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 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 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 risk factors for postoperative infectious endophthalmitis,distribution of pathogens and peripheral blood interleukin-17(IL-17),matrix metalloproteinase-2(MMP-2)and insulin-like growth factor-1(IGF-1)in the patients with cataract and analyze the significance.METHODS A total of 60,000 patients with cataract who received surgical procedures in Daqing Eye Hospital from Jan.2018 to Jun.2024 were recruited as the research subjects.The aqueous humor and vitreous humor were collected from the patients with postoperative infectious endophthalmitis,and the isolated pathogens were identified.The baseline data were com-pared,the risk factors for the infectious endophthalmitis were analyzed.The levels of serum IL-17,MMP-2 and IGF-1 were compared,and the efficiencies of the indexes in prediction of infectious endophthalmitis were analyzed.RESULTS Totally 65,600 eyes involving 60,000 patients were enrolled in the study,21 of which(21 patients)were diagnosed with infectious endophthalmitis,with the incidence rate 0.032％.All of the 21 eyes were cultured positive for pathogens,among which gram-positive bacteria(73.08％)were dominant.Univariate analysis and multivariate analysis showed that complication with diabetes mellitus and vitreous overflow were the risk factors for the postoperative infectious endophthalmitis in the cataract patients.There were significant differences in the levels of serum IL-7,MMP-2 and IGF-1 between the infection group and the non-infection group after the surgery for 3 days(P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the levels of serum IL-17,MMP-2 and IGF-1 after the surgery for 3 days could predict the occurrence of postoperative infectious endoph-thalmitis in the cataract patients,and the joint detection of the three indexes has highest predictive efficiency(P＜0.05),the area under the curve was 0.950,with the sensitivity 95.24％,the specificity 81.91％.CONCLUSIONS The incidence rate of postoperative endophthalmitis is 0.032％among the cataract patients.The complication with diabetes mellitus and vitreous outflow are the risk factors.The gram-positive bacteria are dominant among the pathogens.The changes of serum IL-17,MMP-2 and IGF-1 levels are closely associated with the occurrence of en-dophthalmitis,which has predictive value.

This study aims to establish an indirect ELISA method for detecting RVFV antibodies u-sing recombinant proteins of Rift Valley fever virus(RVFV)Gn protein Ⅱ-Ⅲ structural domains as the encapsulated antigen which was expressed by the Escherichia coli(E.coli)expression sys-tem.The gene sequences encoding the Ⅱ and Ⅲ subdomains of RVFV Gn protein were inserted in-to pET-30a(+)to construct the recombinant plasmid pET-RVFV Gn-D Ⅱ-Ⅲ.After transforma-tion of the recombinant plasmid into DE3(BL21)competent cells,the recombinant Gn-D Ⅱ-Ⅲ protein was induced with IPTG and purified using affinity chromatography.An indirect ELISA method for the detection of RVFV antibodies was developed using purified recombinant protein as coating antigen and SPA-HRP as the enzyme-labelled secondary antibody.Western blot analysis confirmed that the RVFV Gn-D Ⅱ-Ⅲ protein was successfully expressed.The optimal expression conditions for RVFV Gn-D Ⅱ-Ⅲ protein were induced with 0.8 mmol/L IPTG at 37 ℃ for 5 h.The Gn-D Ⅱ-Ⅲ protein was purified using affinity chromatography with a purity of 91.9％,and the purified protein was used as the encapsulated antigen to develop an ELISA assay for RVFV anti-bodies.The specificity evaluation showed that the method specifically detected RVFV-positive sera and did not cross-react with sera positive for West Nile virus(WNV),Ebola virus(EBOV),Mar-burg virus(MARV)and tick-borne encephalitis virus(TBEV).When the RVFV Gn-D Ⅲ-Ⅲ posi-tive serum was diluted to 6 400 times,the test result still showed positive results,demonstrating the method had good sensitivity.The repeatability evaluation results indicated that the variation co-efficients for both intra-and inter-batch responses was less than 10％,indicating that the method had good repeatability.In conclusion,the RVFV Gn-D Ⅱ-Ⅲ protein was successfully expressed u-sing the E.coli expression system.The purified recombinant Gn-D Ⅱ-Ⅲ protein was used as the encapsulated antigen to develop an indirect ELISA assay for RVFV antibodies,which provides a preliminary basis for the diagnosis of RVF and the research and development of RVF vaccines.

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.

Small cell lung cancer(SCLC)is a neuroendocrine tumor that is highly heterogeneous and invasive.SCLC is prone to distant meta-stasis,and most patients are diagnosed in the extensive stage(ES-SCLC)after metastasis has occurred.Immune checkpoint inhibitors(ICIs)combined with chemotherapy currently serve as standard first-line treatment for ES-SCLC.However,the accompanying immune-related ad-verse events(irAEs)may affect patients'quality of life and treatment efficacy.Studies suggest a correlation between irAE occurrence and treatment response rates as well as survival benefits,although the mechanisms underlying this correlation are not fully understood.This art-icle provides a comprehensive review of the application of ICIs in ES-SCLC,exploring the association between irAEs and clinical ICI efficacy,the potential underlying biological mechanisms of their association,predictive biomarkers of irAEs,and strategies for managing irAEs.This study offers insights for optimizing immunotherapy for treating ES-SCLC.