Objective To analyze the effect of the activation rate of peripheral blood monocytes on the recovery of patients after liver transplantation and to initially explore the possible influencing factors for differences in monocyte activation rates. Methods A total of 139 patients who underwent orthotopic liver transplantation from September 2020 to June 2023 at Department of Liver Surgery and Transplantation of Zhongshan Hospital, Fudan University were selected. The proportion of CD14^＋HLA-DR^＋ monocytes in peripheral blood was defined as the monocyte activation rate. The difference in monocyte activation rates between postoperative day 7 (POD7) and postoperative day 1 (POD1) was calculated as Δ, and patients were divided into Δ＞0 group (n＝73) and Δ＜0 group (n＝66). The two groups were compared in terms of complete blood count, liver and kidney function, coagulation indicators, infection indicators, ICU length of stay, total length of hospitalization, and 90-day mortality. Changes in the proportions of different monocytes subsets (Mo0, Mo1, Mo2, and Mo3) and HLA-DR expression in peripheral blood on POD1 and POD7 were detected using flow cytometry. Results The ICU length of stay in the Δ＜0 group was significantly longer than that in the Δ＞0 group (18[12, 26] days vs 14[10, 20.5] days, P＝0.018). On POD1, the proportion of Mo0 in the Δ＞0 group was significantly lower than that in the Δ＜0 group (P＜0.05); on POD7, the proportion of Mo0 in the Δ＞0 group was significantly lower than that in the Δ＜0 group (P＜0.001), while the proportions of Mo1, Mo2, and Mo3 were significantly higher than those in the Δ＜0 group (P＜0.001). Compared to POD1, the HLA-DR expression level of Mo0 in peripheral blood of patients with liver transplantation significantly decreased on POD7 (P＜0.01), while there was no significant difference in HLA-DR expression levels of Mo1, Mo2, and Mo3. Conclusions Increased proportion of Mo0 (CD14^lowCD16⁻HLA-DR^low) among peripheral blood monocyte subsets may be one of the influencing factors for the differences in monocyte activation rates in patients with liver transplantation. The difference in monocyte activation rate can serve as a new clinical indicator for assessing changes in the immune status and postoperative recovery of patients with liver transplantation.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Objective:To study the growth trajectory and the incidence of malnutrition and clinical events in infants with congenital heart disease in 1 year after surgery.Methods:Children at the age of 1 year or younger who were diagnosed with congenital heart disease and underwent surgery at Guangzhou Women and Children's Medical Center affiliated to Guangzhou Medical University from January 2018 to January 2019 were included. The age, gender, birth weight and length, and parental height and weight were collected, and the occurrence of clinical events of interest and the children's health as evaluated by caregiver within 1 year after surgery were followed up through questionnaire survey. Malnutrition was defined as a weight-for-age z-score (WAZ) ≤-2 at 1 year after surgery and a WAZ>-2 was defined as non-malnourished.Results:Among the 502 children, 301 were boys and 201 were girls, aged 4.1 (range: 2.0 to 6.8) months, of whom 64.7% were with simple congenital heart disease and 35.3% complex congenital heart disease. The children were generally with mild malnutrition (WAZ<-1 and >-2) before surgery. At 3 months and 6 months after surgery, the children showed a rapid growth catch-up, although failing to reach the normal level, and the trend plateaued at 1 year after surgery. The proportion of children with malnutrition decreased gradually within 1 year after surgery. 47.0% of included children had malnutrition before surgery, and the proportion decreased significantly at 3 months and 6 months, to 17.9% at 1 year after surgery. After discharge, these children suffered from upper respiratory infection most commonly (74.5%), followed by pneumonia (41.2%) and diarrhea (36.7%), and vomiting and constipation (22.1%). In terms of children's health status as evaluated by parents, about 32.0% of families considered their children in poor health before surgery, and the proportion decreased to 6.9% within 1 year after surgery.Conclusion:Infants with congenital heart disease continued to grow and catch up within 1 year after surgery, showing significantly improved nutrition status, but some children still experienced malnutrition at 1 year after surgery.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of Asp,Guad,Adeno,Arg,Ade,Cyti,Phe,Leu,Ile,Glu,Ser,Gln,Gly,Ala,Hyp,Thr,Pro and Lys in Asini Corii Colla.METHODS The analysis was performed on a 45℃ thermostatic Waters BEH C18column(2.1 mm×50 mm,1.7 μm),with the mobile phase comprising of acetonitrile(containing 0.1% formic acid)-water flowing at 0.35 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive ion scanning with multiple reaction monitoring mode.Subsequently,chemical pattern recognition was performed by hierarchical clustering analysis,principal component analysis and orthogonal partial least squares-discriminant analysis.RESULTS Eighteen nucleosides and free amino acids showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 98.0%-104.9% with the RSDs of 1.6%-4.9% .Seventeen batches of samples were clustered into two categories,two principal components demonstrated the accumulative variance contribution rate of 60.75%,Leu,Phe,Ade and Guad were potential index constituents.CONCLUSION This stable and reliable method can be used for the quality control of Asini Corii Colla.

Objective:To explore and screen the immunophenotypic characteristics of acute promyelocytic leukemia (APL) by multiparameter flow cytometry (MFC).Methods:A retrospective and descriptive study. A total of 130 acute myeloid leukemia (AML) patients who registrated in Hebei Yanda Lu Daopei Hospital were studied, among which there were 44 classical APL (cAPL), 24 microgranular variant of APL (APLv) and 62 non-APL patients (including NPM1 mut AML and AML with KMT2A rearrangement). MFC immunotyping was used to analyze and compare the median expression intensity (MEI) of side scatter (SSC), along with the ratio of the MEI on leukemic cells with those on lymphocytes (T/L MEIR), the median fluorescence intensity (MDFI) of CD34, myeloperoxidase (MPO), CD64 and CD9 on leukemic cells, as well as the ratios of these MDFIs on leukemic cells with those on lymphocytes (T/L MDFIR). Receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic efficiency of the multiparameters model for distinguishing cAPL and non-APL, APLv and non-APL. Results:The MEI and T/L MEIR of SSC in the cAPL group were higher than those in the APLv and non-APL groups ( P<0.05), and these two parameters in APLv group were higher than those in the non-APL group, respectively ( P<0.05). The MDFIs of CD34 in cAPL and APLv groups were higher than those in the non-APL group ( P<0.05), and the T/L MDFIR of CD34 was higher in APLv group than non-APL group ( P<0.05). The MDFIs of MPO and CD9, as well as the T/L MDFIRs in cAPL and APLv groups were both higher than those in the non-APL group, respectively ( P<0.05). The MDFI and T/L MDFIR of CD64 in the cAPL group were higher than those in non-APL group, respectively ( P<0.05). ROC curve results showed that the area under the curve (AUC) of MEI of SSC, the MDFI of CD64 and CD9, as well as the T/L MEIR of SSC and T/L MDFIR of CD9 were 0.932, 0.816, 0.893, 0.960 and 0.894 for diagnosing cAPL, respectively, and the AUC of these parameters were 0.725, 0.737, 0.791, 0.729 and 0.736 for diagnosis APLv, respectively ( P<0.05). Conclusion:MFC method can analyze and screen the immunophenotypic characteristics of APL for differential diagnosis of cAPL, APLv and non-APL patients.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31～240 s,31～120 s,151～240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P＜0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P＜0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.

Objective To evaluate the Mandarin tracking of noise tolerance(TNT)test material and compare the differences between the average tolerable noise level(aTNL)value obtained from assessment and the program-estimated tolerable noise level(eTNL).Methods A total of 25 subjects with normal hearing and aural communica-tional ability were selected to undergo two of the mandarin TNT tests successively(respectively test 1,C1;test 2,C2),and 13 of them completed the third test(C3)under the same test condition as test 2 at least 1 week later.The stimulus for the three test conditions was presented with"speech 0°,continuous noise 180°".Results The aTNL of 25 participants for C1 and C2 was 83.42±3.09 dB SPL and 83.50±3.18 dB SPL,respectively.The eTNL of 25 participants for C1 and C2 were 84.08±3.53 dB SPL and 83.95±3.85 dB SPL,respectively.The aTNL and eT-NL for 13 subjects who participated in C3 was 83.16±2.13 dB SPL and 83.18±2.64 dB SPL,respectively.The intra-session(C1 vs C2)and inter-session(C2 vs C3)test-retest reliability were 2.36 dB and 2.75 dB,respectively.Pearson correlation analysis showed that intra-session(r=0.837,P＜0.001)and inter-session(r=0.867,P＜0.001)test-retest reliability was good.There was no statistical difference between aTNL and eTNL in the other TNT tests(P＞0.05 for both)except that aTNL and eTNL were statistically different in C1(P＜0.01),and more than 90％of the subjects could obtain eTNL within 1 minute.Conclusion The test-retest reliability of Mandarin tracking of noise tolerance test is good,with advantages of high reliability and efficiency.

Objective To investigate the role and mechanism of epithelial-mesenchymal transition(EMT)in a rat model of bronchopulmonary dysplasia(BPD).Methods The experiment consisted of two parts.(1)Forty-eight preterm rats were randomly divided into a normoxia group and a hyperoxia group,with 24 rats in each group.The hyperoxia group was exposed to 85%oxygen to establish a BPD model,while the normoxia group was kept in room air at normal pressure.Lung tissue samples were collected on days 1,4,7,and 14 of the experiment.(2)Rat type II alveolar epithelial cells(RLE-6TN)were randomly divided into a normoxia group(cultured in air)and a hyperoxia group(cultured in 95%oxygen),and cell samples were collected 12,24,and 48 hours after hyperoxia exposure.Hematoxylin-eosin staining was used to observe alveolarization in preterm rat lungs,and immunofluorescence was used to detect the co-localization of surfactant protein C(SPC)and α-smooth muscle actin(α-SMA)in preterm rat lung tissue and RLE-6TN cells.Quantitative real-time polymerase chain reaction and protein immunoblotting were used to detect the expression levels of EMT-related mRNA and proteins in preterm rat lung tissue and RLE-6TN cells.Results(1)Compared with the normoxia group,the hyperoxia group showed blocked alveolarization and simplified alveolar structure after 7 days of hyperoxia exposure.Co-localization of SPC and α-SMA was observed in lung tissue,with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 7 and 14 days of hyperoxia exposure compared to the normoxia group.In the hyperoxia group,the mRNA and protein levels of TGF-β1,α-SMA,and N-cadherin were increased,while the mRNA and protein levels of SPC and E-cadherin were decreased at 7 and 14 days of hyperoxia exposure compared to the normoxia group(P<0.05).(2)SPC and α-SMA was observed in RLE-6TN cells,with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 24 and 48 hours of hyperoxia exposure compared to the normoxia group.Compared to the normoxia group,the mRNA and protein levels of SPC and E-cadherin in the hyperoxia group were decreased,while the mRNA and protein levels of TGF-β1,α-SMA,and E-cadherin in the hyperoxia group increased at 48 hours of hyperoxia exposure(P<0.05).Conclusions EMT disrupts the tight connections between alveolar epithelial cells in a preterm rat model of BPD,leading to simplified alveolar structure and abnormal development,and is involved in the development of BPD.

Objective To explore the value of nomogram model based on clinical data and MRI findings for predicting simultaneous liver metastasis(SLM)of rectal cancer.Methods Clinical and MRI data of 356 patients with rectal cancer were randomly divided into training set(n=249,45 cases of SLM)and validation set(n=107,27 cases of SLM)at a ratio of 7∶3.Logistic regression analysis were used to screen the independent factors for predicting SLM of rectal cancer.The nomogram model was then constructed,and the efficacy of this model was evaluated.Results Tumor N-stage,serum carcinoembryonic antigen,carbohydrate antigen 19-9 and involvement of mesorectal fascia(MRF)or not were all independent factors for predicting SLM of rectal cancer.The area under the curve(AUC)of this nomogram model for predicting rectal cancer SLM in training set and validation set was 0.834(95％CI[0.776,0.893])and 0.769(95％CI[0.662,0.877]),respectively.The calibration curve showed good consistency between the predicted values and the measured values,and the decision curve analysis showed that the nomogram model had good clinical practicality.Conclusion The nomogram model based on clinical data and MRI findings could be used to predict SLM of rectal cancer.