BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective:To compare the efficacy of biplanar fixation combined with bone grafting and proximal femoral nail anti-rotation (PFNA) in the treatment of critically complicated osteoporotic intertrochanteric femoral fracture .Methods:A retrospective cohort study was conducted to analyze the clinical data of 28 patients with critically complicated osteoporotic intertrochanteric femoral fracture, admitted to Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 2020 and December 2022, including 3 males and 25 females, aged 70-91 years [(79.4±6.3)years]. T score for bone mineral density was -2.5~-4.1 SD［（-3.3±0.6）SD］. All the patients were found with type A2.2-A3.3 fracture based on AO classification, and were complicated with trochanteric lateral wall fracture. Among them, 16 patients underwent biplanar fixation combined with bone grafting (biplanar fixation group), while 12 underwent PFNA internal fixation (PFNA group). All the patients received anti-osteoporosis therapy after surgery. The two groups were compared in terms of the operative time, intraoperative blood loss, hemoglobin levels at 3 days postoperatively, and time to weight-bearing. The visual analogue scale (VAS) scores and Harris hip scores at 1, 3, 6 months postoperatively, and at the last follow-up and the incidence of complications were also detected in the two groups.Results:All the patients were followed up for 12-16 months [(14.1±1.4)months]. In the biplanar fixation group, the operative time was (75.1±15.3)minutes, significantly longer than (45.6±14.2)minutes in the PFNA group ( P<0.01); the intraoperative blood loss was (234.1±11.8)ml, significantly more than (170.0±13.4)ml in the PFNA group ( P<0.01); the hemoglobin level at 3 days postoperatively was (82.6±9.3)g/L in the biplanar fixation group, higher than (64.8±6.8)g/L in the PFNA group ( P<0.01). The time to weight-bearing was (1.1±0.7)weeks in the biplanar fixation group, significantly shorter than (3.2±1.2)weeks in the PFNA group ( P<0.01). There were no statistically significant differences between the two groups in VAS scores and Harris hip scores at 1, 3, 6 months postoperatively, and at the last follow-up ( P>0.05). The VAS scores and Harris hip scores in the two groups were gradually improved with the prolongation of postoperative time ( P<0.05 or 0.01). No complications such as neurovascular injuries were observed in either group. One patient in the biplanar fixation group developed lower extremity deep vein thrombosis (DVT), with a complication rate of 6.3%, while 2 patients in the PFNA group developed lower extremity DVT and 4 hypostatic pneumonia, with a complication rate of 50.0% ( P<0.05). Conclusion:Compared with PFNA internal fixation, biplanar fixation with bone grafting has the advantages of less postoperative blood loss, earlier weight-bearing exercises and lower incidence of complications in the treatment of critically complicated osteoporotic intertrochanteric femoral fracture, despite longer operative time and more intraoperative blood loss.

BACKGROUND:Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine,which is secreted in different types of stem cells and can regulate the proliferation,differentiation and migration of various types of stem cells.Our previous research has confirmed that human embryonic stem cells secrete MIF and that its concentration in the culture medium is relatively stable.However,whether MIF is involved in the survival,proliferation and differentiation of human embryonic stem cells remains unclear. OBJECTIVE:To investigate the effects of MIF on survival,proliferation,and differentiation of human embryonic stem cells. METHODS:(1)Human embryonic stem cells H9 were cultured.The growth curve of cells was detected and plotted by CCK-8 assay.Enzyme-linked immunosorbent assay was used to determine the level of MIF in the medium.(2)To determine the effects of exogenous MIF on the survival and proliferation of human embryonic stem cells,different groups were established:the control group,which was cultured in stem cell medium without any modifications;the exogenous MIF group,which was treated with different concentrations(30,100,300 ng/mL)of MIF in the stem cell medium;the MIF inhibitor ISO-1 group,which was treated with different concentrations(2,7,21 μmol/L)of ISO-1 in the stem cell medium;and the MIF+ISO-1 group,which was treated with different concentrations of ISO-1 along with 100 ng/mL of MIF.Cell viability was assessed using the CCK-8 assay.(3)To further elucidate the effect of MIF gene on survival and proliferation of human embryonic stem cell,the MIF knockout H9 cell line was constructed by CRISPR-Cas 9 technology to observe the lineage establishment.(4)To determine the effect of high concentrations of MIF on human embryonic stem cell differentiation,100 ng/mL MIF and 100 ng/mL of CXCR4 neutralizing antibody were separately added to the normal stem cell culture medium.The expression levels of self-renewal factors(KLF4,c-MYC,NANOG,OCT4,and SOX2)and differentiation transcription factors(FOXA2,OTX2)were measured using real-time quantitative polymerase chain reaction,immunofluorescence staining,and western blot analysis. RESULTS AND CONCLUSION:(1)The logarithmic growth phase of H9 cells was between 3-6 days.Under normal growth conditions,human embryonic stem cells secreted MIF at a concentration of approximately 20 ng/mL,independent of cell quantity.(2)Compared to the control group,the addition of different concentrations of MIF had no effect on the proliferation of human embryonic stem cells(P>0.05).ISO-1 significantly inhibited the proliferation of human embryonic stem cells,with a stronger inhibition observed at higher concentrations of ISO-1(P<0.05).The addition of MIF in the presence of ISO-1 reduced the inhibitory effect of ISO-1(P<0.05).(3)Real-time quantitative polymerase chain reaction showed that knocking out 50%of the MIF gene resulted in a significant decrease in the growth vitality of human embryonic stem cells and failure to establish cell lines.(4)Adding 100 ng/mL exogenous MIF to the culture medium resulted in a decrease in the mRNA,protein,and fluorescence expression levels of the self-renewal transcription factor KLF4,while the mRNA,protein,and fluorescence expression levels of the differentiation factor FOXA2 increased.(5)When 100 ng/mL CXCR4 neutralizing antibody was added to the culture medium,the mRNA and protein expression levels of KLF4 increased,while the mRNA and protein expression levels of FOXA2 decreased,contrary to the expression trend observed in the MIF group.In conclusion,the endogenous secretion of MIF by human embryonic stem cells is essential for their survival.The addition of MIF to the culture medium does not promote the proliferation of human embryonic stem cells.However,it can lead to a decrease in the expression of the self-renewal factor KLF4 and an increase in the expression of the transcription factor FOXA2.This provides a clue for further investigation into the effects and mechanisms of MIF on the differentiation of human embryonic stem cells.The MIF-CXCR4 axis plays a regulatory role in this process.

BACKGROUND:There are still great controversies in the etiology,clinical manifestations,diagnosis and treatment of pigmented villonodular synovitis.Bibliometric and visualization studies on pigmented villonodular synovitis can clarify the research development context and point out the direction for future research.OBJECTIVE:To analyze the global research status,hotspot,and trend of pigmented villonodular synovitis.METHODS:All publications related to pigmented villonodular synovitis from 1995 to 2023 were retrieved from Web of Science and CNKI.Citespace and bibliometrics were used to analyze the clustering,co-occurrence,and emergent words of all articles.The Web of Science database adopts subject headings plus free words for retrieval,while the CNKI database retrieves through subject headings.Finally,986 English articles and 599 Chinese articles were included.RESULTS AND CONCLUSION:(1)The United States has an absolute leading position in research in this field,ranking first in the number of published papers,H index,and cited times.China ranks the 4th in the total volume of published articles and 12th in the H index.The quality of published articles and international cooperation still need to be improved.(2)Cluster analysis of pigmented villonodular synovitis studies showed that the top five clusters were radiotherapy,soft tissue sarcoma,rheumatoid arthritis,magnetic resonance imaging,and diagnosis.(3)The key words that continued to emerge until 2023 were colony-stimulating factor 1,giant cell tumor of tendon sheath,case report,chromosome translocation,radiotherapy,expression,and kinase.(4)Based on keyword analysis and co-citation analysis,it is found that the research on the clinical characteristics of pigmented villonodular synovitis,the development of new colony-stimulating factor 1 inhibitors,and the application of colony-stimulating factor 1 inhibitors in the treatment process are current research hotspots.(5)Combining thematic evolution with the analysis of current research hotspots,based on clarifying the etiology,pathogenesis,and clinical characteristics of pigmented villonodular synovitis,improving the diagnostic accuracy of pigmented villonodular synovitis,enhancing the precision of treatment,and reducing the recurrence rate after treatment will be key issues that require focus in the future.

Objective To explore the mechanism through which dexmedetomidine(Dex)alleviates doxorubicin(Adr)-induced myo-cardial injury via regulating nuclear factor κB(NF-κB)expression.Methods Sprague-Dawley rats were divided into control,Adr,and Adr+Dex groups.Theirs hearts were harvested for hematoxylin and eosin(HE)staining,immunohistochemical staining,real-time polymerase chain reaction(PCR),and Western blotting anlyses.The rat primary cardiomyocytes,breast cancer cell line MDA-MB-23,lung cancer cell line H226,gastric cancer cell line AGS,and bladder cancer cell line 5637 were cultured and divided into control,Adr,Adr+Dex,Dex,and Adr+Dex+NF-κBi groups.CCK-8 and immunofluorescence staining were performed to detect the reactive oxygen species(ROS)contents.Results The myocardial arrangement of the rats in the Adr group was disordered,myocardial cell activity was lower,the mitochondrial membrane potential was lower,ROS production was higher,and NF-κB mRNA and protein contents were sub-stantially lower than those in the control group.The cardiomyocyte morphology was improved,cell activity was higher,mitochondrial mem-brane potential was increased,ROS production decreased,and NF-κB expression significantly increased in the Adr+Dex group compared with those in the control group.The mitochondrial membrane potential in the Adr+Dex+NF-κBi group was lower,and ROS generation was increased compared with the control group.The activity of the tumor cells in the Adr group was lower,and no statistically significant diffe-rences were found compared with that in the Adr+Dex group.Conclusion Treatment with Dex may not affect the chemotherapeutic effects of Adr.Dex administration may increase the myocardial mitochondrial membrane potential and reduce ROS generation by regu-lating NF-κB levels,thereby reducing Adr-induced myocardial damage.

BACKGROUND:There are still great controversies in the etiology,clinical manifestations,diagnosis and treatment of pigmented villonodular synovitis.Bibliometric and visualization studies on pigmented villonodular synovitis can clarify the research development context and point out the direction for future research.OBJECTIVE:To analyze the global research status,hotspot,and trend of pigmented villonodular synovitis.METHODS:All publications related to pigmented villonodular synovitis from 1995 to 2023 were retrieved from Web of Science and CNKI.Citespace and bibliometrics were used to analyze the clustering,co-occurrence,and emergent words of all articles.The Web of Science database adopts subject headings plus free words for retrieval,while the CNKI database retrieves through subject headings.Finally,986 English articles and 599 Chinese articles were included.RESULTS AND CONCLUSION:(1)The United States has an absolute leading position in research in this field,ranking first in the number of published papers,H index,and cited times.China ranks the 4th in the total volume of published articles and 12th in the H index.The quality of published articles and international cooperation still need to be improved.(2)Cluster analysis of pigmented villonodular synovitis studies showed that the top five clusters were radiotherapy,soft tissue sarcoma,rheumatoid arthritis,magnetic resonance imaging,and diagnosis.(3)The key words that continued to emerge until 2023 were colony-stimulating factor 1,giant cell tumor of tendon sheath,case report,chromosome translocation,radiotherapy,expression,and kinase.(4)Based on keyword analysis and co-citation analysis,it is found that the research on the clinical characteristics of pigmented villonodular synovitis,the development of new colony-stimulating factor 1 inhibitors,and the application of colony-stimulating factor 1 inhibitors in the treatment process are current research hotspots.(5)Combining thematic evolution with the analysis of current research hotspots,based on clarifying the etiology,pathogenesis,and clinical characteristics of pigmented villonodular synovitis,improving the diagnostic accuracy of pigmented villonodular synovitis,enhancing the precision of treatment,and reducing the recurrence rate after treatment will be key issues that require focus in the future.

Objective To explore the mechanism through which dexmedetomidine(Dex)alleviates doxorubicin(Adr)-induced myo-cardial injury via regulating nuclear factor κB(NF-κB)expression.Methods Sprague-Dawley rats were divided into control,Adr,and Adr+Dex groups.Theirs hearts were harvested for hematoxylin and eosin(HE)staining,immunohistochemical staining,real-time polymerase chain reaction(PCR),and Western blotting anlyses.The rat primary cardiomyocytes,breast cancer cell line MDA-MB-23,lung cancer cell line H226,gastric cancer cell line AGS,and bladder cancer cell line 5637 were cultured and divided into control,Adr,Adr+Dex,Dex,and Adr+Dex+NF-κBi groups.CCK-8 and immunofluorescence staining were performed to detect the reactive oxygen species(ROS)contents.Results The myocardial arrangement of the rats in the Adr group was disordered,myocardial cell activity was lower,the mitochondrial membrane potential was lower,ROS production was higher,and NF-κB mRNA and protein contents were sub-stantially lower than those in the control group.The cardiomyocyte morphology was improved,cell activity was higher,mitochondrial mem-brane potential was increased,ROS production decreased,and NF-κB expression significantly increased in the Adr+Dex group compared with those in the control group.The mitochondrial membrane potential in the Adr+Dex+NF-κBi group was lower,and ROS generation was increased compared with the control group.The activity of the tumor cells in the Adr group was lower,and no statistically significant diffe-rences were found compared with that in the Adr+Dex group.Conclusion Treatment with Dex may not affect the chemotherapeutic effects of Adr.Dex administration may increase the myocardial mitochondrial membrane potential and reduce ROS generation by regu-lating NF-κB levels,thereby reducing Adr-induced myocardial damage.

Objective:To compare the efficacy of biplanar fixation combined with bone grafting and proximal femoral nail anti-rotation (PFNA) in the treatment of critically complicated osteoporotic intertrochanteric femoral fracture .Methods:A retrospective cohort study was conducted to analyze the clinical data of 28 patients with critically complicated osteoporotic intertrochanteric femoral fracture, admitted to Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 2020 and December 2022, including 3 males and 25 females, aged 70-91 years [(79.4±6.3)years]. T score for bone mineral density was -2.5~-4.1 SD［（-3.3±0.6）SD］. All the patients were found with type A2.2-A3.3 fracture based on AO classification, and were complicated with trochanteric lateral wall fracture. Among them, 16 patients underwent biplanar fixation combined with bone grafting (biplanar fixation group), while 12 underwent PFNA internal fixation (PFNA group). All the patients received anti-osteoporosis therapy after surgery. The two groups were compared in terms of the operative time, intraoperative blood loss, hemoglobin levels at 3 days postoperatively, and time to weight-bearing. The visual analogue scale (VAS) scores and Harris hip scores at 1, 3, 6 months postoperatively, and at the last follow-up and the incidence of complications were also detected in the two groups.Results:All the patients were followed up for 12-16 months [(14.1±1.4)months]. In the biplanar fixation group, the operative time was (75.1±15.3)minutes, significantly longer than (45.6±14.2)minutes in the PFNA group ( P<0.01); the intraoperative blood loss was (234.1±11.8)ml, significantly more than (170.0±13.4)ml in the PFNA group ( P<0.01); the hemoglobin level at 3 days postoperatively was (82.6±9.3)g/L in the biplanar fixation group, higher than (64.8±6.8)g/L in the PFNA group ( P<0.01). The time to weight-bearing was (1.1±0.7)weeks in the biplanar fixation group, significantly shorter than (3.2±1.2)weeks in the PFNA group ( P<0.01). There were no statistically significant differences between the two groups in VAS scores and Harris hip scores at 1, 3, 6 months postoperatively, and at the last follow-up ( P>0.05). The VAS scores and Harris hip scores in the two groups were gradually improved with the prolongation of postoperative time ( P<0.05 or 0.01). No complications such as neurovascular injuries were observed in either group. One patient in the biplanar fixation group developed lower extremity deep vein thrombosis (DVT), with a complication rate of 6.3%, while 2 patients in the PFNA group developed lower extremity DVT and 4 hypostatic pneumonia, with a complication rate of 50.0% ( P<0.05). Conclusion:Compared with PFNA internal fixation, biplanar fixation with bone grafting has the advantages of less postoperative blood loss, earlier weight-bearing exercises and lower incidence of complications in the treatment of critically complicated osteoporotic intertrochanteric femoral fracture, despite longer operative time and more intraoperative blood loss.