Objective:To explore the clinical features, genetic traits and prognosis status of acute myeloid leukemia (AML) patients with TP53 mutation.Methods:A retrospective case series study was performed. Clinical data of 42 AML patients with TP53 mutation abundance of at least 10% who were admitted to the First Hospital of Jilin University from April 2018 to August 2023 were collected. Chromosomal karyotypes were detected using fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) was performed on bone marrow samples from these patients. The Kaplan-Meier method was utilized to analyze the recurrence-free survival (RFS) of 22 patients who achieved complete remission (CR) after induction therapy, as well as the overall survival (OS) of 39 patients who underwent treatment. The Cox proportional hazards model was employed to analyze the factors influencing RFS and OS. Thirty-one patients who underwent induction therapy for ≥ 2 courses were divided into the non-refractory group (22 cases) and the refractory group (9 cases) based on whether CR was achieved after induction therapy, and the clinical and genetic characteristics and prognosis of the two groups were compared.Results:Among the 42 AML patients with TP53 mutation, there were 26 males and 16 females, with a median age [ M( Q1, Q3)] of 57.0 (44.0, 63.5) years. At the initial stage, the median white blood cell count in peripheral blood was 4.06×10 9/L (2.59×10 9/L, 27.36×10 9/L), the median proportion of bone marrow primitive cells was 45.25% (29.00%, 80.63%), the proportion of primitive and immature cells in bone marrow cell immune analysis was 28.70% (12.71%, 61.48%), and the median TP53 mutation abundance was 55.48% (38.72%, 73.31%). Among the 42 patients, 23 cases (54.76%) had complex chromosomal karyotypes, with the most frequent abnormal chromosomes being chromosome 5 (47.62%, 20 cases), chromosome 7 (45.24%, 19 cases) and chromosome 17 (26.19%, 10 cases). The mutant genes with high mutation frequency were DNMT3A (19.05%, 8 cases), N/KRAS (19.05%, 8 cases), ASXL1 (16.67%, 7 cases) and NPM1 (16.67%, 7 cases). Among the 39 patients with detailed TP53 mutation data, 36 had missense mutations and 3 had frameshift mutations. In the non-refractory and refractory groups, the N/KRAS mutation rates were 13.6% (3/22) and 55.6% (5/9), respectively ( P = 0.027). The median RFS time of 22 CR patients after induction therapy was 109 d (95% CI: 57-483 d). The results of multivariate Cox regression analysis showed that complex chromosomal karyotype was an independent risk factor for RFS ( HR = 11.819, 95% CI: 1.345-103.880, P = 0.028). The median RFS time of patients without and with complex chromosomal karyotypes was 842 d (95% CI: 0-1 716 d) and 148 d (95% CI: 88-208 d), respectively, and the difference in RFS between the two groups was statistically significant ( P = 0.001). The median OS time of 39 patients receiving treatment was 151 d (95% CI: 75-227 d). The results of multivariate Cox regression analysis showed that NPM1 gene mutation was an independent protective factor for OS ( HR = 0.289, 95% CI: 0.075-1.114, P = 0.071). The median OS time of patients with and without NPM1 gene mutation was 1 562 d (95% CI: 610- 1 710 d) and 136 d (95% CI: 99-173 d), respectively, and the difference in OS between the two groups was statistically significant ( P = 0.020). Conclusions:TP53-mutant AML patients often have poor chromosomal karyotypes and genetic abnormalities, while refractory AML patients often have N/KRAS mutation. The complex chromosomal karyotype is a risk factor for RFS, while NPM1 gene mutation is a protective factor for OS.

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

Objective: To investigate the effect of aloperine (Alo) on the proliferation , migration and invasion of gastric cancer cells. Methods: Human gastric cancer cell lines HGC⁃27 and AGS were treated with 0 , 100 , and tion. Flow cytometry was used to detect apoptosis. Scratch and Transwell migration assays were used to detect cell migration. Transwell invasion assay was used to detect cell invasion. Western blot was used to detect the expression of proteins related to proliferation , apoptosis , migration , invasion and Hippo pathway. Results: Compared with the control group , the cell viability , number of colony formation , cell migration and invasion were significantly reduced after 100 and 200 μmol/L Alo treatment , and the apoptosis rate significantly increased (P < 0. 05) . Additionally , the expressions of proliferating cell nuclear antigen (PCNA) , B -cell lymphoma/leukemia⁃2 protein (Bcl⁃2) , neural cadherin ( N⁃cadherin) , Vimentin , and transcriptional co⁃activator with PDZ⁃binding motif ( TAZ)were significantly reduced , whereas the expressions of Bcl⁃2 ⁃associated X protein (Bax) , phosphorylated yes⁃asso⁃ciated protein (p⁃YAP) , and large tumor suppressor 1/2 (LATS1/2) significantly increased (P < 0. 05) . Conclusion Alo inhibits the proliferation , migration and invasion of gastric cancer cells HGC⁃27 and AGS by regulating the Hippo signaling pathway.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Aim To investigate the intestinal protection and possible mechanism of magnolol(MG)in newborn rats with necrotizing enterocolitis(NEC).Methods The rats were randomly divided into control group(Ctrl group),model group(NEC group)and treatment group(MG group).The NEC model was induced by hypoxia,cold stimulation,deep formula milk and LPS intragastric administration in 7-day-old rats for four days.They were killed after five days of treatment with MG(20 mg·kg-1).HE staining was used to observe the intestinal pathological injury.Western blot was used to detect the expressions of IL-1 β,TNF-α,NL-RP3,ASC,caspase-1 and tight junction protein in the distal ileum of rats.Colon contents were collected for 16S rDNA sequencing to understand the gut microbio-ta.Results MG improved the body mass and intesti-nal injury of NEC neonatal rats.The expressions of in-testinal IL-1β,TNF-α,NLRP3,ASC and caspase-1 proteins were down-regulated,and the expressions of Claudin,Occludin and ZO-1 proteins were up-regula-ted.16S rDNA showed that MG increased the diversity of intestinal flora,and at the phylum level,MG in-creased the abundance of firmicutes and bacteroides in NEC model,and decreased the abundance of pro-teobacteria.At the genus level,MG treatment in-creased the abundance of Lactobacillus,unclassified_Muribaculaceae,Racteroides,but decreased the abun-dance of Escherichia_Shigella,Rodentibacter and Fuso-bacterium.Conclusion MG intervention can protect the intestinal tract of NEC rats by potentially improving barrier function,and regulating the intestinal microbiota through the NLRP3/ASC/caspase-1 signaling pathway.

Objective:To investigate the molecular characteristics of low-risk acute myeloid leukemia(AML)at recurrence,and analyze the factors affecting retreatment efficacy and prognosis.Methods:A retrospective analysis was conducted on the clinical and laboratory data of 31 patients with newly diagnosed low-risk AML who relapsed during consolidation treatment or follow-up after treatment in our hospital from April 2017 to January 2023.Gene mutations before and after relapse were compared,retreatment efficacy following relapse was evaluated,and univariate and multivariate analyses were performed to identify factors influencing treatment efficacy and prognosis.Results:Gene sequencing results after relapse showed that the most common newly acquired mutation was FLT3-ITD,while RAS mutation detected at initial diagnosis were predisposed to loss of expression during relapse.The median overall survival(OS)after relapse for the entire cohort was 349(170-528)days,with non-hematopoietic stem cell transplantation(HSCT)group and HSCT group demonstrating median survival times of 210(106-314)days and not reached,respectively(P=0.001).Multivariate analysis revealed that age ≥60 years was a significant risk factor for achieving remission after retreatment in initially diagnosed low-risk AML patients who experienced relapse(OR=18.222,95％CI:1.188-279.597,P=0.037).Additionally,DNMT3A mutation was identified as an independent risk factor for OS(HR=13.165,95％CI:2.018-85.877,P=0.007),while HSCT post-relapse demonstrated significant survival benefits(HR=0.133,95％CI:0.025-0.698,P=0.017)and served as an independent protective factor for OS.Conclusion:Relapsed low-risk AML is often associated with loss of RAS and novel mutations in FLT3-ITD.Age ≥ 60 years and DNMT3A mutations were identified as independent adverse factors for achieving subsequent remission and post-relapse survival,respectively,while HSCT significantly improved patient outcomes.

Aim To explore the protective effect of icariin on the damage of tight junctional function of Sertoli cells in naturally aging mice and the related mechanism.Methods 15-month-old C57BL/6J male mice were randomly divided into three groups:aging model group,low-dose and high-dose icariin treatment group(5 and 20 mg·kg-1).Another 1-month-old C57BL/6J male mice were considered as adult control group(n=10).The mice in adult control group and aging model group were given the vehicle(0.5％sodi-um carboxymethyl cellulose solution)by intragastric administration,while the mice in icariin-treated groups were given different concentrations of icariin,respec-tively.After continuous administration of icariin for three months,the testes and epididymis were immedi-ately removed,weighed,and the organ index was calcu-lated.Sperm viability and sperm concentration in epi-didymis were measured.The morphological changes of testes were observed by HE staining.The ultrastructur-al changes of tight junctions of Sertoli cells were ob-served by transmission electron microscopy.The ex-pression levels of tight junction-related proteins ZO-1,Occludin,and Claudin11 of testicular Sertoli cells were detected by Western blot.The expression and localiza-tion of ZO-1,Occludin,Raptor,Rictor,p-70S6K,and p-rps6 were detected by immunofluorescence.Results Compared with the aging model group,icariin signifi-cantly increased testicular weight and its index,and ep-ididymal index,improved sperm viability and increased sperm concentration in naturally aging mice.In addi-tion,icariin improved the degeneration of testicular morphology and the damage of ultrastructure of Sertoli cell tight junction with aging.Furthermore,Western blot results showed that icariin up-regulated the expres-sion of ZO-1 and Occludin,but had no significant effect on the expression of Claudin 11.Immunofluorescence assay showed that icariin up-regulated the expression of Rictor,and down-regulated the expression of p-70S6K,p-rps6 and Raptor.Conclusions Icariin improves the tight junction damage of Sertoli cells in naturally aging mice,and its mechanism may be related to restoring the balance between mTORC1 and mTORC2.

Objective:To explore the independent risk factors for uremic encephalopathy(UE)in maintenance hemodialysis(MHD)patients and provide evidence for early clinical warning and intervention.Methods:A case-control study was conducted,enrolling 67 MHD patients diagnosed with UE(UE group)at Laibin People's Hospital from January 2010 to December 2024,and 67 non-UE patients during the same period(control group).Demographic characteristics,dialysis parameters,laboratory indicators,and infection events were collected.Univariate and multivariate logistic regression analyses were used to identify independent risk factors for UE.Results:The UE group had significantly higher rates of infection(58.2％vs.29.9％),serum creatinine(789 vs.702 μmol/L),and iPTH levels(568 vs.385 pg/mL)compared to the control group(P＜0.05).Multivariate analysis revealed that concurrent infection(OR=3.022,95％CI:1.312-6.958),elevated serum creatinine(OR=1.004,95％CI:1.000-1.008),and elevated iPTH(OR=1.002,95％CI:1.001-1.003)were independent risk factors for UE(P＜0.05).The combined prediction model achieved an AUC of 0.878(95％CI:0.822-0.934),with 82.1％sensitivity and 80.6％specificity.Conclusion:Infection,elevated serum creatinine,and elevated iPTH significantly increase the risk of UE in MHD patients.Clinical management should emphasize infection prevention,toxin clearance optimization,and parathyroid function regulation to reduce UE incidence.