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.

AIM:To investigate the therapeutic efficacy of curcumin(Cur)-loaded engineered cell membrane mimetic nanoparticles(PD1-Cur@PLGA NPs)in treating breast cancer in mice,and to explore their tumor immunomodu-latory effects.METHODS:Engineered mouse breast cancer 4T1-PD1 cell line expressing programmed death 1(PD1)was established,and PD1 expression level was analyzed by flow cytometry.The 4T1-PD1 cell membranes were extracted and coated on the surface of Cur-loaded poly(lactic-co-glycolic)acid(PLGA)nanoparticles(Cur@PLGA NPs)using ice bath sonication to obtain PD1-Cur@PLGA NPs.The Cur loaded in various NPs was detected using UV-visible spectropho-tometry.Particle size and morphology were analyzed by using dynamic light scattering and transmission electron microsco-py.The 4T1 cells were divided into negative control(PLGA NPs and PD1-NVs),experimental(PD1-Cur@PLGA NPs),parallel control(Cur@PLGA NPs),and positive control(Cur)groups.In each group,cell viability was assessed by CCK-8 assay,and cell apoptosis was determined through flow cytometry.To perform treatment experiments in vivo,4T1 cell-bearing tumor mice were randomly divided into PBS,PD1-NVs,and PD1-Cur@PLGA NPs groups.At the end of treat-ments,tissues of major organs were stained to detect pathological changes,as well as indicators of tumor proliferation(Ki67),apoptosis(TUNEL),and infiltration and activity of T cells(CD4+and CD8+)in tumor tissues.RESULTS:The PD1 expression in 4T1-PD1 cell lines reached 78%.PD1-Cur@PLGA NPs exhibited a core-shell structure with particle sizes ranging from 100 to 200 nm.PD1-Cur@PLGA NPs enhanced the biocompatibility compared to free Cur and exhibited a strong apoptosis-inducing effect on 4T1 cells.Compared with control group,PD1-Cur@PLGA NPs significantly inhibited 4T1 breast tumor growth in vivo(P<0.01),without apparent toxic side effects.Treatment with PD1-Cur@PLGA NPs re-duced Ki67 expression,increased cell apoptosis,and enhanced infiltration and activity of CD4+and CD8+T cells in tumor tissues.CONCLUSION:PD1-Cur@PLGA NPs enhanced Cur biocompatibility and exhibited cytotoxicity against mouse breast cancer cells.This nanoformulation demonstrated promising therapeutic efficacy and safety in vivo,exerting poten-tial antitumor immune regulatory effects.

Objective:To compare the clinical efficacy of ultrasound-guided spinal nerve block (SNB) and paraverteral nerve block (PVB) in treating postherpetic neuralgia.Methods:A total of 52 patients with postherpetic neuralgia who visited the Pain Clinic of the Xiangya Hospital, Central South University from February 2020 to December 2022 were selected and randomly divided into an ultrasound-guided SNB group and a PVB group using a random number table method, with 26 patients in each group. Patients in the SNB group received ultrasound-guided spinal nerve block therapy; The PVB group received ultrasound-guided paraverteral nerve block treatment. Visual Analog Scale (VAS) scores, 36-Item Short Form Survey (SF-36) scores, and total effective rate were observed in two groups of patients before treatment, 2 weeks after treatment, 1 month after treatment, 3 months after treatment, and 6 months after treatment. Complications during treatment were also observed.Results:The total effective rates of SNB group patients at 1, 3, and 6 months after treatment were significantly higher than those of PVB group (all P<0.05). After treatment, the VAS scores of both groups of patients at each time point were significantly reduced compared to before treatment (all P<0.05); The VAS scores of patients in the SNB group were lower than those in the PVB group at 1, 3, and 6 months after treatment, but the difference was not statistically significant (all P>0.05). There was no statistically significant difference in Physical Component Summary (PCS) and Mental Component Summary (MCS) scores between SNB and PVB groups before nerve block treatment (all P>0.05). The MCS and PCS scores of the two groups of patients were significantly higher than before treatment at 2 weeks, 1 month, 3 months, and 6 months after treatment (all P<0.05). The MCS scores of the SNB group were significantly higher than those of the PVB group at 2 weeks, 1 month, 3 months, and 6 months after treatment (all P<0.05), but there was no statistically significant difference in PCS scores between the two groups (all P>0.05). Both groups of patients did not experience any serious complications related to the treatment in this study during the follow-up period. Conclusions:Both ultrasound-guided spinal nerve block and paraverteral nerve block can safely and effectively treat postherpetic neuralgia. The clinical effect of ultrasound-guided spinal nerve block in treating postherpetic neuralgia is better than that of paraverteral nerve block.

Objective:Analysis of surgical strategies for atrial functional mitral regurgitation with atrial fibrillation.Methods:Retrospective analysis of 112 patients with mitral regurgitation and atrial fibrillation between June 2017 and January 2023. Among them, 56 cases were severe atrial functional mitral regurgitation with atrial fibrillation, and the other 56 cases were degenerative mitral regurgitation with atrial fibrillation. All patients underwent maze Ⅳ procedure and mitral valve surgery. Follow up will be conducted through outpatient follow-up and telephone calls. The condition of postoperative mitral valve is obtained through echo. The postoperative cardiac rhythm is based on the patient's conscious symptoms, electrocardiogram, 24 hour dynamic electrocardiogram.Results:The comparison of preoperative basic data shows that the age, duration of atrial fibrillation, and comorbidity of patients with atrial functional mitral regurgitation are significantly higher than those in the degenerative mitral regurgitation group. All patients successfully completed the surgery. Postoperative death occurred in 2 cases in the atrial mitral regurgitation group. The causes of death were ARDS and pulmonary infection, respectively. The main postoperative complications include bleeding, low cardiac output, pulmonary infection, and acute kidney injury. During follow-up, 43 patients (79.6%) in the atrial mitral regurgitation group maintained sinus rhythm, while 49 patients (87.5%) in the degenerative group. However, there was no statistically significant difference in the Kaplan- Meier curves. In the atrial mitral regurgitation group, there were 47 cases with no mitral regurgitation, 4 cases with mild regurgitation, and 1 case with moderate regurgitation. In the degenerative group, there were 42 cases with no mitral regurgitation, 6 cases with mild regurgitation, 1 case with moderate regurgitation, and 1 case with severe regurgitation. The risk for atrial fibrillation recurrence in the atrial mitral regurgitation is related to postoperative left atrial diameter greater than 50 mm, while in the degenerative group, atrial fibrillation recurrence is related to postoperative left atrial diameter greater than 50 mm and residual mitral regurgitation. Conclusion:Mitral valve repair combined with maze Ⅳ procedure is an effective treatment for patients with severe atrial functional mitral regurgitation and atrial fibrillation. Further improving the success rate of atrial fibrillation and reducing surgical trauma will benefit patients in the future.

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.

Objective: To understand the relationship between childhood abuse and uncertainty stress among college students and their interaction with depressive symptoms, so as to provide evidence for psychological intervention among college students. Methods: A total of 1 830 college students from Xuzhou, Nanjing and Wuhan were selected by multistage stratified cluster random sampling method to conduct a questionnaire survey from March to May 2021 using Adverse Childhood Experience Scale, Uncertainty Stress Scale, and 10-Item Center for Epidemiological Studies Depression Scale. Results: Overall, 361 (19.73%), 507 (27.70%) and 607 (33.17%) college students had childhood abuse experiences, high uncertainty stress and depressive symptoms respectively. After controlling for confounding factors, multivariate Logistic regression analysis showed that the risk of depressive symptoms in college students with childhood abuse experiences was 2.84 times higher than those without childhood abuse experiences ( OR= 2.84 , 95%CI =2.17-3.71). The risk of depressive symptoms among college students with high uncertainty stress was 7.88 times higher than those without high uncertainty stress ( OR=7.88, 95%CI =6.21-9.99). The results of interaction analysis showed that childhood abuse and uncertainty stress had no multiplication interaction but additive interaction on depressive symptoms of college students: RERI (95% CI )=12.73(3.24-22.23), AP (95% CI )=0.57(0.37-0.76), S (95% CI )=2.47(1.53-3.98). Conclusion High uncertainty stress and childhood abuse have additive interaction on depression symptoms of college students. Eliminating childhood abuse and scientific management of uncertainty stress can reduce the risk of depressive symptoms among college students.

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.

Objective:To study the influence of Mei mini maze procedure for atrial functional mitral regurgitation.Methods:The data of 33 patients with atrial fibrillation and atrial functional mitral regurgitation from January 2017 to June 2020 were retrospectively analyzed. All patients received Mei mini maze procedure for atrial fibrillation. The procedure is carried out thoracoscopically through the left thoracic approach. The ablation of atrial fibrillation includes bilateral circumferential pulmonary vein ablation, isolation of the left atrium posterior wall, left atrial appendage resection, ablation of Marshall's ligament and autonomic ganglion, etc. Follow-up was conducted by outpatient follow-up and telephone. Postoperative heart rhythm was recorded by the patient's symptoms, electrocardiogram, 24 h holter and other examinations. Postoperative mitral valve lesions were obtained by echocardiography.Results:33 patients successfully completed the operation. There was no conversion to thoracotomy and no perioperative death. Thirty patients(90.9%) maintained sinus rhythm at discharge. Before discharge, 16 patients had no mitral regurgitation in echocardiography, 8 patients had mild mitral regurgitation, and 9 patients had moderate mitral regurgitation. Follow-up was 1-4 years after discharge, with a mean of(2.6±1.1) years. Sinus rhythm was maintained in 23 patients(69.7%). 17 patients had no mitral regurgitation, 9 had mild mitral regurgitation, 6 had moderate, and 1 had severe mitral regurgitation. The degree of regurgitation in 25 patients was reduced compared with pre-operation, 5 patients remained unchanged, and 3 patients mitral regurgitation aggravated. Unreduced atrial functional mitral regurgitation was associated with recurrence of atrial fibrillation by Cox multivariate analysis.Conclusion:This study found a close relationship between atrial fibrillation rhythm and atrial functional mitral regurgitation. Most moderate atrial functional mitral regurgitation can be alleviated by effective treatment for atrial fibrillation. It is not recommended that patients with severe atrial functional mitral regurgitation only receive treatment for atrial fibrillation.

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*