Methods: This study enrolled 40 patients with AIS, 20 patients with congenital scoliosis (CS), and 20 patients with spinal degenerative disease (SDD). All patients underwent open posterior surgery in our hospital, and a paravertebral muscle (multifidus muscle) biopsy was performed intraoperatively. This study included many indexes that describe muscle, especially dystrophin staining. The above pathological results were compared among the AIS, CS, and SDD groups. The correlation between the Cobb angle and Nash–Moe classification and the above pathological results was analyzed in patients with AIS. Results: Significant reductions in the dystrophin staining of dystrophin-1 (p<0.001), dystrophin-2 (p<0.001), and dystrophin-3 (p<0.001) were observed in the AIS group than in the CS and SDD groups. The higher the Nash–Moe classification in the AIS group, the more significant the loss of dystrophin-2 (p=0.042) in the convex paraspinal muscles. Additionally, a significantly positive correlation was observed between the reductions of dystrophin-2 on the concave side of the AIS group and Cobb angle (p=0.011). Conclusions Dystrophin protein deficiency in the paraspinal muscles plays a crucial role in AIS formation and progression. The severity of scoliosis in patients with AIS is correlated with the extent of dystrophin loss in the paravertebral muscles. Therefore, dystrophin dysfunction may be relevant to AIS occurrence and development.

Methods: This study enrolled 40 patients with AIS, 20 patients with congenital scoliosis (CS), and 20 patients with spinal degenerative disease (SDD). All patients underwent open posterior surgery in our hospital, and a paravertebral muscle (multifidus muscle) biopsy was performed intraoperatively. This study included many indexes that describe muscle, especially dystrophin staining. The above pathological results were compared among the AIS, CS, and SDD groups. The correlation between the Cobb angle and Nash–Moe classification and the above pathological results was analyzed in patients with AIS. Results: Significant reductions in the dystrophin staining of dystrophin-1 (p<0.001), dystrophin-2 (p<0.001), and dystrophin-3 (p<0.001) were observed in the AIS group than in the CS and SDD groups. The higher the Nash–Moe classification in the AIS group, the more significant the loss of dystrophin-2 (p=0.042) in the convex paraspinal muscles. Additionally, a significantly positive correlation was observed between the reductions of dystrophin-2 on the concave side of the AIS group and Cobb angle (p=0.011). Conclusions Dystrophin protein deficiency in the paraspinal muscles plays a crucial role in AIS formation and progression. The severity of scoliosis in patients with AIS is correlated with the extent of dystrophin loss in the paravertebral muscles. Therefore, dystrophin dysfunction may be relevant to AIS occurrence and development.

Methods: This study enrolled 40 patients with AIS, 20 patients with congenital scoliosis (CS), and 20 patients with spinal degenerative disease (SDD). All patients underwent open posterior surgery in our hospital, and a paravertebral muscle (multifidus muscle) biopsy was performed intraoperatively. This study included many indexes that describe muscle, especially dystrophin staining. The above pathological results were compared among the AIS, CS, and SDD groups. The correlation between the Cobb angle and Nash–Moe classification and the above pathological results was analyzed in patients with AIS. Results: Significant reductions in the dystrophin staining of dystrophin-1 (p<0.001), dystrophin-2 (p<0.001), and dystrophin-3 (p<0.001) were observed in the AIS group than in the CS and SDD groups. The higher the Nash–Moe classification in the AIS group, the more significant the loss of dystrophin-2 (p=0.042) in the convex paraspinal muscles. Additionally, a significantly positive correlation was observed between the reductions of dystrophin-2 on the concave side of the AIS group and Cobb angle (p=0.011). Conclusions Dystrophin protein deficiency in the paraspinal muscles plays a crucial role in AIS formation and progression. The severity of scoliosis in patients with AIS is correlated with the extent of dystrophin loss in the paravertebral muscles. Therefore, dystrophin dysfunction may be relevant to AIS occurrence and development.

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 compare the efficacy and tolerability of the novel bowel-cleansing agent TCIC-001 and the traditional polyethylene glycol (PEG) regimen for bowel preparation prior to colonoscopy. Methods Prospective inclusion of 62 patients who were scheduled to undergo colonoscopy at Zhongshan Hospital, Fudan University from July 2021 to July 2022. They were randomly divided into TCIC-001 group (n=31) and PEG group (n=31) using a random number table method. The TCIC-001 group took TCIC-001 orally, drinking water in stages, with a total liquid intake of 1 500 mL; the PEG group took PEG orally, taking it in 4 doses, with a total liquid intake of 3 000 mL. The primary endpoint indicator is the quality of intestinal hygiene evaluated by the Boston Bowel Preparation Scale (BBPS), the secondary endpoint indicators were medication adherence, medication duration, frequency of bowel movements, duration of bowel movements, and incidence of adverse events between two groups. Results No significant differences were observed in sex, age, or defecation frequency between the two groups. For efficacy, both groups achieved equivalent bowel cleanliness, with a “good preparation” rate of 93.55% and comparable BBPS score of each intestinal segment and total scores. For tolerability, the TCIC-001 group had a shorter medication duration compared to the PEG group ([48.8±25.9] min vs [82.8±28.4] min, P<0.001), a longer defecation duration ([288.6±74.0] min vs [236.5±74.3] min, P<0.001), and a lower incidence of first defecation before medication completion (9.68% vs 41.94%, P=0.004). Regarding safety, no significant differences were observed between the TCIC-001 group and the PEG group in incidences of chloride disturbances (0% vs 9.68%) and calcium disturbances (3.23% vs 6.45%), and no other adverse events. Conclusions TCIC-001 demonstrated comparable bowel-cleansing efficacy to PEG while significantly improving tolerability (reduced medication time and lower risk of premature defecation) and maintaining favorable safety.

Sex-determining region Y-related high-mobility group box 11(SOX11)was initially considered as one of the trans-acting factors supporting the differentiation of stem cells and the survival of neural precursors.However,in recent studies,it was found that SOX11 played an important role in the transcriptional regulation of the development,shaping and regeneration of neurons,and it was expected to be a target for the regeneration of injured nerves.This article reviews the physiological and pathophysiological functions of SOX11 in the central nervous system and its role in nerve regeneration.

Objective To study the splenic injuries caused by high-altitude falling and underwater explosion and the 2-dimensional ultrasound and contrast-enhanced ultrasound(CEUS)characteristics.Methods Twenty-three healthy Beagle dogs were divided into high-altitude falling group(n=13)and underwater explosion group(n=10).Free-fall high-platform device and gram-grade trinitrotoluene were used to simulate high-altitude falling injury and underwater explosion injury in Beagle dogs,respectively.Ultrasound examination of the spleen was performed immediately after injury,with follow-up examinations every hour.CEUS examination was performed in surviving dogs.Spleen specimens were taken from deceased dogs after injury to observe gross injuries.Pathological changes in tissue morphology and cell apoptosis were observed by hematoxylin-eosin(H-E)staining.Results In the high-altitude falling model,6,2,1,and 1 dogs died in the 6 m,7 m,8 m,and 9 m groups,respectively;in the underwater explosion model,1 and 4 dogs died in the buoyancy and frogman groups,respectively.Two-dimensional ultrasound examination of the high-altitude falling model showed spleen rupture(disruption of splenic parenchymal structure),perisplenic fluid accumulation,subcapsular hematoma,intrasplenic hematoma,increased splenic vein echo,and uneven splenic parenchymal echo.Two-dimensional ultrasound examination of the underwater explosion model showed increased splenic vein echo and uneven splenic parenchymal echo,which were less serious compared with the high-altitude falling model.CEUS results indicated 4 major contrast patterns in both models.The Beagle dogs with type Ⅰ(large focal contrast defect),type Ⅱ(diffuse contrast defect),or type Ⅲ(no contrast agent entry into the splenic vein)contrast patterns all had splenic rupture after injury.H-E staining results showed true splenic rupture,diffuse intrasplenic hemorrhage,splenic hematoma/ecchymosis,subcapsular hematoma/ecchymosis,and venous congestion after spleen injury,which were consistent with the 2-dimensional ultrasound findings.Conclusion High-altitude falling causes more serious spleen injuries in Beagle dogs compared with underwater explosions.Routine ultrasound performs well in diagnosing typical splenic injuries,while CEUS has advantages in evaluating atypical splenic injuries and has good predictive ability for delayed splenic rupture.

Objective To investigate the impact of total parathyroidectomy with autotransplantation (tPTx+AT)on bone mineral density and serum soluble Klotho (sKlotho)level in patients with secondary hyperparathyroidism (SHPT).Methods A total of 86 patients undergoing tPTx+AT in the Second Affiliated Hospital of Anhui Medical University from June 2019 to May 2022 were recruited in this study.Their demographic characteristics were collected before surgery,along with serum levels of corrected calcium,phosphorus,intact parathyroid hormone (iPTH),alkaline phosphatase (ALP),fibroblast growth factor 23 (FGF23),and sKlotho before and at 5 d,and 1,3,6,12 and 24 months after surgery.Dual energy X-ray absorptiometry was used to determine the BMD values of the lumbar spine L1-L4 before surgery and at 3,6,12 and 24 months after surgery.The changes in BMD and serum FGF23 and sKlotho levels before and after tPTx+AT were observed.Results Surgical treatment was successfully completed in all 86 patients,with their clinical symptoms such as bone pain and skin itching significantly improved postoperatively,and markedly decreased serum calcium,phosphorus,iPTH,ALP and FGF23 levels.The sKlotho level was significantly lower at 5 d postoperatively than that preoperatively,with that at 1 month after surgery increased by approximately 24.5％ than the preoperative level,and then the level was in a stable trend.The BMD values at the lumbar spine L1-L4 were increased postoperatively,and reached the highest levels at 12 months postoperatively.Further analyses showed that dialysis vintage,duration of SHPT,and ALP,iPTH and FGF23 levels were negatively correlated with the Z-scores of the lumbar spine L1-L4,while sKlotho level was positively correlated with the Z-scores.Conclusion tPTx+Atcan significantly improve the clinical symptoms of SHPT patients,regulate the balance of calcium and phosphorus metabolism,increase sKlotho level and reduce FGF23 level.It is an effective method to improve BMD.

Craniocerebral injury with seawater immersion is a special kind of compound injury, with low temperature, high permeability, high alkali, high salt content, and bacterial infection being the main causes. The injury is also characterized with complex damage mechanisms, difficulty to treat, and poor prognosis. At present, the damage mechanisms of craniocerebral injury with seawater immersion are mainly studied by establishing the experimental animal models at the levels of tissue, cell, organelle, molecule, etc. However, the craniocerebral injury with seawater immersion is more complex than the simple onshore craniocerebral injury, therefore, a stable disease model is not easy to construct. Most researches on the specific injury mechanisms are relatively single and one-sided, with many different views in existence, and the damage mechanisms of craniocerebral injury with seawater immersion have hitherto not been clear. The authors reviewed the research progress in the damage mechanisms of craniocerebral injury with seawater immersion, in order to promote the in-depth study of the mechanism of craniocerebral injury with seawater immersion and provide reference for its clinical treatment.