.

Grapevine leafroll-associated virus 1 (GLRaV-1) is a major pathogen associated with grapevine leafroll disease. However, the molecular mechanisms underlying GLRaV-1 interactions with plant cells are unclear. Using Agrobacterium infiltration-mediated RNA-silencing assays, we demonstrated that GLRaV-1 p24 protein (p24G1) acts as an RNA-silencing suppressor (RSS), inhibiting local and systemic RNA silencing. Electrophoretic mobility shift assays showed that p24G1 binds double-stranded 21-nucleotide small interfering RNA (siRNA), and that siRNA binding is required but not sufficient for its RSS activity. p24G1 localizes in the nucleus and can self-interact through its amino acid 10 to 210 region. Dimerization is needed for p24G1 interaction with importin α1 before moving to the nucleus, but is not required for its siRNA binding and RSS activity. Expression of p24G1 from a binary pGD vector or potato virus X-based vector elicited a strong hypersensitive response in Nicotiana species, indicating that p24G1 may be a factor in pathogenesis. Furthermore, p24G1 function in pathogenesis required its RSS activity, dimerization and nuclear localization. In addition, the region of amino acids 122-139 played a crucial role in the nuclear import, siRNA binding, silencing suppression and pathogenic activity of p24G1. These results contribute to our understanding of the molecular mechanisms underlying GLRaV-1 infection.