BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

BACKGROUND:Pauwels type Ⅲ femoral neck fractures may be subjected to more shear and bending forces,and may be prone to complications such as internal fixation failure,bone nonunion,or femoral head necrosis. There is no consensus on the optimal selection of internal fixation devices.OBJECTIVE:To compare the biomechanical properties of four types of internal fixation methods for Pauwels type Ⅲ femoral neck fracture by finite element analysisMETHODS:Femur CT data of a healthy young volunteer were imported into Mimics software to construct a three-dimensional model of normal femur. Pauwels type Ⅲ femoral neck fracture was simulated based on 70° fracture line. Four types of fracture internal fixation models were optimized and constructed using Geomagic and UG software:conventional inverted triangle hollow screw,femoral neck fixation system,femoral neck fixation system plus anterior or posterior hollow screw treatment. Finally,Ansys software was used to analyze the stress distribution,peak stress,and peak displacement of proximal femur fracture block in four types of different internal fixation models. The displacement distribution and peak displacement of internal fixation device and femoral neckfracture were observed.RESULTS AND CONCLUSION:(1) The peak stress of proximal fracture fragments in the four groups was concentrated near the fracture line. The peak stress in the femoral neck fixation system group was the largest,and that in the conventional inverted triangle hollow screw group was the smallest. (2) The peak displacement of fracture fragments was located at the top of the femoral head. The peak displacement of the conventional inverted triangle hollow screw group was the largest,and that in the femoral neck fixation system+hollow screw (posterior) group was the smallest. (3) The peak displacement of the internal fixation model was located at the top of the model. The peak displacement was maximum in the conventional inverted triangle hollow screw group and minimum in the femoral neck fixation system+hollow screw (posterior) group. (4) The displacement of the fracture surface in the femoral neck fixation system+hollow screw (posterior) group was at the upper part of the fracture end. The peak displacement was the largest in the conventional inverted triangle hollow screw group and the smallest in the femoral neck fixation system+hollow screw (posterior) group. (5) It is indicated that compared with the other three internal fixation methods,femoral neck fixation system+hollow screw (posterior) group showed good biomechanical stability. When Pauwels type Ⅲ femoral neck fracture occurs in a young person,from the point of view of finite element analysis,it may be a more favorable choice to treat the Pauwels type Ⅲ femoral neck fracture.

Objective:To explore the potential profiles of health literacy in patients with chronic atrophic gastritis (CAG) and analyze their influencing factors.Methods:A cross-sectional study was conducted to select CAG patients admitted to Nanjing Hospital of Traditional Chinese Medicine or attending outpatient clinics from January 2023 to June 2024 by convenience sampling method, and all patients participated in this study two months after treatment. The General Information Questionnaire, the General Self-Efficacy Scale, and the All-around Health Literacy Measurement Scale (AAHLS) were used to conduct the questionnaire survey. The three dimensions of AAHLS were used as exogenous indicators for potential profile analysis, to compare the differences in general information and self-efficacy of patients with different potential profiles, and to analyze the influencing factors of different potential profiles of health literacy in CAG patients by multi classification Logistic regression.Results:The recovery rate of valid questionnaires was 97.71%(256/262). Among the 256 patients, there were 164 males and 92 females, with 86 patients aged 18-44 years old, 110 patients aged 45-59 years old, and 60 patients aged ≥ 60 years old. The health literacy of CAG patients was categorized into 3 potential profiles, including the high health literacy-appraisal and application competence group (14.84%, 38/256), the medium health literacy-appraisal and application competence group (32.81%, 84/256), and the low health literacy-appraisal and application competence group (52.34%, 134/256). The results of multi classification Logistic regression analysis showed that when the low health literacy-appraisal and application competence group was used as a reference, aged 18-44 years old ( OR=8.954, 95% CI 2.049-39.127), poor self-efficacy ( OR=0.089, 95% CI 0.027-0.293), duration of disease <5 years ( OR=0.049, 95% CI 0.014-0.169), per capita monthly household income<3 000 yuan ( OR=0.072, 95% CI 0.018-0.299), and primary school education or below ( OR=0.016, 95% CI 0.003-0.088) were independent influences in the the high health literacy-appraisal and application competence group (all P<0.05); poorer self-efficacy ( OR=0.458, 95% CI 0.251-0.834) and per capita monthly household income<3 000 yuan ( OR=0.212, 95% CI 0.100-0.453) were independent influences in the medium health literacy-appraisal and application competence group (both P<0.05). Conclusions:The health literacy of CAG patients is obviously heterogeneous, and healthcare professionals in clinical work should adopt targeted assessment and intervention according to the different characteristics of each category in order to improve the health literacy of CAG patients.

BACKGROUND:Pauwels type Ⅲ femoral neck fractures may be subjected to more shear and bending forces,and may be prone to complications such as internal fixation failure,bone nonunion,or femoral head necrosis. There is no consensus on the optimal selection of internal fixation devices.OBJECTIVE:To compare the biomechanical properties of four types of internal fixation methods for Pauwels type Ⅲ femoral neck fracture by finite element analysisMETHODS:Femur CT data of a healthy young volunteer were imported into Mimics software to construct a three-dimensional model of normal femur. Pauwels type Ⅲ femoral neck fracture was simulated based on 70° fracture line. Four types of fracture internal fixation models were optimized and constructed using Geomagic and UG software:conventional inverted triangle hollow screw,femoral neck fixation system,femoral neck fixation system plus anterior or posterior hollow screw treatment. Finally,Ansys software was used to analyze the stress distribution,peak stress,and peak displacement of proximal femur fracture block in four types of different internal fixation models. The displacement distribution and peak displacement of internal fixation device and femoral neckfracture were observed.RESULTS AND CONCLUSION:(1) The peak stress of proximal fracture fragments in the four groups was concentrated near the fracture line. The peak stress in the femoral neck fixation system group was the largest,and that in the conventional inverted triangle hollow screw group was the smallest. (2) The peak displacement of fracture fragments was located at the top of the femoral head. The peak displacement of the conventional inverted triangle hollow screw group was the largest,and that in the femoral neck fixation system+hollow screw (posterior) group was the smallest. (3) The peak displacement of the internal fixation model was located at the top of the model. The peak displacement was maximum in the conventional inverted triangle hollow screw group and minimum in the femoral neck fixation system+hollow screw (posterior) group. (4) The displacement of the fracture surface in the femoral neck fixation system+hollow screw (posterior) group was at the upper part of the fracture end. The peak displacement was the largest in the conventional inverted triangle hollow screw group and the smallest in the femoral neck fixation system+hollow screw (posterior) group. (5) It is indicated that compared with the other three internal fixation methods,femoral neck fixation system+hollow screw (posterior) group showed good biomechanical stability. When Pauwels type Ⅲ femoral neck fracture occurs in a young person,from the point of view of finite element analysis,it may be a more favorable choice to treat the Pauwels type Ⅲ femoral neck fracture.

Objective:To explore the potential profiles of health literacy in patients with chronic atrophic gastritis (CAG) and analyze their influencing factors.Methods:A cross-sectional study was conducted to select CAG patients admitted to Nanjing Hospital of Traditional Chinese Medicine or attending outpatient clinics from January 2023 to June 2024 by convenience sampling method, and all patients participated in this study two months after treatment. The General Information Questionnaire, the General Self-Efficacy Scale, and the All-around Health Literacy Measurement Scale (AAHLS) were used to conduct the questionnaire survey. The three dimensions of AAHLS were used as exogenous indicators for potential profile analysis, to compare the differences in general information and self-efficacy of patients with different potential profiles, and to analyze the influencing factors of different potential profiles of health literacy in CAG patients by multi classification Logistic regression.Results:The recovery rate of valid questionnaires was 97.71%(256/262). Among the 256 patients, there were 164 males and 92 females, with 86 patients aged 18-44 years old, 110 patients aged 45-59 years old, and 60 patients aged ≥ 60 years old. The health literacy of CAG patients was categorized into 3 potential profiles, including the high health literacy-appraisal and application competence group (14.84%, 38/256), the medium health literacy-appraisal and application competence group (32.81%, 84/256), and the low health literacy-appraisal and application competence group (52.34%, 134/256). The results of multi classification Logistic regression analysis showed that when the low health literacy-appraisal and application competence group was used as a reference, aged 18-44 years old ( OR=8.954, 95% CI 2.049-39.127), poor self-efficacy ( OR=0.089, 95% CI 0.027-0.293), duration of disease <5 years ( OR=0.049, 95% CI 0.014-0.169), per capita monthly household income<3 000 yuan ( OR=0.072, 95% CI 0.018-0.299), and primary school education or below ( OR=0.016, 95% CI 0.003-0.088) were independent influences in the the high health literacy-appraisal and application competence group (all P<0.05); poorer self-efficacy ( OR=0.458, 95% CI 0.251-0.834) and per capita monthly household income<3 000 yuan ( OR=0.212, 95% CI 0.100-0.453) were independent influences in the medium health literacy-appraisal and application competence group (both P<0.05). Conclusions:The health literacy of CAG patients is obviously heterogeneous, and healthcare professionals in clinical work should adopt targeted assessment and intervention according to the different characteristics of each category in order to improve the health literacy of CAG patients.

Background and aim:Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA discontinuation. Methods:Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment.Demographic,clinical,and laboratory data were collected and analyzed after NA discontinuation. Results:Ninety-six patients who finished 5 years of follow-up were included.HBsAg remained unde-tectable in 29 patients with end of treatment(EOT)HBsAg negativity.Among 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9％)patients with an estimated annual inci-dence of HBsAg seroclearance of 3.6％.Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of＞1000 IU/mL(33.3％vs.5.4％).The pro-portion of patients with HBsAg ≤1000 IU/mL increased during follow-up.Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL.The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. Conclusions:Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg sero-clearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation.Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

Objective:To compare the clinical efficacy of femoral distraction and homeopathic double reverse traction reduction assisted internal fixation in the treatment of Schatzker type IV-VI tibial plateau fractures.Methods:A total of 51 patients (28 males and 23 females) with Schatzker IV-VI tibial plateau fractures treated with femoral distraction or homeopathic double reverse traction reduction from January 2017 to June 2021 in the Second Affiliated Hospital of Wenzhou Medical University were retrospectively analyzed. The average age was 49.6±11.9 years (range, 28-71 years). The time from injury to operation was 4.5±3.0 days (range, 1-15 days). There were 5 cases with combined anterior cruciate ligament injuries and 9 cases with posterior cruciate ligament injuries. Twenty-five cases were treated with femoral distraction reduction (distraction reduction group) and 26 cases with homeopathic double reverse traction reduction (traction reduction group). The operation time, intraoperative blood loss, visual analogue scale (VAS) on the first day after operation, hospitalization time, fracture healing time, and incidence of complications were compared between the two groups. Hospital for Special Surgery (HSS) knee function score at 1, 3, 6, 12 months after operation were also compared.Results:All patients were operated successfully. The operation time was 125.9±35.1 min (range, 60-220 min), and the intraoperative blood loss was 138.4±85.4 ml (range, 30-400 ml). 15 patients received autologous iliac bone grafting and 36 patients received allogeneic bone grafting. The VAS score on the first day after operation was 2.4±0.7 (range, 1-4), the hospital stay was 12.6±3.6 days (range, 7-24 days), and the fracture healing time was 14.6±2.2 weeks (range, 12-21 weeks). All patients were followed up for 16.8±2.8 months (range, 13-25 months). The operation time, intraoperative blood loss and hospital stay in the traction reduction group were 106.2±21.7 min, 86.9±42.6 ml and 11.6±3.3 days, respectively, which were less than 146.4±34.9 min, 192.0±86.2 ml and 13.7±3.6 days in the distraction reduction group. The differences were statistically significant ( P<0.05). The HSS scores of traction reduction group at 1 month and 3 months after operation were 83.8±1.7 and 86.7±2.0, which were higher than those of distraction reduction group (81.0±2.6 and 84.9±2.6), and the differences were statistically significant ( P<0.05). There was no significant difference in HSS score between the two groups at 6 and 12 months after operation ( P>0.05). Conclusion:The internal fixation treatment of Schatzker type IV-VI tibial plateau fracture assisted with homeopathic double reverse traction reduction can reduce the amount of intraoperative blood loss, operation time and hospital stay, and improve the knee function in the early postoperative period.

Objective To study the effect of empathetic nursing combined with solution-focused mode on sleep and psychological stress in patients with hysterectomy.Methods Totally 100 patients who underwent hysterectomy in the Gynecology Department of our hospital from August 2021 to July 2022 were selected.They were numbered according to the order of admission and divided into two groups by random envelope method.The control group was given routine nursing care intervention.The experimental group implemented the empathetic nursing combined with the solution-focused mode.The scores of Self-rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS),Pittsburgh Sleep Quality Index(PSQI)and General Self-Efficacy Scale(GSES)were compared between the two groups.Results On the 3rd day after operation,the SAS score and SDS score of the experimental group were significantly lower than those of the control group,the differences were statistically significant(P<0.05).The PSQI score of the experimental group 3 days after operation was significantly higher than that of the control group,the difference was statistically significant(P<0.05).The GSES score of the experimental group 3 days after operation was significantly higher than that of the control group,the difference was significantly different(P<0.05).Conclusion The application of empathetic nursing combined with solution-focused mode in the nursing of patients with hysterectomy can significantly reduce the psychological stress response of the patients,improve the self-efficacy and sleep quality of the patients,and is beneficial to postoperative rehabilitation of the patients.

OBJECTIVE: To explore the genetic and clinical characteristics of near-tetraploidy/tetraploidy karyotype (NT/T) in patients with myelodysplastic syndrome (MDS). METHODS: Cytogenetic findings of 1576 inpatients with primary MDS were retrospective analyzed, among which 9 were diagnosed with NT/T. Clinical data including gender, age, morphology, genetic feature and prognosis were analyzed. RESULTS: The prevalence of MDS patients with NT/T (NT/T-MDS) among all cases was 0.57%. Karyotyping analysis suggested that eight MDS patients had sole NT/T, while the remainder one had a complex karyotype. In addition to the typical morphology of MDS, NT/T-MDS had unique morphology including huge blast, double-nuclear cell and irregular nuclear membrane. One NT/T-MDS patient gave up therapy, and the remaining eight underwent the first course of treatment, albeit with poor prognosis. Only one patient had complete remission, one had partial remission, three had no remission; and three had converted to acute myeloid leukemia. CONCLUSION NT/T-MDS is rare and has unique morphology. Generally, NT/T-MDS patients have poor prognosis. However, NT/T cannot be simply classified as high-risk group, but with consideration whether they have affected particular chromosomal structures as well as other clinical data.
Humans ; Karyotype ; Leukemia, Myeloid, Acute/complications* ; Myelodysplastic Syndromes/pathology* ; Prognosis ; Retrospective Studies ; Tetraploidy

Objective: To investigate the health status of occupational mercury workers and reveal the effects of mercury exposure on the cardiovascular system. Methods: In June 2019, a total of 2651 mercury workers participated in the occupational health examination between 2016-2018 from a thermometer manufacturing plant and a fluorescent lamp manufacturing plant were included in this study. Then, they were divided into a high-level mercury exposure group (425 workers whose urine mercury concentration >35 μg/g creatinine) and a low-mercury mercury exposure group (2226 workers whose urinary mercury concentration <35 μg/g creatinine) . Mercury concentration in the workplace was also detected. Finally, the results of electrocardiogram (ECG) , blood routine, blood biochemistry and other physical examinations were analyzed. The measurement data of age and exposure years were analyzed by test. Urinary mercury and blood parameters were analyzed by Mann-Whitney nonparametric test. Chi-square test was used for the analyses of gender, ECG abnormality rate and other categorical data. Results: The 8-hour weighted average allowable concentration (CTWA) of mercury in the workplace of high-exposure group was 0.002 2-0.152 mg/m³. The abnormal rate of ECG in the high-exposed group (29.6%) was higher than that in the low-exposure group (10.1%) in 2018 (P<0.01) . Compared with the low-exposure group, the WBC of the high-exposure group from 2016 to 2018 was increased, with statistically significance (P<0.05) ; the RBC of the high-exposure group in 2016 and 2017 was decreased, with statistically significance (P<0.01) ; the total bilirubin concentration in the high-exposure group was decreased from 2016 to 2018, with statistically significance (P<0.05) . Conclusion Long-term exposure to high concentration of mercury in the workplace may influence cardiovascular system. Therefore, engineering protection and individual protection should be implemented well.