[Objective] To explore the relationship between neutrophil activation under cardiopulmonary bypass (CPB) and the incidence of cardiac surgery-associated acute kidney injury (CS-AKI). [Methods] This prospective cohort study enrolled adult patients who scheduled for cardiac surgery under CPB at West China Hospital between May 1, 2022 and March 31, 2023. The primary outcome was acute kidney injury (AKI). Blood samples (5 mL) were obtained from the central vein before surgery, at rewarming, at the end of CPB, and 24 hours after surgery. Neutrophils were labeled with CD11b, CD54 and other markers. To assess the effect of neutrophils activation on AKI, propensity score matching (PSM) was employed to equilibrate covariates between the groups. [Results] A total of 120 patients included into the study, and 17 (14.2%) developed AKI. Both CD11b⁺ and CD54⁺ neutrophils significantly increased during the rewarming phase and the increases were kept until 24 hours after surgery. During rewarming, the numbers of CD11b⁺ neutrophils were significantly higher in AKI compared to non-AKI (4.71×10⁹/L vs 3.31×10⁹/L, Z=-2.14, P<0.05). Similarly, the CD54⁺ neutrophils counts were also significantly higher in AKI than in non-AKI before surgery (2.75×10⁹/L vs 1.79×10⁹/L, Z=-2.99, P<0.05), during rewarming (3.12×10⁹/L vs 1.62×10⁹/L, Z=-4.34, P<0.05), and at the end of CPB (4.28×10⁹/L vs 2.14×10⁹/L, Z=-3.91, P<0.05). An analysis of 32 matched patients (16 in each group) revealed that CD11b⁺ and CD54⁺ neutrophil levels of AKI were 1.74 folds (4.83×10⁹/L vs 2.77×10⁹/L, Z=-2.72, P<0.05) and 2.34 folds (3.32×10⁹/L vs 1.42×10⁹/L, Z=-4.12, P<0.05), respectively, of non-AKI at rewarming phase. [Conclusion] Neutrophils are activated during CPB, and they can be identified by CD11b/CD54 markers. The activated neutrophils of AKI patients are approximately 2 folds of non-AKI during the rewarming phase, with disparity reached peak between groups during rewarming. These findings suggest the removal of 50% of activated neutrophils during the rewarming phase may be effective to reduce the risk of AKI.

ObjectiveTo investigate the effects of Danhong injection on mitochondrial dynamics， morphology， and function in the rat model of chronic heart failure by mediating the adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK）/dynamin-related protein 1 （Drp1） pathway. MethodsFrom 75 SD rats， 15 rats were randomly selected as the sham group， and the remaining 60 rats were used to prepare a rat model of chronic heart failure by abdominal aortic constriction （AAC）. The modeled rats were randomly allocated into model， Danhong Injection （6 mL·kg^-1）， and captopril （8.8 mg·kg^-1） groups and administrated with corresponding agents for 15 consecutive days. The levels of N-terminal pro-brain natriuretic peptide （NT-pro BNP）， adenosine diphosphate （ADP）， adenosine triphosphate （ATP）， interleukin （IL）-6， IL-1β， and tumor necrosis factor （TNF）-α and the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ were determined by enzyme-linked immunosorbent assay. The changes in cardiac function were detected by echocardiography. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to assess the protein levels of AMPK， p-AMPK， Drp1， p-Drp1， optic atrophy 1 （Opa1）， mitofusin （Mfn2）， and fission l （Fis1） in the myocardial tissue. Real-time PCR was performed to determine the mRNA levels of Opa1， Mfn2， and Fis1， and immunohistochemistry to detect the expression of p-AMPK. ResultsCompared with the sham group， the model group showed elevated levels of NT-pro BNP， ADP， TNF-α， IL-6， and IL-1β （P<0.01）， declined ATP level （P<0.01）， weakened activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ （P<0.01）， decreased left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） （P<0.01）， and increased left ventricular internal diameter at end-diastole （LVDd） and leaf ventricular internal diameter at end-systole （LVIDs） （P<0.01）. Electron microscopy results showed that the model group presented heavily abnormal myocardial structure， with large areas of myofilament structure destroyed and dissolved， significantly enlarged residual structural gaps， and fragmented mitochondria. Western blot results showed that the model group demonstrated down-regulated protein levels of p-AMPK， Mfn2， and Opa1 （P<0.01） and up-regulated protein levels of p-Drp1 and Fis1 （P<0.01） in the myocardial tissue. Real-time PCR results showed that the model group presented up-regulated mRNA level of Fis1 （P<0.01） and down-regulated mRNA levels of Mfn2 and Opa1 （P<0.01）. Immunohistochemistry results showed reduced expression of p-AMPK in the model group compared with sham group （P<0.01）. Compared with the model group， Danhong injection lowered the levels of NT-pro BNP， ADP， TNF-α， IL-6， and IL-1β （P<0.01）， raised the level of ATP （P<0.01）， increased the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ （P<0.05， P<0.01）， increased the LVEF and LVFS （P<0.01）， decreased the LVDd and LVIDs （P<0.05， P<0.01）， alleviated mitochondrial damage， up-regulated the protein levels of p-AMPK， Mfn2， and Opa1 （P<0.05， P<0.01）， down-regulated the protein levels of p-Drp1 and Fis1 （P<0.01）， reduced the mRNA level of Fis1 （P<0.01）， elevated the mRNA levels of Mfn2 and Opa1 （P<0.05， P<0.01）， and promoted the expression of p-AMPK （P<0.05）. ConclusionDanhong injection repairs the imbalance of mitochondrial dynamics， restores the mitochondrial function， improves the myocardial energy metabolism， and reduces the inflammatory response by regulating the AMPK/Drp1 pathway， thus improving the cardiac function.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

Objective:To investigate the effect of different acquisition duration of brain image of 18F-florbetaben(18F-FBB)positron emission tomography(PET)on standardized uptake value(SUV).Methods:Eight subjects who underwent 18F-FBB PET examination in Chinese PLA General Hospital from May 2021 to June 2021 were selected,including 5 persons of healthy control and 3 patients with mild cognitive impairment(MCI).All subjects underwent 18F-FBB PET imaging,and the dynamic PET images of them on brains were continuously acquired for 20 min between 90 and 110 min after the 18F-FBB injection was injected as(3.7-5.5 MBq/kg).Under the situation that other reconstruction parameters did not change,the images were reconstructed at 0-1,0-3,0-5,0-10,0-15 and 0-20 min,respectively.The same of region of interest(ROI)ranges were delineated in bilateral frontal cortex,bilateral temporal cortex,bilateral parietal cortex,posterior cingulate gyrus and cerebellar cortex of each group of images.And then,the corresponding mean standardized uptake value(SUVmean)of each region was obtained.The differences of SUVmean values of different ROI values between each group of data images and the images of 0-20 min were compared and analyzed.Results:There were significant differences in SUVmean between the acquired images in 0-1,0-3,0-5 and 0-10 min and the acquired standard images of 0-20 min(t=-7.569--2.410,P<0.05),respectively.There were no significant differences in SUVmean between the acquired images of 0-15 min and the acquired standard images of 0-20 min in the bilateral frontal lobe,bilateral temporal lobe,bilateral parietal cortex and posterior cingulate gyrus(P>0.05),only there was significant difference in the cerebellar cortex area between them(t=-5.597,P<0.001).Conclusion:The results of 15 min can reach to the similar results of 20 min in acquiring images,which can shorten the time of examination,and enhance the degrees of comfort and cooperation of patients in examination.It has clinical application value.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Objective:To investigate the efficacy and prognosis of CLAG±DAC (Clofarabine, Cytarabine, G-CSF±Decitabine) chemotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) .Methods:Continuous cases of R/R AML treated with the CLAG+DAC protocol or CLAG alone at the First Affiliated Hospital of Soochow University from January 2017 to December 2021 were retrospectively analyzed. The baseline characteristics, individual treatment regimen, treatment effect, disease progression, and survival status of patients were recorded. The factors influencing the efficacy of the CLAG±DAC chemotherapy regimens were analyzed, and the overall survival (OS) time after reinduction was calculated using the Kaplan-Meier method.Results:This study included a total of 53 patients, with 33 male patients and an average age of 40.6 years. Thirty-three patients achieved complete remission (CR+CRi) of the disease after the CLAG±DAC chemotherapy regimen and six patients achieved partial remission (PR), while 14 did not. Thirty-two patients eventually underwent hematopoietic stem cell transplantation, and the median OS of the patients was 55.9 months until follow-up. Patients with disease remission after the application of the CLAG±DAC chemotherapy had a significantly longer survival time than those without remission ( P<0.001). The results of the multifactorial analysis have revealed that combined DAC ( OR=4.60, 95% CI 1.14-23.5, P=0.04) and DNMT3A mutation ( OR=0.14, 95% CI 0.01-0.89, P=0.05) were the factors influencing the efficacy of the CLAG±DAC chemotherapy regimen. The remission rate was relatively higher in patients with R/R AML combined with FLT3-ITD mutation by applying the DAC+CLAG regimen ( OR=10.84, 95% CI 1.48-288.50, P=0.04) . Conclusion:The CLAG±DAC regimen is considered effective in patients with R/R AML, whereas decitabine combined with the CLAG regimen is more suitable for patients with R/R AML combined with FLT3-ITD mutation.

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.

The traditional experimental teaching mode of forensic science and biological evidence is mostly confined to experimental operation, which is not capable of cultivating students' comprehensive quality and post competency. Therefore, it is urgent to seek an innovative teaching and training mode. At present, the experimental teaching of forensic science and biological evidence is dominated by teachers. There are some problems, such as insufficient training of students' scientific thinking and innovation ability, single teaching and evaluation model, and disconnection from the practical application. This paper proposes an experimental teaching design scheme of forensic science and biological evidence based on post competency training. The course is implanted in the framework of simulated cases, and the virtual simulation experiment platform and group discussion learning method are used to achieve a training model oriented by social needs and centered on students. In the preliminary study on the students who were trained in this mode of selected sections, we found that, compared with traditional teaching, the time for students to complete the prescribed experimental operation in this teaching mode was shortened by 4 minutes on average, and the average score of theoretical course test case analysis questions was increased by 1.5 points. In conclusion, the instructional design of the experiment teaching forensic science and biological evidence can effectively improve students' post-competency, and it deserves further exploration and application.