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.

ObjectiveTo investigate the mechanisms of Runmu Dihuang decoction （RMDHD） in treating perimenopausal dry eye with liver-kidney Yin deficiency syndrome based on the silent information regulator 3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α）/nuclear factor-κB （NF-κB） signaling pathway. MethodsSixty female Sprague-Dawley rats were randomly divided into six groups （n=10 per group）： Sham operation group， model group， sodium hyaluronate eye drop group， and low-， medium-， and high-dose RMDHD groups （5.625， 11.25， 22.50 g·kg^-1）. Except for the sham operation group， all rats underwent bilateral ovariectomy and were administered 0.1% benzalkonium chloride eye drops combined with long-term chronic irritation to establish a perimenopausal dry eye model with liver-kidney Yin deficiency syndrome. Drug administration began in the 11th week after modeling and continued for 21 days. General conditions， screen-grip test scores， tear secretion volume， tear film breakup time （TFBUT）， and corneal fluorescein staining were recorded. Serum levels of reactive oxygen species （ROS）， follicle-stimulating hormone （FSH）， estradiol （E₂）， and progesterone （PROG） were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the lacrimal glands， corneas， and uteri were observed using hematoxylin-eosin （HE） staining. Protein expression levels of SIRT3， HIF-1α， phosphorylated NF-κB p65 （p-NF-κB p65）， and total NF-κB p65 in the lacrimal glands were detected by Western blot. The expression of inflammatory cytokines interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the lacrimal glands was assessed by immunohistochemistry （IHC）. ResultsAfter model establishment， no significant differences were observed among the groups except the sham operation group. Compared with the sham operation group， the other groups exhibited slowed movement， dull responses， increased irritability， reduced body weight， elevated rectal temperature， decreased screen-grip test scores， reduced tear secretion， and significantly shortened TFBUT （P<0.05）. After treatment， compared with the model group， the sodium hyaluronate eye drop group and all RMDHD groups showed improved general conditions， significantly increased tear secretion （P<0.05）， prolonged TFBUT （P<0.05）， and elevated screen-grip test scores （P<0.05）. Serum ROS and FSH levels were significantly decreased， while E₂ and PROG levels were significantly increased （P<0.05）. Pathological damage to the cornea， lacrimal glands， and uterus was ameliorated. In addition， protein expression levels of SIRT3 and HIF-1α in the lacrimal glands were significantly upregulated （P<0.05）， whereas the expression of p-NF-κB p65， IL-1β， and TNF-α was significantly downregulated （P<0.05）. ConclusionRMDHD increases tear secretion and TFBUT， improves lacrimal gland and corneal injury， and alleviates dry eye symptoms in a perimenopausal dry eye rat model with liver-kidney Yin deficiency syndrome. The underlying mechanism may be related to regulation of the SIRT3/HIF-1α/NF-κB signaling pathway， inhibition of oxidative stress and inflammatory responses， and reduction of ocular surface tissue damage.

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.

Hygroscopicity research has long been a key focus and hot topic in Chinese materia medica（CMM）. Elucidating hygroscopic mechanisms plays a vital role in formulation design， process optimization， and storage condition selection. Hygroscopic models serve as essential tools for characterizing CMM hygroscopic mechanisms， with various types available. The double exponential model is a kinetic mathematical model constructed based on the law of conservation of energy and Fick's first law of diffusion， tailored to the physical properties of CMM extracts. In recent years， this model has been extensively applied to simulate the dynamic moisture absorption behavior of CMM extracts and solid dosage forms under varying humidity conditions. It has revealed the correlation between moisture absorption kinetic parameters and material properties， offering a new perspective for characterizing the moisture uptake behavior of CMM. This paper systematically reviews the application progress of this model in the field of CMM， analyzes its advantages， disadvantages， and challenges in this domain， and explores its potential application trends in other fields. It aims to provide references for elucidating the moisture absorption mechanisms of CMM and researching moisture-proofing technologies， while also offering insights for its broader application in food and polymer materials.

Objective:To focus on clinical mini-lectures characterized by flexible teaching formats and significant challenges in scoring during supervision, systematically explore the roles and characteristics of raw scores (directly assigned by supervisory experts) and standard scores (revealing the relative position of instructors withing the group through Z-score conversion) in evaluating the teaching level and development trends of residency training teachers, investigate the feasibility of flexibly combining these two scoring methods, and provide new ideas for comprehensive, scientific, and objective teaching evaluations. Methods:In May 2024, 24 teachers who were supervised by three or more experts at a standardized training base for residents from 2019 to 2023 were selected as the research subjects. The study analyzed differences in mean rankings and development trends between raw and standard scores. Excel and SPSS were used for score transformation and statistical analysis of differences.Results:The mean rankings of standard scores differed from those of raw scores for 17 (70.83%) teaching staff members, among which 8 (33.33%) had a lower mean ranking of standard scores than raw scores, and 9 (37.50%) had an improved mean ranking of standard scores. For 10 (41.67%) teaching staff members, the differences in raw scores given among different supervisors were reversed after standardization conversion. The changes in the trends of scores for 17 (70.83%) teaching staff members throughout the years were inconsistent before and after score conversion.Conclusions:There were significant differences between the statistical results of standard scores and raw scores, and the two types of results evaluated the teaching level of teachers in terms of absolute situation and their relative positions in the entire teaching staff group, respectively. Therefore, combining the two types of scores with distinct characteristics for teaching evaluation can help teaching management departments comprehensively and objectively reveal the teaching level of teachers, while enhancing the confidence of faculty in teaching.

Objective To deeply analyze the free-text comments of patients with cardiovascular disease regarding medical services,in order to identify their concerns and emotional tendencies during the medical journey,and to gain insights into the value elements of medical services from the patient perspective.Methods An open-ended question allowing free-text comments was embedded in the patient satisfaction survey to collect genuine evaluations of medical services from patients hospitalized for cardiovascular disease from Sept 2022 to Jul 2023,forming a large text corpus of patient opinions.Supervised machine learning algorithms and the BERT model were used to conduct topic modeling and sentiment analysis on the text corpus.Logistic regression was employed to analyze the relationship between negative comment themes and patient satisfaction and loyalty.Results A total of 4 693 comments were collected from patients with cardiovascular disease during the study period.The most frequently mentioned subjects in patient comments were nurses(25.1%),followed by doctors(14.9%).Sentiment analysis results showed that 3 592 patients(76.5%)made positive comments,977 patients(20.8%)made negative comments,102 patients(2.2%)made mixed comments,and 22 patients(0.5%)made neutral comments.Topic analysis results indicated that the five most frequently mentioned themes by patients with cardiovascular disease were humanistic care(14.4%),information education and communication(9.0%),technical proficiency(6.6%),diet(6.2%),and effectiveness of diagnosis and treatment(4.2%).Logistic regression analysis showed that negative evaluations of dimensions such as humanistic care,information education and communication and response to needs were significantly associated with lower patients'satisfaction and loyalty.Conclusion Interpersonal interaction and functionality are dual important dimensions in medical services,especially interpersonal interaction,which often becomes the decisive factor for patients with cardiovascular disease to assess the quality of medical services.

Coronary artery calcification often appears a variety of complex lesions,increasing coronary intervention of the difficulty of treatment,especially the severe calcification lesions,usually cannot be fully dilated,resulting in a reduced success rate of surgery,an increased rate of acute stent thrombosis and restenosis,and even a serious impact on the prognosis of patients.Intravascular lithotripsy(IVL)is increasingly used in calcified lesions.There is more and more evidence of using in stable angina pectoris and unstable angina pectoris,but its use in acute ST-segment elevation myocardial infarction is limited,and only a few cases have been reported abroad.Moreover,the consensus of Chinese experts in the diagnosis and treatment of coronary artery calcification in 2021 edition lists thrombotic lesions as contraindications of shock wave balloon.This case is the first time in China to report the use of shock wave balloon in patients with acute ST elevation myocardial infarction complicated with thrombus.In this case,the patient with acute ST elevation myocardial infarction complicated with thrombus was severely under expanded stent after stent implantation,and obtain good curative effect using shockwave balloon at selected time in hospital after intensive anticoagulant therapy.

Objective:To investigate the relationship between the quick sequential organ failure assessment (qSOFA) score, procalcitonin (PCT), blood lactate, hypersensitive C-reactive protein (hs-CRP) levels, and the prognosis of patients with severe acute pancreatitis (SAP).Methods:This retrospective analysis included 225 pancreatitis cases admitted to the Department of Gastroenterology at Ganzi Tibetan Autonomous Prefecture People's Hospital between February 2020 and February 2025. Patients were categorized into three groups based on severity: SAP group ( n=125), moderately severe acute pancreatitis (MSAP) group ( n=50), and mild acute pancreatitis (MAP) group ( n=50). General patient data, qSOFA scores, PCT, lactate, and hs-CRP levels were compared among the groups. Within the SAP group, patients were further divided into a favorable prognosis group ( n=101) and a poor prognosis group ( n=24) based on 28-day survival. The relationship between qSOFA score, PCT, lactate, hs-CRP, and SAP prognosis was analyzed. Normally distributed continuous data were expressed as Mean±SD. Independent samples t-test was used on comparison between two groups, while one-way ANOVA was used on comparison among multiple groups. LSD test was used on post-hoc pairwise comparison. Categorical data were expressed as n(%) and compared by χ2 test. Spearman correlation analysis assessed the correlation between qSOFA score, PCT, lactate, hs-CRP levels, and acute pancreatitis (AP) severity. Multivariable logistic regression modeling was used for joint prediction, incorporating qSOFA score, serum PCT, lactate, and hs-CRP levels to calculate combined predictive efficacy. The predictive performance of each indicator for prognosis was evaluated using receiver operating characteristic (ROC) curves. The areas under the ROC curves (AUC) were compared using DeLong's test. Results:Significant differences were observed among the MAP, MSAP, and SAP groups for qSOFA score [(0.63±0.29), (1.32±0.37), (1.70±0.33) points], serum PCT [(4.06±0.74), (5.35±0.89), (6.12±0.98) μg/L], lactate [(1.74±0.32), (2.77±0.70), (4.29±1.06) mmol/L], and hs-CRP levels [(15.38±3.75), (27.64±5.09), (35.26±6.42) mg/L] ( F values=187.51, 91.83, 169.18, 223.92, respectively, all P<0.001). The SAP group had significantly higher levels of qSOFA score, serum PCT, lactate, and hs-CRP compared to both the MAP and MSAP groups (all P<0.05), and the MSAP group levels were significantly higher than the MAP group (all P<0.05). The poor prognosis group had significantly higher levels of qSOFA score [(1.92±0.19) points], PCT [(6.65±0.47) μg/L], lactate [(5.14±0.62) mmol/L], and hs-CRP [(40.65±4.73) mg/L] compared to the favorable prognosis group [(1.65±0.25) points, (5.99±0.84) μg/L, (4.09±0.94) mmol/L, (34.16±6.09) mg/L] ( t values=4.96, 3.71, 5.20, 4.88, respectively, all P<0.001). Multivariate logistic regression analysis identified qSOFA score ( OR=14.658, 95% CI: 2.612-82.253), PCT ( OR=2.809, 95% CI: 1.288-6.129), lactate ( OR=3.658, 95% CI: 1.635-8.187), and hs-CRP ( OR=1.168, 95% CI: 1.055-1.293) as independent influencing factors for SAP patient prognosis ( P=0.002, 0.010, 0.002, 0.003, respectively). ROC curve analysis showed that the AUCs for qSOFA score, PCT, lactate, and hs-CRP in predicting poor prognosis in SAP patients were 0.754, 0.856, 0.766, and 0.809, with sensitivities of 87.50%, 83.33%, 83.33%, 85.50%, and specificities of 60.40%, 77.20%, 64.40%, 75.20%, respectively. The combined prediction model yielded an AUC of 0.934, with a sensitivity of 95.80% and specificity of 72.30%. Conclusion:The qSOFA score, PCT, blood lactate, and hs-CRP levels are associated with the severity of AP and possess reference value for predicting the prognosis of SAP patients.

Objective:To explore the value of fetal heart quantification technology in assessing the morphology and function of the fetal heart during normal pregnancy.Methods:This prospective cohort study selected normal fetuses from healthy pregnant women who underwent prenatal ultrasound examinations at Hunan Provincial People's Hospital from January 2023 to October 2024. Using the GE Voluson E10 color Doppler diasonography, routine obstetric ultrasound and fetal echocardiography were performed to assess fetal growth and development and to exclude intracardiac and extracardiac malformations. Clear four-chamber view (4CV) dynamic images of the heart showing the endocardium (duration ≥3 s) were collected. Speckle-tracking analysis was performed using fetal heart quantification software. The measured indicators included the global spherical index (GSI), end-diastolic length of the heart (L-ED), end-diastolic width of the heart (W-ED), and the global longitudinal strain (GLS), fractional area change (FAC), and 24-segment spherical index (SI) of the left ventricle (LV) and right ventricle (RV). The cases were divided into five groups based on gestational age at the time of prenatal ultrasound: 20 +0 to 23 +6, 24 +0 to 27 +6, 28 +0 to 31 +6, 32 +0 to 35 +6, and 36 +0 to 40 +6 weeks. One-way analysis of variance, two independent samples t-test, univariate linear regression analysis, and Pearson correlation analysis were used to explore the differences in the above indicators among different gestational age groups and their correlation with gestational age. Results:A total of 200 pregnant women were included in the cohort, four cases were excluded due to poor image quality that prevented accurate tracking and measurement of relevant indicators. Ultimately, 196 cases (20 +0 to 23 +6 weeks 40 cases, 24 +0 to 27 +6 weeks 34 cases, 28 +0 to 31 +6 weeks 41 cases, 32 +0 to 35 +6 weeks 48 cases, and 36 +0 to 40 +6 weeks 33 cases) were included in the study, with a successful image analysis rate of 98.0%. (1) There were statistically significant differences in 4CV L-ED, 4CV W-ED, LV-FAC, and RV-FAC among the groups at 20 +0 to 23 +6, 24 +0 to 27 +6, 28 +0 to 31 +6, 32 +0 to 35 +6, and 36 +0 to 40 +6 weeks [4CV L-ED: 28.0±3.0, 32.6±4.3, 40.9±4.3, 46.7±4.8, 53.1±5.8, F=3.72; 4CV W-ED: 21.9±1.8, 25.1±4.2, 31.7±3.0, 37.4±4.0, 42.0±4.9, F=2.61; LV-FAC: (51.4±8.0)%, (49.0±10.4)%, (47.3±7.3)%, (43.1±7.5)%, (40.7±8.2)%, F=2.94; RV-FAC: (49.9±10.8)%, (46.2±12.0)%, (46.3±8.3)%, (43.2±8.0)%, (41.9±5.6)%, F=3.09; all P<0.05].(2) The size of the normal fetal heart gradually increased with gestational age, while the heart morphology remained relatively stable (4CV L-ED and 4CV W-ED were positively correlated with gestational age, with regression coefficients of 1.313 and 1.325, respectively, both P<0.001;LV-FAC and RV-FAC were negatively correlated with gestational age with regression coefficients of -0.783 and -0.552, respectively, both P<0.001; GSI, LV-GLS and RV-GLS had no correlations with gestational age, all P>0.05). (3) The SI of LV segments 1 to 17 were higher than the SI of the corresponding RV segments, and the SI of RV segments 20-24 were higher than that of the corresponding LV segments (all P<0.001). Conclusion:Fetal heart quantification technology has a certain value in the assessment of fetal cardiac morphology and function.

AIM To investigate the effects of Rutong Ruanjian Tablets on angiogenesis in cancer tissues of rats with preneoplastic breast cancer(PBC).METHODS 60 female SD rats were randomly divided into a blank group of 10 rats and a model group of 50 rats for the establishment of the PBC models of Liver-Qi Stagnation and Blood Stasis Pattern with 9 weeks of oral administration of 7,12-dimethylbenz[a]anthracene(DMBA)and cervical ligation.After successful modeling,the rats were randomly divided into the model group,the tamoxifen group(3.2 mg/kg),the Rutong Ruanjian Tablets group(128 mg/kg),the 3,5-difluorobenzoyl group(DAPT,5 mg/kg),and the Rutong Ruanjian Tablets(128 mg/kg via gavage)+DAPT(5 mg/kg intraperitoneal injection)group,for 1 month corresponding drug administration,with 10 rats in each group.Then the rats had their cancer progression and syndrome scores observed;their angiogenesis evaluated by assessment of microvascular density(MVD);their vascular endothelial growth factor(VEGF)expression assessed by immunohistochemistry;and their mRNA and protein expressions of proteins related to the DLL4/Notch1/Hes1 pathway measured using RT-qPCR,immunohistochemistry and Western blot.RESULTS During carcinogenesis of rats induced by DMBA,there was gradual disappearance of E-cadherin expression and consistency of HE staining result with the PBC progression confirming the success of the modeling.Compared with the blank group,the model group showed increased MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).Compared with the model group,the Rutong Ruanjian Tablets group exhibited reduced MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).The Rutong Ruanjian Tablets+DAPT group showed reduced mRNA expression of Notch1 and Hes1,and protein expressions of DLL4,Notch1 and Hes1 compared to the Rutong Ruanjian Tablets group(P＜0.05,P＜0.01).CONCLUSION Rutong Ruanjian Tablets can inhibit angiogenesis and attenuate cancer progression in PBC rats of Liver-Qi Stagnation and Blood Stasis Pattern,and the mechanism may lie in the downregulation of DLL4/Notch1/Hes1 signaling pathway related proteins.