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

ObjectiveTo investigate the effects of thyme herbal tea （BLX） on the proliferation of human coronavirus OC43 （HCoV-OC43） in vitro and in vivo. MethodThe chemical composition of BLX was analyzed by UPLC-MS. The cytotoxicity of BLX in HRT-18 cells and the effect of BLX treatment on the proliferation of HCoV-OC43 in cells were analyzed. Copies of viral gene were detected by real-time PCR. The effect of BLX treatment on the life cycle of HCoV-OC43 was detected by time-of-addition assay. The maximum tolerated dose of BLX and the influences of BLX on the body weight and survival time of suckling mice infected with HCoV-OC43 were determined. The expression of viral protein in the brain and lung tissue was analyzed by immunohistochemistry. ResultThere were 11 chemical components identified in BLX by UPLC-MS. BLX showed the 50% cytotoxic concentration （CC₅₀） of （13 859.56±319） mg·L^-1， the median inhibitory concentration （IC₅₀） of （1 439.09±200） mg·L^-1， and the selection index of 8.26-11.44 for HCoV-OC43 in HRT-18 cells. Compared with the cells infected with HCoV-OC43， BLX at the concentrations of 1 500， 1 000， 500 mg·L^-1 inhibited the proliferation of this virus （P<0.05， P<0.01）. BLX exhibited antiviral effect in the early stage of virus infection， and the inhibition role in the attachment stage was more significant than that in the entry stage （P<0.05）. In the suckling mice infected with HCoV-OC43， BLX at 1200 and 600 mg·kg^-1·d^-1 alleviated the symptoms， prolonged the survival period， reduced the death rate， and down-regulated the mRNA level of nucleocapsid protein in the mice. Moreover， BLX at 1 200 mg·kg^-1·d^-1 down-regulated the expression of nucleocapsid protein in the brain （P<0.01） and the lung （P<0.01）. ConclusionBLX contained multiple antiviral ingredients. It inhibited the proliferation of HCoV-OC43 both in vitro and in vivo by interference with viral attachment. This study provides theoretical reference for the treatment of acute respiratory tract infection with HCoV-OC43 and for further development and application of BLX.

ObjectiveTo analyze and construct a curriculum framework and content system of the vocational college rehabilitation therapy technology exercise therapy technology course, based on World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF) and rehabilitation competency framework (RCF). MethodsUsing educational psychology and curriculum theory, and applying the ICF and RCF, the curriculum system for rehabilitation therapy technology curriculum system was constructed. A systematic analysis of the existing exercise therapy technology course content was conducted to identify the core elements related to ICF and RCF. Through the design of course modules, these core elements were integrated into theoretical courses, skills training and practical courses to form a comprehensive curriculum structure. ResultsCombining the ICF and RCF, a curriculum system for rehabilitation therapy technology curriculum system was constructed, covering theoretical courses, skills training and practical courses. This system enabled students to systematically master rehabilitation assessment and treatment techniques and develop clinical decision-making abilities and interdisciplinary collaboration skills. The introduction of the ICF framework allowed students to acquire knowledge, skills and abilities in the field of exercise therapy technology through the course. Developing competency-oriented courses based on RCF framework helped students develop comprehensive professional competencies through learning. ConclusionBy integrating the ICF and RCF, a curriculum for exercise therapy technology course in vocational colleges has been constructed. Based on the ICF framework, the content of the course has been aligned with the bio-psycho-social theory of functioning and health, covering three levels: body function, activity and participation, and environmental factors. The curriculum content should include the analysis, assessment and intervention of these functioning. RCF provides a theoretical structure and methodology for developing competency-oriented courses. When designing the course modules, teaching objectives have been established based on the core competency framework, aiming to develop students' comprehensive professional competence and professionalism through theoretical courses, practical training and clinical internships.

Objective:To analyze long-term prognosis and influencing factors of recurrence in vocal fold leukoplakia treated by endoscopic cordectomy with CO 2 laser. Methods:A retrospective review was conducted on 599 patients with vocal fold leukoplakia [566 males and 33 females, aged 17-84 years (median age 55 years)], undergoing endoscopic cordectomy by CO 2 laser under general anesthesia at the Department of Otorhinolaryngology Head and Neck Surgery of Beijing Tongren Hospital, Capital Medical University, from January 2000 to December 2023. The study analyzed the clinical features, pathological grade, surgical methods, postoperative voice function, recurrence, malignant changes and analyzed the long-term efficacy and and its influencing factors. The patients were followed up for a duration of 6-249 months postoperatively, with a median follow-up time of 48 months. SPSS 20.0 software was used for statistical analysis. Results:Among the 599 patients, the histopathological grades included simple squamous cell hyperplasia in ( n=264, 44.08%), mild dysplasia ( n=96, 16.03%), moderate dysplasia ( n=74, 12.35%), severe dysplasia( n=43, 7.81%), carcinoma in situ( n=35, 5.84%), and carcinoma in situ with microinvasion( n=87, 14.52%). The 3-year and 5-year overall recurrence rates were 12.91% and 16.00%, respectively. In patients with precancerous lesion, 3.91% of recurrences presented with an upgraded pathologic grade and 2.34% evolved into carcinoma. The risk of recurrence was higher in lesions involving the anterior commissure, larger lesions, significant reduction/absence of mucosal waves, neovascularization/suspected neovascularization, and pathology of dysplasia/carcinoma in situ/carcinoma in situ with microinvasion( F=44.76,21.54,11.55,8.78,23.20,respectively, P<0.05). Additionally, patients with recurrent disease exhibited higher reflux symptom index scores compared to those without recurrence. Exophytic lesion characteristics and the inability to cease smoking postoperatively were identified as independent risk factors for recurrence with an upgraded pathological grade, with odds ratios of 8.675 and 11.380 times greater than those with non-exophytic lesions and successful smoking cessation, respectively. At the 6-months postoperative assessment, patients who underwent subepithelial cordectomy (typeⅠ) demonstrated a statistically significant increase in fundamental frequency ( t=-3.38, P<0.05), and while other voice acoustic parameters were not significantly different.Conversely, those who underwent transmuscular cordectomy (TypeⅢ) exhibited significant alterations in multiple voice acoustic parameters when compared to preoperative values ( P<0.05). Furthermore, postoperative vocal fold adhesions developed in 84 patients with 13 of these individuals requiring surgical intervention for adhesion release. Conclusions:Lesions involving the anterior commissure, larger lesions, pathology of dysplasia/carcinoma in situ/carcinoma in situ with microinfiltration, significant reduction/absence of vocal fold mucosal waves, and neovascularization visible under NBI are indicative of an increased risk of recurrence, whereas exophytic lesions and the inability to cease smoking postoperatively significantly increase the risk of recurrence with elevated pathologic grade. Recovery of postoperative voice quality is procedure-dependent, underscoring the importance of surgical approach selection in the management of vocal fold leukoplakia.

Objective:To compare the clinical efficacy between robot-assisted and free-hand percutaneous cannulated screwing (PCS) in the treatment of femoral neck fractures in the middle-aged and young patients.Methods:A retrospective study was conducted to analyze the clinical data of 53 patients with femoral neck fracture who had been treated with PCS from May 2020 to May 2022 at Department of Traumatic Surgery, Maoming Hospital Affiliated to Southern Medical University. In the robot group of 25 patients subjected to robot-assisted PCS, there were 11 males and 14 females with an age of (48.2 ± 11.9) years; in the free-hand group of 28 patients subjected to free-hand PCS, there were 13 males and 15 females with an age of (48.5 ± 9.8) years. The 2 groups were compared in terms of operation time, intraoperative bleeding, intraoperative guide drills, intraoperative fluoroscopy frequency, fracture union time, Harris hip score at the last follow-up and postoperative complications. Postoperative imaging examination was performed to evaluate distribution accuracy of the cannulated screws in the femoral neck (deviation between the screws and the femoral neck axis, parallelism between the screws and distance between the screws and the neck cortex).Results:There was no statistically significant difference between the robot and free-hand groups in the general clinical data before operation, showing comparability ( P>0.05). The robot group showed significantly shorter operation time [(32.7 ± 4.8) min], significantly less intraoperative bleeding [(14.6 ± 4.8) mL], significantly less intraoperative guide drillings [(3.5 ± 0.7) times] and significantly less intraoperative fluoroscopy frequency [(7.9 ± 1.4) times] than the free-hand group [(56.9 ± 11.3) min, (27.0 ± 7.3) mL, (9.1 ± 1.8) times and (16.3 ± 6.0) times)] (all P<0.05). Postoperative imaging showed that the deviation between the screws and the femoral neck axis was 4.4° ± 1.1° on the anteroposterior X-ray film and 3.2° ± 0.8° on the lateral X-ray film, the parallelism between the screws 4.9° ± 0.8° on the anteroposterior X-ray film and 3.0° ± 0.7° on the lateral X-ray film, and the distance between the screws and the femoral neck cortex (10.4 ± 2.7) mm in the robot group, all significantly smaller than those in the free-hand group [10.5° ± 2.8°, 4.9° ± 1.1°, 12.1° ± 4.0°, 5.1° ± 1.3°, and (15.4 ± 3.2) mm] (all P<0.05). All the 53 patients were followed up for (22.2 ± 8.5) months. All fractures got united. The fracture union time in the robot group [(20.6 ± 4.6) weeks] was insignificantly shorter than that in the free-hand group [(23.7 ± 7.7) weeks] ( P>0.05). At the last follow-up, the Harris hip score in the robot group [(88.6 ± 5.6) points] was significantly higher than that in the free-hand group [(84.8 ± 6.3) points] ( P<0.05). Follow-ups revealed 2 cases of internal fixation loosening, 1 case of screw head cutting and 1 case of femoral head necrosis in the free-hand group but none of such complications in the robot group. Conclusion:In the treatment of femoral neck fractures in the middle-aged and young patients, compared with free-hand PCS, robot-assisted PCS shows advantages of shorter intraoperative time, less bleeding, less fluoroscopic radiation, higher accuracy of screw placement, a lower incidence of postoperative complications and better functional recovery of the hip joint.

Objective:To explore the surgical techniques and outcomes of closed reduction for geriatric subtrochanteric femoral fractures with certain radiological characteristics.Methods:A retrospective analysis was conducted in the 38 aged patients with subtrochanteric femoral fracture who had been treated at Department of Geriatric Orthopedics, Guangdong Provincial Hospital of Chinese Medicine from January 2015 to December 2019. There were 24 females and 14 males, aged from 62 to 95 years (average, 80.9 years). According to the Seinsheimer classification, there were one case of type ⅡB, 7 cases of type ⅡC, 18 cases of type ⅢA, 9 cases of type Ⅳ, and 3 cases of type Ⅴ. The time from injury to operation averaged 2.3 days (from 0.5 to 8.0 days). The fractures of this cohort were characterized by: ①The starting point of the medial fracture line was at the proximal end and the lesser trochanter separated. ②The fracture end was shortened and overlapped on the medial side and angled outward, showing a varus deformity. ③The alignment returned to normal after traction, with only partial lateral displacement left. Before fixation with proximal femoral nail antirotation (PFNA), all these patients were treated by closed reduction in a supine traction bed. In those whose reduction was unsatisfactory, a main nail was inserted or after the main nail was inserted reduction by leverage was performed through the screw blade incision. Intraoperatively, the quality of fracture reduction was evaluated according to the modified Baumgaertner assessment. Recorded were the patients’ operation time, intraoperative blood loss, fracture healing time, hip function and complications.Results:All the fractures achieved 100% of good to excellent reduction (38/38). The operation time ranged from 25 to 120 min (average, 55.6 min) and the intraoperative blood loss from 10 to 150 mL (average, 42.9 mL). This cohort of 38 patients was followed for 10 to 20 months (average, 15.3 months). All the fractures united after 3 to 8 months (average, 4.8 months). The Harris hip scores at the last follow-up ranged from 70 to 94 (average, 81.5). The follow-ups revealed no such complications as internal fixation failure, fracture re-displacement, malunion or nonunion.Conclusion:Closed reduction and PFNA fixation in a supine traction bed can lead to satisfactory clinical effects for the subtrochanteric femoral fractures with certain radiological characteristics in the aged patients.

Objective:To investigate the effect of indocyanine green angiography (ICGA) in the design of pre-expanded perforator flaps in the reconstruction of large defects.Methods:From October 2018 to October 2019, there were 22 patients undergoing facial and cervical reconstructive surgeries based on pre-expanded perforator flaps in the back region in Shanghai Ninth Peoples′ Hospital. 12 male and 10 female patients, ranging from 4 to 26 years old with an average age of 19, were all suffered from inferior facial and cervical defects after burns. Single-pedicled or multi-pedicled perforator flaps from back region were designed for treatment. ICGA was conducted after flap dissection intra-operatively to evaluate perfusion areas of perforators, which helped surgeons to determine whether supercharging should be conducted. After flap transplantation, ICGA was conducted again to evaluate the blood supply. Statistics of post-operative complications such as flap necrosis were collected.Results:the average flap size was 27 cm ×17 cm. With the guidance of ICGA, 15 cases remained the design of single pedicle including 5 superficial cervical artery (SCA) flaps and 10 free circumflex scapular artery (CSA) perforator flaps. Supercharging was performed in 7 cases: including 2 SCA flaps supercharged with CSA perforator and 5 free CSA perforator flaps supercharged with thoracodorsal artery (TDA) perforator. Venous thrombus occurred in 1 case but recovered after re-anastomosis of vessels. Except for 2 tip necroses, 20 flaps survived completely one week postoperatively. 2 tip necroses were recovered after dressing changes. All the patients were followed up for 5 to 16 months, with good flap color and texture, and improved function of head and neck.Conclusions:ICGA can be used as a safe and effective intraoperative detection method to guide the selection of appropriate perforators and the decisions on whether to conduct supercharging, which optimizes flap design and improves the success of surgery.

Introduction: At 11:20 on 26 May 2018, a physician from Lianyungang No. 1 People’s Hospital, China, reported that six family members were being treated in the hospital with symptoms from an unknown cause. Methods: A case series for a food poisoning investigation and an environmental survey were conducted. The patients and their relatives were interviewed in person with a questionnaire contained on a digital tablet, and an investigation of the patients’ home was conducted in the presence of police officers. Probable case and confirmed case were defined to serve as a basis for identifying additional cases. Confirmed cases were defined as those probable cases in which blood, stool or vomitus specimens tested positive for paliperidone palmitate and/or its metabolites. A descriptive analysis was performed. Follow-up by telephone was conducted four months later. Results: There were six probable cases. The median age was 35 years (range: 5–76 years). The attack rate was 100% (n = 6/6) of persons who consumed a family dinner, and the hospitalization rate was also 100% (n = 6/6). The median period between exposure and symptom onset was two hours. The main symptoms included vomiting, nausea, drowsiness, dizziness and severe abdominal pain for adults, and vomiting and severe lethargy for children. An 8-year-old girl further showed changes in the ST segment of her electrocardiogram, and a 5-year-old boy showed QT prolongation. The poisoning substance was suspected to be paliperidone palmitate based on the patients’ symptoms and epidemiological findings. Discussion: We investigated the household food poisoning outbreak through epidemiological analysis and an environmental investigation and determined that it was caused by paliperidone palmitate. The source of the paliperidone palmitate was found to be aluminium containers, taken home by the eldest son who worked at a pharmaceutical company. The containers were sent to a drug disposal centre, and the pharmaceutical company was required to enhance the regulation on the pharmaceutical waste materials to prevent drug poisoning events. By the end of September 2018, the six patients recovered and were released from the hospital, and they did not show any clinical sequelae in four follow-up visits.

Sequencing technology has been greatly improved in terms of throughput and cost. The single-molecule nanopore DNA sequencing, one of the major branches of the third-generation sequencing technology, has made great contributions in the fields of medicine and life sciences due to its advantages of ultra-long reading length, real-time detection and direct detection of base methylation modification, etc. This article briefly describes the principle of nanopore sequencing technology, and discusses its application in clinical, animal, plant, bacterial and virus fields and its future development direction.
Animals ; Base Sequence ; DNA ; chemistry ; genetics ; Humans ; Nanopore Sequencing ; trends ; Nanopores ; Research ; trends ; Sequence Analysis, DNA ; trends

Objective:To investigate the effect of indocyanine green angiography (ICGA) in the design of pre-expanded perforator flaps in the reconstruction of large defects.Methods:From October 2018 to October 2019, there were 22 patients undergoing facial and cervical reconstructive surgeries based on pre-expanded perforator flaps in the back region in Shanghai Ninth Peoples′ Hospital. 12 male and 10 female patients, ranging from 4 to 26 years old with an average age of 19, were all suffered from inferior facial and cervical defects after burns. Single-pedicled or multi-pedicled perforator flaps from back region were designed for treatment. ICGA was conducted after flap dissection intra-operatively to evaluate perfusion areas of perforators, which helped surgeons to determine whether supercharging should be conducted. After flap transplantation, ICGA was conducted again to evaluate the blood supply. Statistics of post-operative complications such as flap necrosis were collected.Results:the average flap size was 27 cm ×17 cm. With the guidance of ICGA, 15 cases remained the design of single pedicle including 5 superficial cervical artery (SCA) flaps and 10 free circumflex scapular artery (CSA) perforator flaps. Supercharging was performed in 7 cases: including 2 SCA flaps supercharged with CSA perforator and 5 free CSA perforator flaps supercharged with thoracodorsal artery (TDA) perforator. Venous thrombus occurred in 1 case but recovered after re-anastomosis of vessels. Except for 2 tip necroses, 20 flaps survived completely one week postoperatively. 2 tip necroses were recovered after dressing changes. All the patients were followed up for 5 to 16 months, with good flap color and texture, and improved function of head and neck.Conclusions:ICGA can be used as a safe and effective intraoperative detection method to guide the selection of appropriate perforators and the decisions on whether to conduct supercharging, which optimizes flap design and improves the success of surgery.