ObjectiveTo investigate the independent risk factors for concurrent myocardial injury before intervention in patients with primary hepatic carcinoma （PHC）， to construct and validate a nomogram prediction model for the early identification of such patients， and to provide a basis for early clinical prevention and management. MethodsA retrospective analysis was performed for the clinical data of 1 822 patients with PHC in two medical institutions from January 2019 to June 2025， among whom the 1 518 patients from The Third People’s Hospital of Kunming were used as the training set to construct the nomogram prediction model， and the 304 patients from The Second People’s Hospital of Baoshan were used as the validation set. According to the result of high-sensitivity cardiac troponin T measurement before intervention， the patients with PHC were divided into myocardial injury group and non-myocardial injury group. The univariate analysis， the LASSO regression analysis， and the multivariate Logistic regression analysis were used to identify the risk factors of concurrent myocardial injury in PHC patients before intervention， and then a nomogram prediction model was constructed based on these findings. The independent data of the 304 patients in the validation set were used for external validation， and the area under the receiver operating characteristic curve （AUC）， the Hosmer-Lemeshow test， the calibration curve， decision curve analysis， and clinical impact curve were used to assess model performance. ResultsIn the training set， there were 346 patients in the myocardial injury group and 1 172 patients in the non-myocardial injury group， and the prevalence rate of concurrent myocardial injury was 22.79%. The mean age was 56.44±9.45 years， and the male patients accounted for 81.49%. The patients with drinking， smoking， chronic hepatitis B， chronic hepatitis C， hypertension， diabetes， Child-Pugh class A liver disease， BCLC stage B liver disease， or abnormal electrocardiographic findings accounted for 49.34%， 57.44%， 61.73%， 32.48%， 22.66%， 17.19%， 50.53%， 33.86%， and 62.12%， respectively. The univariate analysis， the LASSO regression analysis， and the multivariate Logistic regression analysis showed that age （odds ratio ［OR］=1.051， 95% confidence interval ［CI］： 1.036 — 1.067， P<0.001）， history of diabetes （OR=1.862， 95%CI： 1.346 — 2.574， P<0.001）， electrocardiographic findings （OR=1.446， 95%CI： 1.077 — 1.940， P=0.014）， hemoglobin （HGB） （OR=0.993， 95%CI： 0.988 — 0.998， P=0.003）， albumin （Alb） （OR=0.951， 95%CI： 0.930 — 0.972， P<0.001）， and creatinine （Cr） （OR=1.021， 95%CI： 1.016 — 1.026， P<0.001） were independent influencing factors for myocardial injury in PHC patients. A regression equation was established as Logit（Y）=-3.406+0.050×age+0.621×history of diabetes+0.369×electrocardiogram－0.007×HGB－0.051×Alb+0.021×Cr， and a nomogram prediction model was constructed based on these factors. The Bootstrap internal validation of the model yielded an AUC of 0.743 （95%CI： 0.707 — 0.778）， and the model had an AUC of 0.766 （95%CI： 0.738 — 0.794） in the training set and 0.730 （95%CI： 0.688 — 0.793） in the validation set. The Hosmer-Lemeshow goodness-of-fit test yielded a P value of 0.716 for the training set and 0.408 for the validation set， suggesting that the model had a good degree of fitting. Calibration curves， decision curve analysis， and clinical impact curves in both the training set and the validation set showed that the model had a good clinical application value. ConclusionAge， history of diabetes， electrocardiographic findings， HGB， Alb， and Cr are independent influencing factors for myocardial injury in patients with PHC， and the nomogram prediction model constructed based on these factors has good discriminatory ability， accuracy， and clinical practicability.

Objective:To investigate the long-term prognosis and related factors in children with multiphasic myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).Methods:A bidirectional cohort study was conducted. This study included 41 children with MOGAD who were treated at the Children′s Medical Center of Peking University First Hospital between January 2013 and December 2024, with a disease duration of ≥5 years. Demographic characteristics, clinical episodes, therapy, and prognostic indicators (including the expanded disability status scale (EDSS) and modified Rankin scale (mRS)) were collected. Children were stratified into relapse and non-relapse groups based on the presence or absence of relapse within 5 years of the last follow-up. χ2 test or Mann-Whitney U test was used to analyze factors associated with relapse. The Log-rank test was used to compare relapse-free rates between children with disease onset 0-<5 years and those with onset at 5-10 years. Results:A total of 41 children were enrolled, including 20 boys and 21 girls. The age at onset was 5.3 (3.8, 8.5) years, the age at last follow-up was 16.1 (13.2, 17.5) years, and the disease duration was 9.4 (8.1, 10.9) years. The annualized relapse rate (ARR) during follow-up was 0.34 (0.19, 0.56) times/year. The duration to first relapse was 0.8 (0.4, 1.5) years. At the last follow-up, the EDSS score was 0.0 (0.0, 0.0) score, and the mRS score was 0 (0, 0) score. A total of 40 children (98%) experienced relapses within the first 5 years after onset, while only 1 child (2%) relapsed at 6.7 years. The relapse rate between 5-10 years was lower than that between 0-<5 years ( HR=0.27, 95% CI 0.16-0.47, P<0.001). A total of 25 children (61.0%) exhibited clustered relapses during the disease course. There were 20 children (49%) in non-relapse groups, who were aged 16.6 (14.8, 17.6) years, disease duration 9.8 (9.3, 10.8) years at the last follow-up. Among those 20 children, 15 children (75%) had discontinued corticosteroids and immunosuppressants. The relapse group had higher clinical event rates and ARR compared to the relapse-free group (both P<0.01), the age at last follow-up was yonger ( P<0.05), while no significant differences were observed in age at onset, disease duration, or timing of immunosuppressant use (all P>0.05). Conclusions:Pediatric multiphasic MOGAD generally has a favorable prognosis, about half of patients remain relapse-free for ≥5 years at last follow-up. Relapses predominantly occur early in the disease course (mostly within 5 years of onset) and often exhibit a clustered pattern.

Objective:To identify the trajectories of dietary choline intake in middle-aged and older population, and to analyze its longitudinal association with cognitive function.Methods:Subjects aged 55 to 79 years with at least two rounds of completed population economics, lifestyle, disease history, cognitive function, dietary assessments and physical measurements in 1997-2018 and those with at least three rounds of dietary measures in 1991-2015 were selected from the China Health and Nutrition Survey. Dietary survey was conducted using three consecutive 24-hour dietary recalls combined with a weighing inventory at the household level. Cognitive assessment was performed using part of the Telephone Interview for Cognitive Status Scale. Group-based univariate trajectory modeling was used to identify trajectory of choline intake, and three-level linear mixed-effects models or three-level logistic mixed-effects models was employed to analyze the relationship between trajectory groups and cognitive function. Subgroup analyses were conducted by gender and age at baseline.Results:Four trajectories of dietary choline intake were identified in the whole population, named as low-intake-stable group (61.0%), medium-intake-stable group (23.9%), medium-intake-slowly-declined group (11.2%), and high-intake-stable group (3.9%). Three trajectories were identified for each subgroup. Low-intake-stable group accounted for more than 60% in total population as well as each subgroup, especially in women and 55-59 years group. After adjusting for covariates, global cognitive scores were 0.54 (95% CI: 0.26-0.82), 0.77 (95% CI: 0.36-1.18), and 0.85 (95% CI: 0.21-1.48) points higher in medium-intake-stable, medium-intake- slowly-declined and high-intake-stable groups in the whole population, respectively, compared with the low-intake-stable group. The likelihoods of cognitive decline were 18.4% ( OR=0.816,95% CI: 0.709-0.939), 17.6% ( OR=0.824, 95% CI: 0.680-0.998), 24.4% ( OR=0.756, 95% CI: 0.589-0.970) and 22.4% ( OR=0.776,95% CI: 0.623-0.968) lower in medium-intake-stable group of dietary choline in the whole population, medium-intake-stable group in males, medium-intake-slightly-increased group in females and medium-intake-slowly-increased group in 55-59 years at baseline than in low-intake-stable group, respectively. Conclusions:Dietary choline intake is generally lower in the Chinese population aged 55-79 years. Long-term lower choline intake has a negative impact on cognitive function in middle-aged and older adults and may increase the risk of cognitive decline. The increment in the consumption of choline-enriched foods should be recommended.

Establishing a one-stop diagnosis and treatment mode centered on patients and linked by diseases is of great significance for optimizing the medical process and improving the medical experience. In March 2024, a tertiary hospital integrated pediatric outpatient and emergency resources, established a pediatric diagnosis and treatment island through reasonable department settings, strengthened talent team construction, optimized diagnosis and treatment processes, and established supporting guarantee mechanisms. It was officially put into use in June of the same year, providing one-stop diagnosis and treatment services for children and achieving the goal of " not leaving the island for minor illnesses and not leaving the hospital for major illnesses". Before the operation of island (January May 2024), the complaint rate and waiting time for pediatric outpatient and emergency department were 39 cases per 100 000 patients and 15 to 30 minutes, respectively; After operation (June August 2024), the complaint rate and waiting time decreased to 17 cases per 100 000 people and 10 to 20 minutes respectively; The average monthly comprehensive income of outpatient and emergency departments increased by 33%. The pediatric diagnosis and treatment island mode could assist in the sustainable high-quality development of pediatrics in hospital, and provide references for optimizing outpatient and emergency department management in other tertiary public hospitals. In the future, we should further enrich the service content of the island and strengthen information technology construction.

Background Job burnout and depressive symptoms are prevalent among occupational populations, with a close relationship between them. Sleep quality, as a potential mediating factor, significantly affects the mental health of workers. Objective To explore the relationship between job burnout, sleep quality, and depressive symptoms, and determine whether sleep quality mediates the relationship between job burnout and depressive symptoms. Methods From April 25 to May 1, 2024, this study employed cluster sampling to conduct a questionnaire survey among individuals engaged in various occupations across five cities in the Ningxia Hui Autonomous Region. The questionnaires included socio-demographic information, as well as the Chinese Maslach Burnout Inventory (CMBI), the Pittsburgh Sleep Quality Index (PSQI), and the Patient Health Questionnaire-9 (PHQ-9) for assessing burnout, sleep quality, and depressive symptoms, respectively. Out of the 4106 questionnaires distributed, a total of 3837 questionnaires were valid, and the valid recovery rate was 93.45%. The distribution among demographic variables in burnout, sleep quality and depressive symptoms were statistically analyzed. A binary logistic regression model was used for multifactor correlation analysis; Pearson correlation was used to test the correlation between burnout, sleep quality, and depressed mood. Modelling and mediated effect path mapping were performed using Amos 24.0 software. Results The postive rate of occupational burnout in the workers was 97.49% (3741/3837), the positive rate of poor sleep quality was 66.77% (2526/3837), and the positive rate of depressive symptoms was 75.68% (2904/3837). There were statistically significant differences in depressive symptoms by ages, shift types, working years, marital status, smoking habits, drinking habits, and exercising frequency (P < 0.05). The logistic model indicated that working years, drinking habits, job burnout, and overall sleep quality were significant factors influencing the occurrence of depressive symptoms (P < 0.05). The correlation analysis revealed positive correlations between depressive symptom scores and job burnout scores (r=0.045, P < 0.01), between depressive symptom scores and sleep quality scores (r=0.480, P < 0.01), and between job burnout scores and sleep quality scores (r=0.054, P < 0.01). Furthermore, the indirect effect of job burnout on depressive symptoms through sleep quality was 0.100 (95%CI: 0.204, 0.252; P < 0.01). Conclusion Job burnout and sleep quality are significant factors associated with the occurrence of depressive symptoms among occupational populations, and sleep quality plays a partial mediating role in depressive symptoms associated with job burnout. This finding may provide a scientific basis for developing intervention strategies to control depressive symptoms among workers.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.