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 explore the safety and long-term efficacy of transvaginal reconstructive pelvic surgery (TVRPS) in ≥70-year-old women with severe pelvic organ prolapse (POP).Methods:A single-center, prospective cohort study was conducted on 343 elderly women patients with severe POP who received TVRPS at the Fourth Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA from March 2007 to September 2024. There were 297 cases (86.6%, 297/343) of Ⅲ degree and 46 cases (13.4%, 46/343) of Ⅳ degree prolapse respectively. Among them, anterior pelvic prolapse accounted for 80.8% (277/343), and those with prolapse in two or more sites accounted for 30.0% (103/343). The age was (74.2±3.4) years (range: 70 to 89 years old). There were 300 cases (87.5%, 300/343) with more than one internal medicine disease. Preoperative general conditions were assessed using American Society of Anesthesiologists physical status classification system (ASA) and American College of Surgeons National Surgical Quality Improvement Program-frailty index (ACS NSQIP-FI). TVRPS surgeries included transvaginal hysterectomy, salpingooophorectomy, high uterosacral ligament suspension, sacrospinous ligament fixation, native tissue and mesh repair of the anterior and posterior vaginal walls, mid-urethral sling for anti-urinary incontinence, and levator anal muscle folding suture and perineal repair. Perioperative complications were evaluated using Clavien-Dindo classification system. The objective effect of TVRPS was determined based on pelvic organ prolapse quantification system (POP-Q), and the subjective results were evaluated using pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire-short form 7 (PFIQ-7) and patient global impression of improvement (PGI-I).Results:All patients had a preoperative ASA grade of ≤gradeⅡ, and ACS NSQIP-FI score of ≤0.27. All patients safely and successfully underwent all TVRPS surgeries. The operation time was (154.2±43.2) minutes. The perioperative morbidity and mortality rate were 0.6% (2/343) and 0 (0/343) respectively. None of the patient needed blood transfusion. The follow-up time was (7.5±4.3) years, with the longest being 17 years. Thirty-four cases (9.9%, 34/343) were lost to follow-up, and 22 cases (6.4%, 22/343) died of internal diseases during the follow-up period. The point values of Aa, Ba, C, Ap and Bp in the POP-Q system were significantly decreased after the operation (all P<0.01), the genital hiatus was significantly shortened (all P<0.01), and the perineal body was significantly elongated (all P<0.01). The scores of PFDI-20 and PFIQ-7 were significantly lower than those before the operation (all P<0.01). There were 332 cases (96.8%, 332/343) with an overall symptom impression improvement score of PGI-I≤2. Conclusion:The results on 343 elderly women with severe POP aged an average of 74.2 years show that for elderly POP patients who still have the desire to preserve the vagina and do not meet the conditions for colpocleisis, as long as there is a comprehensive understanding and strict evaluation of the overall condition before the operation, TVRPS is a safe, feasible and long-lasting therapeutic procedure.

Objective:To observe the clinical efficacy of azithromycin for the treatment of Mycoplasma pneumoniae pneumonia(MPP)with gene mutations at site A2063G of 23S rRNA in children.Methods:Data were retrospectively collected for 242 children diagnosed with MPP at Sichuan Provincial Maternity and Child Health Care Hospital from January to December 2023,in whom MPP was detected using targeted next-generation sequencing(tNGS).According to the presence or absence of mutations,the children were classified into mutation group(88 cases)and non-mutation group(154 cases).Results:Gene mutations at site A2063G of 23S rRNA were detected in 88 patients.The chest X-rays of both groups showed more lesions in the right lung than in the left lung.Both groups were treated with azithromycin and compared for differences in age,sex,duration of fever,C-reactive protein level,time to improvement of chest X-rays,days of medication,and response rate,with no significant differences found in the above indicators(P>0.05).However,the duration of respiratory symptoms was significantly longer in the mutation group than in the non-mutation group[(11.51±3.31)d vs.(10.06±3.63)d,P<0.05].Conclusion:Azithromycin is effective in treating MPP with gene mutations at site A2063G of 23S rRNA.

OBJECTIVE To study the anatomic characteristics of the anterior ethmoidal canal(AEC)based on 0.1 mm ultra-high resolution CT.METHODS Nine cadavers(18 side orbits)fixed in 10%buffered formalin were enrolled and underwent U-HRCT and MSCT.Divided AEC into horizontal,superior oblique,and inferior oblique segments and observed the displaying rate of each section.Subjective evaluation of display situation was performed by two experienced radiologists independently.The diameter of each AEC segment was measured.RESULTS No significant difference was found in the display rate of the horizontal and superior oblique segments between U-HRCT and MSCT groups(P>0.05),the display rate of inferior oblique segment of U-HRCT group was significantly higher than MSCT group(P<0.05).There was no significant difference in the objective evaluation results between two evaluators and consistency was strong.Subjective scores of each segment of AEC in U-HRCT group were 10.00 points(9.75 points,10.00 points),2.00 points(2.00 points,3.00 points)and 8.00 points(6.00 points,10.00 points),in MSCT group were7.00 points(5.75 points,8.00 points),2.00 points(2.00 points,2.00 points)and 2.00 points(2.00 points,4.00 points).Subjective scores of horizontal and inferior oblique segments of AEC in U-HRCT were higher than MSCT(P<0.05).The anteroposterior diameter of the horizontal section of AEC is(0.92±0.12)mm,the axial diameter is(1.04±0.22)mm.The anteroposterior diameter of the inferior oblique segment is(0.47±0.08)mm,and the transverse diameter is(0.50±0.06)mm.The anteroposterior diameter of the superior oblique segments is(0.66±0.11)mm,and the transverse diameter is(0.72±0.20)mm.CONCLUSION U-HRCT is better to evaluate AEC than MSCT.It could be used to help to study the anatomic characteristics of AEC before surgery to avoid complications.

Animal quarantine is essential for controlling the spread of animal diseases,ensuring the healthy development of the livestock industry,and safeguarding public health and food safety.This paper reviews and organizes the development history,achievements,and current dilemmas of China's animal quarantine.It proposes further policy reflections and suggestions from the aspects of man-agement concepts,system design,and specific implementation to adapt to the requirements of the new era.

Animal quarantine is essential for controlling the spread of animal diseases,ensuring the healthy development of the livestock industry,and safeguarding public health and food safety.This paper reviews and organizes the development history,achievements,and current dilemmas of China's animal quarantine.It proposes further policy reflections and suggestions from the aspects of man-agement concepts,system design,and specific implementation to adapt to the requirements of the new era.