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.

Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Targeted protein degradation via nanoparticle-based universal strategy modifies nanoparticles with antibodies and ingeniously utilizes its cellular transport characteristics. This strategy achieved targeted degradation of extracellular proteins without complex design.Image 1.

OBJECTIVE: To explore the preventive effect of transcutaneous phrenic nerve stimulation on ventilator-induced diaphragmatic dysfunction (VIDD) in patients requiring invasive mechanical ventilation. METHODS: A randomized controlled trial was conducted. The patients requiring invasive mechanical ventilation admitted to the intensive care unit (ICU) of Jiaxing First Hospital from November 2022 to December 2023 were enrolled. Participants were randomized into the control group and the observation group using a random number table. The control group was given ICU standardized nursing intervention, including turning over and slapping the back, raising the head of the bed, sputum aspiration on demand, aerosol inhalation, oral care, and monitoring of airbag pressure and gastric retention, the observation group was given additional transcutaneous phrenic nerve stimulation intervention on the basis of ICU standardized nursing intervention. The stimulation intensity was set to 10 U, the pulse frequency was set to 40 Hz, and the stimulation frequency was set to 12 times/min. Transcutaneous phrenic nerve stimulation was administered once a day for 30 minutes each time, for a total of 5 days. Diaphragm thickening fraction (DTF) and arterial blood gas parameters on days 1, 3, and 5 of intervention were compared between the two groups. After 5 days of intervention, other parameters including the incidence of VIDD, duration of mechanical ventilation, and length of ICU stay were compared. RESULTS: A total of 120 patients requiring invasive mechanical ventilation were enrolled, with 16 dropouts (dropout rate was 13.33%). Ultimately, 51 patients in the control group and 53 patients in the observation group were analyzed. Baseline characteristics, including gender, age, body mass index (BMI), acute physiology and chronic health evaluation II (APACHE II) score, albumin (Alb), hemoglobin (Hb), and disease type, showed no significant differences between the two groups. DTF in both groups gradually increased over duration of intervention [DTF on days 1, 3, and 5 in the control group was (20.83±2.33)%, (21.92±1.27)%, and (23.93±2.33)%, respectively, and that in the observation group was (20.89±1.96)%, (22.56±1.64)%, and (25.34±2.38)%, respectively], with more significant changes in DTF in the observation group, showing time effects (F_time = 105.975, P < 0.001), intervention effects (F_intervention = 7.378, P = 0.008), and interaction effects (F_interaction = 3.322, P = 0.038). Arterial blood gas parameters did not differ significantly before intervention between the groups, but after 5 days of intervention, arterial partial pressure of oxygen (PaO₂) in the observation group was significantly higher than that in the control group [mmHg (1 mmHg≈0.133 kPa): 100.72±15.75 vs. 93.62±15.54, P < 0.05], and arterial partial pressure of carbon dioxide (PaCO₂) was significantly lower than that in the control group (mmHg: 36.53±3.10 vs. 37.69±2.02, P < 0.05). At 5 days of intervention, the incidence of VIDD in the observation group was significantly lower than that in the control group [15.09% (8/53) vs. 37.25% (19/51), P < 0.05], and both duration of mechanical ventilation and length of ICU stay were significantly shorter than those in the control group [duration of mechanical ventilation (days): 7.93±2.06 vs. 8.77±1.76, length of ICU stay (days): 9.64±2.35 vs. 11.01±2.01, both P < 0.05]. CONCLUSIONS Transcutaneous phrenic nerve stimulation can improve diaphragmatic and respiratory function in patients receiving invasive mechanical ventilation, reduce the incidence of VIDD, and shorten the duration of mechanical ventilation and length of ICU stay.
Humans ; Transcutaneous Electric Nerve Stimulation ; Respiration, Artificial/adverse effects* ; Diaphragm/physiopathology* ; Phrenic Nerve ; Intensive Care Units ; Male ; Female ; Middle Aged

Objective: To construct a scientific and perfect evaluation index system of infectious disease prevention and control ability in colleges and universities, so as to provide reference tools for colleges and universities to effectively respond to infectious disease. Methods: The initial framework of the evaluation index system of infectious disease prevention and control ability in colleges and universities was constructed by using literature analysis method. Experts familiar with infectious disease prevention and control or school health work were selected to conduct two rounds( n =16，18) of Delphi expert consultation for determining the evaluation index system. Analytical hierarchy process was used to calculate the index weights and combined weights. About 198 prevention and control personnel were conveniently selected from 3 universities in Inner Mongolia Autonomous Region to comprehensively evaluate the evaluation indicators by using fuzzy comprehensive evaluation method. Results: After two rounds of Delphi consultation questionnaire, the effective recovery rates were 80.0% and 90.0%, the expert authority levels were 0.89 and 0.86, the expert harmony coefficients for Kendall W were 0.166 and 0.310, and the variation coefficient of each index was <0.25. Finally, the evaluation index system of infectious disease prevention and control ability of colleges and universities included 4 first level indicators, 14 second level indicators and 75 third level indicators. The weights of prevention and monitoring and early warning, organizational system guarantee, emergency management, rehabilitation and summary were 0.176, 0.476, 0.268 and 0.080, respectively. The top 3 weights of the secondary indexes were 0.623 for infectious disease surveillance and early warning, 0.595 for loss assessment and 0.370 for emergency response. The score of fuzzy comprehensive evaluation of the index system of infectious disease prevention and control ability in colleges and universities was 79.148, suggesting a high level. Conclusion The established evaluation index system of infectious disease prevention and control ability in colleges and universities is scientific and reasonable, which is conducive to provide tool reference for the evaluation of infectious disease prevention and control ability in colleges and universities.

Objective:To build a big data analysis model of comprehensive performance of medical equipment,so as to improve the management efficiency and fine management level for medical equipment of hospital.Methods:The big data analysis model of comprehensive performances of medical equipment was developed through building a data integration platform,and integrating multi-business system data of hospital,and including quantified social benefit data and relative data of the process of procurement and maintenance,which established index system of performance analysis with multi-dimensions and multi-layers.It realized the presentation of evaluation results of performance of medical equipment in the form of visual data reports.Results:The big data analysis model for the comprehensive performance of medical equipment has set a system with more than 10 indicators,which included social-benefit indicators,evaluation indicators of comprehensive performance,income indicators,and the indicator of recovery period of investment,and visual report with 35 pages.Each layer of the performance of equipment was analyzed from 35 angles,which realized a comprehensive,multi-dimensional and refined evaluation for the performance of medical equipment of hospital.Its'agile,easy-to-use,efficient response and automation features can significantly improve work efficiency of business.The model realized automatic data collection through interfaces and other means,and reduced manual input errors,which data accuracy rate was＞99%.The results of testing the performance data of equipment for three consecutive years by using this model indicated that the consuming time of single calculation of business system of hospital was shortened from＞20 min to 5-8 s.Conclusion:The big data analysis model of comprehensive performance of medical equipment can help hospital to identify,prevent and control risks in advance,and improve the efficiency of internal control,and enhance management efficiency and fine management level for hospital,and provide support for management decision for medical equipment of hospital.

Objective:To investigate the status of development and application of information system of central sterile supply department(CSSD)in hospitals of China,so as to provide references for the promotion of CSSD information system in hospital.Methods:Hierarchical sampling method was adopted to combine with CSSD Professional Committee of Chinese Nursing Association to design questionnaire for Questionnaire Star Network Survey about basic information,CSSD information system,whether the CSSD information system connected with equipment,tracing links and tracing levels,identification method of apparatuses,automation of equipment in 3,074 hospitals of 22 provinces,4 municipalities directly under the central government,and 5 autonomous regions.Results:In 3,074 hospitals,1,811 hospitals(accounting for 58.91%)adopted the CSSD information system.The utilization rate of tertiary hospitals was 81.90%for the information system,which was higher than that(34.51%)in secondary hospitals,and the difference was statistically significant(x2=636.65,P<0.05).The proportion of hospitals that included the recycling,cleaning,disinfection,inspection and packaging,sterilization,storage,and distribution links of CSSD internal management into information management was all>88%,while the utilization link only accounted for 15.18%.The proportion that surgical apparatuses and the apparatuses of clinical diagnosis and treatment were included in management was higher in 1811 hospitals that used CSSD information system,which were respectively 88.02%and 84.70%,while the proportion of surgical soft endoscope was lower,which only was 49.20%.A total of 84.37%of hospitals conducted informatization management for using extracorporeal apparatuses and implants.The connection rates of the main CSSD equipment,which included the washing and disinfection machine,the pressure steam sterilizer and the low-temperature sterilizer,were connected with information system were respectively 56.60%,63.06%and 43.95%.The full compatibility between the information system and all monitoring methods did not be realized in these hospitals.Barcode was the main identification form(69.91%)of the CSSD information system,and personnel management was the most common management module(53.62%)of the information system.The utilization rate(2.93%-5.14%)of automated equipment was low,and 35.45%of the CSSD information systems had the function of automatic emergency handling.Conclusion:The CSSD informatization management of China has achieved remarkable results,but there are still problems such as insufficient connection of equipment,inclusion of monitoring data,and insufficient automation and intelligence.It is necessary to increase the promotion efforts to promote the high-quality development of hospitals.

Objective:To explore the clinical significance of trisomy 7 signaled by non-invasive prenatal testing (NIPT).Methods:Pregnant women with high risk for trisomy 7 by NIPT from January 2017 to December 2023 were selected as the study subjects, and the results of prenatal diagnosis and follow-up were analyzed. Literature related to pregnant women with a high risk for trisomy 7 by NIPT from January 2016 to July 2024 was retrieved from China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure and PubMed database. Relevant information such as the incidence of trisomy 7 by NIPT, positive predictive value (PPV), and pregnancy outcomes were collected. This study has been approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No. JS2022010).Results:A total of 51 women with a high risk for trisomy 7 by NIPT were identified. Thirty-two of them had chosen chromosomal microarray analysis (CMA) of amniotic fluid cells, and 1 case of mosaic trisomy 7 was detected, which had yielded a PPV of 3.13%. Four women had opted termination of pregnancy, 1 had miscarriage, 4 had pre-term and/or low weight birth, whilst the remaining 42(82.4%) had full-term delivery. In total 19 literature were retrieved, which had involved 278 cases of trisomy 7 signaled by NIPT, among which 5 fetuses with mosaic trisomy 7 (3.14%) were confirmed. Among the 211 women with follow-up outcomes, 2 (0.95%) had intrauterine growth restriction, 3 (1.42%) had abnormal fetal structure detected by ultrasound, 2 (0.95%) had miscarriage, 9 (4.27%) underwent pregnancy termination, 28 (13.27%) had preterm and/or low weight birth, whilst 167 (79.14%) had normal delivery. In 18 cases, chromosomal analysis of placental tissue was carried out, and 17 were confirmed to have mosaicism trisomy 7.Conclusion:The PPV for trisomy 7 signaled by NIPT is extremely low. Although most of such women had a full term delivery, adverse pregnancy outcomes may still occur in a minority of cases. Clinicians should provide adequate genetic counseling for such women and recommend appropriate prenatal diagnosis strategies and optimal perinatal management plans.

Objective:New HIV infections serve as a crucial indicator for assessing the dynamic changes in the HIV epidemic. This study aims to estimate the number of new HIV infections in Dehong Dai and Jingpo Autonomous Prefecture of Yunnan Province (Dehong), using a back-calculation method that integrates diagnosis delay approaches and Bayesian theory. Additionally, it compares the differences between these two estimation methods.Methods:Data were obtained from the Chinese Information System for Disease Control and Prevention. Based on CD4 + T lymphocytes (CD4) counts depletion model, the first CD4 count prior to antiretroviral therapy of HIV-infected individuals diagnosed in Dehong from 2010 to 2023 was utilized to retroactively determine the infection date of HIV-infected individuals and ascertain the annual number of new HIV infections who had been diagnosed. Subsequently, the diagnosis delay distribution method and Bayesian theory were leveraged to assess the diagnosis probability of newly infected individuals, thereby projecting the number of new HIV infections in the region over the specified period. Results:During 2010-2023, a total of 5 693 individuals aged 15 and above, excluding mother-to-child transmission, were diagnosed with HIV in Dehong. After excluding 364 cases due to missing CD4 count results or abnormal first CD4 counts (≥2 000 cells/μl), 5 329 HIV-infected individuals were included in the final analysis. Through CD4 counts back-calculation from 2010 to 2023, the annual number of new infections diagnosed was 479, 427, 337, 305, 256, 219, 194, 193, 131, 166, 120, 71, 42 and 47. When using the diagnosis delay distribution method and life table analysis, the cumulative diagnosis probability rose from 0.301 within one year to 0.913 within 14 years, leading to a reduction in the number of estimated new infections from 577 in 2010 to 168 in 2023, with a total estimate of 4 412 (95% CI:4 350-4 480). Alternatively, based on Bayesian theory, the diagnosis probability increased from 0.413 within one year to 0.946 within 14 years, leading to a reduction in the number of estimated new infections from 557 in 2010 to 122 in 2023, with a total of 3 814 (95% CI: 3 787-3 837). Conclusions:Both methods yielded consistent results in estimating new HIV infections in Dehong from 2010 to 2023. Given the region's ongoing expansion of HIV testing, the estimates derived from Bayesian theory may more accurately reflect the actual situation. These findings provide a reference basis for formulating and optimizing HIV/AIDS prevention and control strategies in Dehong, facilitating progress toward the goal of eliminating AIDS by 2030 in the region.