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.

To construct a single-cell transcriptomic map of testicular tissue under hypobaric hypoxia exposure and perform diversity analysis of supportive cells, aiming to provide new insights into the mechanisms of reproductive toxicity for future research.

This paper discusses the treatment of polycystic ovary syndrome(PCOS)based on the midnight-noon ebb-flow theory.The midnight-noon ebb-flow theory is a Chinese medicine science that combines the time and space of nature with the internal rhythm of the human body.PCOS is characterized by disappearance of the reproductive monthly rhythm.Its etiology is based on kidney deficiency.The key to its pathogenesis is the excess of yin and deficiency of yang,the hyperactivity of yang and deficiency of yin,and the lack of smooth connection between yin and yang.PCOS patients have circadian rhythm disorders,and the oscillation of the core clock gene is attenuated,which leads to the interruption of the circadian rhythm gene in the ovary,the imbalance of yin and yang trans-formation in the kidney,and the asynchrony of qi and blood flow with the time rhythm.Therefore,the treatment focuses on harmonizing yin and yang and rebuilding the normal reproductive rhythm of women.Using the midnight-noon ebb-flow theory,combined with the reproductive physiological characteristics of women,choosing different drug administration time and selecting meridians and acupoints according to the time will be helpful to unlock the"time code"of the female reproductive system,and assist clinical menstruation regu-lation,pregnancy and treatment of diseases.

Objective:To evaluate the safety and efficiency of robotic visualization system(RVS)-assisted microsurgical re-construction of the reproductive tract in male rats and the satisfaction of the surgeons.Methods:We randomly divided 8 adult male SD rats into an experimental and a control group,the former treated by RVS-assisted microsurgical vasoepididymostomy(VE)or vaso-vasostomy(VV),and the latter by VE or VV under the standard operating microscope(SOM).We compared the operation time,me-chanical patency and anastomosis leakage immediately after surgery,and the surgeons'satisfaction between the two groups.Results:No statistically significant difference was observed the operation time between the experimental and the control groups,and no anasto-mosis leakage occurred after VV in either group.The rate of mechanical patency immediately after surgery was 100％in both groups,and that of anastomosis leakage after VE was 16.7％in the experimental group and 14.3％in the control.Compared with the control group,the experimental group achieved dramatically higher scores on visual comfort(3.00±0.76 vs 4.00±0.53,P＜0.05),neck/back comfort(2.75±1.16 vs 4.38±1.06,P＜0.01)and man-machine interaction(3.88±1.55 va 4.88±0.35,P＜0.05).There were no statistically significant differences in the scores on image definition and operating room suitability between the two groups.Conclusion:RVS can be used in microsurgical reconstruction of the reproductive tract in male rats and,with its advantages over SOM in ergonomic design and image definition,has a potential application value in male reproductive system micosurgery.

AIM To explore the mechanism of Dabugan Decoction's action on a rat model of generalized anxiety disorder(GAD).METHODS The rat models established by 21 days exposure to chronic unpredictable mild stress(CUMS)were then randomly divided into the model group,the paroxetine group(1.8 mg/kg)and the high-dose,medium-dose and low-dose Dabugan Decoction groups(13.2,6.6 and 3.3 g/kg),in contrast to the other normal rats assigned into the blank group,for the following 28 days administration of the corresponding drugs by gavage.After the intervention,the rats had their anxiety intensity analyzed by behavioral tests;their hippocampal pathological changes and Nissl's body differences observed by HE staining and Nissl staining;their cerebral ROS activity detected by immunofluorescence;their hippocampal activities of SOD and CAT,and levels of MDA and GSH detected by kit;and their hippocampal mRNA and protein expressions of Nrf2,Keap1,HO-1,NQO1,BDNF,5-HT1A,caspase-3 and GSH detected by RT-qPCR and Western blot.RESULTS Compared with the model group,the Dabugan Decoction groups displayed improved anxiety responses;increased movement distance at the open arm end and total distance as well,more entries and duration at the open box,more time and entries at the open field center in elevated plus maze(P＜0.05,P＜0.01);increased number of hippocampal neurons,ameliorated cell body damage,increased Nissl bodies in cells,decreased hippocampal ROS activity and MDA level(P＜0.05,P＜0.01);increased activities of SOD and CAT,and GSH level(P＜0.05,P＜0.01);increased hippocampal mRNA and protein expressions of Nrf2,HO-1,NQO1,BDNF and 5-HT1A(P＜0.05,P＜0.01),and decreased mRNA and protein expressions of p62,Keap1 and caspase-3(P＜0.05,P＜0.01).CONCLUSION Dabugan Decoction can effectively improve the anxiety of GAD rats,and its mechanism may be related to the recovery of oxidative stress-induced injury in hippocampal neurons via ROS/Nrf2/HO-1 signaling pathway.

Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To develop an artificial intelligence (AI) quality control model of fetal heart in the first trimester and verify its effectiveness.Methods:A total of 18 694 images of the four-chamber view(4CV) and three-vessel and tracheal view(3VT) of fetal heart in the first trimester were selected from Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University since January 2022 to December 2022. A total of 14 432 images were manually annotated. The one-stage target detection algorithm YOLO V5 was used to train the AI quality control model in the first trimester of fetal heart, and 4 262 images (golden standard set by expert group) were used to evaluate the application effectiveness of AI quality control model. Kappa consistency test was used to compare the results of section classification and standard degree judgment from AI quality control model, Doctor 1(D1) and Doctor 2(D2).Results:①Precision of the AI quality control model was 0.895, recall was 0.852, mean average precision (mAP 50) was 0.873.The average precision(AP) of the AI quality control model for section classification was 0.907 (4CV) and 0.989 (3VT), respectively. ②Compared with the gold standard, the overall coincidence rate and consistency of section classification of AI quality control model, D1 and D2 were 99.91% (Kappa=0.998), 100% (Kappa=1.000), 100% (Kappa=1.000), respectively. The coincidence rate and consistency of the plane standard degree evaluation from the AI quality control model, D1 and D2 were 97.46% (Weighted Kappa=0.932), 93.73% (Weighted Kappa=0.847), and 93.12% (Weighted Kappa=0.832), respectively. Strong consistency was displayed. Moreover, AI quality control model showed the highest coincidence rate and the strongest consistency in judging section standard degree, which was superior to manual quality control. The time-consuming of AI quality control (0.012 s/sheet) was significantly less than the way of manual quality control (4.76-6.11 s/sheet)( Z=-8.079, P<0.001). Conclusions:The use of artificial intelligent fetal heart quality control model in the first trimester can effectively and accurately control the image quality.

Objective:To evaluate the immunogenicity of a novel influenza virus mRNA vaccine based on conserved antigens delivered by lipopolyplex (LPP) platform in a mouse model.Methods:Four copies of genes coding for extracellular domain of matrix 2 protein (M2e) and nucleoprotein (NP) of influenza A virus were synthetized after codon optimization. The fusion antigens were transcribed in vitro and delivered by LPP platform, named as LPP-4M2eNP. Expression of M2e and NP in eukaryotic cells was detected by immunofluorescence assay (IFA). BALB/c mice were inoculated intramuscularly twice with 10 μg or 30 μg LPP-4M2eNP vaccine at an interval of four weeks. Antibody response was detected by ELISA and cellular-mediated immunity (CMI) was detected by enzyme-linked immunospot assay (ELISPOT). Results:IFA showed that NP and M2e were expressed correctly in eukaryotic cells. Single dose immunization could induce significant antigen (NP, M2e)-specific CMI and antigen (NP, M2e)-specific antibody response was induced in mice with Th1 type bias after boost immunization. Moreover, NP-specific CMI was increased significantly after the second immunization, while no significant change in M2e-specific CMI was observed.Conclusions:Stronger CMI was triggered in mice by single dose of LPP-4M2eNP vaccine. Furthermore, robust humoral and cellular immune responses were induced after boost immunization. This study suggested that LPP-4M2eNP vaccine, which based on conserved antigen of influenza A and delivered by LPP platform, had great potential for development and application.

Objective: To explore the feasibility and short-term effect of tensor tympani muscle Tenotomy in the treatment of Meniere's disease under otoscope. The possible pathogenesis was discussed and our views were put forward. Methods: The clinical data of 9 cases of Meniere's disease treated by otoscopic Tenotomy were analyzed retrospectively, including 2 males, 7 females, 5 right ones, 2 left ones and 2 bilateral ones. The average age was (56.33± 10.56) years, ranging from 38 to 75 years. We evaluated intraoperative findings and short-term postoperative efficacy, respectively evaluated postoperative aural fullness, tinnitus and hearing recovery, and evaluated postoperative vertigo attack in a short time. Results: Nine patients were completed the operation under general anaesthesia and otoscopy, and no serious complications occurred. We found new pathological changes in tympanic cavity in some cases during operation. There were rupture of round window membrane in 1 case, severe fibrous hyperplasia near the round window membrane and vestibular window and adhesion with ossicular chain in 1 case, fibrous cord and membranous hyperplasia near vestibular window and round window membrane in 1 case, fibrous hyperplasia and adhesion near the round window membrane in 2 cases, membranous hyperplasia and adhesion around vestibular window in 1 case. No fibrous hyperplasia was found in 3 cases in the tympanic cavity. The round window membrane can be exposed in 4 cases and failed in 5 cases. After 3 months of follow-up, we found that we found that 5/5 cases of aural fullness disappeared, 2/2 cases of earache disappeared, 3/8 cases of tinnitus improved, 5/8 cases presented with improvement and no aggravation, 3/3 cases of hearing allergy improved, 4/9 cases of hearing improved, and 5/9 cases showed no improvement or decrease. 9 patients were followed up for 3 months, of whom 8 patients had no vertigo, one patient suffered from vertigo twice within 3 months after operation, and the patient suffered from rupture of round window membrane. Conclusions: Endoscopic Tenotomy for Meniere's disease has obvious curative effect and quick recovery after operation. During the operation, we find that most of Meniere's patients have fibrous cord hyperplasia near the inner ear window membrane, which may be the pathological manifestation after repeated rupture and repair of the inner ear window membrane. The vertigo of Meniere's disease may be related to the destruction and repair of inner ear membrane structure caused by improper contraction or spasm of tympanic tensor muscle.
Aged ; Female ; Humans ; Hyperplasia/pathology* ; Male ; Meniere Disease/surgery* ; Middle Aged ; Otoscopes/adverse effects* ; Retrospective Studies ; Tenotomy/adverse effects* ; Tensor Tympani/surgery* ; Tinnitus/complications* ; Vertigo/etiology*