Objective::Pulmonary hypertension secondary to left heart failure is associated with an abnormal response to exercise and poor prognosis. The objective of this study is to develop an algorithm by using data from cardiopulmonary exercise testing (CPET) to assess the severity of pulmonary hemodynamics and predict clinical worsening and mortality in patients with heart failure.Methods::From April 2017 to December 2018, a total of 102 patients with heart failure who underwent CPET and invasive right heart catheterization participated in this prospective study. All enrolled patients had their clinical characteristics, hemodynamic parameters, and CPET results. Based on the CPET data namely peak oxygen uptake, the minute ventilation/carbon dioxide production slope, resting end-tidal carbon dioxide, oxygen uptake/work rate flattening, exercise oscillatory ventilation, and oxygen uptake efficiency slope, a Heart Failure Cardiopulmonary Exercise (HFCE) score was developed. The total score was then calculated to categorize patients into 3 groups: low score (0-3) ( n = 31), intermediate score (4-7) ( n = 45), and high score (8-14) ( n = 26). Clinical events were defined as all-cause death and rehospitalization for heart failure, which were recorded and tracked for at least 12 months. Pearson’s correlation coefficients were calculated to assess the relationship between the HFCE score and hemodynamic parameters, 6-minute walk distance, and N-terminal-pro hormone brain natriuretic peptide. Cox proportional hazards regression analysis was used to identify independent predictors of clinical events. Survival curves for clinical events were generated using the Kaplan-Meier method and compared among the 3 groups with different HFCE scores with a log-rank test. Results::The high HFCE score group had a higher prevalence of New York Heart Association class Ⅲ-Ⅳ (high score vs. intermediate score vs. low score: 85% (22/26) vs. 56% (25/45) vs. 45% (14/31), P = 0.008), higher N-terminal-pro hormone brain natriuretic peptide levels (high score vs. intermediate score vs. low score: (3,039 ± 2,171) ng/L vs. (2,039 ± 2,353) ng/L vs. (1,438 ± 947) ng/L, P = 0.035), lower 6-minute walk distance (high score vs. intermediate score vs. low score: (312 ± 79) m vs. (362 ± 84) m vs. (363 ± 76) m, P = 0.042) compared to intermediate score or low score. The high HFCE score correlated well with high levels of pulmonary vascular resistance ( r = 0.539, P < 0.01), pulmonary artery wedge pressure ( r = 0.292, P < 0.01), and mean pulmonary artery pressure ( r = 0.474, P < 0.01), as well as low levels of cardiac output ( r = -0.357, P < 0.01). Moreover, 46 patients developed composed clinical events at 12 months. In the multivariate model, the HFCE score was an independent predictor of composed clinical events (hazard ratio = 1.142, 95% confidence interval: 1.041-1.253, P = 0.005). Kaplan-Meier analysis showed a significantly higher probability of composed clinical events in patients with a higher HFCE score ( P log-rank = 0.004). Conclusion::The HFCE score—obtained through CPET—provides valuable prognostic information by indicating the severity of hemodynamics in patients with pulmonary hypertension secondary to left heart failure. It can likely serve as a reliable predictor for clinical worsening and mortality.

Objective:To construct a perioperative pain nursing protocol for thoracoscopic surgery patients, providing a reference for clinical pain nursing practice.Methods:An evidence-based approach was used to search relevant guidelines and extract the best evidence. The initial draft was created through discussions among the research team, followed by two rounds of Delphi expert consultations. Based on the experts' suggestions, the protocol was revised and the best plan was finalized.Results:A total of 10 guidelines were included, and 22 experts participated in two rounds of consultations. The response rate for the consultation questionnaires was 100.00% (22/22) , with expert authority coefficients of 0.94 and 0.95 for the two rounds, respectively. The coefficient of variation for all indicators in the second round ranged from 0.04 to 0.24. The final pain nursing protocol included four primary indicators: personnel preparation, pain assessment, pain education, and pain intervention, with 10 secondary indicators and 27 tertiary indicators.Conclusions:The constructed perioperative pain nursing protocol for thoracoscopic surgery patients is significant, scientific, comprehensive, and targeted. It provides theoretical support and practical guidance for pain management, helping to reduce postoperative pain in patients.

[Purpose]To analyze the trends of brain tumor incidence and age of onset in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]The incidence data of brain tumors from 2009 to 2019 were obtained from 16 national cancer registration areas of Jiangsu Province.The crude incidence rate,age-standardized incidence rate by Chinese standard popula-tion(ASIRC),average age of onset,standardized age-specific incidence rate,and annual average percentage change(AAPC)by sexes and regions were calculated.[Results]The incidence rate of brain tumor in Jiangsu Province from 2009 to 2019 showed an increasing trend(AAPC=4.12％,95％CI:3.31％～4.95％),and the increase in female(AAPC=5.79％,95％CI:4.44％～7.15％)was higher than that in male(AAPC=2.31％,95％CI:1.66％～2.97％);and the increase in urban areas(AAPC=4.84％,95％CI:3.52％～6.18％)was higher than that in rural areas(AAPC=3.04％,95％CI:2.12％～3.98％).The ASIRC also showed an increasing trend(AAPC=2.14％,95％CI:1.27％～3.02％).Birth cohort analysis showed that within the same age group,the incidence rate of brain tumors increased with increasing birth years.The average age of onset for crude incidence showed a delaying trend of 0.43 years old per year(t=7.09,P＜0.001);that for ASIRC was 0.20 years old per year(t=3.33,P=0.009).The proportion of patients in the age group of 60 years old and above increased from 35.79％in 2009 to 44.18％in 2019.[Conclusion]The incidence of brain tumor in cancer registration areas of Jiangsu Province showed an increasing trend from 2009 to 2019 with a delaying trend of average age of onset.

Objective::Pulmonary hypertension secondary to left heart failure is associated with an abnormal response to exercise and poor prognosis. The objective of this study is to develop an algorithm by using data from cardiopulmonary exercise testing (CPET) to assess the severity of pulmonary hemodynamics and predict clinical worsening and mortality in patients with heart failure.Methods::From April 2017 to December 2018, a total of 102 patients with heart failure who underwent CPET and invasive right heart catheterization participated in this prospective study. All enrolled patients had their clinical characteristics, hemodynamic parameters, and CPET results. Based on the CPET data namely peak oxygen uptake, the minute ventilation/carbon dioxide production slope, resting end-tidal carbon dioxide, oxygen uptake/work rate flattening, exercise oscillatory ventilation, and oxygen uptake efficiency slope, a Heart Failure Cardiopulmonary Exercise (HFCE) score was developed. The total score was then calculated to categorize patients into 3 groups: low score (0-3) ( n = 31), intermediate score (4-7) ( n = 45), and high score (8-14) ( n = 26). Clinical events were defined as all-cause death and rehospitalization for heart failure, which were recorded and tracked for at least 12 months. Pearson’s correlation coefficients were calculated to assess the relationship between the HFCE score and hemodynamic parameters, 6-minute walk distance, and N-terminal-pro hormone brain natriuretic peptide. Cox proportional hazards regression analysis was used to identify independent predictors of clinical events. Survival curves for clinical events were generated using the Kaplan-Meier method and compared among the 3 groups with different HFCE scores with a log-rank test. Results::The high HFCE score group had a higher prevalence of New York Heart Association class Ⅲ-Ⅳ (high score vs. intermediate score vs. low score: 85% (22/26) vs. 56% (25/45) vs. 45% (14/31), P = 0.008), higher N-terminal-pro hormone brain natriuretic peptide levels (high score vs. intermediate score vs. low score: (3,039 ± 2,171) ng/L vs. (2,039 ± 2,353) ng/L vs. (1,438 ± 947) ng/L, P = 0.035), lower 6-minute walk distance (high score vs. intermediate score vs. low score: (312 ± 79) m vs. (362 ± 84) m vs. (363 ± 76) m, P = 0.042) compared to intermediate score or low score. The high HFCE score correlated well with high levels of pulmonary vascular resistance ( r = 0.539, P < 0.01), pulmonary artery wedge pressure ( r = 0.292, P < 0.01), and mean pulmonary artery pressure ( r = 0.474, P < 0.01), as well as low levels of cardiac output ( r = -0.357, P < 0.01). Moreover, 46 patients developed composed clinical events at 12 months. In the multivariate model, the HFCE score was an independent predictor of composed clinical events (hazard ratio = 1.142, 95% confidence interval: 1.041-1.253, P = 0.005). Kaplan-Meier analysis showed a significantly higher probability of composed clinical events in patients with a higher HFCE score ( P log-rank = 0.004). Conclusion::The HFCE score—obtained through CPET—provides valuable prognostic information by indicating the severity of hemodynamics in patients with pulmonary hypertension secondary to left heart failure. It can likely serve as a reliable predictor for clinical worsening and mortality.

[Purpose]To analyze the trends of brain tumor incidence and age of onset in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]The incidence data of brain tumors from 2009 to 2019 were obtained from 16 national cancer registration areas of Jiangsu Province.The crude incidence rate,age-standardized incidence rate by Chinese standard popula-tion(ASIRC),average age of onset,standardized age-specific incidence rate,and annual average percentage change(AAPC)by sexes and regions were calculated.[Results]The incidence rate of brain tumor in Jiangsu Province from 2009 to 2019 showed an increasing trend(AAPC=4.12％,95％CI:3.31％～4.95％),and the increase in female(AAPC=5.79％,95％CI:4.44％～7.15％)was higher than that in male(AAPC=2.31％,95％CI:1.66％～2.97％);and the increase in urban areas(AAPC=4.84％,95％CI:3.52％～6.18％)was higher than that in rural areas(AAPC=3.04％,95％CI:2.12％～3.98％).The ASIRC also showed an increasing trend(AAPC=2.14％,95％CI:1.27％～3.02％).Birth cohort analysis showed that within the same age group,the incidence rate of brain tumors increased with increasing birth years.The average age of onset for crude incidence showed a delaying trend of 0.43 years old per year(t=7.09,P＜0.001);that for ASIRC was 0.20 years old per year(t=3.33,P=0.009).The proportion of patients in the age group of 60 years old and above increased from 35.79％in 2009 to 44.18％in 2019.[Conclusion]The incidence of brain tumor in cancer registration areas of Jiangsu Province showed an increasing trend from 2009 to 2019 with a delaying trend of average age of onset.

Objective:To construct a perioperative pain nursing protocol for thoracoscopic surgery patients, providing a reference for clinical pain nursing practice.Methods:An evidence-based approach was used to search relevant guidelines and extract the best evidence. The initial draft was created through discussions among the research team, followed by two rounds of Delphi expert consultations. Based on the experts' suggestions, the protocol was revised and the best plan was finalized.Results:A total of 10 guidelines were included, and 22 experts participated in two rounds of consultations. The response rate for the consultation questionnaires was 100.00% (22/22) , with expert authority coefficients of 0.94 and 0.95 for the two rounds, respectively. The coefficient of variation for all indicators in the second round ranged from 0.04 to 0.24. The final pain nursing protocol included four primary indicators: personnel preparation, pain assessment, pain education, and pain intervention, with 10 secondary indicators and 27 tertiary indicators.Conclusions:The constructed perioperative pain nursing protocol for thoracoscopic surgery patients is significant, scientific, comprehensive, and targeted. It provides theoretical support and practical guidance for pain management, helping to reduce postoperative pain in patients.

Acute high altitude disease (AHAD) is a general term for a series of clinical reactions that occur when the body fails to adapt to the low-pressure hypoxic environment of high altitudes. Mild cases can cause symptoms such as headache, nausea and vomiting, while more severe cases can lead to life-threatening conditions such as pulmonary edema, cerebral edema and other critical conditions that can be fatal. With the increasing demand for high altitudes deployment, understanding the common preventive measures of AHAD can reduce its morbidity or mortality to a certain extent, which is of great benefit to those who reside temporarily at high altitudes. In recent years, as people's health awareness has improved, there has been a growing attention towards non-pharmacological methods of disease prevention. At the same time, non-pharmacological therapy has significant therapeutic effects in preventing and treating high-altitude diseases, which has attracted the attention of researchers in this field. This review summarizes the major non-pharmacological preventive components of modern medicine and outlines the current non-pharmacological approaches to AHAD from the perspective of traditional Chinese medicine, intending to serve clinical purposes and improve the onset and prognosis of AHAD.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective To establish an improved type Ⅱ cardio-renal syndrome rat model and evaluate it.Methods Twenty male SD rats were randomly divided into sham and model groups with 7 rats in the sham group and 13 rats in the model group.The model group received the method of squeezing the heart under a small animal anesthesia machine to permanently ligate the left anterior descending branch of the coronary artery to cause myocardial infarction.One week later,unilateral nephrectomy(right nephrectomy)was performed.The rats underwent cardiac echocardiography,pathological staining,and blood and urine tests at 6 weeks to verify model establishment.Results Compared with the sham group,the cardiac function assessed by echocardiography and the endogenous creatinine clearance rate in the model group rats were significantly decreased(P<0.01),and the levels of brain natriuretic peptide,blood creatinine,urea nitrogen,and 24 h urine protein in the model group were significantly increased(P<0.01).HE staining revealed a disordered myocardial arrangement,glomerular atrophy,and inflammatory cell infiltration in model group rats.Picric acid-Sirius red staining showed a significant increase in myocardial collagen fibers,an irregular arrangement of renal tubules,and a large amount of collagen deposition in model group rats.The positive staining area ratio was also significantly increased(P<0.01).Conclusions This improved modeling method provided a typeⅡcardio-renal syndrome rat model with s simple operation,minimal surgical trauma,and low mortality rate.This model simulates the early onset of cardiac and renal function damage and pathological changes in type Ⅱ CRS,laying the foundation for systematic and in-depth research on the pathogenesis and pathological mechanism of type Ⅱ cardio-renal syndrome.

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts are still under-represented in genome-wide genetic studies. Here, we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combined with single-cell sequencing data from the developing human brain, we found that the expression of genes with de novo mutations was specifically enriched in the pre-, post-central gyrus (PRC, PC) and banks of the superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and healthy controls, we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls, suggesting the potential structural deficits associated with ASD. Finally, we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas, the insula, as well as the frontal lobes in ASD patients. This work indicated that combinatorial analysis with genome-wide screening, single-cell sequencing, and brain imaging data reveal the brain regions contributing to the etiology of ASD.
Humans ; Autism Spectrum Disorder/metabolism* ; Autistic Disorder ; Exome Sequencing ; DNA Copy Number Variations ; East Asian People ; Brain/metabolism* ; Mutation/genetics* ; Genetic Predisposition to Disease/genetics*