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

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.

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.

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 supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Primary female urethral adenocarcinoma is rare. This paper reports a case of primary urethral mucinous adenocarcinoma complicated with signet ring cell carcinoma. The patient underwent urethral tumor resection in another hospital. Postoperative examination indicated that the tumor remained, and the tumor was completely removed after urethral tumor resection. After 11 months of follow-up, there was no tumor residue or recurrence.

Objective:To analyze the predictive factors of GGU between biopsy and radical prostatectomy pathology based on 2014 ISUP grouping system, then establish and evaluate nomogram.Methods:Patients undergoing radical prostatectomy in Shanghai Ruijin Hospital from March 2012 to March 2019 were reviewed, and the clinical and pathological information were collected. Age(68.1±7.2), body mass indes(BMI) (24.2±3.2)kg/m 2, prostate specific antigen(PSA) 11.5(6.7-20.4)ng/ml, prostate specific antigen destiny(PSAD) 0.35(0.20-0.66). Before March 2017, the number of biopsy cores were 6 to 8; After then, all patients toke 12 cores systemic biopsy. Based on 2014 ISUP grouping system, the differences between biopsy and radical prostatectomy grades were counted. The independent predictors of GGU were analyzed by univariate and multivariate logistic regression analysis, then the nomogram for predicting GGU were established and evaluated. Results:429 patients were enrolled. There were 161 (37.5%) patients in GGU group and 268 (62.5%) patients in non-GGU group. After multivariate logistic regression analysis, body mass index (BMI)>28 kg/m 2( OR=2.54, P=0.021), prostate specific antigen density (PSAD)( OR=1.65, P=0.018)and 2014 ISUP grouping sysyem ( OR=0.53, P<0.001) of biopsy specimen were independent impact factors of GGU. The predicting model was established according to BMI, PSAD and 2014 ISUP grouping system. The area under the ROC cure of the model was 0.735 (95% CI 0.681-0.789). The nomogram model was well calibrated, with the mean absolute error of 6.7%, which means the prediction of GGU is fairly consistent with the actual situation. Conclusions:Based on the 2014 ISUP grouping system, BMI>28 kg/m 2, PSAD and 2014 ISUP grouping of biopsy specimen were independent predictors of GGU. The nomogram model for predicting GGU has a good statistical significance.

Objective:To investigate the value of nomogram predictive model established by the risk factors of upper extremity venous thrombosis risk associated with peripherally venous inserted central catheter (PICC) in cancer patients.Methods:A total of 1 032 patients who underwent PICC insertion between January 2016 and March 2017 in Zhejiang Cancer Hospital were selected by using prospective cohort study and convenience sampling. Risk factors of upper extremity venous thrombosis risk associated with PICC in cancer patients were evaluated by using Cox regression model. The nomogram predictive model of upper extremity venous thrombosis risk associated with PICC insertion was constructed. Bootstrap method was used to complete the inside check, and figure calibration was used to verify the nomogram.Results:A multivariate Cox regression analysis showed that trombosis history ( HR = 27.82, 95% CI 8.17-94.88, P < 0.01) and hyperlipidemia ( HR = 3.01, 95% CI 1.31-6.93, P = 0.009) were independent risk factors for upper extremity venous thrombosis associated with PICC. The nomogram model C-index was 0.71 (95% CI 0.63-0.80) based on the above risk factors, which indicated that the nomogram had a good differentiation. The calibration curve for predicting the probability of upper extremity venous thrombosis risk associated with PICC within one week, two weeks and one month deviated slightly from the standard curve, suggesting that the model might overestimate the risk of upper extremity venous thrombosis associated with PICC in cancer patients. Conclusions:The nomogram model has a good predictive value and strong operability, which can be used to predict the probability of upper extremity venous thrombosis associated with PICC in cancer patients after PICC insertion. It can provide a reference for identifying the high-risk cancer patients and formulating proper therapeutic strategies.

Objective:To explore the incidence and risk factors of peripherally inserted central catheter (PICC) related upper extremity venous thrombosis (UEVT) in patients with head and neck neoplasm so as to provide a basis for preventing thrombosis.Methods:This study used the design of prospective cohort study. From January 2016 to March 2018, UEVT follow-up examination by B ultrasound was carried out for 1 137 head and neck neoplasm patients with PICC selected by convenience sampling. Single factor and multivariate Cox regression were used to determine the risk factors of PICC related UEVT.Results:There were 3.6% (41/1 137) of patients with PICC related UEVT. Multivariate Cox regression showed that the independent risk factors of PICC related UEVT included the older patients ( RR=1.04, 95% CI: 1.01-1.07, P=0.013) , being with a history of PICC catheterization ( RR=3.22, 95% CI: 1.53-6.77, P=0.002) and high frequency of catheter delivery ( RR=1.98, 95% CI: 1.30-3.00, P=0.001) . Conclusions:Patients with head and neck neoplasm have the low incidence of PICC related UEVT. The independent risk factors of PICC related UEVT in patients with head and neck neoplasm include the older ages, history of PICC catheterization and high frequency of catheter delivery. Positive intervention should be carried out for those patients which may reduce the incidence of PICC related thrombosis.

Objective To compare early-stage clinical features and hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine function in first-episode and untreated major depressive disorders with suicide and without suicide. Methods Untreated patients who had a diagnosis as major depression according to ICD-10 were allocated to suicide with major depressive disorder group or non-suicide with major depressive disorder group according to whether the pa?tients had suicidal ideation or behaviours. Patients were assessed before treatment using the 17-item Hamilton Depres?sion Scale (HAMD-17), the Hamilton Anxiety Scale (HAMA), the Yale-Brown Obsessive Compulsive Scale (YBOCS) and the suicide assessment scale. The cortisol (CORT) and adrenocorticotropic hormone (ACTH) levels in serum were measured using a chemiluminescence immunoassay. Results There was no significant difference in demographic data be?tween the two groups (P>0.05). In early-stage clinical features, there were significant differences in changes of sexual ac? tivity and feeling of despair (P<0.05). HAMD total scores were significantly higher in the suicide group (P<0.01), whereas HAMA total scores and Y-BOCS total scores were not significantly different between the two groups (P>0.05). There were no significant differences in CORT or ACTH levels between two groups (P>0.05). There were no significant correlation of suicidal scores with early-stage clinical features, symptom scales scores, CORT or ACTH levels (P>0.05). Conclusion De?creased sexual desire and feeling of despair are more severe in depressed patients with suicide than those without. There is no correlation of early-stage clinical features or HPA axis functions with suicide in patients with depression.