Objective:To discuss the effect of zanubrutinib(BGB-3111)combined with bortezomib(Btz)on the apoptosis of the human multiple myeloma(MM)cells,and to clarify its possible mechanism.Methods:The human MM cell lines U266,PS-R,RPMI8226,KMS28-PE,KMS28-BM,and H929 were cultured in vitro.Western blotting method was used to detect the expression level of Bruton's tyrosine kinase(BTK)protein in various cells;cell counting kit-8(CCK-8)method was used to detect the survival rates of the RPMI8226,U266,and KMS28-BM cells after treated with 0,10,20,30,40,and 50 μmol·L?1 BGB-3111.The RPMI8226,U266,and KMS28-BM cells at the logarithmic growth phase were selected and divided into control group,BGB-3111 group,Btz group,and BGB-3111+Btz group.Flow cytometry was used to detect the apoptotic rates of the cells in various groups;Western blotting method was used to detect the expression levels of myeloid cell leukemia 1(MCL-1),B-cell lymphoma-2(Bcl-2),Bcl-2-interacting mediator of cell death(Bim),phosphorylated Bim(p-Bim),P65,phosphorylated P65(p-P65),tumor necrosis factor receptor-associated factor(TRAF)2,and tumor necrosis factor alpha-induced protein 3(A20)in different kinds of cells.The U266 cells were divided into A20 overexpression group(A20-OE group)and empty vector control group(EV group).Each group was further divided into control group,BGB-3111 group,Btz group,and BGB-3111+Btz group.The corresponding plasmids were transfected;Western blotting method was used to detect the transfection efficiency of the cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups after over-expression of A20.Results:The Western blotting results showed that compared with KMS28-BM cells,the expression levels of BTK protein in the U266,RPMI8226,and H929 cells were significantly increased(P<0.05 or P<0.01).The CCK-8 results showed that compared with 0 μmol·L?1 BGB-3111 group,the survival rates of the RPMI8226 and U266 cells in 10,20,30,40,and 50 μmol·L?1 BGB-3111 groups were significantly decreased(P<0.05 or P<0.01),and the survival rates of the KMS28-BM cells in 20,30,40,and 50 μmol·L?1 BGB-3111 groups were significantly decreased(P<0.05).Compared with RPMI8226 and U266 cells,the survival rates of the KMS28-BM cells in 20,30,and 40 μmol·L?1 BGB-3111 groups were significantly increased(P<0.05).Therefore,10 μmol·L?1 BGB-3111 was selected for subsequent experiments.The flow cytometry results showed that compared with control group,the apoptotic rates of the RPMI8226 and U266 cells in BGB-3111 group,Btz group,and BGB-3111+Btz group were significantly increased(P<0.05 or P<0.01);compared with BGB-3111 group and Btz group,the apoptotic rates of the RPMI8226 and U266 cells in BGB-3111+Btz group were significantly increased(P<0.01);compared with control group,the apoptotic rates of the KMS28-BM cells in Btz group and BGB-3111+Btz group were significantly increased(P<0.01);compared with BGB-3111 group,the apoptotic rate of the KMS28-BM cells in BGB-3111+Btz group was significantly increased(P<0.01);compared with EV group,the apoptotic rates of the cells in A20-OE group in Btz group and BGB-3111+Btz group were significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of Bim protein in the RPMI8226 and U266 cells in BGB-3111 group,Btz group,and BGB-3111+Btz group were significantly increased(P<0.05),while the expression levels of MCL-1,p-Bim,and Bcl-2 proteins in the RPMI8226 and U266 cells in Btz group and BGB-3111+Btz group were significantly decreased(P<0.05);compared with BGB-3111 group and Btz group,the expression levels of Bim protein in the RPMI8226 and U266 cells in BGB-3111+Btz group were significantly increased(P<0.05),while the expression levels of MCL-1,p-Bim,and Bcl-2 proteins were significantly decreased(P<0.05).Compared with control group,the expression levels of p-P65 protein in the RPMI8226 and U266 cells in Btz group and BGB-3111+Btz group were significantly increased(P<0.05),while the expression levels of TRAF2 and A20 proteins were significantly decreased(P<0.05);compared with BGB-3111 group and Btz group,the expression levels of p-P65 protein in the RPMI8226 and U266 cells in BGB-3111+Btz group were significantly increased(P<0.05),while the expression levels of TRAF2 and A20 proteins were significantly decreased(P<0.05).The flow cytometry results showed that compared with EV group,the expression level of A20 protein in A20-OE group cells was significantly increased(P<0.01).Conclusion:BGB-3111 induces apoptosis in the MM cells by inhibiting BTK activity and enhances the pro-apoptotic effect of Btz.Over-expression of A20 increases the sensitivity of the MM cells to the combined treatment.The antitumor effect may be related to the inhibition of the nuclear factor kappa B(NF-κB)signaling pathway.

Objective:To explore the clinical outcome of internal fixation in the treatment of AO C-type distal radius fracture accompanied with dorsoulnar fragment involving 1/8 to 1/3 of the articular surface of the lunate facet.Methods:A total of 55 patients of AO C-type distal radius fracture accompanied with dorsoulnar fragment involving 1/8 to 1/3 of the articular surface of the lunate facet from July 2017 to July 2022 in Tongji Hospital Affiliated to Tongji University were retrospectively analyzed. In the volar plate group (volar locking plate treatment alone), there were 22 cases, 11 males and 11 females, aged 56.7±10.1 years, 10 C1 type, 7 C2 type and 5 C3 type. There were 15 patients in the volar plate+dorsal plate group (treated with volar locking plate combined with dorsal plate), including 6 males and 9 females, aged 55.7±8.1 years old, 4 C1 type, 5 C2 type and 6 C3 type. In the volar plate+dorsal screw group (treated with volar locking plate combined with dorsal screw), there were 18 cases, 8 males and 10 females, aged 53.5±11.6 years, 7 cases of C1 type, 5 cases of C2 type, and 6 cases of C3 type. The operation time, postoperative radiographic indicators, wrist range of motion (ROM), disability of arm, shoulder and hand (DASH) score, visual analogue scale (VAS) and postoperative complications were evaluated and compared between the three groups.Results:All operations were successfully completed. Patients were followed up for 14.9 ± 2.2 months (range, 12-18 months), and the fracture healing time was 12.4±2.3 weeks (range, 9-16 weeks). The operative time of patients in the volar plate group, volar plate+dorsal plate group and volar plate+dorsal screw group was 54.3±7.6 min, 70.7±5.9 min and 65.8± 7.1 min, respectively. Patients in the volar plate group had less operative time ( F=27.04, P<0.001). The residual displacement of the dorsoulnar fragment in sagittal, coronal, and axial CT scans in the three groups were (1.3±0.8 mm, 0.6±0.4 mm, 0.7±0.4 mm), (1.1±0.8 mm, 0.6±0.4 mm, 0.6±0.6 mm), (1.4±0.8 mm, 0.7±0.4 mm, 0.7±0.5 mm). The displacement of the dorsoulnar fragment of the two groups of combined volar and dorsal internal fixation was smaller than that of the volar plate group ( P<0.05). The ROM of wrist flexion of the three groups at 3 months after operation were 44.2°±4.6°, 47.7°±5.9°, 48.8°±5.1°, the ROM of wrist extension were 39.8°±6.2°, 44.3°± 4.6°, 44.7°±5.1°, the wrist DASH scores were 23.0±4.2, 20.1±4.1 and 19.4±3.0, and the VAS were 2.3±1.2, 1.6±1.3 and 1.3±1.0, respectively. The ROM of wrist flexion and extension and DASH score in volar plate+dorsal plate group were better than those in volar plate group ( P<0.05). The ROM of wrist flexion and extension, DASH score and VAS in the volar plate+dorsal screw group were better than those in the volar plate group ( P<0.05). There were no significant differences in terms of the wrist ROM, DASH score and VAS at 12 months after operation among the three groups ( P>0.05). There were 2 patients in the volar plate group with reduction loss, 3 patients with wrist chronic pain; 1 patient in the volar plate combined with dorsal plate group with dorsal tendon irritation, and no complications in the volar plate combined with dorsal screw group. Conclusion:For AO C-type distal radius fractures accompanied with a dorsoulnar fragment involving 1/8 to 1/3 of the articular surface of the lunate facet, the use of combined volar and dorsal internal fixation can improve the reduction accuracy and stability of the dorsoulnar fragment, and contribute to the early rehabilitation of postoperative wrist joint function. The effect of combined dorsal screw is comparable to that of dorsal plate internal fixation, but the complications of screw internal fixation are less.

OBJECTIVE: To evaluate the safety and efficacy of reverse partial lung resection for treatment of pediatric pulmonary cysts combined with lung abscesses or thoracic abscess. METHODS: We retrospectively analyzed the clinical data of children undergoing reverse partial lung resection for complex pulmonary cysts in our hospital between June, 2020 and June, 2021.During the surgery, the patients lay in a lateral position, and a 3-5 cm intercostal incision was made at the center of the lesion, through which the pleura was incised and the fluid or necrotic tissues were removed.The anesthesiologist was instructed to aspirate the sputum in the trachea to prevent entry of the necrotic tissues in the trachea.The cystic lung tissue was separated till reaching normal lung tissue on the hilar side.The proximal end of the striated tissue in the lesion was first double ligated with No.4 silk thread, the distal end was disconnected, and the proximal end was reinforced with continuous sutures with 4-0 Prolene thread.The compromised lung tissues were separated, and the thoracic cavity was thoroughly flushed followed by pulmonary inflation, air leakage management and incision suture. RESULTS: Sixteen children aged from 3 day to 2 years underwent the surgery, including 3 with simple pulmonary cysts, 11 with pulmonary cysts combined with pulmonary or thoracic abscess, 1 with pulmonary cysts combined with tension pneumothorax and left upper lung bronchial defect, and 1 with pulmonary herpes combined with brain tissue heterotaxy.All the operations were completed smoothly, with a mean operation time of 129 min, an mean hospital stay of 11 days, and a mean drainage removal time of 7 days.All the children recovered well after the operation, and 11 of them had mild air leakage.None of the children had serious complications or residual lesions or experienced recurrence of infection after the operation. CONCLUSION Reverse partial lung resection is safe and less invasive for treatment of complex pediatric pulmonary cysts complicated by infections.
Humans ; Child ; Abscess ; Retrospective Studies ; Lung/surgery* ; Cysts/surgery* ; Bronchi

Objective:To compare the clinical outcomes between anatomical locking plate, proximal humerus internal locking system (PHILOS) and anatomical locking plate combined with suture anchors in the treatment of comminuted fractures of humeral greater tuberosity.Methods:A total of 33 comminuted fractures of humeral greater tuberosity were surgically treated from October 2016 to October 2021 at Department of Orthopedics, Tongji Hospital Affiliated to Tongji University. There were 20 males and 13 females, with an age of (53.5±13.6) years. They were assigned into 3 groups according to different internal fixation techniques. Group A of 12 cases was subjected to fixation with anatomical locking plate via the deltoid approach, group B of 10 cases subjected to fixation with PHILOS via the pectoralis major and the deltoid approaches and group C of 11 cases subjected to fixation with anatomical locking plate combined with suture anchors via the deltoid approach. The operation time, intraoperative blood loss, range of shoulder motion, Constant-Murley shoulder score, visual analogue scale (VAS) and postoperative complications were compared between the 3 groups.Results:The 3 groups were comparable because there was no significant difference between them in the general clinical data ( P>0.05). The follow-up duration for all patients was (14.5±4.1) months. All fractures got united at the last follow-up. In groups A, B and C, respectively, the operation time was (57.9±7.8), (73.0±7.1) and (63.6±9.5) min, and the intraoperative blood loss (41.7±18.9), (82.0±22.9) and (46.4±13.6) mL, showing significant differences between the 3 groups ( P<0.05). The operation time and intraoperative blood loss in groups A and C were significantly less than those in group B ( P< 0.05). At the last follow-up, in groups A, B and C, respectively, the shoulder abduction was 144.0°±7.7°, 138.7°±10.7° and 148.5°±6.2°, showing significant differences between the 3 groups ( P<0.05). Group C was significantly better than group B ( P<0.05). There was no statistically significant difference in the forward flexion, external rotation, or internal rotation of the shoulder joint between the 3 groups ( P>0.05). The Constant-Murley scores in groups A, B and C, respectively, were (90.4±5.7), (86.1±6.6) and (93.1±3.4) points, showing significant differences between the 3 groups ( P<0.05). Group C was significantly better than group B ( P<0.05). The VAS scores in groups A, B and C, respectively, were 1 (0, 2), 1 (0, 2), and 1 (0, 1) point, showing insignificant differences between the 3 groups ( P>0.05). Group A had 1 case of shoulder joint stiffness and 1 case of fracture re-displacement complicated with acromial impingement syndrome, group B 1 case of shoulder joint stiffness and 3 cases of fracture re-displacement, but group C no post-operative complication. Conclusions:In the treatment of comminuted fracture of humeral greater tuberosity, all the 3 internal fixation techniques can lead to fine clinical outcomes. Conventional PHILOS may lead to relatively large trauma and a high incidence of postoperative complications. The anatomical locking plate may result in fine functional recovery of the shoulder due to advantages of less invasion, shorter operation time and fewer postoperative complications than PHILOS. The anatomical locking plate combined with suture anchors may lead to the best shoulder functional recovery and the least complications.

Gasdermin E is closely related to neoplasms, which is involved in the occurrence and development of neoplasms through gene methylation, gene mutation or other ways. Pyroptosis mediated by gasdermin E is involved in drug therapy of various neoplasms, which provides a new theoretical basis for drug therapy of neoplasms. The study of gasdermin E aims to deepen the understanding of neoplasms and provide a new perspective for the prevention and treatment of neoplasms.

Objective:To explore the risk factors that may affect the stabilization of dorsal intra-articular fragment in distal radius fracture after volar internal fixation.Methods:A retrospective analysis was performed of the patients with distal radius fracture who had been treated by volar internal fixation at Department of Traumatic Orthopedics, Tongji Hospital Affiliated to Tongji University from July 2016 to July 2020. After 3D reconstruction of their preoperative CT scans by software Mimics 20.0, 66 patients with a dorsal intra-articular fragment were screened out. They were 31 males and 35 females, aged from 23 to 78 years (average, 53.4 years). By the AO classification, there were 17 case of type C1, 22 cases of type C2, and 27 cases of type C3. The displacement of dorsal intra-articular fragment was judged by X-ray observation on postoperative day 2 and X-ray follow-up at the outpatient department. The 13 patients with displacement of dorsal intra-articular fragment>2 mm were assigned into a displacement group while the other 53 ones into a displacement-free group. The 2 groups were compared in terms of preoperative general data and anatomical data of the dorsal intra-articular fragment (total preoperative displacement, radius-ulnar length, dorsal-volar length, aspect ratio, proximal-distal length and volume) to analyze the correlations between them and displacement.Results:There was no significant difference in preoperative general data (age, gender, affected side, cause of injury or AO classification) between the 2 groups, showing comparability between groups ( P>0.05). All patients were followed up for 6 to 24 months (mean, 14 months) after surgery. There were no postoperative complications like neurovascular lesion or infection. None of the patients in the displacement group underwent revision surgery, and the fractures healed successfully during the postoperative follow-up. The total preoperative displacement in the displacement group was(10.0±1.3) mm, significantly larger than that in the displacement-free group [(7.8±1.5) mm]; the radius-ulnar length in the displacement group was (8.2±1.3) mm, significantly shorter than that in the displacement-free group [(10.8±2.3) mm]; the aspect ratio of the fragment in the displacement group was 1.2±0.2, significantly lower than that in the displacement-free group (1.4±0.2); the fragment volume in the displacement group was (690.5± 201.4) mm 3, significantly smaller than that in the displacement-free group [(995.8±295.0) mm 3]. There were significant differences in the above items between the 2 groups ( P<0.05). Conclusion:The total preoperative displacement, radius-ulnar length, aspect ratio and volume of a dorsal intra-articular fragment are important factors which may affect the displacement of the dorsal fragment after volar internal fixation.

Objective:To study the coronal bone structure matching of distal radius in normal population and some patients with postoperative distal radius fracture, and to explore the clinical significance of coronal bone structure reduction of distal radius fracture.Methods:CT scans of 80 asymptomatic wrists were performed. Mimics 20.0 and 3-Matic research software were used to measure the matching data of coronal bone structure of the distal radius. Total of 44 patients with distal radius fractures treated with open reduction and volar plate fixation were collected. According to the data coronal bone structure of the distal radius, the matching group was in the normal range, and the mismatching group was less than the normal range. X-ray films were used to evaluate fracture healing, humeral height, ulnar angle and palm tilt angle at 3 months and 12 months after operation. The clinical indexes of wrist pain, wrist function, grip strength and activity were recorded in 2 groups. The DASH score was used for evaluation, and statistical comparisons was made between the two groups of related indicators.Results:The coronal bone structure matching value of the distal radius in 80 normal adults was 45.0%±16.2%. All the 44 patients with distal radius fracture were followed up for an average of 16 months. The postoperative wound healing was good, and the bone healing standard was reached 3 months after the operation. 3 months after surgery, radius height, ulnar deviation angle and palmar inclination angle of the mismatched group were all smaller than those of the matched group, but the differences had no statistical significance. The pronation angle in the mismatched group (68.82°±11.62°) was lower than that in the matched group (76.91°±9.14°), and the difference was statistically significant ( t=2.567, P=0.014). The DASH score in the mismatched group (15.53±2.36) was higher than that in the matched group (13.62±2.52), and the difference was statistically significant ( t=2.591, P=0.013). 12 months after surgery, the VAS score of the matched group (2.08±2.95) was less than that of the mismatched group (2.95±1.24), and the difference was statistically significant ( t=2.348, P=0.024). There was no significant difference in wrist range of motion, grip strength and DASH score between the two groups. Conclusion:The coronal bone structure matching of distal radius is about 45.0% in normal population. Early wrist dysfunction, limited pronation, and wrist pain may occur when the postoperative matching degree of the distal radius fracture is not within the normal range.

Objective:To explore the mechanism of follicular helper T (Tfh) cells, i.e. CD4 +CXCR5 +T cells, and the secreted cytokine programmed death factor 1 (PD-1) in the pathogenesis of tuberculosis, and to explore the significance of Tfh cells and PD-1 in the treatment of tuberculosis. Methods:Flow cytometry was used to detect the changes of Tfh cells and PD-1 in mononuclear cells during the treatment cycle of tuberculosis.Results:Before treatments, the ratio of Tfh cells/CD4 +T cells in peripheral blood mononuclear cells in the pulmonary tuberculosis group was 3.37%±0.45%, which was significantly higher than 2.21%±0.47% of the healthy control group ( P<0.01), and significantly higher than 2.39%±0.38% after treatments ( P<0.01). Before treatments, the ratio of CD4 +CXCR5 +PD-1 +T cells/Tfh cells in the peripheral blood of the tuberculosis group was 25.33%±10.08%, which was significantly higher than 8.42%±2.31% of the healthy control group ( P<0.01), and significantly higher than 11.35%±2.65% after treatments ( P<0.01). After treatments, the levels of Tfh cells and PD-1 in the sputum smear-negative group and the sputum smear-negative group were lower than that before treatments, and the difference between the groups was statistically significant (all P<0.05). Conclusions:The levels of Tfh cells and PD-1 in patients with tuberculosis are significantly higher than those in healthy people, and after drug treatment, the levels of both can be reduced. With the prolongation of the treatment cycle, the sputum smear-transforming group and the non-negative group began to show significant differences. In the course of pulmonary tuberculosis, monitoring changes in Tfh cells and PD-1 levels is helpful for the diagnosis of tuberculosis, and has certain guiding significance for its treatment and outcome.

Objective:To explore the operative effect and treatment strategies for the low distal humerus fracture.Methods:A retrospective analysis was conducted on the clinical data of 16 patients with the low distal humerus fracture between January 2016 and January 2018 at Department of Orthopaedics, Shanghai Tongji Hospital Affiliated to Tongji University.All fractures were coronal fractures of humeral head, partly combined fractures of humeral trochlea or posterior part. Fractures were classified according to Dubberley classification as 9 cases in type Ⅰ, 3 cases in typeⅡ and 4 cases in type Ⅲ.Selection of the kind of operative approach and internal fixation was made according to the fracture type and shape. For simple coronal fractures of humeral head or combining humeral trochlea fractures, which were relatively stable, single or multiple countersunk screws fixation by the lateral approach were chosen.For humeral head coronal fractures, which combining obviously displaced comminuted humeral trochlea factures, posterolateral locking plates and countersunk screws internal fixation by the olecranon osteotomy approach were chosen. The incision and elbow soft tissues were observed within 2 weeks after operation.The radiographic evaluation of fracture reduction, bone healing, internal fixation, arthritis and elbow range of motion were made at 3, 6, 12 months after operation. The Mayo elbow functional scores were documented for analysis of elbow joint function, and compared between different surgery groups by Kruskal-Wallis H test. Results:The follow-up time was (22.1±9.2)months(range: 15 to 39 months). The incisions healed well in 2 weeks after operation without soft tissue infection, necrosis or vascular complications. There was no fracture reduction loss or internal fixation loosening according to radiographic evaluation 3 months after operation. One case of ectopic ossification was observed 6 months after operation and inhibited by the treatment of non steroidal anti-inflammatory drugs.One case of ulnar neuritis occurred after operation and released after removing the long screw and loosing the ulnar.Osteoarthritis images were observed at the end of follow-up.Arc of motion was (120.4±11.2) ° in flexion and (5.5±1.9) ° in extension. The Mayo score was 88.7±9.1, including 11 excellent, 4 good, and 1 fair.The Mayo score was 90.1±3.7 in Dubberley classification type Ⅰcases, 89.7±4.6 in type Ⅱ cases and 84.5±5.8 in type Ⅲ cases. There were no significant differences in Mayo scores between 3 types cases according to Kruskal-Wallis H test. Conclusion:Choosing the appropriate surgical approach and composite internal fixation according to the fracture types and shapes of low distal humerus fracture, anatomic reduction of the articular surface and early functional exercise are the keys to obtain ideal curative effect.

Objective:To explore the operative effect and treatment strategies for the low distal humerus fracture.Methods:A retrospective analysis was conducted on the clinical data of 16 patients with the low distal humerus fracture between January 2016 and January 2018 at Department of Orthopaedics, Shanghai Tongji Hospital Affiliated to Tongji University.All fractures were coronal fractures of humeral head, partly combined fractures of humeral trochlea or posterior part. Fractures were classified according to Dubberley classification as 9 cases in type Ⅰ, 3 cases in typeⅡ and 4 cases in type Ⅲ.Selection of the kind of operative approach and internal fixation was made according to the fracture type and shape. For simple coronal fractures of humeral head or combining humeral trochlea fractures, which were relatively stable, single or multiple countersunk screws fixation by the lateral approach were chosen.For humeral head coronal fractures, which combining obviously displaced comminuted humeral trochlea factures, posterolateral locking plates and countersunk screws internal fixation by the olecranon osteotomy approach were chosen. The incision and elbow soft tissues were observed within 2 weeks after operation.The radiographic evaluation of fracture reduction, bone healing, internal fixation, arthritis and elbow range of motion were made at 3, 6, 12 months after operation. The Mayo elbow functional scores were documented for analysis of elbow joint function, and compared between different surgery groups by Kruskal-Wallis H test. Results:The follow-up time was (22.1±9.2)months(range: 15 to 39 months). The incisions healed well in 2 weeks after operation without soft tissue infection, necrosis or vascular complications. There was no fracture reduction loss or internal fixation loosening according to radiographic evaluation 3 months after operation. One case of ectopic ossification was observed 6 months after operation and inhibited by the treatment of non steroidal anti-inflammatory drugs.One case of ulnar neuritis occurred after operation and released after removing the long screw and loosing the ulnar.Osteoarthritis images were observed at the end of follow-up.Arc of motion was (120.4±11.2) ° in flexion and (5.5±1.9) ° in extension. The Mayo score was 88.7±9.1, including 11 excellent, 4 good, and 1 fair.The Mayo score was 90.1±3.7 in Dubberley classification type Ⅰcases, 89.7±4.6 in type Ⅱ cases and 84.5±5.8 in type Ⅲ cases. There were no significant differences in Mayo scores between 3 types cases according to Kruskal-Wallis H test. Conclusion:Choosing the appropriate surgical approach and composite internal fixation according to the fracture types and shapes of low distal humerus fracture, anatomic reduction of the articular surface and early functional exercise are the keys to obtain ideal curative effect.