Human proteins curing yeast prions.

Recognition that common human amyloidoses are prion diseases makes the use of the Saccharomyces cerevisiae prion model systems to screen for possible anti-prion components of increasing importance. [PSI+] and [URE3] are amyloid-based prions of Sup35p and Ure2p, respectively. Yeast has at least six anti-prion systems that together cure nearly all [PSI+] and [URE3] prions arising in their absence. We made a GAL-promoted bank of 14,913 human open reading frames in a yeast shuttle plasmid and isolated 20 genes whose expression cures [PSI+] or [URE3]. PRPF19 is an E3 ubiquitin ligase that cures [URE3] if its U-box is intact. DNAJA1 is a J protein that cures [PSI+] unless its interaction with Hsp70s is defective. Human Bag5 efficiently cures [URE3] and [PSI+]. Bag family proteins share a 110 to 130 residue "BAG domain"; Bag 1, 2, 3, 4, and 6 each have one BAG domain while Bag5 has five BAG domains. Two BAG domains are necessary for curing [PSI+], but one can suffice to cure [URE3]. Although most Bag proteins affect autophagy in mammalian cells, mutations blocking autophagy in yeast do not affect Bag5 curing of [PSI+] or [URE3]. Curing by Bag proteins depends on their interaction with Hsp70s, impairing their role, with Hsp104 and Sis1, in the amyloid filament cleavage necessary for prion propagation. Since Bag5 curing is reduced by overproduction of Sis1, we propose that Bag5 cures prions by blocking Sis1 access to Hsp70s in its role with Hsp104 in filament cleavage.

Radiofrequency ablation for solitary T1N0M0 papillary thyroid carcinoma in the danger triangle area: a preliminary analysis.

OBJECTIVES: To evaluate the feasibility, efficacy, and safety of radiofrequency ablation (RFA) for solitary T1N0M0 papillary thyroid carcinoma (PTC) in the danger triangle area. METHODS: 94 participants (mean age 44.45 ± 13.08; 73 females) with solitary T1N0M0 PTC in the danger triangle area who underwent percutaneous RFA at the hospital from January 2018 to April 2020 were retrospectively analyzed. Key ablation procedures included sufficient paratracheal fluid isolation, low-power, and short active tip (5 mm working electrode). Tumor size changes at different time points after RFA, technical success rates, tumor disappearance, disease progression, and complications were recorded and compared. RESULTS: Contrast-enhanced ultrasonography revealed that complete tumor ablation was performed with a 100% success rate in these patients. Post-ablation, the maximum diameter and volume of the ablation zone increased at the first and third month (p < 0.001), followed by a gradual decrease in size, without significant difference by the 6th month. The tumor disappearance rate was 76.59% (72/94), with higher rates in the T1a group compared to the T1b group (80% [64/80] VS57.1% [8/14], p < 0.001). There were no local recurrences. The incidence of new lesions and LNM was 3.2% (3/94), limited to the T1a subgroup. Further ablation was successfully applied to all new lesions and LMN. Mild voice changes were the only complication, with a rate of 3.2% (3/94), resolved within 4 months after RFA. CONCLUSIONS: Sufficient paratracheal fluid isolation combined with a low-power, short active tip radiofrequency ablation strategy is a safe and effective method for treating solitary T1N0M0 PTC in the danger triangle area.

The 'danger triangle' area comprises the dorsal edge of the thyroid gland, the lateral tracheal wall, and the anterior edge of the esophageal wall. When PTC tumors are present within the danger triangle, there is only limited space available for ablation. Furthermore, the proximity of the tumor with the esophagus, trachea, and thyroid capsule can complicate technical treatment success, potentially increasing the chance of local tumor recurrence and nerve injury. Therefore, the most effective approach for managing PTC lesions within the danger triangle remains undetermined. The goal of this study was to clarify the viability of ultrasound-guided RFA as a means of managing solitary T1N0M0 PTC tumors within the danger triangle area, providing a foundation for future clinical decision-making efforts.

Ultrasound-guided percutaneous thermal ablation of parotid tumors: experience from two-centers.

Objective: To evaluate the efficacy and feasibility of ultrasound-guided percutaneous thermal ablation (TA) for treating benign parotid tumors.Methods: Patients with benign parotid tumors who underwent ultrasound-guided microwave ablation (MWA) or radiofrequency ablation (RFA) between January 2020 and March 2023 were included in this retrospective study. Change in tumor size (maximum diameter, tumor volume(V), volume reduction rate (VRR)) and cosmetic score (CS) were evaluated during a one-year follow-up period. We also recorded the incidence of any complications associated with TA.Results: A total of 23 patients (13 males and 10 females; median age 65 years, range 5-91 years) were included. The mean VRR at 1, 3, 6, and 12 months after TA was 37.03%±10.23%, 56.52%±8.76%, 82.28%±7.89%, and 89.39%±6.45%, respectively. Mean CS also changed from 3.39 ± 0.66 to 1.75 ± 0.93 (p < 0.001) by the end of follow-up time. Subgroup analysis showed that tumors with smaller initial maximum diameter had a faster CS reduction rate than those with larger initial diameter. The incidence of facial nerve dysfunction was 8.70%.Conclusion: Ultrasound-guided percutaneous TA is an effective and safe treatment option for patients with benign parotid tumors.

Effect of different retention doses of ultrasound-guided polidocanol chemical ablation for benign cystic-solid thyroid nodules.

OBJECTIVE: To assess the influence of varying retention doses of ultrasound-guided polidocanol chemical ablation for benign cystic-solid thyroid nodules. METHODS: A retrospective study was conducted from December 2019 to January 2022, including 78 patients with benign cystic-solid thyroid nodules, of which 31 received polidocanol chemical ablation alone, 23 received polidocanol chemical plus thermal ablation, and 24 received open surgery. Patients who received polidocanol chemical ablation were assigned into groups based on the retention dose of polidocanol: 0 %, 10 %, 20 %, 30 %, and 50 %. Follow-ups were done at 1, 3, 6, and 12 months postoperatively. The volume of the nodules, postoperative complications, and recurrence of the nodules were examined before treatment and during follow-up visits. RESULTS: Total operation time and intraoperative bleeding volume for patients who received ablation were substantially lower than those for patients who received open surgery (P < 0.001). Among patients in the polidocanol chemical ablation group, volume shrinkage rate of thyroid nodules in the 10 % retention dose group was significantly lower than that in the 0 % retention dose group at 1, 3, and 6 months postoperatively (P < 0.05). The 30 % retention dose group had the highest nodule shrinkage rate (98.46 ± 1.55 %) at 12 months postoperatively, which was significantly higher than that in the 50 % retention dose group (P < 0.05). Among patients in the polidocanol chemical and thermal ablation group, the volume shrinkage rate of thyroid nodules in the 10 % and 30 % retention dose groups at 1 month postoperatively was significantly lower than that in the 0 % retention dose group (P < 0.05). Although volume shrinkage rate in the 20 % retention dose group after thermal ablation was higher than that in the 0 % retention dose group, the difference was not statistically significant (P > 0.05). In terms of adverse reactions, the incidence of hoarseness and coughing was higher in the open surgery group than in the polidocanol chemical ablation and polidocanol chemical and thermal ablation groups, but there was no significant difference (P > 0.05). CONCLUSION: Chemical ablation with polidocanol was safe and effective for therapy of benign cystic-solid thyroid nodules, and the optimal retention dose may be between 20 % and 30 %. Patients with poor efficacy from chemical ablation alone can receive safe and effective treatment through thermal ablation.

Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC.

BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

Iatrogenic Abdominal Aortic Rupture During Transpedicular Bone Grafting for Thoracolumbar Burst Fractures Successfully Treated by Endovascular Stent Implantation.

PURPOSE: Vascular injury resulting from transpedicular bone grafting in the treatment of thoracolumbar burst fractures has not been reported but can be lethal. The management of patients with iatrogenic aortic injury remains a difficult clinical problem. This study describes a case of iatrogenic abdominal aortic rupture at the level of L2 during transpedicular bone grafting for the first time. CASE REPORT: A 55 year-old male patient suffered from a T12 vertebral body mild compression fracture and an L2 vertebral body burst fracture due to falling. This patient was treated with posterior open reduction and pedicle screw fixation combined with transpedicular bone grafting in the L2 vertebrae using a paravertebral approach. Unfortunately, during transpedicular bone grafting, the abdominal aorta was punctured by the tip of the graft funnel. The use of endovascular stent implantation successfully averted a clinical catastrophe. The patient had a good clinical outcome, and no complications associated with vascular trauma were apparent at a 1-year follow-up examination. CONCLUSION: For the repair of vascular injury caused by transpedicular bone grafting, endovascular techniques can provide a safe, minimally invasive, and effective treatment option. CLINICAL IMPACT: Surgeons should carefully evaluate the specificity of the patient's anatomical structures preoperatively and be more cautious during transpedicular bone grafting in the treatment of thoracolumbar burst fractures.

The Application Value of Contrast-Enhanced Ultrasonography in Assessing the Efficacy of Ultrasound-Guided Lauromacrogol Injections in Cesarean Scar Pregnancies.

OBJECTIVE: To investigate the application value of contrast-enhanced ultrasonography (CEUS) in ultrasound-guided lauromacrogol injections in patients with cesarean scar pregnancies (CSP). METHODS: A total of 31 patients diagnosed with CSP, who underwent an ultrasound-guided lauromacrogol injection + curettage in our hospital between February 2019 and December 2020 and had a complete recovery confirmed by a postoperative ultrasound review and serum ß-human chorionic gonadotropin (ß-hCG) assay, were enrolled as the study subjects. According to the volume of intraoperative blood loss and the duration of postoperative vaginal bleeding, the patients were divided into two groups, with 19 in the significantly effective group (Group A) and 12 in the effective group (Group B). The recorded clinical data, including age, duration of amenorrhea, number of pregnancies, number of deliveries, time since last cesarean delivery, number of cesarean deliveries, and preoperative serum ß-hCG levels, were retrospectively analyzed. The morphological indicators in CEUS before the lauromacrogol injection, as well as immediately and 12-24 hours after the injection, were compared between the groups. RESULTS: In Group A, the post-injection CEUS showed no enhancement, single strip enhancement, and sparse punctate enhancement, while in Group B, it showed a more irregular ring and local patch enhancement. In addition, the number of cases where the CEUS showed no enhancement 12-24 hours after the injection was more than that of the immediate CEUS after the injection. In Group A, four (21.1%) cases showed a single strip-like blood flow on the immediate postoperative CEUS, four (21.1%) cases showed a sparsely dotted blood flow on the immediate postoperative CEUS, and three cases turned into no enhancement 12-24 hours after the injection. A total of four cases in Group B showed that the contrast enhancement range 12-24 hours after the injection was reduced compared with that of the immediate contrast after the injection. CONCLUSION: Contrast-enhanced ultrasonography can guide the location selection of the lauromacrogol injection in patients with CSP, and its postoperative morphological indicators can adequately predict the therapeutic effect after curettage and guide clinical management.

Complications after radiofrequency ablation of hyperparathyroidism secondary to chronic kidney disease.

OBJECTIVE: To study the complications of ultrasound-guided radiofrequency ablation (RFA) in chronic kidney disease (CKD) patients undergoing renal replacement therapy with secondary hyperparathyroidism (SHPT). METHODS: This retrospective study reviewed the clinical data, including general information, examination results, treatment times, time interval, and postoperative complications, of 103 SHPT patients who received ultrasound-guided RFA treatment from July 2017 to January 2021. RESULTS: Of 103 patients, 52 required two sessions of RFA within a month. The incidence of recurrent laryngeal nerve injury at the second treatment was significantly higher than that at the first treatment (first session vs. second session, 5.77% vs. 21.15%; p = .021). Of all the enrolled 103 patients, 27 suffered complications after the first session of RFA. When we separated patients into complications group and non-complication group, we detected more ablated nodules in the complications group (Z = -2.222; p = .0026). Subgroup analysis further showed that the patients in the severe hypocalcemia group were younger (p = .005), had more ablated nodules (p = .003) and higher blood phosphorus (p = .012) and alkaline phosphatase (ALP) levels (p = .002). Univariate analysis showed that age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA. CONCLUSIONS: An interval of more than 1 month between two treatments may help to avoid recurrent laryngeal nerve injury. Age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA.

BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of most prevalent malignant endocrine neoplasms, and it is associated with a high frequency of BRAF gene mutations, which lead to lymphatic metastasis and distant metastasis that promote tumor progression. The molecular mechanism of PTC and the role of BRAF mutation in PTC progression and development need to be further elucidated. METHODS: In this study, a comprehensive bioinformatics analysis was performed to identify the differentially expressed genes and signaling pathways in thyroid cancer patients carrying mutant BRAF. Then, we confirmed the prognostic role of WT1 in thyroid cancer patients. Immunohistochemistry was performed to measure the expression profile of WT1 in PTC tissue. Lentivirus shWT1 was transfected into BRAFV600E (mutant) PTC cells to stably inhibit WT1 expression. CCK-8, EdU, immunofluorescence, colony formation, cell migration, cell wound healing, apoptosis and autophagy assays were performed to assess the biological functions of WT1 in BRAFV600E PTC cells. RNA sequencing, immunohistochemistry and immunoblotting were performed to explore the molecular mechanism of WT1 in BRAFV600E PTC cells. RESULTS: The results confirmed that "epithelial cell proliferation", "apoptosis" and "selective autophagy" were closely associated with this BRAF mutant in these thyroid cancer patients. Knocking down BRAF-activated WT1 effectively inhibited the proliferation and migration of BRAFV600E PTC cells. Silencing WT1 significantly inhibited autophagy and promoted the apoptosis of BRAFV600E PTC cells. Mechanistic investigations showed that silencing WT1 expression remarkably suppressed the AKT/mTOR and ERK/P65 signaling pathways in BRAFV600E PTC cells. CONCLUSION: All these results indicate that WT1 is a promising prognostic biomarker and facilitates PTC progression and development of cells carrying the BRAFV600E mutation.

Ultrasound-guided microwave and radiofrequency ablation for primary hyperparathyroidism: a prospective, multicenter study.

OBJECTIVES: To prospectively investigate the efficacy and safety of ultrasound (US)-guided microwave ablation (MWA) and radiofrequency ablation (RFA) for primary hyperparathyroidism (PHPT). METHODS: We performed a prospective multicenter study of MWA and RFA for PHPT between August 2017 and October 2020 at five centers. Laboratory testing was performed pre- and post-ablation and followed for at least 6 months. The primary outcome was the cure rate. Secondary outcomes were complications and dynamic changes in serum levels of PTH, calcium, phosphorus, and ALP after ablation. RESULTS: A total of 132 participants (mean age, 57.33 ± 13.90 years), with 141 parathyroid nodules (median maximal diameter, 1.55 cm) undergoing either MWA or RFA, were enrolled in the study. The technique success rate was 99.29% (140/141). The follow-up period was 6-36 months (median, 12 months). The cure rate was 80.30% (106/132). Pre-ablation PTH level was the independent factor associated with cure rate (Odds ratio (OR), 0.22; 95% CI, 0.07-0.69; p = 0.0090). There was no difference in cure rate between the MWA group and the RFA group (80.22% vs. 80.49%, p = 0.971). The only main complication was hoarseness (5.30%). CONCLUSIONS: US-guided MWA and RFA for PHPT is an effective and safe procedure in the treatment of PHPT. Pre-ablation PTH level is the key factor affecting the cure rate after MWA and RFA. KEY POINTS: • To our knowledge, this is the first prospective multicenter clinical trial with ultrasound-guided MWA and RFA for primary hyperparathyroidism. • There was no difference in cure rate between the MWA and RFA groups for primary hyperparathyroidism. The overall cure rate was 80.30%. • Pre-ablation PTH level was the independent factor associated with cure rate (odds ratio (OR), 0.22; 95% CI, 0.07-0.69; p = 0.0090).

Predicting ultrasound-guided thermal ablation benefit in primary hyperparathyroidism.

OBJECTIVES: Ultrasound (US)-guided thermal ablation for primary hyperparathyroidism (PHPT) is a relatively novel minimally invasive treatment. The recurrence rate after ablation is between 10 and 15%. The characteristics of patients who can benefit from thermal ablation therapy are not clear yet. The aim of this research was to investigate the validity of a parathyroid hormone (PTH)-based classifier for stratifying patients with PHPT. METHODS: A total of 171 patients were screened, 148 (86.5%) of whom were eligible and were divided into development (n = 104) and external validation (n = 44) cohorts. The potential relationship between the PTH-based classifier and the cure rate of patients was initially assessed in the primary cohort and then validated in the external validation cohort. The nomogram was computed from the logistic regression model. RESULTS: A cut-off of PTH < 269.1 pg/mL or ≥ 269.1 pg/mL as the optimal prognostic threshold in the training cohort was generated to stratify the patients into low-risk and high-risk groups. Patients with PTH levels < 269.1 pg/mL in the training cohort had a higher cure rate than patients with PTH levels ≥ 269.1 pg/mL (p < 0.001). The PTH level remained the strongest predictor of the cure rate in all cohorts. Furthermore, a nomogram based on the PTH level was developed to predict the cure rate in the training cohort and it performed well in the external validation cohort (AUC: 0.816, 95%CI 0.703 to 0.930; AUC: 0.816, 95%CI 0.677 to 0.956). CONCLUSIONS: The PTH-based classifier may help with individualised treatment planning for selecting patients who may benefit from thermal ablation. KEY POINTS: • This is the first analysis of predictors affecting the outcome of US-guided thermal ablation of primary hyperparathyroidism and the findings can be used to identify the potential beneficiary population of thermal ablation of primary hyperparathyroidism. • Parathyroid hormone (PTH) was confirmed as an independent prognostic factor, as it not only showed good accuracy in stratifying patients into high- and low-risk groups in the training and validation cohorts but also outperformed the clinical model. • This study developed and validated a model to predict the treatment success of thermal ablation of primary hyperparathyroidism.

Innate immunity to prions: anti-prion systems turn a tsunami of prions into a slow drip.

The yeast prions (infectious proteins) [URE3] and [PSI+] are essentially non-functional (or even toxic) amyloid forms of Ure2p and Sup35p, whose normal function is in nitrogen catabolite repression and translation termination, respectively. Yeast has an array of systems working in normal cells that largely block infection with prions, block most prion formation, cure most nascent prions and mitigate the toxic effects of those prions that escape the first three types of systems. Here we review recent progress in defining these anti-prion systems, how they work and how they are regulated. Polymorphisms of the prion domains partially block infection with prions. Ribosome-associated chaperones ensure proper folding of nascent proteins, thus reducing [PSI+] prion formation and curing many [PSI+] variants that do form. Btn2p is a sequestering protein which gathers [URE3] amyloid filaments to one place in the cells so that the prion is often lost by progeny cells. Proteasome impairment produces massive overexpression of Btn2p and paralog Cur1p, resulting in [URE3] curing. Inversely, increased proteasome activity, by derepression of proteasome component gene transcription or by 60S ribosomal subunit gene mutation, prevents prion curing by Btn2p or Cur1p. The nonsense-mediated decay proteins (Upf1,2,3) cure many nascent [PSI+] variants by associating with Sup35p directly. Normal levels of the disaggregating chaperone Hsp104 can also cure many [PSI+] prion variants. By keeping the cellular levels of certain inositol polyphosphates / pyrophosphates low, Siw14p cures certain [PSI+] variants. It is hoped that exploration of the yeast innate immunity to prions will lead to discovery of similar systems in humans.

Small single perivascular hepatocellular carcinoma: comparisons of radiofrequency ablation and microwave ablation by using propensity score analysis.

OBJECTIVES: We aimed to compare the therapeutic outcomes of radiofrequency ablation (RFA) and microwave ablation (MWA) as first-line therapies in patients with small single perivascular hepatocellular carcinoma (HCC). METHODS: A total of 144 eligible patients with small (≤ 3 cm) single perivascular (proximity to hepatic and portal veins) HCC who underwent RFA (N = 70) or MWA (N = 74) as first-line treatment were included. The overall survival (OS), disease-free survival (DFS), and local tumor progression (LTP) rates between the two ablation modalities were compared. The inverse probability of treatment weighting (IPTW) method was used to reduce selection bias. Subgroup analysis was performed according to the type of hepatic vessels. RESULTS: After a median follow-up time of 38.2 months, there were no significant differences in OS (5-year OS: RFA 77.7% vs. MWA 74.6%; p = 0.600) and DFS (5-year DFS: RFA 24.7% vs. MWA 40.4%; p = 0.570). However, a significantly higher LTP rate was observed in the RFA group than the MWA group (5-year LTP: RFA 24.3% vs. MWA 8.4%; p = 0.030). IPTW-adjusted analyses revealed similar results. The treatment modality (RFA vs. MWA: HR 7.861, 95% CI 1.642-37.635, p = 0.010) was an independent prognostic factor for LTP. We observed a significant interaction effect of ablation modality and type of peritumoral vessel on LTP (p = 0.034). For patients with periportal HCC, the LTP rate was significantly higher in the RFA group than in the MWA group (p = 0.045). However, this difference was not observed in patients with perivenous HCC (p = 0.116). CONCLUSIONS: In patients with a small single periportal HCC, MWA exhibited better tumor control than RFA. KEY POINTS: • Microwave ablation exhibited better local tumor control than radiofrequency ablation for small single periportal hepatocellular carcinoma. • There was a significant interaction between the treatment effect of ablation modality and type of peritumoral vessel on local tumor progression. • The type of peritumoral vessel is vital in choosing ablation modalities for hepatocellular carcinoma.

Single-stage debridement via autogenous iliac bone graft through the OLIF corridor and lateral fixation in treating spontaneous single-level lumbar pyogenic spondylodiscitis.

BACKGROUND: The aim of the present study was to investigate the efficacy and safety of mini-open oblique debridement and lumbar interbody fusion combined with lateral screw fixation for treating single-level pyogenic spondylodiscitis. METHODS: Twelve patients with single-level lumbar pyogenic spondylodiscitis underwent OLIF combined with lateral screw fixation were analyzed. Patients underwent follow-up for 12 to 24 months. The clinical characteristics, etiological examinations, operative time, intraoperative blood loss, Oswestry Disability Index (ODI), visual analog scale score (VAS), postoperative complications, and the bony fusion rate were recorded. RESULTS: The mean follow-up period of time was 14.8 months. The average operative time and intra-operative blood loss were 129.0 ± 19.76 min and 309.2 ± 92.96 mL, respectively. No severe intra-operative complications were observed during surgery, except in 1 case that develops abdominal pain and distension after surgery, 2 cases that develop left-sided transient thigh pain/numbness and 8 cases that complains of donor site (iliac crest) pain. All of these symptoms disappeared 8 weeks after surgery. Tissue sample cultures were obtained from all patients intraoperatively and four (33.3%) were positive, including 2 with Staphylococcus aureus, 1 with Staphylococcus epidermidis, and 1 with Escherichia coli. During an average of 22.5 ± 2.1 days (range, 14-29 days) after surgery, WBC, CPR, and ESR levels in all patients had returned to normal. All patients were pain free with no recurring infection. Solid bony fusions were observed in all cases within 6 months, including 10 with I grade fusion, 2 with II grade fusion according to the classification suggested by Burkus et al. No fixation failure was observed during follow up and solid bony fusions were observed in all 12 patients at finally follow-up. A significant postoperative increase was also observed in the mean segmental height and lordosis (P < 0.05), followed by a slight decrease of segmental height and lordosis at final follow-up. At the final follow up, the mean VAS (1.5 ± 0.6) and ODI (18.9 ± 7.6) were significantly lower than VAS (8.4 ± 2.7) and ODI (71.2 ± 16.5) before surgery (P < 0.01). CONCLUSION: Single-stage debridement with autogenous iliac bone graft through the OLIF corridor and lateral fixation was a feasible surgical approach in our consecutive 12 cases of pyogenic spondylitis.

Long non-coding RNA SUMO1P3 promotes hepatocellular carcinoma progression through activating Wnt/ß-catenin signalling pathway by targeting miR-320a.

In this study, we aimed to investigate expression profile of long non-coding RNA (lncRNA) SUMO1P3, and its role and molecular mechanisms in the progression of hepatocellular carcinoma (HCC). The expression of SUMO1P3 in HCC tissues and cells was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The chi-squared test was used to estimate the relationship between SUMO1P3 levels and clinical characteristics of HCC cases. Cellular biological behaviours were investigated using MTT, transwell assays and wound healing assay. Bioinformatics and dual-luciferase reporter assays were performed to identify potential target of SUMO1P3 in HCC. Additionally, protein analysis was carried out using Western blot. The expression of SUMO1P3 was significantly higher in HCC tissues and cells than in non-cancerous specimens and normal cells (P < .01). Moreover, its up-regulation was closely correlated with lymph node metastasis (P = .027) and TNM stage (P = .019). SUMO1P3 knockdown inhibited the proliferation, migration and invasion of HCC cells. MiR-320a was a potential target of SUMO1P3, and its expression was negatively regulated by SUMO1P3 in HCC SUMO1P3 could activate Wnt/ß-catenin pathway, which was mediated by miR-320a. Elevated expression of SUMO1P3 predicts malignant progression among HCC patients. SUMO1P3 enhances Wnt/ß-catenin pathway through sponging miR-320a, thus contributing to aggressive progression of HCC.

Differences in the therapeutic effects of high-intensity focused ultrasound (HIFU) ablation on uterine fibroids with different shear wave velocity (SWV): a study of histopathological characteristics.

OBJECTIVE: To explore correlations between the therapeutic effect of high intensity focused ultrasound (HIFU) and histopathological characteristics of uterine fibroids with different Shear Wave Velocity (SWV) values. METHODS: A retrospective study was conducted on 36 women (43 fibroids) who had undergone high intensity focused ultrasound (HIFU) uterine fibroids ablation between January 2019 and January 2020. Preoperative fibroids tissue sections were obtained for histopathological examination. The pathological sections were stained with Masson-trichrome, and were observed and imaged under a Low-power microscope (4 × 10), while the smooth muscle cell (SMC) and collagen fiber content were semi-quantitatively measured. Preoperative fibroid SWV was measured using the Virtual Touch tissue quantification (VTQ) technique. Within one month after HIFU ablation, all patients had undergone a pelvic cavity MRI examination, which measured the size, volume, and non-perfused volume (NPV) of the fibroids. The formula: the ablation rate = NPV/target fibroid volume × 100% was used to calculate the ablation rate of the uterine fibroids. Correlation analysis of SWV values, HIFU ablation rate, along with the smooth muscle cell (SMC) and collagen fiber content, were conducted using the Spearman's correlation test. RESULTS: The collagen fiber and SMC content of the preoperative fibroids were 32.09 ± 15.90%/view and 37.61 ± 15.32%/view, respectively. Preoperative fibroid SWV value was 3.56 ± 0.71 m/s. Preoperative fibroid SWV was negatively correlated with SMC content (r = -0.445, p = 0.003), but positively correlated with collagen fiber content (r = 0.454, p = 0.002). The ablation rate was negatively correlated with collagen fiber content (r = -0.377, p = 0.013), but positively correlated with SMC content (r = 0.402, p = 0.007). CONCLUSION: Differences in histopathological characteristics may be important factors that induce differences in the therapeutic effects of HIFU ablation on uterine fibroids with different SWV values.

The value of acoustic radiation force impulse imaging in preoperative prediction for efficacy of high-Intensity focused ultrasound uterine fibroids ablation.

Objective: To investigate the application value of acoustic radiation force impulse imaging in preoperative prediction for efficacy of High-Intensity Focused Ultrasound uterine fibroids ablationMethods: A prospective study was conducted on 32 women (41 fibroids) undergoing HIFU uterine fibroids ablation between January 2019 and September 2019. The virtual touch tissue quantification (VTQ) technique was used for the preoperative determination of uterine fibroids shear wave velocity (SWV). The stiffness of the preoperative uterine fibroids was graded on a virtual touch tissue image (VTI). All uterine fibroids were ablated with a single point ablation acoustic power of 400 W. All patients underwent pelvic cavity MRI examination for the measurement of the size, volume and non-perfused volume (NPV) of fibroids within the first month after HIFU ablation. The ablation rate of uterine fibroids was calculated according to the formula: ablation rate = NPV × 100/target fibroid volume. The patients were divided into two groups based on the postoperative ablation rate: ≥70% ablation rate group, and＜70% ablation rate group. The preoperative SWV and VTI grade of uterine fibroids were compared between the two groups. The correlation of preoperative uterine fibroids' SWV and VTI grade with HIFU ablation rate were analyzed using the Spearman's correlation coefficient. The optimal cutoff points in preoperative uterine fibroids SWV of 70% ablation rate were determined by receiver operating curve (ROC) analysis.Results: A total of 30 patients (73.17%, 30/41) showed ablation rate ≥70%, with preoperative uterine fibroids' SWV values of (3.42 ± 0.71) m/s. Of these, 24 patients (80%, 24/30) had VTI grades II-III. On the other hand, 26.83% (11/41) showed ablation rate <70%, with preoperative uterine fibroids' SWV values of (4.02 ± 0.69) m/s; of these, 63.6% (7/11) had VTI grade IV. The SWV values and VTI grades of preoperative uterine fibroids were significantly different in the two groups (p < 0.05). Interestingly, postoperative ablation rate was negatively correlated with preoperative uterine fibroids' SWV values (r= -0.536, p = 0.0003) and VTI grades (r= -0.511, p = 0.001). The area under the ROC curve of preoperative uterine fibroids' SWV values with ablation rate <70% was 0.75 at a cutoff value of 3.915 m/s (p < 0.05). Specificity was 72.7% and sensitivity was 80.1%; the positive predictive value was 72.7%, and the negative predictive value was 80%.Conclusion: ARFI technique is an effective and feasible noninvasive ultrasound technique for the preoperative prediction of the efficacy of HIFU uterine fibroids ablation.

How Do Yeast Cells Contend with Prions?

Infectious proteins (prions) include an array of human (mammalian) and yeast amyloid diseases in which a protein or peptide forms a linear ß-sheet-rich filament, at least one functional amyloid prion, and two functional infectious proteins unrelated to amyloid. In Saccharomyces cerevisiae, at least eight anti-prion systems deal with pathogenic amyloid yeast prions by (1) blocking their generation (Ssb1,2, Ssz1, Zuo1), (2) curing most variants as they arise (Btn2, Cur1, Hsp104, Upf1,2,3, Siw14), and (3) limiting the pathogenicity of variants that do arise and propagate (Sis1, Lug1). Known mechanisms include facilitating proper folding of the prion protein (Ssb1,2, Ssz1, Zuo1), producing highly asymmetric segregation of prion filaments in mitosis (Btn2, Hsp104), competing with the amyloid filaments for prion protein monomers (Upf1,2,3), and regulation of levels of inositol polyphosphates (Siw14). It is hoped that the discovery of yeast anti-prion systems and elucidation of their mechanisms will facilitate finding analogous or homologous systems in humans, whose manipulation may be useful in treatment.

Virus-mediated suppression of host non-self recognition facilitates horizontal transmission of heterologous viruses.

Non-self recognition is a common phenomenon among organisms; it often leads to innate immunity to prevent the invasion of parasites and maintain the genetic polymorphism of organisms. Fungal vegetative incompatibility is a type of non-self recognition which often induces programmed cell death (PCD) and restricts the spread of molecular parasites. It is not clearly known whether virus infection could attenuate non-self recognition among host individuals to facilitate its spread. Here, we report that a hypovirulence-associated mycoreovirus, named Sclerotinia sclerotiorum mycoreovirus 4 (SsMYRV4), could suppress host non-self recognition and facilitate horizontal transmission of heterologous viruses. We found that cell death in intermingled colony regions between SsMYRV4-infected Sclerotinia sclerotiorum strain and other tested vegetatively incompatible strains was markedly reduced and inhibition barrage lines were not clearly observed. Vegetative incompatibility, which involves Heterotrimeric guanine nucleotide-binding proteins (G proteins) signaling pathway, is controlled by specific loci termed het (heterokaryon incompatibility) loci. Reactive oxygen species (ROS) plays a key role in vegetative incompatibility-mediated PCD. The expression of G protein subunit genes, het genes, and ROS-related genes were significantly down-regulated, and cellular production of ROS was suppressed in the presence of SsMYRV4. Furthermore, SsMYRV4-infected strain could easily accept other viruses through hyphal contact and these viruses could be efficiently transmitted from SsMYRV4-infected strain to other vegetatively incompatible individuals. Thus, we concluded that SsMYRV4 is capable of suppressing host non-self recognition and facilitating heterologous viruses transmission among host individuals. These findings may enhance our understanding of virus ecology, and provide a potential strategy to utilize hypovirulence-associated mycoviruses to control fungal diseases.