Objective To investigate the effect and mechanism of dabrafenib （DAB） combined with tremelimumab （TREM） on melanoma. Methods The effects of DAB combined with TREM on cell viability, cytotoxicity and cell migration of A375 cells were evaluated by Cell Counting Kit-8 （CCK-8） method, lactate dehydrogenase （LDH） method and scratch assay. The levels of reactive oxygen species （ROS）, adenosine triphosphate （ATP）, malondialdehyde （MDA）, and superoxide dismutase （SOD） were detected to evaluate the effects of combined drugs on oxidative stress and energy metabolism. In addition, A375 tumor-bearing nude mice model was used to evaluate the inhibitory effect of the combined treatment on tumor growth in vivo, and the degree of cell apoptosis and cell proliferation in tumor tissues were analyzed by terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling （TUNEL） and proliferating cell nuclear antigen （PCNA） immunohistochemical staining. Results The combined treatment significantly inhibited the survival rate and migration ability of A375 cells and enhanced the cytotoxicity. The combined intervention also significantly increased ROS level, decreased ATP, SOD and MDA levels. It effectively inhibited tumor growth in tumor-bearing nude mice, increased the apoptosis rate of tumor cells and inhibited cell proliferation. Conclusion DAB combined with TREM may improve the therapeutic effect of melanoma by enhancing oxidative stress, inhibiting energy metabolism, and promoting cell apoptosis. This combination therapy may provide a new therapeutic strategy to overcome the limitations of singledrug therapy.

Objective:To investigate the relationship between the CT images of a lateral condylar tibial plateau fractures and complete medial collateral ligament (MCL) injury.Methods:Data of 59 patients with lateral condylar fracture of tibial plateau complicated with MCL injury admitted to Tianjin Hospital from January 2020 to November 2021 were collected, including 32 males and 27 females, aged 42.4±12.3 years (range, 19-65 years), there were 26 cases of extension injury and 33 cases of flexion injury. The patients were separated into two groups: those with partial MCL injury and those with total rupture based on preoperative MR examination and intraoperative valgus stress test following fracture fixation. According to the ABC fracture classification of lateral condyle tibial plateau proposed by Sun et al., the fracture locations were determined on CT images, and the lateral plateau collapse depth (LPD) was measured. The relationship between LPD and MCL complete rupture was analyzed by receiver operating characteristic (ROC) curve.Results:Among 59 patients with lateral condylar tibial plateau fracture and MCL injury, 42 had partial injuries and 17 had complete ruptures. According to the ABC fracture classification, there were 26 cases of extension injury (involving area A), 21 cases of AB type, and 5 cases of ABC type; and 33 cases of flexion type injury, 19 cases of B type, 12 cases of BC type, and 2 cases of C type. All the 17 cases of MCL complete fracture occurred in extension injury, including type AB (14 cases) and type ABC (3 cases). The difference between the mean LPDs of the MCL full rupture group and the partial injury group was not statistically significant ( t=0.11, P=0.567), and the mean LPDs of both groups were 11.7±5.3 mm (range, 4.3-28.1 mm) and 11.5±4.8 mm (range, 3.8-23.6 mm), respectively. The area under the curve (AUC) of the ROC curve analysis was 0.504, and there was no statistical correlation between lateral platform collapse depth and MCL injury. Among the 26 patients with extensional injury area, MCL was completely ruptures in 17 cases and partially injury in 9 cases, LPD was 11.7±5.3 mm (range, 4.3-28.1 mm) and 6.6±1.8 mm (range, 3.8-9.4 mm), respectively, and the difference was statistically significant ( t=3.57, P=0.009). The best predictive cut-off value of LPD was 7.25 mm, the sensitivity was 88.2%, the specificity was 77.8%, and the AUC was 0.868. Conclusion:When the lateral condyle fracture of the tibial plateau is located in the extensional injury area (involving the A area in the ABC fracture classification) and the LPD measured on the CT image is greater than 7.25 mm, the complete rupture of the MCL should be considered. Clinical MCL repair is required after the fracture fixation surgery for improved surgical outcomes.

Restoration of teeth after removal of previous restorations is a common problem in the dental clinic. The situation of teeth after removal of previous restoration is complex and often requires multidisciplinary cooperation. However, there is a lack of systematic and concise guidelines for determining the treatment plan for those teeth. Through a combination of restorative clinical experience and the opinions of endodontic specialists, the author systematically described the problems that may exist after the removal of previous restorations in the teeth that have not undergone or have undergone root canal treatment (RCT) and those with post and core restorations. And summarized the corresponding treatment recommendations according to their pulpal and periapical status, the quality of RCT and the presence or absence of post and core restorations. ①For teeth without RCT, the vitality of the pulp, the occurrence of pulpal/periapical disease and the amount of re-preparation need to be assessed to determine whether RCT is necessary. ②For teeth with RCT, if the quality of RCT is good and no periradicular lesion exists, direct restorative treatment can be considered. If the quality of the RCT is unsatisfactory but no periradicular lesion exists, root canal retreatent (re-RCT), follow up or direct restorative treatment should be performed as appropriate and treatment plan can be developed in conjunction with the endodontist if necessary. If the quality of the RCT is unsatisfactory and periradicular lesion exists, re-RCT is necessary before restorative treatment.③For teeth with post and core restorations, if the quality of RCT is good and no periradicular lesion exists, direct restorative treatment can be considered. If the quality of the RCT is unsatisfactory but no periradicular lesion exists, follow up or direct restorative treatment should be performed as appropriate and treatment plan can be developed in conjunction with the endodontist if necessary. If the quality of RCT is unsatisfactory and periradicular lesion exists, for teeth with thin post and thick root canal walls, re-RCT after removal of the post can be attempted. For teeth with thick post and thin root canal walls, preservation of the post and apical surgery can be considered. For the teeth with excessively large defects or extremely poor periodontal conditions, extraction is recommended. The author refined the above recommendations into a set of treatment procedures, aiming to provide a reference for the selection of treatment options for teeth after removal of previous restorations.

Bacillus cereus belongs to Gram-positive bacteria, which is widely distributed in nature and shows certain pathogenicity. Different B. cereus strains carry different subsets of virulence factors, which directly determine the difference in their pathogenicity. It is therefore important to study the distribution of virulence factors and the biological activity of specific toxins for precise prevention and control of B. cereus infection. In this study, the hemolysin BL triayl was expressed, purified, and characterized. The results showed that the bovine pathogenic B. cereus hemolysin BL could be expressed and purified in the prokaryotic expression system, and the bovine pathogenic B. cereus hemolysin BL showed hemolysis, cytotoxicity, good immunogenicity and certain immune protection in mice. In this study, the recombinant expression of hemolysin BL triayl was achieved, and the biological activity of hemolysin BL of bovine pathogenic ceroid spore was investigated. This study may facilitate further investigating the pathogenic mechanism of B. cereus hemolysin BL and developing a detection method for bovine pathogenic B. cereus disease.
Cattle ; Animals ; Mice ; Bacterial Proteins/metabolism* ; Bacillus cereus/metabolism* ; Hemolysin Proteins/metabolism* ; Virulence Factors/metabolism* ; Enterotoxins/metabolism*

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Objective:To analyze the risk factors of deep venous thrombosis (DVT) in patients with tibial plateau fracture during preoperative period.Methods:From July 2017 to October 2019, a total of 264 patients undergoing surgeries of tibial plateau fractures were enrolled. Duplex ultrasonography (DUS) during hospitalization was used to screen for DVT of the bilateral lower extremities. Patients were divided into DVT group and non-DVT group according to results of DUS. Data on demographics, comorbidities, injury-related data, fracture type, laboratory biomarkers were collected and compared between groups with and without DVT.Results:The incidence of preoperative DVT was 39.0% (103/264) among 264 patients with traumatic tibial plateau fractures, and distal thrombosis predominated in DVT group. There were 103 cases in DVT group. 55 were males and 48 were females. The average age was 54.00±11.12. According to the Schatzker classification of tibial plateau fractures, 7 cases belonged to type I, 37 to type II, 2 to type III, 11 to type IV, 29 to type V, and 17 to type VI. There were 161 cases in non-DVT group. 89 were males and 72 were females. The average age was 48.57±13.25. According to the Schatzker classification of tibial plateau fractures, 23 cases belonged to type I, 76 to type II, 2 to type III, 10 to type IV, 33 to type V, and 17 to type VI. Univariate analysis showed that age ( t=3.451, P=0.001), the type of tibial plateau fracture ( χ2=8.314, P=0.004), D-dimer ( χ2=18.552, P<0.001), APTT ( t=2.869, P=0.004), ALB ( t=2.292, P=0.023) and Hb ( t=1.983, P=0.048) were statistically different than those in non-DVT group. Multivariate analysis showed age ( OR=1.033, 95% CI: 1.009, 1.058; P=0.007), the type of tibial plateau fracture ( OR=1.829, 95% CI: 1.014, 3.299; P=0.045) and D-dimer ( OR=1.914, 95% CI: 1.057, 3.464; P=0.032) were independent risk factors. Conclusion:The incidence of DVT in patients with tibial plateau fractures during preoperative period is high, and distal thrombosis is the main part of venous thrombosis of lower extremity. The type of tibial plateau fracture, age and the level of D-dimer are independent risk factors of preoperative DVT in patients with tibial plateau fractures.

Objective:To explore the efficacy and safety of anti-tumor necrosis factor alpha (TNFα) monoclonal antibodies (mAbs) for severe/refractory vasculo-Behcet′s disease (BD).Method:The clinical data of severe/refractory vasculo-BD patients treated with anti-TNFα mAbs were retrospectively analyzed. Response of anti TNFα mAbs was analyzed. The dosage changes of glucocorticoid, the level of erythrocyte sedimentation rate (ESR) and hypersensitive C-reactive protein (hsCRP) before and after treatment were recorded, as well as side effects.Result:Sixteen patients were enrolled. Arterial lesions were reported in 12 patients, including 9 with arterial aneurysm, 6 with arterial dilation, 2 with stenosis and 2 with occlusion. Seven patients presented venous thrombosis, including lower extremity veins ( n=6), cerebral venous sinus ( n=2) and inferior vena cava system ( n=2). Two cases had both arterial and venous involvement. Before the application of TNFα mAbs, all 16 patients failed to response to prednisone or its equivalent dose of 40 (7.5-90) mg/d in combination with cyclophosphamide, methotrexate, thalidomide or azathioprine for median 4 (0-156) months. After a mean duration of treatment for (17.1±6.5) months, 15 patients achieved complete remission and 1 patient achieved partial remission. Three patients received surgery without any postoperative complications. After using anti TNFα mAbs, the dosage of prednisone [5(0-12.5)mg/d vs. 40(7.5-90)mg/d, P<0.01], ESR [(7.3±4.6) mm/1h vs. (33.5±26.7) mm/1h, P<0.01] and hsCRP [1.9(0.2-11.4) mg/L vs. 24.3(0.4-113.9) mg/L, P<0.01] were significantly decreased. Side effects were observed in 2 patients. One developed pulmonary infection 12 months after adalimumab with conventional treatment. Another patient had allergy to infliximab then switched to adalimumab. Conclusion:In combination with corticosteroids and immunosuppressants, anti-TNF α mAbs are effective and well-tolerated in severe/refractory vasculo-BD, with a favorable steroid -sparing effect and rare postoperative complications.

Objective To assess the clinical value of cross raft screws technique in preventing postoperative collapse of tibial plateau fracture.Methods From September 2014 to November 2017,data of 14 patients with tibial plateau fracture who were treated by cross raft screws technique were retrospectively analyzed.There were 9 males and 5 females aged from 30-65 years old (average,44.4± 1.7 years).There were 8 patients that the thickness of subchondral cancellous bone measured preoperatively by CT data was less than 4 mm,and 6 patients that the thickness of subchondral cancellous bone measured intraoperatively was less than 4 mm.1/4 tubular plate was placed along the anterior rim of lateral tibial plateau,and the 3.5 mm cortical bone screws were fixed as bamboo raft from anterior to posterior through the plate.The collapse of tibial plateau after surgery were measured by CT scan after union of the fracture.The function of knee was evaluated by Rasmussen Anatomical and Functional Grading.Results The time of tubular plate procedure was 18 to 35 min (average,24.1±5.4 min).All 14 patients were successfully followed-up for 13.8±5.1 months.The height of collapse preoperatively by CT scan was 5-21 mm (average,8.00± 1.40 mm).3 days after the operation,the height between articular line and lateral articular surface was 0-2 mm (average,0.80±0.06 mm).Compared with CT data preoperatively,the collapse was corrected postoperatively that was proved by CT scan (P＜ 0.05).After the fracture was healed,according to CT data,the height between articular line and lateral articular surface was 0-2 mm (average,0.70±0.08 mm).Compared with CT data postoperatively,there was no postoperative collapse happened (P=0.466).The position and length of nails were placed appropriately.The average healing time of fracture was 3.6 months.There were no infection,nonunion and pain of tendon happened.The plate could be touched subcutaneously in 2 patients,who had no discomfort feelings.The patient's postoperative Rasmussen Anatomical Grading were 13-18 (average,16.7),including 8 cases excellent and 6 cases good.The postoperative Rasmussen Functional Grading was 18-28 (average,25.7),including 11 cases excellent and 3 cases good.Conclusion The cross raft screws technique is a good way to prevent the postoperative collapse of the lateral articular surface of tibial plateau.

Objective To assess the prognostic value of progesterone receptor (PR) in Luminal B HER2(-) lymph-node-negative breast cancer.Methods The clinical data of 196 Luminal B HER2 (-) lymph-node-negative breast cancer patients were collected in this study.The correlation between PR and clinicopathological factors and its influence on prognosis was analyzed.Results Among 196 patients with Luminal B HER2 (-) lymph-node-negative breast cancer,14.8％(29/196)were PR-negative and 85.2％(167/196)were PR-positive (HR=3.25,95.0％ CI:0.73-1.45,P=0.123).PR negativity indicated postmenopausal status (P=0.029) and high tumor grade (P=0.001).Mter a median follow-up of 60 months,9.7％(19/196) of the patients had relapses and 4.1％(8/196) died of breast cancer.The 5-year disease-free survival(DFS) was 75.9％ in PR-negative group and 92.8％ in PR-positive group (Log-rank P=0.001).The 5-year overall survival (OS) was 89.7％ in PR-negative group and 97.0％ in PR-positive group (Log-rank P=0.023).In multivariate analysis,PR negativity was significantly associated with a poor 5-year DFS (HR=2.85,95.0％ CI:1.05-7.72,P=0.039)but not with 5-year OS (HR=1.78,95.0％ CI:0.34-9.35,P=0.495).Conclusion In this study,PR is a prognostic factor for relapse in Luminal B HER (-) lymph-node-negative breast cancer.