Objective To establish an acute rejection model of cervical heart transplantation in mice and evaluate the survival and dynamic rejection process post-transplantation. Methods Mice were randomly divided into sham operation group (n=10), syngeneic transplantation group (n=21), and allogeneic transplantation group (n=65). Sham operation, syngeneic cervical heart transplantation, and allogeneic cervical heart transplantation were performed respectively. The survival of recipient mice and grafts, histopathological changes of graft tissues, subpopulations of splenic lymphocytes, and expression of inflammatory factors in serum and grafts were observed. Results The survival rate and graft survival rate of the sham operation group and syngeneic transplantation group were 100% at 7 days after surgery. In the allogeneic transplantation group, 5 cases failed and died on the first day after surgery. The survival rate at 7 days after surgery was 86%, and all surviving mice had grafts that stopped beating at 7 days after surgery. The allogeneic transplantation group showed significant rejection at 7 days after surgery, accompanied by tissue damage and CD8⁺ T cell infiltration. The proportion of CD8⁺ T cells in the spleen continued to rise post-operation, while the proportion of CD4⁺ T cells showed a downward trend. The expression of interferon-γ in serum and grafts peaked at 5 days after surgery, while the expression of tumor necrosis factor-α showed no statistical significance. Conclusions Acute rejection following heart transplantation in mice intensifies between 5 to 7 days after surgery, which may be a critical time window for immunological intervention.

Objective:To classify the etiology of secondary hemophagocytic syndrome (sHLH) and explore its clinical, laboratory and therapeutic characteristics in order to deepen the understanding of the disease.Method:A retrospective observational study was conducted on sHLH patients who were treated at Peking University People's Hospital from January 2016 to December 2021. Patients under the age of 18 and those with missing clinical data were excluded. The distribution of departments visited and etiologies of sHLH were analyzed. Baseline data, clinical characteristics, complications, laboratory data, treatment, and in-hospital outcomes of sHLH were collected. The sHLH patients were then divided into 3 groups including malignancy group, macrophage activation syndrome (MAS) group and other etiologies (mainly infection) group. Intergroup comparisons were performed using chi-square tests, analysis of variance, Mann-Whitney tests, and other statistical methods.Results:A total 169 patients were enrolled, among these patients, 27.8% were malignancy-related HLH, 47.9% were MAS, and 24.3% were other etiologies related HLH. Statistical analysis revealed that the clinical characteristics of other etiological group was highly consistent with the malignancy group, including more and severer peripheral blood cell reduction, higher sCD25 levels, more Epstein-Barr virus infection, and the prognosis was similar, both were with more than 50% in-hospital mortality. And the incidence of hemophagocytosis was highest in other etiological groups (65.9%). In contrast, MAS group was with an obviously lower mortality of 17.3% ( P<0.05). Meanwhile, treatments including methylprednisolone pulse, cyclosporine A and interleukin-2 were used frequently in MAS group. Conclusion:Malignancy related HLH and other etiologies related HLH exhibit more similar clinical characteristics and prognosis, while the MAS group, has a milder overall condition and better prognosis.

Objective:To summarize the clinical characteristics in of different antibody subtypes in of patients with antisynthetase syndrome (ASS) complicated with interstitial lung disease (ILD).Methods:A retrospective analysis was conducted on 132 ASS-ILD patients at the First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People′s Hospital), encompassing a period from December 2019 to June 2023. The data included were basic demographic information, clinical features, laboratory test results, chest computed tomography (CT) scans, and pulmonary lung function tests. Patients were categorized into distinct subtypes based on anti-aminoacyl tRNA synthetase (ARS) antibodies. Statistical analysis was performed using a t-test for comparing means between two samples with equal variance, the Mann-Whitney U test for non-normally distributed continuous data, and the chi-square ( χ2) test or Fisher′s exact test for categorical variables. Results:The most prevalent subtype of anti-synthetase antibody was anti-histidine antibody (Jo-1), accounting for 60 of 132 cases (45.5%), followed by anti-glycine-based tRNA synthetase antibody (EJ) (33/132, 2 5.0%), anti-tRNA synthase antibody (PL-7) (26/132, 19.7%), anti-alanine-based tRNA synthetase antibody (PL-12) (7.6%, 10/132), anti-isoleucine-tRNA synthase antibody (OJ) (3/132, 2.2%). The presence of anti-Ro-52 antibodies was significantly associated with rapidly progressive ILD. In patients with different subtypes of ASS-ILD, the presence of anti-Jo-1 antibodies is was positive in 28 cases (46.7%), and the combination of infection is was more common than in other groups ( χ2=0.15, P=0.047). The group with positive anti-EJ antibodies has had a significant decline in lung function, and cough is was more common in 31 cases (93.9%) than in other groups ( P<0.05); the group with positive anti-PL-12 antibodies has had a more pronounced decline in lung function than other groups ( P<0.05), and fever (7 cases, 70.0%) wais more common than in other groups ( χ2=0.02, P=0.022). Conclusion:Anti-Jo-1, Anti-PL-7, and Anti-PL-12 antibodies were are observed more frequently in patients with ILD. Furthermore, a significant deterioration in lung function was is observed in patients testing positive for anti-PL-12 and anti-EJ antibodies.

Background::Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods::Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. Results::Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). Conclusions::YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

Objective To analyze the clinical characteristics and related to risk factors of late-life depression patients with venous thromboembolism in the elderly ward.Methods A retrospective analysis was conducted on 143 hospitalized depression patients(aged≥60 years)including 65 depression patients with VTE(VTE group)and 78 depression patients without VTE(control group)in the elderly ward of Beijing Anding Hospital from January 2023 to September 2023.The clinic and laboratory data was collected such as general demographic information,relevant clinical data,VTE history,personal history,thyroid function,hormone levels,blood lipid levels and D-dimer to analyze and compare the clinical characteristics of two group patients,and Logistic regression was used to analyze the related risk factors of VTE in patients with depression.Results Compared with control group,patients in the VTE group were older[(70.94±5.88)years vs.(68.04±4.92)years,P<0.05],had a higher total HAMD score(26.35±9.28 vs.23.19±5.94,P<0.05),a higher proportion of a history of VTE[13 cases(20.0%)vs.6 cases(7.7%),P<0.05],a higher proportion of bedridden for more than 72 hours[42 cases(64.6%)vs.31 cases(39.7%),P<0.05],lower HDL-C levels[(1.27±0.27)mmol/L vs.(1.39±0.28)mmol/L,P<0.05],and higher levels of D-dimer[1.91(0.82,3.51)mg/L FEU vs.0.48(0.25,0.80)mg/L FEU,P<0.05].Logistic regression analysis showed that total HAMD scores(OR=1.077,P=0.018),history of VTE(OR=4.339,P=0.023),bedridden for more than 72 hours(OR=2.449,P=0.044),and D-dimer level(OR=2.404,P<0.001)were risk factors for hospitalized late-life depression patients with VTE in the elderly ward.Conclusions Depression patients with VTE in the elderly ward have several clinical characteristics including older age,more severe depressive symptoms,lower HDL-C levels,higher D-dimer levels,and higher proportion of a history of VTE and bedridden for more than 72 hours.Depressive symptoms,a history of VTE,bedridden for more than 72 hours,and D-dimer levels may be risk factors for late-life depression patients with VTE in the elderly ward.

Objective:To develop college students' proactive aggression questionnaire (CPAQ) and test its reliability and validity.Methods:From March 2023 to April 2024, a questionnaire survey was conducted among 1 552 college students(618 individuals in Sample 1, 783 individuals in Sample 2, 151 individuals in Sample 3 (retested after a 6-month interval), and 49 individuals in Sample 4 (randomly selected from Sample 3)).The reliability and validity of CPAQ were assessed using SPSS 24.0 and Mplus 8.3 software through item analysis, exploratory factor analysis, confirmatory factor analysis, internal consistency reliability, test-retest reliability, compatibility validity, discriminant validity, and empirical validity.Results:The results of the project analysis showed that the 33 items in the CPAQ were significantly correlated with the total score( r=0.25-0.78, P<0.05), and item scores between the high and low group were significantly different (all P<0.001). Exploratory factor analysis retained 28 items, which belonged to three dimensions of proactive aggression (instrumental motivation, moral inhibition, and moral disengagement). The results of confirmatory factor analysis showed that the three-dimensional model of the questionnaire was well fitted ( χ2/ df=3.25, CFI=0.96, TLI=0.95, RMSEA=0.05, SRMR=0.06). The Cronbach's α coefficients for the total score of CPAQ and its sub dimensions were 0.93, 0.95, 0.89 and 0.75, respectively(all P<0.05). The test-retest reliability was 0.64, 0.63, 0.67 and 0.60, respectively(all P<0.01). In the compatibility validity test, the instrumental motivation dimension score was positively correlated with the proactive aggression dimension score of reactive-proactive aggression questionnaire(RPQ)( r=0.50, P<0.05), while moral inhibition dimension was negatively correlated with empathy and guilt scores( r=-0.30, -0.39, P<0.05). The dimension of moral disengagement was positively correlated with the score of the moral disengagement scale( r=0.58, P<0.05). In the discriminant validity test, the correlation of CAPQ and RPQ reactive aggression dimension score was not significant( r=0.08, P=0.16). In the criterion related validity test, the correlation coefficients between the score of CAPQ and each calibration questionnaire and scale were 0.70-0.83. In the empirical validity test, there was a significant difference in the different CPAQ score groups for proactive aggressive behavior(high group: (1.16±0.18), low group: (1.04±0.08), t=2.60, P<0.05). Conclusion:CPAQ has good discrimination, reliability, and validity, which could be used as a tool to measure proactive aggressive behavior among college students.

Micronutrients (MNs), including vitamins and trace elements, play an indispensable role in human metabolism, immune function and other aspects. Due to the chronic microinflammation and long-term chemoradiotherapy, patients with malignant tumors often suffer from malnutrition, resulting in different degrees of MNs deficiency. In severe cases, MNs deficiency is closely related to the adverse clinical outcomes. Therefore, reasonable MNs supplementation is of great significance in improving the prognosis and quality of life of patients with tumors. Recently, multiple guidelines have made recommendations on the application of MN supplementation in various clinical settings, providing evidence for the standardized MN supplementation in patients with malignant tumors.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To investigate the role of HIS (hyperinflammatory syndrome) score in predicting the prognosis of anti-melanoma differentiation associated gene 5(MDA5) antibody-positive dermatomyositis (DM) patients with interstitial lung disease (ILD).Methods:A total of 43 patients with anti-MDA5 antibody-positive dermatomyositis and 228 connective tissue disease (CTD) patients with ILD hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2018 to April 2021 were enrolled into this study. All patients were complicated with ILD and their HIS score were assessed. Non-parametric Mann-Whitney U test, Chi-squared test, Fisher exact probability and receiver operating characteristic (ROC) curve were used for data analysis. Results:The HIS score of 43 patients with anti-MDA5 antibody-positive dermat-omyositis were collected. Among 228 CTD-ILD patients in the control groups, the primary disease consisted of 33(14.5%) anti-synthetase antibody syndrome (ASS), 44(19.3%) rheumatoid arthritis (RA), 65(28.5%) Sj?gren's syndromes (SS), 43 (18.9%) systemic sclerosis (SSc) and 43 (18.9%) systemic lupus erythematosus(SLE). The HIS score of anti-MDA5-positive DM-ILD patients [2(1, 3)] was higher than those in ASS patients [1(0, 2), Z=-2.06, P<0.05] and significantly higher than those in RA-ILD [1(0, 2), Z=-2.87, P<0.01], SS-ILD [0(0,1), Z=-5.78, P<0.01], SSC-ILD [1(0, 1), Z=-3.84, P<0.01] and SLE-ILD [1(0, 2), Z=-3.81, P<0.01]. Comparing HIS score of anti-MDA5-positive DM-ILD patients, the 3-months mortality rate in the low, medium and high groups was 0(0/15), 38.1%(8/21) and 85.7%(6/7). The area under ROC curve (95% CI) was 0.857[(0.747, 0.967), P<0.001] for HIS score in predicting 3-months mortality probability of anti-MDA5-positive DM-ILD. Conclusion:HIS score of anti-MDA5-positive DM-ILD is higher than that in CTD-ILD patients and the baseline level is related to the 3-months mortality rate.

Objective:To explore the clinical effects of combined medial and lateral approaches in treating of calcaneal fractures combined with sustentaculum tali fractures and/or dislocations of sustentaculum tali-talus joint.Methods:Four adult cadaver specimens (8 feet) were selected, of which two (4 feet) were dissected on the medial side of the calcaneus to observe the adjacency and exposure range of sustentaculum tali. The other two specimens were simulated as medial and lateral approaches to reduce and fix calcaneal fractures. Retrospective analysis of 9 cases (9 feet) of Sanders II-IV type calcaneal fractures with combined medial and lateral approaches in the treatment of fractures and/or dislocations of sustentaculum tali-talus joint was performed. The average age was 49.9±11.3 (25-58) years. During the operation, the medial incision was made first, and the sustentaculum tali fracture was temporarily reduced and fixed to the talus. Then the lateral incision was made to expose the lateral side of the calcaneus, and the fracture fragments were reduced and fixed; the sustentaculum tali was fixed laterally with screws, and 2 cases were additionally fixed medially with absorbable rods. At the same time, six cases (8 feet) of calcaneal fractures with sustentaculum tali fractures and/or dislocations of sustentaculum tali-talus were treated with lateral approach as a control group. The lateral sides of both groups were fixed with calcaneal locking plate and implanted with demineralized bone matrix into the cavity after articular surface reduction. The B?hler and Gissane angles of the two groups of patients were measured at 1 year after operation. The American Orthopaedic Foot and Ankle Society (AOFAS) scoring system was used to evaluate the clinical efficacy.Results:The sustentaculum tali-talus joint had a shape of an inverted "V" with two divided parts. The tip of the sustentaculum tali was exposed through the front window of the posterior tibial tendon. The sustentaculum tali and the medial side of the calcaneal body was completely exposed and fixed through the window between the posterior tibial tendon and the flexor digitorum longus tendon. The postoperative incision blood loss in the combined medial and lateral approach group was 73.6±4.3 ml, which was greater than that in the lateral approach group (70.6±7.1 ml) ( t=2.18, P=0.045). The lateral incision healed in both groups. The medial incision healed delayed in 1 patient in the combined medial and lateral approach group. The fractures in the combined medial-lateral approach group and the lateral approach group were both healed. The healing duration was 12.2±2.1 weeks and 12.8±2.8 weeks, respectively, without significant difference ( t=0.50, P=0.622). The B?hler angles of the combined medial-lateral approach group and the lateral approach group were 37.0°±5.7° and 27.9°±4.0° at 1 year after operation, respectively. These values were greater than the preoperative values of 4.7°±3.4° and 3.9°±2.9° ( P<0.05), with significant difference between groups ( t=3.76, P=0.002). The Gissane angles were 133.2°±9.8° and 139.1°±9.4° respectively, which were lower than those of 172°±7.3° and 175.6°±5.6° before operation ( P<0.05). There was no significant difference between the groups ( t=1.26, P=0.226). The AOFAS score of the combined medial and lateral approach group was 93.6±4.0 points, which was higher than that of the lateral approach group (84.3±8.2 points) ( t=3.03, P=0.008). Conclusion:Intra-articular calcaneal fractures combined with a high probability of sustentaculum tali fractures and/or dislocations of sustentaculum tali-talus joint. Compared with the simple lateral approach, the use of the combined medial-lateral approach and the medial-lateral surgical sequence is beneficial to restore the calcaneal alignment and anatomic shape, especially the alignment relationship of the medial calcaneus and talus, so as to obstain better early clinical outcomes.