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.

Infectious diseases continue to pose a threat to global public health. Successive global shocks caused by emerging and re-emerging pathogens have continuously challenged existing surveillance systems, highlighting the urgent need to build efficient and precise pathogen surveillance networks. Pathogen genomic databases have been developed rapidly in recent two decades, significantly improving the molecular identification, evolutionary analysis, and transmission tracking of pathogens, and changing disease surveillance strategies and patterns. This paper summarizes the developmental history and current state of pathogen genomic databases, and discusses their applications in public health, including pathogen variation surveillance, emerging or suspected pathogen identification, and epidemiological tracing. Furthermore, this paper systematically analyzes the limitations and key challenges faced by current global health prevention and control system, and suggests the focus of the development of online pathogen databases to address existing shortcomings, ultimately improve global infectious disease surveillance and early warning

Objective:To analyze the survival time and influencing factors of human immunodeficiency virus（HIV）infected individuals and acquired immunodeficiency syndrome（AIDS）patients in Yancheng City from 2016 to 2020.Methods:The survival and death information of HIV/AIDS patients in Yancheng city from 2016 to 2020 was collected through the National AIDS Comprehensive Prevention and Control Information System. A retrospective cohort study was conducted，and the survival status of HIV/AIDS patients was analyzed using life tables. The Cox proportional hazards regression model was used to analyze the influencing factors of survival time.Results:A total of 1 411 HIV/AIDS patients were included in this study. By the end of the study，the cumulative survival rates of patients at 1-5 years were 93.90%，91.95%，91.24%，90.35%，and 90.12%，respectively. The multivariate Cox proportional hazards model analysis results showed that the risk of death for the age group of ≥60 years at the first diagnosis of HIV positive was 1.54 times that of the <45 years age group（95% CI：1.05-2.28）；the risk of death for the CD4 +T lymphocyte（CD4）count groups of 200-349 cells/μl，350-499 cells/μl，and ≥500 cells/μl was 0.30 times（95% CI：0.19-0.47），0.21 times（95% CI：0.11-0.42），and 0.12 times（95% CI：0.04-0.37）that of the <200 cells/μl group，respectively；the risk of death for those who received antiviral treatment was 0.08 times（95% CI：0.05-0.12）that of those who did not receive antiviral treatment；and the risk of death from HIV/AIDS for cases detected through medical institution testing is 2.23 times（95% CI：1.14-3.51）that of cases detected through testing and counseling. Conclusion:The study of HIV/AIDS in Yancheng city from 2016 to 2020 shows that older age at diagnosis，lower initial CD4 +T lymphocyte count，no antiviral treatment，and detection by medical institutions are associated with higher risk of death. It is recommended to expand testing，improve treatment compliance，and promote early detection and treatment of high-risk groups to prolong survival.

ObjectiveTo investigate the main risk factors for liver cirrhosis in chronic hepatitis B （CHB） patients with high metabolic risk， to establish a noninvasive predictive model， and to compare the diagnostic efficiency of this model and other models including fibrosis-4 （FIB-4）， aspartate aminotransferase-to-platelet ratio index （APRI）， gamma-glutamyl transpeptidase-to-platelet ratio （GPR）， and Forns index. MethodsA total of 527 CHB patients with high metabolic risks who were admitted to The Second Affiliated Hospital of Guangxi Medical University from September 1， 2017 to October 31， 2022 were enrolled as subjects， and they were randomly divided into modeling group with 368 patients and validation group with 159 patients at a ratio of 7∶3. The LASSO regression analysis and the multivariate Logistic regression analysis were performed for the modeling group to identify independent risk factors， and a nomogram model was established. The receiver operating characteristic （ROC） curve， the calibration curve， and the decision curve analysis were used to validate the nomogram prediction model in the modeling group and the validation group and assess its discriminatory ability， calibration， and clinical practicability. The Delong test was used to compare the area under the ROC curve （AUC） of the nomogram prediction model and other models. ResultsThe multivariate Logistic regression analysis showed that prealbumin （odds ratio ［OR］ = 0.993， 95% confidence interval ［CI］： 0.988 — 0.999， P= 0.019）， thrombin time （OR=1.182， 95% CI： 1.006 — 1.385， P=0.047）， log₁₀ total bilirubin （TBil） （OR=1.710， 95%CI： 1.239 — 2.419， P=0.001）， and log₁₀ alpha-fetoprotein （AFP） （OR=1.327， 95%CI： 1.052 — 1.683， P=0.018） were independent influencing factors for liver cirrhosis in CHB patients with high metabolic risks. A nomogram model for risk prediction was established based on the multivariate analysis， which had an AUC of 0.837 （95%CI： 0.788 — 0.888）， a specificity of 73.5%， and a sensitivity of 84.7%， as well as a significantly higher diagnostic efficiency than the models of FIB-4 （0.739）， APRI （0.802）， GPR （0.800）， and Forns index （0.709） （Z=2.815， 2.271， 1.989， and 2.722， P=0.005， 0.017， 0.045， and 0.006）. ConclusionThe nomogram model established based on prealbumin， thrombin time， log₁₀ TBil， and log₁₀ AFP has a certain clinical application value.

Bone is a highly calcified and vascularized tissue. The vascular system plays a vital role in supporting bone growth and repair, such as the provision of nutrients, growth factors, and metabolic waste transfer. Moreover, the additional functions of the bone vasculature, such as the secretion of various factors and the regulation of bone-related signaling pathways, are essential for maintaining bone health. In the bone microenvironment, bone tissue cells play a critical role in regulating angiogenesis, including osteoblasts, bone marrow mesenchymal stem cells (BMSCs), and osteoclasts. Osteogenesis and bone angiogenesis are closely linked. The decrease in osteogenesis and bone angiogenesis caused by aging leads to osteoporosis. Long noncoding RNAs (lncRNAs) are involved in various physiological processes, including osteogenesis and angiogenesis. Recent studies have shown that lncRNAs could mediate the crosstalk between angiogenesis and osteogenesis. However, the mechanism by which lncRNAs regulate angiogenesis‒osteogenesis crosstalk remains unclear. In this review, we describe in detail the ways in which lncRNAs regulate the crosstalk between osteogenesis and angiogenesis to promote bone health, aiming to provide new directions for the study of the mechanism by which lncRNAs regulate bone metabolism.
RNA, Long Noncoding/physiology* ; Osteogenesis/physiology* ; Humans ; Neovascularization, Physiologic/genetics* ; Bone and Bones/metabolism* ; Animals ; Mesenchymal Stem Cells ; Signal Transduction ; Osteoblasts ; Osteoclasts ; Angiogenesis

Coronavirus disease 2019 (COVID-19) is a multi-system disease that can lead to various severe complications. Acute limb ischemia (ALI) has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis. However, the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood. Hypercoagulability and thrombosis are considered important mechanisms, but we also emphasize the roles of vasospasm, hypoxia, and acidosis in the pathogenesis of the disease. The angiotensin-converting enzyme 2 (ACE2) pathway, inflammation, and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19. Furthermore, we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic, age, and gender perspectives based on our analysis of molecular mechanisms. Additionally, we summarize therapeutic approaches such as use of the interleukin-6 (IL-6) blocker tocilizumab, calcium channel blockers, and angiotensin-converting enzyme inhibitors, providing insights for the future treatment of coronavirus-associated limb ischemic diseases.
Humans ; COVID-19/physiopathology* ; Ischemia/etiology* ; SARS-CoV-2 ; Extremities/blood supply* ; Risk Factors ; Interleukin-6/antagonists & inhibitors* ; Acute Disease ; Angiotensin-Converting Enzyme 2

Critically ill patients often experience significant skeletal muscle wasting due to prolonged bed rest, metabolic disorders, inflammatory responses and malnutrition, which affects the patient's mobility and may also lead to increased mortality. Timely and accurate assessment of muscle status is important for optimizing treatment strategies and improving patient prognosis. There are various limitations in the current methods of assessing muscle mass, and muscle ultrasound, as a noninvasive, convenient, low-cost and suitable technique for bedside monitoring, has received increasing attention for its application in muscle assessment of critically ill patients. However, there are still a number of challenges in its practical application, such as the lack of uniform standards for the measurement method, the high dependence on the operation, and the reproducibility of the data that needs to be optimized, and so on. The aim of this article is to systematize the research progress of muscle ultrasound in muscle assessment of critically ill patients, and to discuss the advantages and limitations of its clinical application, in order to provide a scientific basis for future research and clinical practice.
Humans ; Critical Illness ; Ultrasonography ; Muscle, Skeletal/diagnostic imaging*

ObjectiveTo observe the clinical effect of modified Huanglian Wendantang on cardiovascular risk factors in patients with metabolic syndrome under the guidance of treating disease before its onset. MethodsA total of 82 patients with metabolic syndrome treated in the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from July 2023 to July 2024 were selected and allocated into an observation group （41 cases） and a control group （41 cases） by the random number table method. The control group received routine treatment， and the observation group was treated with modified Huanglian Wendantang on the basis of routine treatment. Both groups were treated for 8 weeks. The therapeutic effects on TCM symptoms after treatment in the two groups were evaluated. The levels of obesity degree indicators， blood pressure indicators， glucose and lipid metabolism indicators， inflammatory factors， and vascular endothelial function indicators before and after treatment in the two groups were measured， and the treatment safety was evaluated. ResultsAfter treatment， the total response rate of TCM symptoms in the observation group was 97.56% （40/41）， which was higher than that （87.80%， 36/41） in the control group （χ²=5.205， P<0.05）. After treatment， both groups showed declines （P<0.05） in systolic blood pressure （SBD）， diastolic blood pressure （DBP）， triglyceride （TG）， total cholesterol （TC）， low density lipoprotein cholesterol （LDL-C）， fasting blood glucose， 2-hour postprandial blood glucose （2 h PG）， glycosylated hemoglobin （HbA1c）， fasting insulin （FINS）， Homeostatic Model Assessment for Insulin Resistance （HOMA-IR）， body mass index （BMI）， waist circumference （WC）， waist-to-hip ratio （WHR）， leptin （LEP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， endothelin-1 （ET-1）， and inducible nitric oxide synthase （iNOS）. Moreover， the declines in the observation group were more obvious than those in the control group （P<0.05， P<0.01）. After treatment， both groups showed elevated levels of high density lipoprotein cholesterol （HDL-C）， adiponectin （ADP）， nitric oxide （NO）， and endothelial nitric oxide synthase （eNOS） （P<0.05）， and the above indexes in the observation group were higher than those in the control group （P<0.01）. ConclusionUnder the guidance of the thought of treating disease before its onset， modified Huanglian Wendantang was used to treat patients with metabolic syndrome. The decoction improved the clinical efficacy by ameliorating IR to improve insulin sensitivity， reducing inflammation， and protecting the vascular endothelial function. It inhibits cardiovascular risk factors without inducing adverse reactions， being worthy of clinical application and promotion.

Background Manganese is an essential trace element for the human body and maintains normal development of many organs including the brain. However, long-term exposure to a high manganese environment or excessive manganese intake will lead to manganese poisoning and result in neurological diseases, and currently no effective treatment plan is available. Objective To develop an animal model for subchronic manganese exposure and assess the impact of Dendrobium nobile Lindl. alkaloids (DNLA) on manganese associated behavioral and hippocampal effects in rats. Methods Fifty male SPF SD rats were randomly allocated into a control group (0.9% normal saline by intraperitoneal injection), two experimental groups [7.5 mg·kg⁻¹ (low) or 15 mg·kg⁻¹ (high) of MnCl₂·4H₂O by intraperitoneal injection], and two DNLA antagonistic groups [15 mg·kg⁻¹ MnCl₂·4H₂O by intraperitoneal injection then either 20 mg·kg⁻¹ (low) or 40 mg·kg⁻¹ (high) DNLA by oral administration]. All groups of rats were adminaistered 5 d per wek, once a day, for consecutive 13 weeks. Following modeling, neurobehavioral assessments were conducted using open field, Morris water maze, and Y maze. Inductively coupled plasma mass spectrometry (ICP-MS) was utilized to measure manganese levels in the blood and brain tissues of the rats, and hematoxylin-eosin (HE) staining was employed to examine neuronal morphological changes in the hippocampal tissues of the rats. Results The neurobehavioral tests revealed that the manganese-exposed rats exhibited decreased total movement distance, prolonged central zone dwelling time, and reduced motor activity in the open field test, indicating tendencies toward depression and anxiety (P<0.05). In the Y-maze test, the mean exploration distance in the novel arm, the number of entries into the novel arm, and the time spent in the novel arm of the managanses-exposed rats were all reduced, while the latency period increased, suggesting impaired spatial exploration and learning-memory functions (P<0.05). In the Morris water maze navigation test, the escape latency was significantly longer in the manganese-exposed rats compared to the control group, and the number of platform crossings decreased in the spatial probe test, indicating a significant decline in spatial learning and memory (P<0.05). The ICP-MS analysis showed elevated manganese concentrations in the blood and hippocampus of the exposed rats (P<0.05), and the histopathological observation revealed hippocampal damage. Following the DNLA intervention, the manganese-exposed rats showed increased total movement distance and reduced central zone dwelling time in the open field test (P<0.05). In the Y-maze test, the mean exploration distance in the novel arm, the number of entries into the novel arm, and the time spent in the novel arm increased, while the latency period decreased, suggesting alleviation of anxiety and improved exploratory behavior (P<0.05). In the Morris water maze test, the escape latency gradually shortened, and both the number of platform crossings and the percentage of time spent in the target quadrant increased, indicating improved spatial learning and memory (P<0.05). Additionally, the manganese levels in the blood and hippocampus decreased (P<0.05), and the hippocampal pathological changes were partially restored. Conclusion DNLA demonstrates the ability to counteract multiple neurotoxic effects following the elevation of manganese levels in the blood and hippocampal tissues of rats induced by subchronic manganese exposure. Specifically, DNLA is shown to ameliorate the behavioral alterations observed in rats after manganese exposure, and mitigate the hippocampal damage in manganese-exposed rats.