BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Five previously undescribed diterpenoids, named succipenoids D‒H (1‒5), along with four undescribed lignans, named succignans A‒D (6‒9), were isolated from the dichloromethane extract of Chinese medicinal succinum. Compounds 1‒5 were characterized as nor-abietane diterpenoids, while compounds 6‒9 were identified as lignans polymerized from two groups of phenylpropanoid units. The structures of these novel compounds, including their absolute configurations, were determined through spectroscopic and computational methods. Biological assessments of renal fibrosis demonstrated that compounds 6 and 7 effectively reduce the expression of proteins associated with renal fibrosis, including α-smooth muscle actin (α-SMA), collagen I, and fibronectin in transforming growth factor-β1 (TGF-β1) induced normal rat kidney proximal tubular epithelial cells (NRK-52e).
Animals ; Rats ; Lignans/isolation & purification* ; Diterpenes/isolation & purification* ; Fibrosis/drug therapy* ; Drugs, Chinese Herbal/pharmacology* ; Molecular Structure ; Cell Line ; Kidney Diseases/pathology* ; Transforming Growth Factor beta1/genetics* ; Kidney/metabolism* ; Actins/genetics* ; Fibronectins/genetics* ; Collagen Type I/genetics* ; Epithelial Cells/metabolism*

Objective:To investigate the trend of radiological diagnostic examination frequency and the related influencing factors in a general hospital in recent four years.Methods:The hospital information system and the radiology information system were used to collect the information on the numbers of the outpatients, the emergency patients, and the inpatients and the radiology examination information from 2019 to 2022. The examination frequency and proportion of various imaging equipment were counted by using the perspective table of data, and the examination items and the proportion of the radiological diagnostic examinations were calculated. The positive rates of the radiological examinations were measured from 2019 to 2022. The gender and age distribution of the patients were analyzed. Spearman correlation analysis was used to analyze the relationships between the numbers of the patients undergoing radiological examinations and the numbers of the outpatients, emergency patients and the inpatients.Results:The annual frequency of radiological diagnostic examinations from 2019 to 2022 were 307 306, 245 418, 317 250 and 325 625, respectively, with a total of 1 195 599. Among them, the proportions of CT, X-rays, bedside X-rays, bone density, gastrointestinal imaging and mammography were 59.74%, 38.04%, 1.39%, 0.42%, 0.21% and 0.19%, respectively. In each year, the proportion of CT in all radiological diagnostic examinations was 49.58%, 63.40%, 60.40% and 65.20%, respectively. The frequency of emergency CT and emergency chest CT was correlated with the number of emergency patients( r =0.63, 0.61, P<0.05), and the frequency of non-emergency CT was correlated with the number of outpatients and inpatients ( r =0.61, 0.66, P<0.05). The positive rates of the CT examinations were higher than 80% except the lowest of 79.95% in 2021. Conclusions:Radiological examinations especially CT examinations have increased significantly, and played an important role in the diagnosis of diseases. However, attention should be paid to the Justification of the CT examinations. Timely statistical analysis of radiological examination information can provide data supports and references for scientific management of radiological examinations.

Objective:This study aimed to evaluate the immunoprotective effect of anti-rabies virus cocktail monoclonal antibody Zamerovimab/Mazorelvimab after rabies exposure.Methods:The dynamic data of rabies virus neutralizing antibody (RVNA) were analyzed in the Zamerovimab/Mazorelvimab Chinese phase Ⅲ study (clinical trial registration number: CTR20201819).Results:The full analysis set showed that RVNA geometric mean titers (GMT) on the 4 th, 8 th, 15 th, 43 rd, and 99 th day in the Zamerovimab/Mazorelvimab group were 4.413 IU/ml, 5.178 IU/ml, 17.062 IU/ml, 14.672 IU/ml, and 2.836 IU/ml, respectively, while those in the human rabies immunoglobulin (HRIG) group were 0.299 IU/ml, 0.451 IU/ml, 11.374 IU/ml, 18.063 IU/ml, and 6.769 IU/ml, respectively. The positive rates of RVNA on the 4 th, 8 th, 15 th, 43 rd, and 99 th day in the Zamerovimab/Mazorelvimab group were 99.9%, 99.6%, 100%, 100%, and 97.4%, respectively, while those in the HRIG group were 23.3%, 34.1%, 97.6%, 99.6%, and 98.4%, respectively. Conclusions:Compared with HRIG, Zamerovimab/Mazorelvimab cocktail monoclonal antibody reached the required protection level of RVNA very soon, thus effectively provided an immediate neutralizing effect of passive immunization therapies against rabies virus.

Objective To employ the mesh meta analysis to compare the effectiveness and safety of short-term reaching-standard treatment in the patients with moderate to severe atopic dermatitis among the different biologics.Methods The randomized controlled trials (RCT) were retrieved from the databases of CNKI,Chinese Biomedical Literature Database,Wanfang,VIP,PubMed,Cochrane Library and Embase data-bases.The retrieval time was from the database establishment to August,2023.The related literatures on the biologics for treating moderate to severe atopic dermatitis were collected.The literatures were screened by the inclusion and exclusion standards,the literature quality was evaluated and the data were extracted.Then the mesh meta analysis was performed by using RevMan 5.3 and Stata 16.0 softwares.Results A total of 754 ar-ticles were retrieved,and 11 articles were finally included,involving in 14 RCT with a total sample number of 5528 cases.There were 4 intervention methods,including placebo and 3 kinds of drugs.The drugs were Dupi-lumab,Lebrikizumab and Tralokinumab.The results showed that for each of effectiveness indicator,different medication regimens had different performance,after comprehensively meeting the treatment criteria,Dupri-uliumab was superior to Lebrikizumab,and Lebrikizumab was superior to Tralokinumab.There was no statis-tical difference in adverse reactions between the three drugs and placebo (P>0.05).Conclusion Dupilumab is currently the most effective biologic agent for short-term target treatment,capable of reducing inflamma-tion and improving skin symptoms.Future studies should further evaluate its long-term efficacy and safety to guide clinical application.

OBJECTIVE To investigate the feasibility of ultra-high resolution CT(U-HRCT)in demonstrating and evaluating ethmoidal foramen in the medial wall of the orbit.METHODS Nine cadavers(18 side orbits)fixed in 10%buffered formalin were enrolled and underwent U-HRCT and multislice helical CT(MSCT).Subjective and objective evaluations of image quality were performed by two experienced radiologists independently.Anterior,middle,and posterior ethmoidal foramen(AEF,MEF,and PEF)were recorded and the distance among them was measured.RESULTS The results of subjective and objective evaluations were not significant differences between evaluators and consistency was strong.CNR of U-HRCT and MSCT were 43.09±8.87 and 11.04±0.66 and SNR were 2.13±1.45 and 0.55±0.13,respectively.CNR and SNR of U-HRCT were significantly higher than MSCT(P<0.05).Objective scores of the U-HRCT and MSCT groups were 10.00 points(9.00 points,10.00 points)and 6.00 points(5.75 points,7.00 points).Objective scores of the U-HRCT were higher than MSCT(P<0.05).All eighteen AEF were shown by U-HRCT and MSCT.Among 18 PEF showed by U-HRCT,17 of them demonstrated by MSCT,and no significant difference was found in the display rate between groups(P>0.05).Nine MEF(7 single hole and 2 double holes)were found by U-HRCT,but only 2 of them were shown by MSCT.The MEF display rate of U-HRCT was higher than MSCT(P<0.05).The distance from MEF to AEF,from MEF to PEF,and from AEF to PEF were(9.43±1.13)mm,(4.75±1.09)mm,(14.18±1.14)mm,respectively.CONCLUSION U-HRCT is better to evaluate ethmoidal foramen than MSCT.It could be used to show the number and position of ethmoidal foramen before surgery to avoid complications.

Objective:To explore and compare the impacts of different scanning protocols on image quality and radiation dose in chest computed tomography (CT) scans.Methods:A retrospective analysis was conducted for the data of 65 randomly selected patients who underwent chest CT scans using a tube voltage of 120 kV, the automatic modulation technique for tube current, and z-axis radiation dose modulation at the Emergency Department of our hospital from June to July 2023. The enrolled cases were divided into two groups: the high-resolution group ( n = 34) and the conventional group ( n = 31), with the settings for scanning protocols identical to those for phantom scans. For patients in both groups, thin-layer images of the cross-sections in the lung and mediastinal windows were reconstructed using thickness/intervals of 1 mm/1 mm and 2 mm/1 mm, respectively. Meanwhile, high-resolution and conventional CT scans were conducted using a Catphan500 phantom under a tube voltage of 120 kV and a tube current of 150 mAs. Of both scanning protocols, the high-resolution CT scan utilized the lung nodule-orientated scanning mode, pitch of 1.5, and a detector combination providing a collimation of 16 × 0.75 mm. In contrast, the conventional CT scan was performed using the body-orientated scanning mode, pitch of 0.813, and a detector combination providing a collimation of 16 × 1.5 mm. Then, the high-contrast resolutions of the phantom images obtained using the two scanning protocols were objectively evaluated. Both coronal chest images in the lung window and cross-sectional images in the mediastinal window were reconstructed with a thickness/interval of 5 mm/5 mm for both groups. Then, the obtained images were imported into the Radimetrics system to compare the body size-specific dose estimation (SSDE), doses to sensitive organs on the body surface, and scanning time of both groups. For the cross-sectional images in the mediastinal window, the contrast-noise-ratio (CNR), signal-to-noise ratio (SNR), and figure-of-merit (FOM) were measured and calculated at the fixed anatomical parts. For the cross-sectional images in the lung window, their quality was subjectively evaluated by two senior diagnostic radiologists. Results:The result of phantom scans indicated that high-resolution CT scans yielded images with an approximately 5% increase in the spatial resolution in the xy-plane and a nearly 20% increase in the spatial resolution along the z-axis compared to conventional CT scans. The result of clinical data demonstrated that the conventional group exhibited significantly higher doses to the thyroid and the female breast ( t = 2.8, 2.3, P < 0.05), along with notably elevated SNR, CNR, and FOM values of the right trapezius, compared to the high-resolution group ( t = 4.1, 5.8, z=4.4, P < 0.001). However, the high-resolution group manifested significantly higher SNR, CNR, and FOM values of the thoracic aorta compared to the conventional group ( t = 3.4, 4.4, z=3.4, P < 0.001). In addition, the cross-sectional and coronal images in the lung window of the clinical cases in the high-resolution group exhibited more stable quality, with subjective scores exceeding 4 and the average scores of both groups not statistically significantly different. Conclusions:For chest CT examination, high-resolution CT scans are more suitable for observations focusing on the details of the lungs and mediastinum, while conventional CT is more suitable for those centering on soft tissues on the body surface.