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

Under the Healthy China strategy, the training of preventive medicine professionals should conform to the development of the times and the needs of public health. The article analyzed the problem of "disconnection between medical care and prevention" in teaching the course of Obstetrics and Gynecology for students majoring in preventive medicine, and proposed to strengthen the strategy of "integration of medical care and prevention". Guided by the concepts of "Comprehensive Health", with the cornerstone of cultivating morality and talents, the reform focused on enhancing the post competency of preventive medicine talents. Course content was optimized by reinforcing prevention-focused elements, student-centered teaching method innovation was advocated, and simulation-based training teaching system was established. Moreover, projects integrating science and education were used to improve faculty teaching capacity with tiered and diversified approaches. Course assessment methods were revised and "ideological and political education" was incorporated to establish the education concept of "emphasis on prevention and integration of medical care and prevention". The survey showed that these reform measures effectively improved the comprehensive clinical literacy of preventive medicine students in obstetrics and gynecology, which is of great significance for building a "integration of medical care and prevention" public health talent training model. In the future, the long-term effectiveness of course reform will be ensured from the perspectives of teaching resources, personnel investment, and policy support.

Traumatic brain injury(TBI)is mostly caused by motor vehicle traffic accidents or competitive sports,with high mortality and disability.TBI mainly includes primary injury and secondary injury.Primary injuries were caused directly by external forces.Secondary injuries include brain edema,excitotoxic effect of neuron cells,oxidative stress and neuroinflammation,etc.Effective intervention of secondary injury not only helps to improve the prognosis of patients with TBI,but also reduces the risk of Parkinson's disease and other neurodegenerative diseases related to TBI.Autophagy is one of approaches to regulate homeostasis in cells,and autophagy dysfunction has been found in several neurodegenerative diseases and TBI.It is speculated that autophagy dysfunction may play an important role in TBI and explain why patients with TBI have higher risk of neurodegenerative disease.Discovering the role of autophagy in the pathological mechanism of TBI may provide new targets for TBI clinical treatment and cognitive impairment prevention in patients with TBI.

OBJECTIVE To estimate the cost-effectiveness of penpulimab combined with chemotherapy versus chemotherapy alone in first-line treatment of advanced squamous non-small-cell lung cancer （sq-NSCLC）. METHODS From the perspective of Chinese health system， cost-utility analysis was used to evaluate the cost-effectiveness of penpulimab combined with chemotherapy （paclitaxel + carboplatin） versus chemotherapy （paclitaxel + carboplatin） in first-line treatment of sq-NSCLC. A three-health states Markov model was constructed with R packages， and clinical data used in the model were derived from the AK105-302 clinical trial. Costs and utilities were collected from the open-access database and published literature. The quality-adjusted life-years （QALY） was used as the utility index， and the willingness-to-pay （WTP） threshold was set at three times China’s per capita GDP in 2024， equivalent to 287 247 yuan/QALY. The cost-effectiveness of the schemes was evaluated by comparing the incremental cost- utility ratios （ICER） of the two schemes with the WTP threshold. One-way sensitivity analysis and probabilistic sensitivity analysis （PSA） were used to verify the stability of the basic analysis results. RESULTS Compared with chemotherapy， penpulimab combined with chemotherapy increased 0.73 QALY with an incremental cost of 150 681.93 yuan， and the ICER was 206 413.60 yuan/QALY. One-way sensitivity analysis showed that the utility of progression-free survival was the most sensitive factor on ICERs. At the WTP threshold of 3 times China’s per capita GDP， the economic probability of this scheme was 98.80%. At the WTP threshold of 1 times China’s per capita GDP， the probability of ICER being cost-effective was less than 0.01%. CONCLUSIONS For patients with advanced sq-NSCLC， penpulimab combined with chemotherapy is a cost-effective first-line treatment option when WTP threshold is 3 times China’s per capita GDP.

Objective To investigate the clinical effect of hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligature and suspension in the treatment of mixed hemorrhoids with annular prolapse.Methods A retrospective analysis was conducted to select 80 patients with annular prolapse mixed hemorrhoids admitted to the anorectal Department of our hospital from January 2022 to April 2023.According to different treatment plans,they were divided into control group(n=40 cases)who received external stripping and internal ligation combined with tape ligation,and study group(n=40 cases)who received hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligation and suspension.The operative effect,operative status,postoperative anal pain,anal edema,stool blood score and quality of life were evaluated.Results The effective rate of the study group was 97.50％,which was higher than that of the control group(77.50％)(P＜0.05).The operation time,intraoperative blood loss,hospital stay and wound healing time of the research group were(25.03±10.00)minutes,(10.00±5.32)ml,(7.25±1.54)days and(12.21±2.00)days respectively.[is better than that of control group(29.85±14.00)minutes,ml(17.85±10.25),(11.87±2.35),(18.89±4.85)days],two groups of comparison,the difference was statistically significant(P＜0.05).The VAS scores of anal pain in the study group on 1 day,3 days and 7 days after the operation were(4.25±0.85)points,(2.89±0.54)points and(2.00±0.30)points,respectively.The scores of perianal edema were(1.87±0.36)points,(1.41±0.30)points,and(1.00±0.20)points,respectively.The hematochezia scores were(1.85±0.21)points,(1.34±0.18)points,and(0.85±0.13)points,respectively.Which were better than that of control group[(7.56±1.10),(6.54±1.03),(4.87±1.00)][(2.40±0.58),(2.03±0.49),(1.87±0.45)][(2.45±0.55),(2.03±0.47),(1.88±0.25)],and the differences were statistically significant(P＜0.05).The recurrence rate was 2.50％in the study group and 17.50％in the control group(P＜0.05).The scores of SF,MH,PF and GH of the Modified Health Survey Summary Form(SF-36)in the study group were(88.54±10.22,87.87±10.58,88.97±10.00,89.95±10.05)higher than those of the control group(67.52±10.00,70.10±11.25,71.10±9.85,70.00±10.00)(P＜0.05).Conclusion Hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligature and suspension in the treatment of patients with annular prolapse mixed hemorrhoids has ideal surgical effect and little trauma,which is beneficial to promoting postoperative rehabilitation,alleviating anal pain,improving anal edema and hematostoecium,and improving quality of life.

Objective To construct a prediction model for the progression of knee osteoarthritis(KOA)based on ultrasound score,magnetic resonance imaging(MRI)score,and serum levels of transforming growth factor-β1(TGF-β1)and cathepsin D(Cat D).Methods Clinical data from 270 patients with KOA in Hengshui People's hospital from December 2022 to June 2024 were retrospec-tively analyzed.The patients were randomly divided into a modeling set(n=189)and validation set(n=81)at a ratio of 7∶3.The patients in the modeling set were categorized into mild-to-moderate and severe groups based on the degree of disease progression.Mul-tivariate logistic regression analysis was used to identify factors influencing KOA progression,and a prediction model was constructed using R software.Results Multivariate logistic regression analysis showed that body mass index,knee injury history,ultrasound score,WORMS score,TGF-β1,and Cat D were significant predictors of KOA progression(P＜0.05).A nomogram-based prediction model was developed using these variables.The areas under the curve(AUC)of the nomograms for predicting disease progression in the modeling and validation sets were 0.889 and 0.860,respectively.The calibration curves showed that the predicted probability was in good agreement with the actual probability.Conclusion The prediction model developed in this study is effective in identifying patients at high-risk of KOA progression and may servce as a valuable tool for clinical assessment and decision making.

Objective To investigate the clinical effect of hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligature and suspension in the treatment of mixed hemorrhoids with annular prolapse.Methods A retrospective analysis was conducted to select 80 patients with annular prolapse mixed hemorrhoids admitted to the anorectal Department of our hospital from January 2022 to April 2023.According to different treatment plans,they were divided into control group(n=40 cases)who received external stripping and internal ligation combined with tape ligation,and study group(n=40 cases)who received hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligation and suspension.The operative effect,operative status,postoperative anal pain,anal edema,stool blood score and quality of life were evaluated.Results The effective rate of the study group was 97.50％,which was higher than that of the control group(77.50％)(P＜0.05).The operation time,intraoperative blood loss,hospital stay and wound healing time of the research group were(25.03±10.00)minutes,(10.00±5.32)ml,(7.25±1.54)days and(12.21±2.00)days respectively.[is better than that of control group(29.85±14.00)minutes,ml(17.85±10.25),(11.87±2.35),(18.89±4.85)days],two groups of comparison,the difference was statistically significant(P＜0.05).The VAS scores of anal pain in the study group on 1 day,3 days and 7 days after the operation were(4.25±0.85)points,(2.89±0.54)points and(2.00±0.30)points,respectively.The scores of perianal edema were(1.87±0.36)points,(1.41±0.30)points,and(1.00±0.20)points,respectively.The hematochezia scores were(1.85±0.21)points,(1.34±0.18)points,and(0.85±0.13)points,respectively.Which were better than that of control group[(7.56±1.10),(6.54±1.03),(4.87±1.00)][(2.40±0.58),(2.03±0.49),(1.87±0.45)][(2.45±0.55),(2.03±0.47),(1.88±0.25)],and the differences were statistically significant(P＜0.05).The recurrence rate was 2.50％in the study group and 17.50％in the control group(P＜0.05).The scores of SF,MH,PF and GH of the Modified Health Survey Summary Form(SF-36)in the study group were(88.54±10.22,87.87±10.58,88.97±10.00,89.95±10.05)higher than those of the control group(67.52±10.00,70.10±11.25,71.10±9.85,70.00±10.00)(P＜0.05).Conclusion Hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligature and suspension in the treatment of patients with annular prolapse mixed hemorrhoids has ideal surgical effect and little trauma,which is beneficial to promoting postoperative rehabilitation,alleviating anal pain,improving anal edema and hematostoecium,and improving quality of life.

Objective To construct a prediction model for the progression of knee osteoarthritis(KOA)based on ultrasound score,magnetic resonance imaging(MRI)score,and serum levels of transforming growth factor-β1(TGF-β1)and cathepsin D(Cat D).Methods Clinical data from 270 patients with KOA in Hengshui People's hospital from December 2022 to June 2024 were retrospec-tively analyzed.The patients were randomly divided into a modeling set(n=189)and validation set(n=81)at a ratio of 7∶3.The patients in the modeling set were categorized into mild-to-moderate and severe groups based on the degree of disease progression.Mul-tivariate logistic regression analysis was used to identify factors influencing KOA progression,and a prediction model was constructed using R software.Results Multivariate logistic regression analysis showed that body mass index,knee injury history,ultrasound score,WORMS score,TGF-β1,and Cat D were significant predictors of KOA progression(P＜0.05).A nomogram-based prediction model was developed using these variables.The areas under the curve(AUC)of the nomograms for predicting disease progression in the modeling and validation sets were 0.889 and 0.860,respectively.The calibration curves showed that the predicted probability was in good agreement with the actual probability.Conclusion The prediction model developed in this study is effective in identifying patients at high-risk of KOA progression and may servce as a valuable tool for clinical assessment and decision making.

Under the Healthy China strategy, the training of preventive medicine professionals should conform to the development of the times and the needs of public health. The article analyzed the problem of "disconnection between medical care and prevention" in teaching the course of Obstetrics and Gynecology for students majoring in preventive medicine, and proposed to strengthen the strategy of "integration of medical care and prevention". Guided by the concepts of "Comprehensive Health", with the cornerstone of cultivating morality and talents, the reform focused on enhancing the post competency of preventive medicine talents. Course content was optimized by reinforcing prevention-focused elements, student-centered teaching method innovation was advocated, and simulation-based training teaching system was established. Moreover, projects integrating science and education were used to improve faculty teaching capacity with tiered and diversified approaches. Course assessment methods were revised and "ideological and political education" was incorporated to establish the education concept of "emphasis on prevention and integration of medical care and prevention". The survey showed that these reform measures effectively improved the comprehensive clinical literacy of preventive medicine students in obstetrics and gynecology, which is of great significance for building a "integration of medical care and prevention" public health talent training model. In the future, the long-term effectiveness of course reform will be ensured from the perspectives of teaching resources, personnel investment, and policy support.