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 observe the effect of therapeutic listening on social interaction function in children with autism spectrum(ASD)disorder. Methods From January,2022 to January,2023,40 ASD children in Beijing Bo'ai Hospital were randomly divided into group A(n = 20)and group B(n = 20).Both groups received routine rehabilitation and occupational therapy,while group B received therapeutic listening as occupational therapy,for eight weeks.They were assessed with Pediatric Evaluation of Disability Inventory(PEDI),Childhood Autism Rating Scale(CARS),Autism Behavior Checklist(ABC),Peabody Developmental Motor Scales 2(PDMS-2)and Canadian Occupational Performance Measure(COPM)before and after treatment. Results All the indexes improved in both groups after treatment(|t|>3.194,P<0.01),and they were better in group A than in group B(|t|>2.122,P<0.05),except the score of ABC. Conclusion Combination of therapeutic listening is more effective on sensory processing and social interaction in ASD children.

Myocardial fibrosis （MF） is a prevalent pathological process in a spectrum of cardiac conditions， including myocardial infarction， hypertensive heart disease， and dilated cardiomyopathy. It is marked by an overabundance of extracellular matrix deposition， diminished myocardial compliance， and impaired cardiac function， which can lead to arrhythmias and sudden cardiac death. The current therapeutic approach primarily aims to suppress the progression of fibrosis， yet the therapeutic outcomes are poor. The pathogenesis of MF involves multiple signaling pathways， including the transforming growth factor-beta （TGF-β）/Smads signaling pathway， nuclear factor-kappa B （NF-κB） signaling pathway， phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， and mitogen-activated protein kinase （MAPK） signaling pathway. Traditional Chinese medicine （TCM） boasts a rich history in the treatment of cardiovascular diseases， offering distinctive benefits such as minimal side effects and high safety， and it has demonstrated promising therapeutic effects in the treatment of MF. In recent years， research has turned its attention to the application of TCM in modulating the signaling pathways associated with MF. It has been demonstrated that TCM can modulate the MF-related signaling pathways to exert anti-inflammatory effects， regulate cellular autophagy， cell proliferation， and apoptosis， reduce myocardial oxidative stress and damage， and inhibit the activation of fibroblasts and collagen synthesis， thereby exhibiting the potential to mitigate or even reverse the progression of MF. Experimental research and clinical observations indicate that TCM formulas such as Yixin Futing decoction， Luhong prescription， Zhilong Huoxue Tongyu capsules， and Kangjian Yixin prescription can effectively ameliorate MF and enhance cardiac function through the multi-component regulation of multiple cellular pathways. Specific TCM constituents， including isoliquiritigenin and astragaloside， have been shown to inhibit the expression of TGF-β₁， thereby disrupting the Smad signaling pathway. Compounds like glycyrrhizic acid and allicin can suppress the NF-κB signaling pathway and curtail collagen synthesis in myocardial cells， and forsythoside can activate the PI3K/Akt signaling pathway， contributing to its anti-fibrotic effects.

At present, the incidence and mortality of tumors are increasing, and the treatment of tumors has attracted much attention. Radiotherapy is a key method for tumor treatment; however, its effectiveness is often constrained by radioresistance. During tumor radiotherapy, DNA damage response (DDR) is a key factor in the radioresistance of tumor cells. Research has shown that the radiosensitivity of tumor cells can be effectively improved by regulating the expression of key proteins in the DDR pathway. Targeting the DDR signaling pathway has become an effective strategy to reduce tumor radioresistance. This article focuses on the mechanisms, clinical research status, limitations, and current challenges associated with the key DDR proteins DNA-PKcs, ATM, ATR, and PARP as therapeutic targets for tumor radiotherapy sensitization, in order to provide a reference for the development of radiotherapy sensitization agents.

Objective:To construct a mutant strain of hypervirulent Klebsiella pneumoniae NTHU-K2044 with hfq gene deletion and to analyze its biological characteristics. Methods:The hfq gene of NTUH-K2044 was knocked out by homologous recombination technology to construct △ hfq mutant strain. Its biological characteristics including growth rate, environmental stress tolerance, biofilm formation, capsular polysaccharide synthesis, resistance to neutrophil phagocytosis and lethality to Galleria mellonella larvae were analyzed by comparing with the wild-type strain using phenotypic experiments. Results:The △ hfq mutant strain of hypervirulent Klebsiella pneumoniae NTHU-K2044 was successfully constructed. Phenotypic experiments showed that the △ hfq mutant strain had significantly slower growth rate, smaller colonies and decreased hypermucoviscosity. Its growth was significantly inhibited under different environmental stress conditions such as pH9, pH5.5, 0.7 mmol/L SDS, 5% NaCl, 0.1% H 2O 2 and high temperature of 50℃. In terms of virulence and pathogenicity, the △ hfq mutant strain showed decreased ability to form biofilm and capsule, significantly down-regulated expression of magA and rmpA genes required for capsule synthesis, lower survival rate in the neutrophil bactericidal test and obviously reduced lethality to Galleria mellonella larvae. Conclusions:As a RNA chaperone, Hfq protein could participate in post-transcriptional regulation and play an important role in regulating the physiology, environmental adaptability and virulence of hypervirulent Klebsiella pneumoniae. This study provided reference for further study on hypervirulent Klebsiella pneumoniae.

Objective:To understand the comprehensive geriatric assessment (CGA) scores in chronic kidney disease (CKD) patients aged 65 years and older, and analyze the related influencing factors of quality of life.Methods:A total of 189 patients who were over 65 years old and diagnosed with CKD in the Department of Nephrology of Shanxi Provincial People's Hospital from October 2016 to October 2019 were included retrospectively. The patients were divided into dialysis group ( n=90 cases) and non-dialysis group ( n=99 cases) according to whether dialysis or not. The concise CGA scores included age, basic activities of daily living (BADL), instrumental activities of daily living (IADL), and modified cumulative illness rating score for geriatrics (MCIRS-G). Pearson correlation analysis was used to analyze the relationship between different scale scores and clinical indexes. Multiple linear regression analysis was used to further analyze independent related factors of the quality of life in elderly CKD patients. Results:Compared with the non-dialysis group, the BADL score and IADL score in the dialysis group were significantly reduced [(70.00±33.28) vs (93.38±14.32), t=6.166, P<0.001; (9.78±7.12) vs (15.95±5.74), t=6.520, P<0.001], while the MCIRS-G score was significantly increased [(31.13±4.00) vs (27.29±5.17), t=-5.741, P<0.001]. Linear regression analysis performed on the data of non-dialysis group patients showed that estimated glomerular filtration rate (eGFR), serum uric acid (SUA), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood potassium and chlorine were positively correlated with BADL and IADL scores (all P<0.05). B-type natriuretic peptide (BNP) was negatively correlated with BADL score ( P<0.01). BNP and age were negatively correlated with IADL score (both P<0.05). Fasting blood glucose (FBG) was positively correlated with MCIRS-G or MCIRS-G other than kidney (both P<0.05), and eGFR, SUA, total cholesterol, and HDL-C were negatively correlated with MCIRS-G or MCIRS-G other than kidney (all P<0.05). Multiple linear regression analysis showed that eGFR was an independent influencing factor for BADL ( P<0.01). Age and eGFR were independent influencing factors for IADL (both P<0.05). Conclusions:The decline of quality of life in elderly CKD patients is related with eGFR, SUA, age, BNP and HDL-C levels, and eGFR and age are independent influencing factors.

OBJECTIVETo observe the efficacy and explore the effect mechanism on visual display terminal syndrome treated withtherapy ofmedicine.

METHODSSixty-five patients of visual fatigue induced by the visual display terminal operation were treated withtrigeminy therapy ofmedicine, e.g. massage manipulation, acupuncture and cupping; acting on the specific stimulating areas inmedicine, relevant with orbit, temple, forehead, ear and Baihui (GV 20). Each treatment lasted 40 min, once every two or three days. Totally, 10 to 14 treatments were required. The scores of visual symptoms and the ocular hemodynamics before and after treatment were observed, and clinical effect were evaluated in the two groups.

RESULTSAfter treatment, the scores of visual symptoms were reduced apparently as compared with those before treatment (all<0.05). The total effective rate was 84.6% (55/65). The peak systolic velocity (PSV), the end diastolic velocity (EDV) in anterior ciliary artery (ACA) and the central retinal artery (CRA) were improved obviously, indicating the significant differences before and after treatment (all<0.05).

CONCLUSIONSThetherapy ofmedicine alleviates the visual symptoms in patients of visual fatigue and improves visual quality. The effects are related to the improvement of ocular microcirculation.

Objective: To investigate the effects of long time video display terminal (VDT) operation on the ocular vascular hemodynamic and visual acuity. Methods: During March and October 2015, 120 cases of video monitoring warriors were selected as study group, another 155 cases of logistics personnel as the control group. The low vision of the two groups was calculated and compared, and the color Doppler flow imaging was used to measure the central retinal artery (CRA) , short posterior ciliary artery (SPCA) , anterior ciliary artery (ACA) , (peak systolic velocity, PSV) , end diastolic velocity (EDV) and (resistance index (RI) . The differences of hemodynamic parameters between these two groups were evaluated, and the relationship between the visual acuity and each hemodynamic parameter was analyzed. Results: The visual acuity of the study group was[0.8 (0.4-1.2) ], much lower than the control group, and the rate of low version in the study group was 40.00%, much higher than that of the control group. Compared with the control group, both of ACA and CRA of SPCA, PSV and EDV in the study group were decreased, while RI of CRA, ACA were increased (P<0.05) ; Compared with the control group, no statistical significance was found in the RI of SPCA in the study group (P>0.05) . The PSV and EDV were negatively correlated with visual acuity (r value of PSV and visual acuity were -0.352, -0.265 and -0.304; r value of EDV and visual acuity were -0.324, -0.348 and -0.365, while RI was positively correlated with visual acuity (r value were 0.363, 0.326 and 0.344) . Conclusion Our data suggest that long time video operation may be associated with changes of ocular vascular hemodynamic parameters and raise the incidence of low vision.

Objective: To investigate the influence of long-time video operation on hemodynamics of the retrobulbar arteries in operators. Methods: From March to October, 2015, a total of 120 soldiers for office work engaged in video surveillance were enrolled as study group, and 155 fire fighters were enrolled as control group. The incidence of eye discomfort was compared between the two groups. Color Doppler ultrasound was used to measure and compare the peak systolic velocity (PSV) , end-diastolic velocity (EDV) , and resistance index (RI) of the central retinal artery (CRA) and the short posterior ciliary artery (SPCA) , and the correlation of video operation time with the hemodynamic parameters of the retrobulbar arteries was analyzed. Results: The study group had a significantly higher incidence rate of eye discomfort than the control group (P<0.05) . Compared with the control group, the study group had significant reductions in the PSV and EDV of the CRA and the SPCA and a significant increase in the RI of the CRA (P<0.05) . Video operation time was negatively correlated with the PSV and EDV of the CRA and the SPCA (r=-0.61, -0.54, -0.65, and-0.68, all P<0.05) and positively correlated with the RI of the CRA and the SPCA (r=0.56 and 0.63, P<0.05) . Conclusion Long-time video operation can increase the incidence of eye discomfort and lead to increased blood resistance of the CRA and the SPCA and reduced retinal perfusion.

Objective:To analyze the clinical outcome and feasibility for patients who underwent total parathyroidectomy without autotransplantation (TPTX) for secondary hyperparathyroidism (SHPT).Methods:From April 2012 to December 2015,220 SHPT patients underwent TPTX in the department of Breast and Thyroid Surgery of China-Japan Friendship Hospital.The clinical data and effect were assessed retrospectively.Results:All the 220 patients were on permanent dialysis with mean duration of dialysis (7.93 ± 3.75) years.A durable reduction in mean PTH,Ca and P were observed after TPTX (P＜0.01).The mean hospital stay was (7.8 ± 2.8) days.TPTX produced a rapid improvement in clinical symptoms.Incidence of hypocalcemia was 73.46％.Severe complications such as recurrent laryngeal nerve palsy or inactive dynamic osteopathia,haven't been observed postoperatively.The rate of persistent status (PTH≥300 pg/mL) was 9.1％.One (0.45％) died of infectious shock perioperatively.Conclusions:TPTX was a safe and feasible surgical procedure for patients with SHPT.It was worth of being applied.Not missing the parathyroid during operation was the key point for successful TPTX.Intensive monitoring and maintaining stable normocalcemia were the key point to reduce complication.