OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

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*

OBJECTIVES: To develop an early atrial fibrillation (AF) risk prediction model based on large-scale electrocardiogram (ECG) data from the Chinese population. METHODS: The data of multiple ECG records of 30 383 patients admitted in the Chinese PLA General Hospital between 2009 and 2023 were randomly divided into the training set and the internal testing set in a 7:3 ratio. The predictive factors were selected based on the training set using univariate analysis, LASSO regression, and the Boruta algorithm. Cox proportional hazards regression was used to establish the ECG model and the composite model incorporating age, gender, and ECG model score. The discrimination power, calibration, and clinical net benefits of the models were evaluated using the area under the receiver operating characteristic curve (AUROC), calibration curves, and decision curves. RESULTS: The cohort included 51.1% male patients with a median age of the patients of 51 (36, 62) years and an AF incidence of 4.5% (1370/30 383). In the ECG model, the parameters related to the P wave and QRS complex were identified as significant predictors. In the testing set, the AUROC of the ECG model for predicting 5-year AF risk was 0.77 (95% CI: 0.74-0.80), which was increased to 0.81 (95% CI: 0.78-0.83) after incorporating age and gender, with a net reclassification improvement of 0.123 and an integrated discrimination improvement of 0.04 (P<0.05). The calibration curve of the model was close to the diagonal line. Decision curve analysis showed that the clinical net benefit of the composite model was higher than that of the ECG model across the majority of threshold probability. CONCLUSIONS The composite model incorporating quantitative ECG features during sinus rhythm, along with age and gender, can effectively predict AF risk in the Chinese population, thus providing a low-cost screening tool for early AF risk assessment and management.
Humans ; Atrial Fibrillation/epidemiology* ; Electrocardiography ; Middle Aged ; Male ; Female ; China/epidemiology* ; Proportional Hazards Models ; Adult ; Risk Factors ; Risk Assessment ; East Asian People

A new method was developed for simultaneous and efficient determination of linear perfluorooctanoic acid(n-PFOA)and linear perfluorooctane sulfonate(n-PFOS),and their typical branched isomers in seawater by online solid phase extraction-liquid chromatography-tandem mass spectrometry(Online SPE-LC-MS/MS).Only centrifugation of the seawater sample was required to remove the particulate matter,and then the seawater sample was directly injected and analyzed by online SPE-LC-MS/MS.An Eclipse Plus-C18 guard column was selected as SPE column for online enrichment of linear and branched isomers,and a F5 PFP column(150 mm×2.1 mm,2.7 μm)was used as the analytical column.Under the optimized experimental conditions,the separation and detection of all PFOA and PFOS linear and branched isomers could be completed within 20 min.The spiked recoveries of various target compounds ranged from 82.9%to 107.7%with detection limits and limits of quantification of 0.10-1.05 ng/L and 0.30-2.11 ng/L,respectively.The method was characterized by good precision(RSD≤9.10%)and linearity(R2≥0.990).Subsequently,linear and branched isomers of PFOA and PFOS in surface and bottom seawater samples collected from the Laizhou Bay of China were determined.The results showed that the detection rate of all the four branched PFOA isomers were 100%,with the highest average concentration of 25.85 ng/L found for 6m-PFOA,which accounted for 11.79%of the∑PFOA.For the five branched isomers of PFOS,the highest detection rate of 90.84%was found for 5m-PFOS.The highest average concentration of 0.64 ng/L was observed for 3m-PFOS,accounting for 19.88%of ∑PFOS.The proposed method provided an effective detection tool for qualitative and quantitative detection of PFOA and PFOS isomers in the marine aquatic environment.

Objective To investigate the effects of remimazolam(REM)on cerebral ischemia-reperfusion injury(CIRI)rats and the AMP-activated protein kinase(AMPK)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods One hundred rats were selected to construct the CIRI rat model(Mod)and stochastically separated into a Mod group,low,medium,and high dose remifentanil groups(REM-L,REM-M,REM-H),and high dose remifentanil+pathway inhibitor Compound C group(REM-H+Compound C),with 20 rats in each group.Another 20 healthy rats were included as the control(Ctrl)group.All rats were subjected to neurobehavioral scoring.The water content,infarct area,and oxidative stress indicators of brain tissue were detected.The morphology and apoptosis of brain tissue were observed by HE and TUNEL staining.Western blotting was applied to detect protein expression related to the AMPK/NLRP3 signaling pathway.Results Compared with the Mod group,with the increase of REM dose,the movement disorders in rats were alleviated,the overall structure of brain tissue gradually recovered,pathological damage was reduced,the area of cerebral infarction,brain water content,and apoptosis rate of brain tissue cells decreased,reactive oxygen species(ROS)level,malondialdehyde(MDA)content,and NLRP3 and Caspase-1 protein expression levels decreased,superoxide dismutase the(SOD)content and AMPK protein expression level increased(P＜0.05).Compared with the REM-H group,the REM-H+Compound C group showed aggravated motor disorders,and more severe pathological damage to brain tissue,the area of cerebral infarction,cerebral water content and apoptosis rate of brain tissue cells increased,the ROS level,MDA content and the protein expression of NLRP3 and Caspase-1 increased,while the content of SOD and the protein expression decreased(P＜0.05).Conclusion Remimazolam can enhance the antioxidant function of the body,reduce brain cell apoptosis,alleviate brain tissue injury,and thus have a certain protective effect on ischemia-reperfusion brain injury in rats,the mechanism of which may be related to the activation of the AMPK/NLRP3 signaling pathway.

Objective To observe the clinical efficacy of acupuncture combined with acupoint catgut embedding therapy on back-shu and front-mu points and external application on shenque(RN8)point for premature ovarian failure(POF).Methods A total of 62 patients with POF were randomly divided into the observation group and the control group,with 31 patients in each group.The observation group was treated with acupuncture combined with acupoint catgut embedding therapy on back-shu and front-mu points and external application on shenque point,and the control group was treated with hormone replacement therapy.After three months of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the traditional Chinese medicine(TCM)syndrome scores,as well as the ovarian volume,number of antral follicle,and antral follicle diameter of the patients in the two groups before and after treatment were observed.The changes of serum follicle stimulating hormone(FSH),luteinizing hormone(LH)and estradiol(E2)levels before and after treatment were compared between the two groups.Results(1)The total effective rate was 93.55%(29/31)in the observation group and 80.64%(25/31)in the control group.The efficacy of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the serum FSH,LH and E2 levels of patients in the two groups were significantly improved(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,with statistically significant differences(P＜0.05).(3)After treatment,ovarian volume,number of antral follicle,and antral follicle diameter were significantly improved in the two groups(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group,and the difference was statistically significant(P＜0.05).Conclusion The treatment of POF with acupuncture combined with acupoint catgut embedding therapy on back-shu and front-mu points and external application on shenque point can significantly improve the clinical symptoms of the patients,conducive to the recovery of ovarian function,and significantly improve the sex hormone levels of the patients,with precise clinical efficacy.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Acute liver injury (ALI) is one of the common severe diseases in clinic, which is characterized by redox imbalance and inflammatory storm. Untimely treatment can easily lead to liver failure and even death. Rosmarinic acid (RA) has been proved to have anti-inflammatory and antioxidant activity, but it is not clear how to protect ALI through antioxidation and inhibition of inflammation. Therefore, this study explored the therapeutic effect and molecular mechanism of RA on ALI through in vitro and in vivo experiments. In the mouse ALI model, the effects of RA on liver function and inflammatory indexes were studied, the pathological changes of liver were observed by HE, the effect of RA on reactive oxygen species in liver was detected by fluorescence method, and the level of F4/80 in liver tissue was detected by immunohistochemical method. The levels of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate specific proteinase-1 (CASPASE-1) in liver tissue were measured by Western blot. All animal welfare and experimental procedures follow the rules of the Animal Ethics Committee of Southwest Minzu University. In vitro, human hepatoma cell line HepG2 was used to establish the model of oxidative damage induced by H₂O₂. The cell viability was detected by CCK-8 method. The level of interleukin-1β (IL-1β) in the supernatant was detected by enzyme linked immunosorbent assay (ELISA), the activity of lactatede hydrogenase (LDH) was detected by LDH kit, and the level of ROS was detected by fluorescence probe DCFH-DA labeling. The mRNA expression of Txnip, Nlrp3, Caspase 1, Il1β was detected by real-time fluorescence quantitative PCR (qPCR), and the protein levels of nuclear factor erythroid-2 related factor 2 (NRF2), TXNIP, NLRP3 and CASPASE-1 were measured by Western blot. The results showed that compared with the model group, the degree of liver swelling, tissue injury, liver function index in RA group were significantly lower than those in model group. And RA significantly attenuated the increases of ROS in liver tissue. The expression levels of TXNIP, NLRP3 and CASPASE-1 in liver tissue were significantly lower than those in model group. Additionally, RA inhibited the expressions of F4/80 and IL-1β. In vitro experiment, compared with model group, RA effectively inhibited the secretion of IL-1β and LDH. The level of ROS also decreased significantly. RA inhibited the mRNA expressions of Txnip, Caspase 1, Il1β. Furthermore, RA significantly increased the expression level of NRF2 protein in nucleus, and decreased the expression level of TXNIP and NLRP3 protein. Specifically, with the addition of ML385, the effect of RA on NRF2, TXNIP, NLRP3, CASPASE-1 protein expression was reversed. Collectively, these findings suggested that RA may inhibit the production of ROS by promoting NRF2 nuclear transfer, and then reduce the activation of NLRP3 inflammatory bodies by TXNIP, reduce cell death and inflammatory response to prevent the liver injury.

Based on the species-specific peptides of Pheretima and its common counterfeit (Metaphire magna), an identification method was established using ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) for quality evaluation of Pheretima and its preparations. Separation was performed on a CORTECS T3 C18 column with 0.1% formic acid and acetonitrile as the mobile phases. Mass spectrometry with multiple reaction monitoring (MRM) using ESI⁺ mode was used to simultaneously monitor three ion pairs. The results indicated that the method was specific and could distinguish Guang Dilong, Hu Dilong, and M. magna, which were consistent with those of DNA barcode identification. The adulteration test showed that the LOD of peptide M was 1 μg·g^-1. Peptide M could be detected when 1% M. magna was added to Guang Dilong, indicating the high sensitivity of the method. Fifty-four batches of commercially available samples contained 35% Guang Dilong, 35% Hu Dilong, and 15% M. magna. No ions were detected in 15% of the samples, and DNA barcode identification revealed that they were mainly from Amynthas, with similar appearance to Hu Dilong. The analysis results of the formulation showed that no peptide ions were detected in 3 batches of Xiaohuoluo pills (3/6) and M. magna were detected in 2 batches of Shenjindan capsules (2/4). The developed method in the study has good specificity, sensitivity, and feasibility, and could be used for quality control of Pheretima and its related preparations. It is of great significance for improving quality standards and regulating the medicinal market of Pheretima.