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.

The study aims to elucidate the existence forms(original constituents and metabolites) of Notoginseng Radix et Rhizoma in rats and reveal its metabolic pathways. After Notoginseng Radix et Rhizoma was administered orally once a day for seven consecutive days to rats, all urine and feces samples were collected for seven days, while the blood samples were obtained 6 h after the last administration. Using the ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technique, this study identified 6, 73, and 156 existence forms of Notoginseng Radix et Rhizoma in the rat plasma, urine, and feces samples, respectively. Among them, 101 compounds were identified as new existence forms, and 13 original constituents were identified by comparing with reference compounds. The metabolic reactions of constituents from Notoginseng Radix et Rhizoma were mainly deglycosylation, dehydration, hydroxylation, hydrogenation, dehydrogenation, acetylation, and amino acid conjugation. Furthermore, the possible in vivo metabolic pathways of protopanaxatriol(PPT) in rats were proposed. Through comprehensive analysis of the liquid chromatography-mass spectrometry(LC-MS) data, isomeric compounds were discriminated, and the planar chemical structures of 32 metabolites were clearly identified. According to the literature, 48 original constituents possess antitumor and cardiovascular protective bioactivities. Additionally, 32 metabolites were predicted to have similar bioactivities by SuperPred. This research lays the foundation for further exploring the in vivo effective forms of Notoginseng Radix et Rhizoma.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacokinetics* ; Rhizome/metabolism* ; Male ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid ; Panax notoginseng/chemistry* ; Tandem Mass Spectrometry ; Feces/chemistry*

With the increasing incidence of esophagogastric junction carcinoma, the application rate of proximal gastrectomy has been rising annually. There is a wide variety of methods for digestive tract reconstruction after proximal gastrectomy, and some of these reconstruction methods have been introduced relatively recently, with limited clinical experience, which led to a lack of standardization. Such a situation will inevitably result in inconsistent clinical outcomes of proximal gastrectomy with digestive tract reconstruction. To promote the standardization of digestive tract reconstruction after proximal gastrectomy, improve the clinical efficacy of proximal gastrectomy, and reduce the occurrence of postoperative complications, this article elaborates on the indications, surgical steps and technical points of the four methods after proximal gastrectomy recommended by the "Chinese consensus on digestive tract reconstruction after proximal gastrectomy (2020 edition)", such as double tract, side overlap, double flaps and gastric tube reconstruction, providing guidance for the application of digestive tract reconstruction after proximal gastrectomy.

Objective:To share the results of laparoscopic assisted proximal gastrectomy λ- shaped modified double tract reconstruction.Method:This study retrospectively included 3 patients during January 2024 from the Department of Gastric Surgery at the First Affiliated Hospital of Nanjing Medical University using the λ-shaped modified double tract reconstruction. The procedure of the λ-shaped modified double tract reconstruction is as follows. After completing proximal gastrectomy, the jejunum is transected 15 cm from the Treitz ligament. A suture is made 18-20 cm from the distal jejunum to mark the esophagojejunal anastomosis site. A circular stapler anvil is inserted through the distal jejunum, and the remaining end of the jejunum is turned to the right. The circular stapler is pierced through the marked site for an esophagojejunal end-to-end anastomosis, which is reinforced with a barbed suture continuously. A 60mm linear stapler is used to close the remaining end of the jejunum. We then mark the gastric side of the gastrojejunal anastomosis with suture in the middle of the anterior wall of the residual stomach, and mark the jejunal side of the gastrojejunal anastomosis at a distance of about 2 cm and 8 cm from the residual end of the distal jejunum. We make an opening of about 0.5 cm and use a 60 mm linear stapler to perform anastomosis on the jejunal side of the anterior wall of the residual stomach according to the markings, so that the distance between the esophagojejunal anastomosis and the gastrojejunal anastomosis is 10-12 cm. The common opening is closed with barbed wire. About 50 cm below the esophagojejunal anastomosis, the small intestine opening is anastomosed side to side using a circular stapler and the common opening is closed. Return the jejunum into the abdominal cavity to complete the reconstruction of the λ-shaped double tract reconstruction. We analyzed the surgery and postoperative conditions, including surgery time, anastomosis time, intraoperative bleeding, tumor size and pathology, postoperative mobilization, passage of gas and water intake time, discharge time, postoperative complications, and postoperative gastrointestinal imaging to observe the passage of food through the gastric and intestinal loops.Results:Three patients successfully received laparoscopic assisted proximal gastrectomy with λ-shaped modified double tract reconstruction. The surgical time was 155 minutes, 240 minutes, and 160 minutes, respectively; The postoperative time for first ambulation was 20 hours, 18 hours, and 26 hours, respectively. The time for passage of gas was 59 hours, 83 hours, and 75 hours, respectively. The drinking time was 66 hours, 87 hours, and 90 hours, respectively. The postoperative discharge days were all 7 days. No surgical related complications occurred. On the 6th day and 3 months after surgery, gastrointestinal angiography was performed. The contrast agent passed smoothly through the jejunal loop and residual stomach jejunal loop, and both sides were unobstructed. No contrast agent was found to retrograde to the esophagojejunal anastomosis.Conclusion:Laparoscopic assisted proximal gastrectomy with λ-shaped modified double tract reconstruction is safe and feasible, as it improves the diversion of food through the residual stomach while ensuring anti-reflux effects.

Objective To screen key genes for ferroptosis in atherosclerosis(AS)using bioinformatics methods and analyze the biological functions of key genes to gain an in-depth understanding of the pathogenesis of AS.Methods AS gene expression profile chip dataset GSE100927 was downloaded from the Gene Expression Omnibus(GEO)database.P＜0.05 and|logFC＞1|were used as the conditions to screen the differential genes of AS.These genes were intersected with ferroptosis gene dataset to screen out the genes related to AS ferroptosis.Gene ontology(GO)functional annotation and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)were carried out.The STRING online analysis tool combined with Cytoscape visualization software was subsequently used to mine genes that play a key role in the biological process of AS,and the AS dataset GSE9874 was used as the verification set to verify the expression of key genes.Blood samples from 30 confirmed AS patients in the cardiovascular department of our hospital from January to March 2023 were collected as the experimental group,while blood samples from 20 healthy volunteers were collected as the control group.Sample RNA was extracted,and quantitative real time polymerase chain reaction(qRT-PCR)was used to verify the selected genes.Results A total of 10 differential genes related to ferroptosis were screened by bioinformatics method.GO functional enrichment analysis showed that differential genes were mainly involved in inflammation,apoptosis,oxidative stress and other biological processes,while KEGG pathway enrichment analysis showed that differential genes were mainly involved in ferroptosis,HIF-1 signaling pathway,and leukocyte migration pathway through endothelial cells.Seven key modules of gene construction were screened out through the protein interaction network,which were FTL,SLC40A1,CYBB,NCF2,HMOX1,DPP4 and ALOX5.GSE9874 was used for verification,and 5 key genes including ALOX5,DPP4,FTL,SLC40A1 and NCF2 were finally screened out.The expression detection of key genes in clinical samples by qRT-PCR showed that compared with the control group,the up-regulated genes in blood of AS group were DPP4(t=1.795,P=0.046),FTL(t=2.218,P=0.029)and SLC40A1(t=2.859,P=0.009),and the down-regulated genes were ALOX5(t=8.039,P＜0.001)and NCF2(t=11.867,P＜0.001),and the differences were significant.The experimental results were consistent with the results of bioinformatics analysis.Subgroup analysis showed that DPP4 expression in plaque group was higher than that in intima thickening group,and the difference was significant(t=2.843,P=0.036).Conclusion The key genes of ferroptosis screened by bioinformatics are AS,ALOX5,DPP4,FTL,SLC40A1 and NCF2,which may be potential targets for the diagnosis and treatment of AS,providing new ideas for the clinical diagnosis and treatment of AS.

Objective To investigate the effect of intrarectal local anesthesia (IRLA) with heated oxybuprocaine gel on pain during transrectal ultrasound guided prostate biopsy (TRUSPB).Methods A total of 150 cases patients who underwent TRUSPB in Huzhou Central Hospital from January to June 2023 were prospectively taken into.The patients were randomly divided into group A (routine group),group B (oxybuprocaine gel for IRLA at room temperature) and group C (oxybuprocaine gel for IRLA at 40℃),with 50 cases in each group.Nurses who were unaware of the anesthesia type used visual analog scale (VAS) to score the pain level of patients at each stage (VAS Ⅰ:when the ultrasound probe was inserted into the rectum;VAS Ⅱ:during the biopsy;VAS Ⅲ:30 minutes after biopsy),and the incidence of complications after biopsy were compared.Results The VAS Ⅱ score of group C was lower than that of group A and group B,and the difference was statistically significant (P<0.05).There was no statistically significant difference (P>0.05) in the VAS Ⅰ,VAS Ⅲ scores,and incidence of complications after biopsy among the three groups.There was no allergic reaction to oxybuprocaine gel.Conclusion In TRUSPB,IRLA with heated oxybuprocaine gel can effectively control pain without increasing incidence of complications.

FLASH radiotherapy (FLASH-RT) has garnered considerable attention globally in recent years. Compared to conventional radiotherapy, FLASH-RT can deliver the total radiation dose to the target volume in an extremely short time, reducing the radiation-induced damage to normal tissue while maintaining similar anti-tumor effects. FLASH-RT has been in the clinical trial stage, with several clinical research result being reported. Based on the collected global clinical research result of FLASH-RT in recent years, this study systematically reviewed FLASH-RT′s safety, radiation-related side effects, treatment efficacy, opportunities, and challenges in clinical trials.

Objective In the traditional laboratory zoology lecture environment,there is less teacher-student interaction,less student interest,and less engagement in learning.To improve the teaching quality of laboratory animal science,this teaching and research department was based on different teaching environments of multimedia and intelligent classrooms,theoretical course teaching of Medical Laboratory Animal Science as the research object,the course lecture format,teaching mode,teaching method,and other aspects of innovation and exploration.Methods This study used questionnaires to understand changes in student engagement in learning and preferences for smart classroom use,and NVivo qualitative analysis software was used to code student classroom behavior.Results The smart teaching environment resulted in higher student interest and more frequent teacher-student interaction in the classroom.Students were significantly more engaged in learning than in traditional teaching with higher correct rates on in-class and post-lesson exercises and a better grasp of concepts related to laboratory animal science.Conclusions A smart teaching environment brings students a better feeling and experience,improves their interest in laboratory animal science,increases classroom learning engagement,and achieves good teaching result.

Objective:To establish the objective of zero inventory management of in vitro diagnostic reagents,to evaluate the quality of supply chain,and to improve the existing problems in the supply of reagents.Methods:The problems existing in the management of in vitro diagnostic reagents were analyzed from the aspects of inventory,supply efficiency and product quality,and the management system of hospital operation,management quality and patient benefit optimization was established,and the zero-inventory management path and quality evaluation model were constructed.85 models of 21 types of in vitro diagnostic reagents purchased by Jiangsu Subei People's Hospital from January 2020 to March 2023 were selected.According to different supply chain quality management methods,on-demand inventory management mode(referred to as mode 1)and zero inventory management mode(referred to as mode 2)were adopted respectively.The demand procurement,inventory management and clinical use effects of the two management modes were compared.Results:The reagent procurement demand compliance rate,supply capacity high-quality quality rate and clinical use matching rate of mode 2 were(93.35±3.62)%,(94.87±2.63)% and(96.08±2.31)%,respectively,which were higher than those of mode 1,the difference was statistically significant(Z=2.489,2.836,2.838,P<0.05).The number of cases of long-term overstocking of products,substandard environment and untimely information in mode 2 were(2.92±2.54)cases,(2.83±1.59)cases and(5.58±3.12)cases,respectively,which were lower than those in mode 1,the difference was statistically significant(Z=2.959,3.037,3.703,P<0.05).The satisfaction of clinical departments,medical technology departments and procurement center with the supply,distribution and information communication of in vitro diagnostic reagents in mode 2 were 97.8% and 93.3%,97.0% and 87.9%,100% and 84.6%,respectively,which were higher than those in mode 1,the difference was statistically significant(x2clinical departments=5.428,6.133,x2medical technology departments=3.958,3.937,x2procurement center=5.159,4.996,P<0.05).Conclusion:The zero inventory management model can improve the standardization of in vitro diagnostic reagent demand procurement,reduce the incidence of backlog failure in inventory management,and improve the quality of clinical supply services.

ObjectiveTo establish a UHPLC-MS/MS quantitative method for the determination of glucuronic acid， tartaric acid， glycolic acid， malic acid， lactic acid， citric acid， DL-2-hydroxybutyric acid sodium， mandelic acid， benzilic acid， hydroxycaprylic acid， lactobionic acid， gluconic acid and N-acetylneuraminic acid in cosmetics. MethodsSamples were prepared by ultrasonic extraction， cleansed by precipitating reagent and followed by high-speed centrifugation of the extraction solution. The supernatant was filtered by 0.22 μm Millipore filter. The continued filtrate was taken for analysis. A reversed phase column， Poroshell 120 EC-C₁₈ （2.7 μm， 4.6 mm×1 000 mm） was used with 0.1% formic acid buffer and acetonitrile as the mobile phase under the condition of gradient elution. The analytes were detected with electrospray ionization source in negative ion mode （ESI^-） and multiple reactions monitoring （MRM）， and quantified by external standard curve. ResultsThe method showed a good linearity of glucuronic acid， tartaric acid， malic acid， DL-2-hydroxybutyric acid sodium， benzilic acid， hydroxycaprylic acid and N-acetylneuraminic acid within the concentration range of 50.0‒2 000.0 μg·L^-1 （r>0.995）. The method showed a good linearity of glycolic acid， lactic acid， citric acid and mandelic acid within the concentration range of 100.0‒5 000.0 μg·L^-1 （r>0.995）. The method showed a good linearity of lactobionic acid and gluconic acid within the concentration range of 50.0‒5 000.0 μg·L^-1 （r>0.995）. The recoveries were in the range of 92.3%‒114.1%； the relative standard deviations （RSD） were in the range of 0.9%‒6.0% （n=3）. The detection limits of glucuronic acid， tartaric acid， malic acid， citric acid， DL-2-hydroxybutyric acid sodium， mandelic acid， benzilic acid， hydroxycaprylic acid， lactobionic acid， gluconic acid and N-acetylneuraminic acid were 0.003% while the detection limits of glycolic acid， lactic acid and mandelic acid were 0.006%. In 10 batches of commercially available cosmetics， eight batches showed positive result. ConclusionThe UHPLC-MS/MS method is efficient， sensitive and accurate and is applicable to the determination of 13 α-hydroxy acidic components in cosmetics.