BACKGROUND:Growth factor is the key effect molecule that plays a role in platelet-rich plasma in clinical treatment.There are differences in the concentration of growth factor after different activators activate platelet-rich plasma,which is an important factor affecting clinical efficacy. OBJECTIVE:To analyze the influence of different activators on the mass concentration of growth factors in platelet-rich plasma. METHODS:Totally 12 healthy volunteers were recruited to collect EDTA-K2 anticoagulant venous blood.Secondary centrifugation was used to prepare platelet-rich plasma.The difference in mass concentrations of growth factors was compared between venous blood and platelet-rich plasma.The platelet-rich plasma was mixed with four activators(normal saline,thrombin,calcium gluconate,calcium gluconate+thrombin)according to the volume ratio of 10:1,and incubated in a constant temperature water bath at 37 °C for 30 minutes.After centrifugation,the supernatant was extracted and the mass concentration of growth factor was detected.The bacterial growth in supernatant was measured by blood agar plate.Pearson correlation was used to analyze the correlation between different activators and the mass concentration of growth factor in platelet-rich plasma,and the correlation between the value of thrombocytometer and the mass concentration of growth factors in platelet-rich plasma. RESULTS AND CONCLUSION:(1)The mass concentrations of platelet-derived growth factor-BB,platelet-derived growth factor-AB,vascular endothelial growth factor,and epidermal growth factor in platelet-rich plasma were 8.7,22.2,2.3,and 2.8 times of those in venous blood,respectively(P<0.05).(2)Compared with normal saline group,the mass concentrations of platelet-derived growth factor BB,platelet-derived growth factor AB,vascular endothelial growth factor,and epidermal growth factor were increased in the thrombin group,calcium gluconate group,and calcium gluconate+thrombin group(P<0.05).The mass concentration of platelet-derived growth factor BB in the thrombin group and calcium gluconate group was higher than that in the calcium gluconate+thrombin group(P<0.05),and the mass concentration of platelet-derived growth factor AB in the thrombin group was higher than that in the calcium gluconate group and calcium gluconate+thrombin group(P<0.05).Epidermal growth factor mass concentration in the thrombin group was lower than that in the calcium gluconate group and calcium gluconate+thrombin group(P<0.05).(3)The results of blood agar plate test showed no bacterial growth in the supernatant of the four groups.(4)Pearson correlation analysis showed that the mass concentration of platelet-derived growth factor BB in platelet-rich plasma was strongly positively correlated with thrombin(r=0.683,P<0.05),and the mass concentration of vascular endothelial growth factor was strongly positively correlated with thrombin,calcium gluconate,calcium gluconate+thrombin stimulant(r=0.730,0.789,0.686,P<0.05).There was no correlation between the value of thrombocytometer and the mass concentration of four kinds of growth factors(P>0.05).(5)The results suggest that different activators have an impact on the concentration of growth factors in platelet-rich plasma.It is suggested to choose different activators to improve clinical efficacy according to different growth factor mass concentrations and treatment needs.

Objective To study the spatial distribution of the incidence of pulmonary tuberculosis in Hubei Province and its influencing factors, so as to improve the theoretical basis for scientific development of tuberculosis prevention and control measures in the future. Methods The data of reported incidence of tuberculosis and related influencing factors in various counties and districts of Hubei Province in 2020 were collected. Global Moran's I index, hotspot analysis and geographically weighted regression (GWR) model analysis were used to calculate the spatial autocorrelation of the incidence of tuberculosis, and to analyze the influencing factors affecting the incidence rate of tuberculosis. Results There were obvious regional differences in the space distribution of the incidence rate of tuberculosis. Hot spot analysis showed positive spatial correlation and obvious clustering. The GWR model (AICc=784.251) in this study had higher AICc value compared to the ordinary least squares regression (OLS) model (AICc=804.2585). The GWR model showed that the increase in the proportion of the population aged 65 and above and the proportion of the ethnic minority population had a significant promoting effect on the increase of the incidence rate of tuberculosis, and there was significant spatial heterogeneity. The effect of PM_2.5 concentration on the incidence rate of pulmonary tuberculosis varied in different regions, and the degree of effect was also different. Conclusion The proportion of people aged 65 and above and the proportion of ethnic minorities may significantly influence the incidence of pulmonary tuberculosis. The effect of PM_2.5 concentration varies in different regions, so targeted measures should be formulated according to the situation in different regions.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

AIM:To observe the effect of curcumin on a C57BL/6J mouse liver cancer model induced by N-ni-trosodiethylamine(DEN)combined with carbon tetrachloride(CCl4),and to explore its mechanism.METHODS:Forty young male C57BL/6J mice were intraperitoneally injected with DEN(25 mg/kg)14 d after birth and randomly divided in-to the following 4 groups at the 4th week(10 in each group):model control group and curcumin(100,200 and 400 mg/kg)groups.Ten male mice of the same age were used as normal control group.The mice in model group and curcumin groups were gavaged with 10%CCl4(5 mL/kg)twice a week from the 8th week on.At the same time,the mice in curcumin groups were gavaged with curcumin,and the mice in normal control group were gavaged with the same volume of distilled water once a day for 14 weeks.After administration,the mice were sacrificed,the liver surface was observed,and the number of tumor nodules was compared.The activity of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum was detected by an automatic biochemical instrument.The pathological changes of liver tissues were ob-served by HE staining.The mRNA expression levels of heme oxygenase-1(HO-1)and NAD(P)H-quinone oxidoreductase 1(NQO1)were detected by RT-qPCR,and the protein expression levels of HO-1,NQO1 and Ki67 were detected by Western blot and immunohistochemistry.RESULTS:Compared with normal control group,the body weight of the mice in model group was decreased significantly(P＜0.01),the liver index was increased significantly(P＜0.01),and the se-rum levels of ALT and AST were increased obviously(P＜0.01).There was no significant difference in the mRNA expres-sion levels of HO-1 and NQO1(P＞0.05),the protein levels of HO-1 and NQO1 were increased distinctly(P＜0.05),and the positive expression rate of Ki67 was increased significantly(P＜0.05).After curcumin treatment,the body weight of the mice was significantly increased(P＜0.01),the liver index was not changed(P＞0.05),and the number of tumor nodules in the liver was decreased significantly(P＜0.05 or P＜0.01).The serum level of AST was decreased significantly(P＜0.01),the mRNA and protein expression levels of HO-1 and NQO1 were decreased significantly(P＜0.05),and the posi-tive expression rate of Ki67 was decreased significantly(P＜0.05).CONCLUSION:Curcumin significantly protects against liver cancer in a C57BL/6J mouse model induced by DEN combined with CCl4,and its mechanism may be related to the inhibition of HO-1 and NQO1 expression.

Objective: To explore the moderating role of estradiol in the relationship between parenting styles and preschool children's behavioral problems, so as to provide a theoretical basis for improving the development of human s emotional health development in early life stage. Methods: During September to November in 2022, 354 children aged 3-6 years and their parents from two kindergartens in Bengbu City were chosen by using stratified cluster sampling method for the questionnaire survey. The Parenting Style Scale and the Child Behavior Checklist (CBCL) were used to collect information on parenting style and child behavioral problems. Salivary estradiol of children was collected and tested. Independent samples t test was applied to compare the scores of the scale for parental up bringing and children s behavioral problems, and Pearson correlation analysis was conducted to explore the relationship among parental upbringing, estradiol and children s behavioral problems. Results: Parents doting, laissez faire, autocratic, and inconsistent parenting styles were positive associated with child behavior problems( r =0.14-0.70); fathers democratic parenting style was negatively associated with child behavior problems( r =-0.14，-0.22，-0.21，-0.17，-0.27，-0.20); mothers democratic parenting styles was negatively correlated with scores on all five dimensions of child behavior problems except the withdrawal dimension ( r =-0.14，-0.12，-0.13，-0.21，-0.12)( P <0.05). Estradiol levels had significant moderating effects on maternal doting parenting style and children s withdrawal ( β =0.68) as well as social problems ( β =-1.00), also moderating laissez faire parenting styles and children s withdrawal problems ( β =0.75)( P <0.05). For children with low levels of estradiol, withdrawal problem scores were negatively associated with mother s doting parenting style and positively associated with laissez faire parenting style, and socialization problem scores were associated with mother s doting parenting style; for children with high levels of estradiol, withdrawal problem scores were positively associated with mother s doting parenting style, and socialization problem scores were associated with mother s doting parenting style ( t=2.84, 6.24, 3.16 , 2.37, 4.49, P <0.05). Conclusions Parenting styles are strongly associated with child behavioral problems; estradiol levels play a moderating role in mothers doting, laissez faire parenting styles and children s withdrawal problems and social problems.Parents should adopt more positive parenting styles and focus on the role of estradiol levels in maternal education to reduce the occurrence of behavioral problems in children.

Objective To compare the early embryonic developmental potential and clinical outcomes of oocytes matured in vivo and those matured by modified in vitro maturation(LVM)technology during the same controlled ovarian hyperstimulation(COH)cycle,and to explore the clinical application of melatonin-supplemented IVM technology.Methods 159 patients were recruited into the study.920 mature oocytes were collected during their COH cycles processed for conventional IVF/ICSI protocols,while 1 283 immature oocytes from the same cycles were matured in a melatonin-supplemented IVM medium before ICSI was performed.A retrospective analysis was conducted to compare the impact of conventional assisted reproductive technology and improved IVM technology on the outcomes of assisted reproductive therapy and pregnancy outcomes.Results Compared with mature oocytes collected from COH cycles treated with conventional IVF/ICSI,oocytes promoted by improved melatonin-supple-mented IVM technology had a lower rate of high-quality blastocyst formation.However,after embryo transfer,there was no significant difference in the clinical outcomes of mature oocytes obtained through two methods,including clinical pregnancy rate,full-term birth rate,neonatal length,and neonatal Apgar score.Conclusion The applica-tion of melatonin-supplemented IVM significantly increases the utilization of immature oocytes collected from COH cycles,improving the pregnancy outcomes of patients assisted by assisted reproductive technology.

Objective To evaluate myocardial microvascular lesions in patients with type 2 diabetes mellitus(T2DM)by 2D-speckle tracking echocardiography(2D-STE)and myocardial contrast echocar-diography(MCE).Methods A total of 45 T2DM patients admitted to the Endocrine Department of The First Affiliated Hospital of Air Force Military Medical University from August to November 2022 were enrolled in this study.All the patients were divided into two groups:simple T2DM group(n=22)and T2DM with microvascular complication group(MIC,n=23).In addition,24 healthy subjects were included as normal control(NC)group.2D-STE obtained the global longitudinal strain(GLS)and global circumferential strain(GCS);MCE obtained the average acoustic intensity(A),perfusion slope(b)of left ventricular segment,then myocardial blood flow(Aβ)was calculated and compared between groups.Results Compared with NC group,GLS,GCS,β and Aβ were lower in T2DM and MIC group(P＜0.05).Among the parameters of 2D-STE and MCE,GLS and Aβ have high diagnostic performance(P＜0.05)and GCS and β have medium diagnostic performance(P＜0.05).ROC curve analysis showed that the early warning values of myocardial microcirculation disorders were-17.63%(GLS),-21.55%(GCS),0.845 s-1(β),7.045 dB/s(Aβ)in patients with T2DM.Conclusion The mechanical strain and perfusion of myocar-dium in T2DM patients have already decreased even no lesion was shown in the peripheral micro-vessels.2D-STE combined with MCE can assess the changes of myocardial elasticity and microcirculation in T2DM in real time,which is helpful for early clinical diagnosis of diabetes cardiomyopathy and intervention guidance.

Objective:To study the prevalence and association factors of depressive and anxiety disorders in the hypertensive population.Methods:Using the database obtained from the 2013 China Chronic Disease and Risk Factor Surveillance and the 2013-2015 China Mental Health Survey,4 861 hypertensive residents were used as study subjects.And using the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)as diagnostic criterion for depressive and anxiety disorders,the 12-month prevalence was calculated.Multifactorial lo-gistic regression models were used to explore the association factors of hypertension comorbid depressive and anxie-ty disorders.Results:The 12-month prevalence rates of depressive disorders and anxiety disorders were 4.1％and 5.0％in 4 861 hypertensive residents.Chinese Han[OR(95％CI):2.00(1.01-3.93)],lack of sleep[OR(95％CI):1.82(1.34-2.48)],having myocardial infarction[OR(95％CI):2.35(1.18～4.67)]and stroke in the past year[OR(95％CI):2.10(1.19-3.72)],and chronic obstructive pulmonary disease[OR(95％CI):2.11(1.11-4.05)]were risk factors of hypertension comorbid depressive disorder.Hypertensive people with controlled blood pressure[OR(95％CI):2.01(1.30-3.13)]had a higher risk of co-morbid depressive disorder than those with blood pressure above the normal range on this measurement.Chinese Han[OR(95％CI):2.51(1.32-4.80)],Southwest China[OR(95％CI):1.64(1.02-2.63)],and lack of sleep[OR(95％CI):1.45(1.09-1.93)]were risk factors of hypertension comorbid anxiety disorder.Former but current non-smoking[OR(95％CI):0.48(0.23-0.99)]was a protective factor of hypertension comorbid anxiety disorder.Conclusion:The 12-month prevalence of anxiety disorder was higher than that of depressive disorder in this hypertensive population.Both Han and sleep deprived hypertensive people had a higher risk of comorbid depressive and anxiety disorders.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Objective:To investigate the effects of remimazolam on hemodynamics during the induction of general anesthesia and postoperative cognitive function in patients undergoing cardiac valve replacement surgery.Methods:A randomized controlled study was conducted involving 80 patients who underwent heart valve replacement surgery at Yan'an University Affiliated Hospital from January 2020 to December 2023. The patients were randomly assigned to either a control group or an observation group, with 40 patients in each group. The control group received routine general anesthesia, while the observation group received additional remimazolam during the routine anesthesia process. Hemodynamic parameters were compared between the two groups at different time points: heart rate and mean arterial pressure were recorded before anesthesia induction (T1), at the beginning of anesthesia induction (T2), 5 minutes after anesthesia induction (T3), at the time of tracheal intubation (T4), and 5 minutes after tracheal intubation (T5). The level of anesthesia during induction was compared between the two groups. Cognitive function in both groups was evaluated before and immediately after surgery. Additionally, the incidence of anesthesia-related adverse events during the perioperative period was compared between the two groups.Results:At T4 and T5, the heart rates in the observation group were (79.23 ± 10.22) beats/min and (78.54 ± 9.94) beats/min, respectively, and the mean arterial pressures were (115.64 ± 21.04) mmHg (1 mmHg = 0.133 kPa) and (108.61 ± 17.99) mmHg. Both values were significantly lower than those in the control group [heart rate: (84.51 ± 10.35) beats/min, (84.31 ± 10.08) beats/min, mean arterial pressure: (130.06 ± 19.25) mmHg, (121.62 ± 18.61) mmHg, t = 2.30, 2.58, 3.20, 3.18, all P < 0.05]. The time taken for the EEG bi-frequency index to drop below 60 and the EEG bi-frequency index before tracheal intubation in the observation group were both significantly lower than those in the control group ( t = 3.03, 3.14, both P < 0.05). Immediately after surgery, the Mini-Mental State Examination (MMSE) score in the control group showed a significant decrease ( t = 6.43, P < 0.05), while the MMSE score in the observation group did not change significantly ( t = 0.60, P > 0.05). Moreover, the immediate postoperative MMSE score in the observation group [(26.98 ± 2.97) points] was significantly higher than that in the control group [(23.15 ± 2.78) points, t = -5.95, P < 0.05]. There was no statistically significant difference in the incidence of anesthesia-related adverse events between the two groups (χ2 = 0.66, P > 0.05). Conclusion:Remimazolam can maintain hemodynamic stability during the induction of anesthesia in patients undergoing cardiac valve replacement surgery, facilitate the rapid attainment of satisfactory sedation, and reduce immediate postoperative cognitive dysfunction. Furthermore, the use of remimazolam in conjunction with routine general anesthesia does not significantly increase anesthesia-related risks, demonstrating a high level of safety.