BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

Objective To analyze the relationship between cognitive function, motor ability and the risk of falls in patients during the rehabilitation period after stroke. Methods A total of 330 patients with stroke who received rehabilitation treatment in the hospital from February 2022 to February 2025 were classified into fall group (n=105) and non-fall group (n=225) based on the occurrence of falls during rehabilitation period. The clinical data of patients were collected, and the motor function of patients was evaluated by Fugl-Meyer scale, and the cognitive function of patients was assessed by mini-mental state examination (MMSE). Univariate and logistic multivariate regression analyses were applied to analyze the factors affecting the occurrence of falls. Spearman correlation analysis was performed to analyze the relationship between motor ability, cognitive function and risk of falls. Results The proportions of osteoporosis, malnutrition, sleep disorder and history of falls in the fall group were higher while the education level, Fugl-Meyer score and MMSE score were lower compared to the non-fall group (P<0.05). After logistic multivariate analysis, it was found that osteoporosis, malnutrition, sleep disorder, history of falls, low education level, low Fugl-Meyer score and low MMSE score were risk factors for falls in patients during post-stroke rehabilitation period (P<0.05). Correlation analysis indicated that the motor ability and cognitive function in patients during post-stroke rehabilitation period were negatively associated with the occurrence of falls (r=-0.579, -0.438, P<0.001). Conclusion The cognitive function, motor ability of patients in the post-stroke rehabilitation period are closely related to the risk of falls. Clinically, the risk of falls in patients during post-stroke rehabilitation period can be reduced by improving the motor ability and cognitive function.

Objective: To investigate the effects of different storage temperatures and durations on the activities of coagulation factor Ⅷ (Factor Ⅷ, FⅧ) and coagulation factor Ⅸ (Factor Ⅸ, FⅨ) after whole blood collection, so as to provide data support for the optimal storage conditions. Methods: A total of 16 mL of whole blood was collected from each of the 20 healthy volunteers at our blood center and aliquoted into 8 sodium citrate anticoagulant tubes. Two tubes were immediately centrifuged for the measurement of FⅧ and FⅨ activity levels. The remaining 6 tubes of whole blood were respectively stored under room temperature and low-temperature conditions. At 2, 4, and 6 h, the whole blood samples were centrifuged and analyzed for FⅧ and FⅨ activity levels. The mean values of the two immediately tested tubes were used as the control group, while other tubes were designated as the experimental groups for comparison. Statistical analysis was performed using SPSS 26.0. Results: The activity of FⅧ in whole blood remained stable after 4 hours of storage at both room temperature and low temperature (116.53±25.95 vs 125.22±27.33, 109.77±23.23 vs 125.22±27.33) (P>0.05 for both). However, by 6 hours, FⅧ activity showed a statistically significant decline compared to the control group (108.65±22.92 vs 125.22±27.33, 100.46±20.19 vs 125.22±27.33) (P<0.05 for both), though the room temperature group results were closer to the control values. The activity of FⅨ in whole blood remained stable after 6 hours of storage under both conditions (97.14±19.48 vs 96.76±19.67, 97.10±17.45 vs 96.76±19.6) (P>0.05 for all comparisons). Conclusion: For whole blood samples after collection, storage at either room temperature or low temperature for up to 4 hours does not compromise the accuracy of test results. When stored for 6 hours, FⅨ activity remains stable, whereas FⅧ activity decreases significantly. Notably, FⅧ activity demonstrates better stability at room temperature than under low-temperature conditions within the 6-hour storage.

Objective: To explore the application effect of a guided self help intervention based on dialectical behavior therapy (DBT) to address non suicidal self injury (NSSI) behavior among college students, so as to provide a reference for reducing the occurrence of NSSI behavior in this population. Methods: A total of 106 college students with NSSI admitted to the Department of Child and Adolescent Psychology, the Second Affiliated Hospital of Jining Medical University from January 2021 to January 2023 were selected and divided into an observation group and a control group, with 53 cases in each group, using a random number table method. The control group received routine medication treatment and psychological intervention, while the observation group, on the basis of the interventions provided to the control group, implemented dialectical behavior therapy based guided self help. The approach combines group activities, individual counseling, and selfdirected learning, covering four core modules: mindfulness training, distress tolerance, interpersonal effectiveness, and emotion regulation. Meanwhile, data collection, skill check ins, and personalized recommendation pushes were conducted through a WeChat. Both groups were intervented for 12 weeks. Before the intervention and after the intervention, the Adolescent Non suicidal Self injury Behavior Questionnaire, Ottawa Self injury Inventory (OSI), and Barratt Impulsiveness Scale (BIS) were used to evaluate the patients, and the levels of serum neurotransmitters were detected. The χ 2 test, t test, and Cochran s Q test were used for data comparison and analysis. Results: The incidence rates of NSSI in the observation group after 3, 6, and 12 weeks of intervention were 47.17%, 16.98%, and 5.66%, respectively, all lower than those in the control group (67.92%, 35.85%, 20.75%) ( χ 2=4.67, 4.85, 5.27,all P <0.05). After 12 weeks of intervention, in the NSSI Behavior Questionnaire, the total score of the observation group was (17.94±2.69) points, which was lower than that of the control group (23.04±5.11) points; in the Function Questionnaire, the total score of the observation group was (53.24±8.94) points, which was higher than that of the control group (47.74±8.00) points（both P ＜0.05）. In terms of the OSI, the total score of the observation group was (4.49±0.62) points, lower than that of the control group (6.25±0.81) points;in the BIS, the total score of the observation group was (80.76±7.94) points, lower than that of the control group (87.74±9.34) points，and the differences between groups were statistically significant(both P<0.05). After the intervention, the level of 5-hydroxytryptamine in the observation group was (67.93±5.42) ng/mL, higher than (44.72±5.54) ng/mL of the control group; the levels of substance P and cortisol in the observation group were (35.82±4.47) ng/L and (75.64±8.02) μg/L, respectively, both lower than (48.14±5.32) ng/L and (94.53±10.78) μg/L of the control group, and the differences were statistically significant (all P <0.05). Conclusion The guided self help intervention based on DBT is helpful for reducing NSSI behavior among college students.

Objective: To study the correlation between activated partial thromboplastin time (APTT) mixing test results and the inhibitor titers in hemophilia A inhibitor-positive patients. Methods: In this cross-sectional study, 41 patients with severe hemophilia A and inhibitors (and negative for lupus anticoagulant) were included from the hemophilia clinic of Shandong Blood Center from February 2022 to February 2024. All patients underwent APTT mixing test. The Rosner's index (RI, including the immediate RI and the RI after 2-hour water bath incubation [water bath 2h RI]), the time-dependent difference (Δ value), and the corrected percentage were calculated based on results of APTT mixing test. The median (interquartile range) of the corresponding indexes were calculated, and the ROC curves for identification of high inhibitor titers using the four indexes (the immediate RI, the water bath 2h RI, the Δ value, and the corrected percentage) were plotted, The correlations between APTT mixing test and inhibitor titers for coagulation factor Ⅷ (Factor Ⅷ, FⅧ) were investigated. Results: The median (lower quartile, upper quartile) of immediate RI, water bath 2h RI, Δ-value and corrected percentage for FⅧ inhibitor positive patients were 11.0 (5.4, 29.3)%, 45.0 (25.7, 75.0)%, 26.2 (7.6, 41.8) s, and 82.2 (58.5, 91.6)%, respectively. The median (lower quartile, upper quartile) of the immediate RI, water bath 2h RI, Δ-value and corrected percentage were 25.2 (13.0, 37.5)%, 64.1 (44.6, 72.6)%, 38.0 (14.3, 38.3) s, and 66.5 (50.1, 82.1)% for the high-titer inhibitor group, and 5.2 (4.2, 9.4)%, 17.9 (8.8, 28.0)%, 13.0 (7.6, 25.4) s, and 92.3 (88.0, 94.3)% for the low-titer inhibitor group. The AUCs of the ROC curves for discrimination between high and low titer inhibitor were: 0.9105 for immediate RI, 0.9118 for water bath 2h RI, 0.8873 for correcter percentage, and 0.6532 for Δ-value. Conclusion: High-titer inhibitors can be highly suspected in hemophiliac patients with an immediate RI >10% and a water bath 2h RI >45%, and the presence of low-titer inhibitors is suspected in patients with a 4-second < immediate RI <10% and a 13% < water bath 2h RI <45%.

Objective: To explore the prevalence and influencing factors of depressive symptoms among university students in some universities in Shandong Province, so as to provide a theoretical reference for implementing corresponding intervention measures. Methods: A cluster sampling method was used to select 8 079 university students studying in universities in Shandong Province from March 2023 to May 2024 as the research subjects. They were randomly divided into a training set (6 463) and a validation set (1 616) according to the 8/2 ratio. The influencing factors of depression among university students were analyzed, and a risk prediction model for depression among university students was constructed and validated. Results: In the training set of university students, the detection rate of depression was 35.09%(2 268/6 463), with 1 632 cases (71.96%) of mild depression, 545 cases (24.03%) of moderate depression, and 91 cases (4.01%) of severe depression. In the validation set of university students, the detection rate of depression was 33.97% (549/1 616), with 384 cases (69.95%) of mild depression, 127 cases (23.13%) of moderate depression, and 38 cases (6.92%) of severe depression. In the training set, the proportions of those who surfed the Internet for more than 3 h/d, occasionally or did not participate in physical exercise, had average or poor relationships with classmates, often drank sugary drinks, occasionally or did not have breakfast, had unsatisfactory academic performance, had an average monthly living expense of less than 1 500 yuan on campus, and had divorced or widowed parents in the depression-detected group were all higher than those in the undetected group( χ 2=1 193.85,1 584.41, 1 115.10 ,826.00,1 424.05,924.58,803.68,797.65, P <0.05). The scores of the Chinese version of the Childhood Trauma Questionnaire (CTQ-SF) in the depression detected group were also higher than those in the undetected group( t =98.48, P <0.05). The results of Logistic regression analysis showed that physical exercise, classmate relationships, academic performance, average monthly living expenses on campus, and CTQ-SF scores were influencing factors for depression among university students( OR =3.87, 4.82, 3.63, 3.75, 4.39, P <0.05). The sensitivity of the model in the training set for predicting depression among university students was 89.0%(95% CI =87.6%-90.2%), the specificity was 93.0% (95% CI =92.2%-93.7%), and the area under the curve was 0.9(95% CI =0.8-1.0); the sensitivity of the model in the validation set for predicting depression among university students was 87.6%(95% CI =84.5%-90.1%), the specificity was 91.3%(95% CI =89.4%-92.9%), and the area under the curve was 0.9(95% CI =0.8-1.0). Conclusions The high detection rate of depressive symptoms among university students in some universities in Shandong Province warrants attention. Constructing a risk prediction model is helpful for early identifying the risk of depression among university students.

Objective To investigate the effects of isoflurane anesthesia on cognitive function and the hippocampal nerve growth factor(NGF)and tyrosine receptor kinase A(TrkA)signaling pathway in Alzheimer's disease(AD)mice,while explore the role of G protein inhibitory α subunit 1/3(Gαi1/3)in this pathway.Methods Twelve wide-type mice and 48 APP/PS1(AD)mice(all males)were respectively assigned into a control group and 4 experimental groups,including AD,AD+postoperative cognitive dysfunction(POCD)group,empty adenovirus group,and Gαi1/3 overexpression group,with 12 mice in each group.Morris water maze and novel object recognition tests were conducted to assess the learning and memory function of each group;Western blotting was applied to detect the expression of amyloid P-protein 1-42(Aβ1-42),IL-6,TNF-α,synaptotagmin-1,synapsin-1,and NGF,p-TrkA,Gαi1/3,and p-Gab1 in hippocampal tissues.Results Compared with the control group and AD group,the avoidance incubation period in the AD+POCD group is significantly extended from days 2 to 4(P＜0.05),enhanced expression of Aβ1-42,IL-6,and TNF-α(P＜0.05),and reduced expression of synaptotagmin-1,synapsin-1,NGF,p-TrkA,Gαi1/3,and p-Gab1(P＜0.05).When compared with the AD+POCD group and the empty adenovirus group,the avoidance latency in the Gαi1/3 overexpression group was significantly shorted on days 2 to 4(P＜0.05),down-regulation of Aβ1-42(2.00±0.39 vs 3.38±0.38),IL-6(1.65±0.37 vs 3.36±0.39),and TNF-α(1.58±0.30 vs 2.90±0.31,P＜0.05),and up-regulation of synaptotagmin-1,synapsin-1,Gαi1/3,and p-Gab1(P＜0.05).Conclusion Isoflurane anesthesia can exacerbate POCD in AD mice,and overexpression of Gαi1/3 can improve cognitive function by activating the phosphorylation of Gab1.

Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.