T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective To investigate the expression of Thymosinβ10(TMSB10)in gastric cancer and its molecular mechanism in promoting the progression of gastric cancer.Methods We collected pathological sections of 70 patients with gastric cancer in our hospital,detected expression of TMSB10 in gastric adenocarcinoma by immunohistochemistry,and analyzed its prognostic effect.In order to study the mechanism of action,the effects of TMSB10 on the proliferation and glycolysis of gastric cancer cells and its related mechanism were observed by trans-fection technique,CCK8 test,EDU assay,Transwell assay,scratch test,glycolysis assay and Western blot.Results Immunohistochemistry showed that TMSB10 was highly expressed in gastric cancer,while the expression level of TMSB10 was correlated with tumor size(P=0.032),TNM stage(P=0.002)and distant metastasis.In the mechanism study,we found that overexpression of TMSB10 promoted the proliferation,invasion,migration and glycolytic phenotype of gastric cancer cells through in vitro CCK-8 test,EDU assay,Transwel assay and glycolysis assay,and vice versa.Western blot results showed that overexpression of TMSB10 may regulate the occurrence of gastric cancer through up-regulation of the AMPK/mTOR signaling pathway.Conclusions TMSB10 promotes the proliferation,invasion,migration and glycolysis gastric cancer through the AMPK/mTOR signaling pathway.

Objective:To explore the therapeutic effect and psychological influence of biofeedback pelvic floor muscle training on fecal incontinence after anorectal surgery in children.Methods:A retrospective case-control study.A total of 37 children who were admitted to the First Affiliated Hospital of Xinxiang Medical University from July 2021 to April 2023 for fecal incontinence after anorectal surgery were collected.Biofeedback pelvic floor muscle training was performed with a Laborie biofeedback therapy device, and pelvic floor muscle contraction function exercise was performed no less than 200 times a day.The anal canal current intensity, basic motion myoelectric value, contractile myoelectric difference and continuous anal contraction time were measured at before treatment, at the end of 1 course, 1 month and 1 year after treatment.Ten healthy children of the same age were selected as the healthy control group.The Strengths and Difficulties Questionnaire was used for psychological evaluation at before treatment and 1 year after treatment.Paired sample t test and independent sample t test were used to compare and analyze the results of this study. Results:Before treatment, at the end of 1 course, 1 month and 1 year after treatment, the anal canal current intensity of children with fecal incontinence were(11.32±1.92) mA, (10.22±1.28) mA, (8.45±1.09) mA, and(7.80±1.23) mA, respectively; the anal canal basic motion myoelectric value were(235.58±55.03) μV, (185.65±34.30) μV, (124.81±36.56) μV, and(93.99±28.29) μV, respectively; the anal canal contractile myoelectric difference were(45.64±20.38) μV, (64.20±16.59) μV, (93.63±25.53) μV, and(109.83±26.95) μV, respectively; the continuous anal contraction time were(1.27±0.43) s, (1.58±0.40) s, (2.04±0.39) s, and(2.47±0.38) s, respectively.These parameters before treatment, at the end of 1 course and 1 month after treatment were significantly different from those in the healthy control group[(7.20±1.09) mA, (88.65±21.76) μV, (120.73±27.57) μV, (2.68±0.29) s](all P<0.05).These parameters at 1 year after treatment were significantly different from those before treatment and 1 month after treatment(all P<0.05).However, there were no significant differences in these parameters between the healthy control group and the treatment group at 1 year after treatment(all P>0.05).There were statistically significant differences in emotional symptoms, hyperactivity symptoms, peer interaction, prosocial behavior and difficulty scores before and after treatment[(3.46±1.88) points vs.(2.59±1.32) points, (5.78±2.12) points vs.(3.70±1.78) points, (3.05±1.72) points vs.(2.49±1.30) points, (7.30±1.54) points vs.(8.27±1.39) points, (21.57±4.57) points vs.(18.54±3.14) points](all P<0.05). Conclusions:Biofeedback pelvic floor muscle training is a reliable and non-invasive method for the treatment of postoperative fecal incontinence after anorectal surgery in children and can effectively relieve the psychological and behavioral problems caused by fecal incontinence in children.

Objective:To explore the outcome of sponge forceps assisted threading with Speedbridge technique for the treatment of acute closed Achilles tendon rupture.Methods:A retrospective case series study was conducted on 20 patients with acute closed Achilles tendon rupture treated in Zhengzhou Orthopedic Hospital from December 2019 to December 2021. There were 18 males and 2 females, with age range of 24-43 years [(29.5±7.6)years]. All patients were with unilateral injury, involving the left side in 13 patients and right side in 7. Examinations revealed a palpable defect in the Achilles tendon and positive Thompson test. A longitudinal incision was made at the medial edge of the ruptured tendon. Three nonabsorbable sutures were passed through the proximal stump with sponge forceps, bypassed the rupture site and fixed directly into the calcaneal bone. The disrupted tendon ends were aligned by the tendon-bundle technique using 4-0 absorbable sutures. The operation time and incision length were documented. The ankle joint range of motion (dorsiflexion/plantar flexion), American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Achilles tendon total rupture score (ATRS) in the affected and healthy side were compared at 3, 6 and 12 months postoperatively. The wound healing and complications were observed.Results:All patients were followed up for 12-16 months [(13.2±2.5)months]. The operation time was 40-66 minutes [(52.0±10.3)minutes], with the incision length of 3-4 cm [(3.3±0.7)cm]. In the affected side at 3 and 6 months postoperatively, the ankle joint dorsiflexion [(5.6±1.5)°, (10.5±0.2)°] and plantar flexion [(28.4±3.2)°, (33.5±1.5)°] showed statistically significant difference compared with the healthy side (all P<0.05). The ankle joint dorsiflexion [(13.9±0.7)°] and plantar flexion [(38.3±4.4)°] in the affected side were not statistically different from that of the healthy side at 12 months postoperatively (all P>0.05). The AOFAS ankle-hindfoot score was (58.3±5.4)points, (84.9±7.1)points and (91.8±6.3)points at 3, 6 and 12 months postoperatively, showing a gradual rise (all P<0.05). The ATRS was (60.5±4.9)points, (85.5±9.0)points and (93.1±5.7)points at 3, 6 and 12 months postoperatively, showing a gradual rise (all P<0.05). All incisions were healed primarily. No patients had wound infection, nerve injury or re-rupture. Pain at the anchor insertion site occurred in 2 patients at 1 month after operation and relieved after active functional rehabilitation at 4 months after operation. Transient pain at the Achilles tendon insertion occurred in 1 patient at 6 months after operation, and relieved after 2 weeks of oral non-steroidal anti-inflammatory drugs treatment. Conclusion:For acute closed Achilles tendon rupture, sponge forceps assisted threading with Speedbridge technique can attain short operation time, small incision and good functional recovery, with few complications.

Humans ; Aminoquinolines/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Standard of Care

Objective:To determine the relationship between uric acid (UA) and mild cognitive impairment (MCI), and its potential effect on inflammation.Methods:450 patients with MCI diagnosed by neuropsychological scale and 450 controls with normal cognitive function were included. All subjects were≥60 years old. There were 184 obese subjects in MCI group and 199 obese subjects in control group.Results:A correlation between increased serum UA level and decreased risk of MCI was found in all MCI patients and non-obese MCI patients ( OR: 0.60, 95% CI 0.45-0.78; OR: 0.42, 95% CI 0.29-0.62), but not in obese MCI patients ( OR: 0.86, 95% CI: 0.54-1.35). The levels of UA and hypersensitive C reactive protein (hs-CRP) in obese patients with MCI were higher than those in non-obese patients ( P<0.01). There was a linear positive correlation between serum UA and hs-CRP levels in obese patients with MCI ( r=0.505, P<0.01), but not in non-obese MCI patients ( r=0.053, P=0.385). Conclusion:A significant correlation between lower serum uric acid levels and higher risk of MCI in non-obese subjects was found. Inflammation caused by obesity may weaken this relationship.

Objective To evaluate Evans lateral lengthening calcaneal osteotomy(E-LLCOT) in the treatment oftalocalcaneal coalitions (TCCs) with forefoot abduction deformity in the teenagers.Methods From February 2014 to August 2018,11 teenaged patients (14 feet) were treated at Department of Foot and Ankle Surgery,Zhengzhou Orthopaedics Hospital for TCCs with severe forefoot abduction deformity.They were 6 males (8 feet) and 5 females (6 feet),aged from 13 to 17 years (average,15 years).Their diseases involved bilateral feet in 3 cases and unilateral foot in 8,the left foot in 7 cases and the right in 7.All patients underwent TCCs resection followed by E-LLCOT.Their talonavicular coverage angles (TCA) and talar-second metatarsal angles (T2-MT) on the anteroposterior film and talar horizontal angles (TH) and talar-first metatarsal angles (T1-MT) on the lateral film were measured preoperatively and at the last follow-up.The foot functions were evaluated preoperatively and at the last follow-up using the ankle-hindfoot scores of American Orthopaedic Foot and Ankle Society (AOFAS) and visual analogue scale (VAS).Results All the 11 patients were followed up for 12 to 24 months (average,16.5 months).The mean preoperative TCA (22.3°,from 20° to 26°) was improved to 10.5° (from 8° to 13°) at the last follow-up;the mean T-2MT was improved from preoperative 17.6° (from 16° to 20°) to 6.5° (from 5° to 11°) at the last follow-up;the mean TH on the lateral view was improved from preoperative 35° (from 25° to 40°) to 17.5° (from 16° to 21°) at the last follow-up;the mean T-1MT was improved from preoperative 15.5° (from 10° to 22°) to 3.5° (from 2° to 6°) at the last follow-up;the mean AOFAS score was improved from 56.5 (from 50 to 62) preoperatively to 90.6 (from 75 to 95) at the last follow-up;the mean VAS score was improved from 6.0 (from 5 to 7) preoperatively to 2 (from 0 to 3) at the last follow-up.Conclusion For TCCs with severe forefoot abduction deformity in the geenagers,E-LLCOT after TCCs resection can effectively correct deformity,relieve pain and achieve significant functional and radiographic improvements.

Objective:To analyze the therapeutic effect of ankle arthrodesis with reverse proximal humerus internal locking system plating plus cannulated screwing via the transfibular approach in the treatment of end-stage ankle arthrosis.Methods:From April 2014 to January 2018, 19 patients (19 ankles) with end-stage ankle osteoarthritis were treated at Department of Foot and Ankle Surgery, Zhengzhou Orthopaedics Hospital by ankle arthrodesis with reverse PHILOS plating plus cannulated screwing via the transfibular approach for multi-plane fixation. They were 9 men and 10 women, aged from 36 to 65 years (average, 46.7 years). The disorder was further diagnosed as traumatic arthritis in 9 cases, as osteoarthritis in 6, as talar necrosis in 2 and as equinovarus in 2, and affected the left ankle in 11 cases and the right in 8. All cases belonged to stage Ⅲ osteoarthritis according to the Morrey-Wiedeman imaging classification. Their American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, visual analogue scale (VAS), joint fusion and complications were observed preoperatively and at the last follow-up.Results:All the 19 patients were followed up for 18 to 62 months (average, 31.5 months). Their AOFAS scores were improved from preoperative 46.3±2.1 to 81.6±0.9 at the last follow-up, and their VAS was reduced from preoperative 7.1±0.2 to 2.0±0.2 at the last follow-up, showing significant differences ( P<0.001). All their ankle joints obtained bony fusion after 9 to 14 weeks (mean, 11.5 weeks). No implant loosening or breakage was observed. All the patients were satisfied with their operative results at the last follow-up. Dorsal lateral foot numbness was observed in one patient who became asymptomatic after neurotrophic medication for 3 months. Lateral distal wound dehiscence happened during removal of stitches at 2 weeks after operation in another patient but healed after debridement. The last follow-up found subtalar joint degeneration in 2 cases and talonavicular joint degeneration in one but no clinical symptoms in the 3. Conclusion:Ankle arthrodesis with reverse PHILOS plating plus cannulated screwing via the transfibular approach is a fine treatment for end-stage ankle arthrosis, because it leads to reliable fixation, short fusion time, alleviated pain and improved ankle function.

Objective To evaluate distractor-assisted reduction for Lisfranc injury complicated with compressive fracture of lateral foot column.Methods A retrospective study was conducted of the 18 patients who had been treated surgically at Department of Foot and Ankle Surgery,Zhengzhou Orthopaedics Hospital between May 2014 and March 2017 for Lisfranc injury complicated with compressive fracture of lateral foot column.They were 10 males and 8 females,with an average age of 38.4 years (from 25 to 65 years).The injury involved the right foot in 11 cases and the left foot in 7.Their concomitant injuries were 12 compressive cuboid fractures and 6 compressive fractures of the calcaneal anterior process.According to the Chiodo-Myerson classification,there were 13 cases of three-column injury,3 ones of middle-lateral column injury and 2 ones of medial-lateral column injury.All the injuries were closed.After the condition of foot soft tissues permitted,open reduction assisted by a distractor and internal fixation with a mini locking plate was performed.Functional outcomes were assessed according to the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot-ankle scores and visual analogue scale (VAS) at the final follow-ups and complications during follow-up.Results The 18 patients were followed up for one to 4 years (average,2 years).Their AOFAS hindfoot-ankle scores ranged from 55 to 96 points (average,80.4 points);their VAS ranged from 0 to 6 points (average,1.5 points).Radiographic evidence of degeneration was noted in 10 patients.Of them,2 reported persistent pain which was cured by arthrodesis after conservative therapy failed and one presented with symptoms of injury to sural and cutaneous nerves which disappeared after oral administration of neurotrophic drugs for half a year.No such complication as skin necrosis,infection or implant failure occurred in other patients.Conclusion Open distractor-assisted reduction and internal fixation of lateral foot column with a mini locking plate,combined with bone graft if necessary,is an effective treatment for Lisfranc injury complicated with compressive fracture of lateral foot column,because it can effectively restore the alignment of lateral column and result in satisfactory therapeutic effects.

Objective To evaluate the surgical treatment of intra-articular calcaneal fractures associated with peroneal tendon dislocation.Methods From February 2014 to June 2017,15 patients (15 feet) with intra-articular calcaneal fracture associated with peroneal tendon dislocation were treated at Department of Foot and Ankle Surgery,Orthopaedics Hospital of Zhengzhou.There were 9 males (9 feet) and 6 females (6 feet),and 8 left feet and 7 right feet.The patients were aged from 20 to 55 years (average,42.5 years).After reduction of calcaneal fractures,titanium plates and screws were used for fixation.The bone canal was established on the lateral malleolus,and the torn superior peroneal retinaculum was fixed to the lateral malleolus by suture after reduction of the peroneal tendon.The ankle joint was immobilized with a plaster brace in the metatarsal flexion for 6 weeks.The postoperative outcomes were evaluated by the American Orthopaedic Foot & Ankle Society (AOFAS) score and visual analogue scale (VAS);complications were recorded.Results All the 15 patients were followed up for 12 to 36 months (average,20.5 months).All the calcaneal fractures fully healed and no re-dislocation of the peroneal tendon occurred.The AOFAS hindfoot-ankle scores ranged from 80 to 95 points,averaging of 87.4 points;the VAS scores ranged from 0 to 5 points,averaging 1.5 points.Delayed wound healing was observed in one case but primary healing was achieved eventually with regular dressing change.Another case presented with symptoms of injury to the cutaneous branch of the sural nerve which disappeared after oral administration of neurotrophic drugs for 6 months.Another case suffered from subtalar arthritis accompanied by persistent pain which disappeared after subtalar arthrodesis.No other complications were observed in the other patients.Conclusion In the surgical treatment of intra-articular calcaneal fractures associated with peroneal tendon dislocation,the peroneal tendon dislocation should be treated simultaneously with the intra-articular calcaneal fracture to achieve satisfactory clinical outcomes.