Metabolome and Transcriptome Combinatory Profiling Reveals Fluconazole Resistance Mechanisms of Trichosporon asahii and the Role of Farnesol in Fluconazole Tolerance.

Trichosporon asahii is a basidiomycete yeast that is pathogenic to humans and animals, and fluconazole-resistant strains have recently increased. Farnesol secreted by fungi is a factor that causes variations in fluconazole resistance; however, few studies have explored the underlying mechanisms. Therefore, this study aims to delineate the fluconazole resistance mechanisms of T. asahii and explore farnesol's effects on these processes. A comparative metabolome-transcriptome analysis of untreated fluconazole-sensitive (YAN), fluconazole-resistant (PB) T. asahii strains, and 25 µM farnesol-treated strains (YAN-25 and PB-25, respectively) was performed. The membrane lipid-related genes and metabolites were upregulated in the PB vs. YAN and PB-25 vs. PB comparisons. Farnesol demonstrated strain-dependent mechanisms underlying fluconazole tolerance between the YAN and PB strains, and upregulated and downregulated efflux pumps in PB-25 and YAN-25 strains, respectively. Membrane lipid-related metabolites were highly correlated with transporter-coding genes. Fluconazole resistance in T. asahii was induced by membrane lipid bio-synthesis activation. Farnesol inhibited fluconazole resistance in the sensitive strain, but enhanced resistance in the resistant strain by upregulating efflux pump genes and membrane lipids. This study offers valuable insights into the mechanisms underlying fungal drug resistance and provides guidance for future research aimed at developing more potent antifungal drugs for clinical use.

[The short-term effectiveness of superior capsular reconstruction using autologous fascia lata graft for irreparable massive rotator cuff tears].

OBJECTIVE: To observe and evaluate the short-term effectiveness of superior capsular reconstruction using autologous fascia lata graft for irreparable massive rotator cuff tears. METHODS: The clinical data of 9 patients with irreparable massive rotator cuff tears treated with arthroscopic superior capsular reconstruction by using autologous fascia lata graft between September 2019 and April 2020 were retrospectively analysed. There were 4 males and 5 females with a median age of 66 years (range, 55-70 years). The disease duration was 6-60 months with an average of 19.1 months. According to Hamada classification, the patients were classified as grade 1 in 2 cases, grade 2 in 2 cases, grade 3 in 2 cases, and grade 4 in 3 cases. Before and after operation, the visual analogue scale (VAS) score was used to evaluate the improvement of shoulder joint pain, the American Shoulder and Elbow Surgeons (ASES) score, Constant score, and the University of California Los Angeles (UCLA) shoulder function score were used to evaluate the improvement of shoulder joint function. The active range of motion of shoulder joint was recorded, including forward flexion, abduction, lateral external rotation, and internal rotation. The changes of subacromial space were recorded by anteroposterior X-ray film of shoulder joint. Sugaya classification was used to judge the integrity of rotator cuff immediately after operation and at last follow-up. RESULTS: The operation time was 210-380 minutes, with an average of 302.3 minutes. All incisions healed by first intention after operation, and there was no complication such as infection and nonunion of incisions. Two patients had numbness of the upper limbs on the surgical side after operation, and the numbness completely relieved at 6 weeks after operation; 5 cases with preoperative pseudoparalysis symptoms recovered after operation. Nine patients were followed up 12-17 months, with an average of 14.1 months. At last follow-up, the patient's active range of motion of shoulder joint (forward flexion, abduction, lateral external rotation, and internal rotation), subacromial space distance, VAS score, ASES score, Constant score, and UCLA score significantly improved when compared with preoperative ones ( P<0.05). There was no significant difference in the Sugaya classification between at last follow-up and immediately after operation ( Z=-1.633, P=0.102). CONCLUSION: Superior capsular reconstruction using autologous fascia lata graft can restore the superior stability and achieve a good short-term effectiveness for irreparable massive rotator cuff tears.

[Short-term effectiveness of arthroscopically capsular vertical mattress suturing for shoulder recurrent anterior dislocation combined with joint laxity].

OBJECTIVE: To evaluate the short-term effectiveness of arthroscopically capsular vertical mattress suturing for shoulder recurrent anterior dislocation combined with joint laxity. METHODS: A retrospective analysis was performed on 6 shoulder recurrent anterior dislocation patients combined with joint laxity treated with arthroscopically capsular vertical mattress suturing between January 2017 and December 2018. There were 5 males and 1 female with an average age of 20.8 years (range, 19-24 years). The number of shoulder dislocation was 3-18 times, with an average of 9.5 times. The disease duration ranged from 2 to 60 months, with an average of 25.3 months. The preoperative Beighton score was 4-7, with an average of 5.8; the Instability Severity Index Score (ISIS) was 2-5, with an average of 3.5. There were 5 cases of simple Bankart injury and 1 case of bony Bankart injury. The range of motion of shoulder joint (including active flexion and lifting, external rotation, abduction and external rotation, and internal ratation) was recorded before operation and at last follow-up; Oxford shoulder instability score, Rowe shoulder instability score, and Simple Shoulder Test (SST) score were used to evaluate shoulder joint function before operation, at 6 months after operation, and at last follow-up, and complications were recorded. RESULTS: All patients were followed up 16-28 months (mean, 19.3 months). During the follow-up, all patients had satisfactory motor function, and no re-dislocation and postoperative neurovascular complications occurred. At last follow-up, the activities of active external rotation and abduction and external rotation were significantly improved when compared with those before operation ( P<0.05); the activities of active flexion and lifting and internal rotation were not limited before and after operation, and the difference was not significant ( P>0.05). The Oxford shoulder instability score, Rowe shoulder instability score, and SST score at 6 months after operation and at last follow-up were significantly improved when compared with those before operation ( P<0.05); there was no significant difference between at 6 months after operation and at last follow-up ( P>0.05). CONCLUSION: The treatment of shoulder recurrent anterior dislocation combined with joint laxity by arthroscopically vertical matress suturing can achieve good short-term effectiveness.

[Mid-term effectiveness of manipulation under anesthesia combined with arthroscopic capsular release and subacromial debridement for primary frozen shoulder].

OBJECTIVE: To evaluate mid-term effectiveness of manipulation under anesthesia combined with arthroscopic capsular release and subacromial debridement for primary frozen shoulder. METHODS: Between January 2013 and December 2017, 33 patients of primary frozen shoulder were treated with manipulation under anesthesia combined with 360° arthroscopic capsular release and subacromial debridement. There were 10 males and 23 females, aged from 37 to 65 years, with a mean age of 50.9 years. The affected shoulder on left side in 17 cases and on right side in 16 cases. The disease duration was 6-13 months (mean, 8.4 months). Before and after operation, the visual analogue scale (VAS) score was used to evaluate the shoulder joint pain, Constant score was used to evaluate the shoulder joint function, and the flexion, abduction, and external rotation of shoulder joint were recorded. The internal rotation function was assessed based on the vertebral plane that the thumb could reach after internal rotation of the affected shoulder joint (the rank of internal rotation vertebra). X-ray film was taken to measure the distance of the subacromial space. RESULTS: There was no fracture or labrum tear in all patients, and all the incisions healed by first intention. All the 33 patients were followed up 20-31 months, with an average of 24.1 months. During the follow-up, there was no complication such as wound infection and nerve injury. At last follow-up, the range of motion of shoulder flexion, abduction, and external rotation, the rank of internal rotation vertebra, the VAS score, Constant score, and subacromial space were significantly improved when compared with preoperative ones ( P<0.05). CONCLUSION: Manipulation under anesthesia combined with arthroscopic capsular release and subacromial debridement can achieve a good mid-term effectiveness without complication for primary frozen shoulder.

Comparison of dorsal closing wedge calcaneal osteotomy versus posterosuperior prominence resection for the treatment of Haglund syndrome.

BACKGROUND: Haglund syndrome is a common disease that causes posterior heel pain. This study compared the clinical outcomes of dorsal closing wedge calcaneal osteotomy (DCWCO) and posterosuperior prominence resection (PPR) for the treatment of Haglund syndrome. METHODS: This retrospective study included 12 patients who underwent DCWCO and 32 patients who underwent PPR from January 2010 to August 2016. Patients were evaluated using the American Orthopedic Foot Ankle Society ankle-hindfoot scale (AOFAS), Victorian Institute of Sport Assessment Scale for Achilles tendinopathy (VISA-A), Fowler-Philip angle, Bohler's angle, and calcaneal pitch angle preoperatively and postoperatively (at 3 months, 6 months, 1 year, and the latest follow-up). RESULTS: Both groups exhibited a significant increase in their AOFAS and VISA-A scores after surgery. The DCWCO group had lower AOFAS scores than the PPR group at 6 months (77.6 ± 5.1 vs. 82.8 ± 7.8; P = 0.037) but had higher scores at the latest follow-up (98.2 ± 2.3 vs. 93.4 ± 6.1; P = 0.030). The DCWCO group had lower VISA-A scores at 3 months (56.9 ± 13.9 vs. 65.2 ± 11.0; P = 0.044) but higher scores at the latest follow-up (98.2 ± 2.6 vs. 94.3 ± 5.0; P = 0.010) than the PPR group. Both groups exhibited significant changes in the Fowler-Philip angle and Bohler's angle after surgery. The postoperative Fowler-Philip angle of the DCWCO group was greater than that of the PPR group (35.9° ± 4.9° vs. 31.4° ± 6.2°; P = 0.026). However, there was no statistically significant difference in any other angle of the two groups postoperatively. CONCLUSIONS: Compared to the PPR group, the DCWCO group had poorer short-term clinical outcomes but provide better long-term function and symptom remission. This method can be a good option for those patients with higher functional expectations.

[Mid-term effectiveness of arthrolysis and hinged external fixation for treatment of stiff elbow caused by heterotrophic ossification].

OBJECTIVE: To evaluate the mid-term effectiveness of arthrolysis and hinged external fixation for the treatment of stiff elbow caused by heterotrophic ossification. METHODS: Between January 2014 and December 2017, 11 patients with stiff elbow caused by heterotrophic ossification were admitted. There were 9 males and 2 females with an average age of 32 years (range, 14-48 years), and left side in 6 cases and right side in 5 cases. The cause of stiff elbow included humerus fracture in 5 cases, ulna fracture in 2 cases, fracture of capitulum radii in 1 case, dislocation of capitulum radii in 1 case, terrible triad of the elbow in 1 case, and soft tissue injury in 1 case. The disease duration ranged from 7 to 18 months (mean, 11 months). Preoperative active range of motion of elbow was (19.6±17.5)° and Mayo score was 34.1±9.7. All patients received the treatment of arthrolysis and debridement of heterotrophic ossification lesion combining hinged external fixator, and active and passive rehabilitation with the help of hinged external fixator. The hinged external fixators were removed after 2 months. RESULTS: All patients were followed up 13-36 months (mean, 19.1 months). All incisions healed by first intention, and no complication of infection or nerve lesion occurred postoperatively. At last follow-up, the results of X-ray films showed that no heterotrophic ossification recurred. The active range of motion of elbow was (116.4±16.6)° and Mayo score was 93.2±7.8, showing significant differences when compared with preoperative ones ( t=17.508, P=0.000; t=16.618, P=0.000). CONCLUSION: The application of arthrolysis and debridement of heterotrophic ossification lesion combining hinged external fixator can improve the elbow's range of motion significantly and obtain a good mid-term effectiveness.