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.

Objective To investigate the effect of Gouteng Jiangya Jieyu Perscription(Uncariae Ramulus cum Uncis,Gastrodiae Rhizoma,Pheretima,Puerariae Lobatae Radix,etc.)modulating the TLR4/NF-кB signaling pathway on the polarization of hippocampal microglia in rats with hypertension complicated with depression(HD)Methods Forty primary hypertensive rats were randomly divided into five groups:the model group,the positive drug group,and the high-,medium-,and low-dose groups of Gouteng Jiangya Jieyu Perscription,with 8 rats in each group;and another 8 SD rats were taken as the control group.The HD model was replicated using 42 days of continuous chronic unpredictable mild stress(CUMS)combined with solitary rearing.The modeling was accompanied by the administration of drugs,including 29.61,14.81,and 7.40 g·kg-1 of Gouteng Jiangya Jieyu Perscription in the high-,medium-,and low-dose groups of Chinese herbal medicine,respectively,and 0.45 mg·kg-1 of Levamlodipine Besylate+1.8 mg·kg-1 of Fluoxetine in the positive group;the volume of the gavage was 10 mL·kg-1,once a day,for 42 consecutive days.The systolic blood pressure of rat tail artery was measured by non-invasive sphygmomanometer before drug administration and in the morning of the last day of each week;the behavioural test of Sucrose Preference Test(SPT)was carried out once in the second week and once in the last week after the start of the modelling;the water maze experiment was carried out after the end of the modelling;the levels of serum inflammatory factor tumor necrosis factor-α(TNF-α),interleukin(IL)1β and IL-10 were determined by ELISA;the pathological changes of rat hippocampal tissue neurons were observed by HE staining and Nissl stain were used to observe the neuronal pathological changes in rat hippocampal tissue;immunofluorescence double staining was used to detect the expressions of microglia M1(CD16)and M2(CD206)types in the hippocampal region;and Western Blot was used to detect the protein expressions of TLR4 and NF-кB p65 in the hippocampal tissue.Results Compared with the control group,the systolic blood pressure in the tail artery of rats in the model group from week 1 to week 6 were all significantly increased(P＜0.01);sucrose preference rate was significantly decreased(P＜0.01);evasion latency was significantly prolonged(P＜0.05,P＜0.01),the number of times of traversing the plateau and the percentage of time spent in the target quadrant were significantly decreased(P＜0.01);the contents of serum TNF-α and IL-1β were significantly increased(P＜0.01),IL-10 content was significantly decreased(P＜0.01);cytosolic nuclei were deeply stained,cytoplasmic solidification and apoptosis were obvious;the fluorescence intensity ratio of CD206/CD16 in hippocampal microglial cells were significantly decreased(P＜0.05);the protein expressions of TLR4 and NF-кB p65 in hippocampal tissues were significantly up-regulated(P＜0.01).Compared with the model group,the systolic blood pressure in the tail artery of rats in the first to sixth weeks of the drug administration group were all significantly reduced(P＜0.01);the sucrose preference rates were all significantly increased(P＜0.05);the contents of serum TNF-α and IL-1β were significantly decreased(P＜0.01),and the content of IL-10 was significantly increased(P＜0.01);the Nissl substances are abundant and apoptosis is significantly reduced,and apoptosis were significantly reduced.The escape latency of rats in the positive drug group and the high-dose group of Gouteng Jiangya Jieyu Perscription was significantly shortened(P＜0.05,P＜0.01),and the number of times of crossing the plateau and the percentage of time spent in the target quadrant were significantly increased(P＜0.05);the ratio of fluorescence intensity of hippocampal microglial cells,CD206/CD16 was significantly increased(P＜0.05,P＜0.01);and the hippocampal tissues,protein expressions of TLR4 and NF-κB p65 were significantly down-regulated(P＜0.05,P＜0.01).Conclusion Gouteng Jiangya Jieyu Perscription may regulate the polarisation state of hippocampal microglial cells,modulate the secretion of inflammatory factors,and attenuate the damage of hippocampal neurons in HD rats by inhibiting the TLR4/NF-кB pathway.

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.

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.