Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE)intervention timing and liver injury periodization in patients with exertional heat stroke(EHS).Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected,then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT,AST,TBIL and DBIL.According to propensity score matching analysis,11 patients in the survival group and 12 patients in the death group were included in the statistical analysis,and 20 of them were treated with TPE.The changes in indicators and clinical outcomes before and after TPE were observed,in order to evaluate the impact of intervention timing on prognosis.Results Among the 23 patients,14 had no liver injury or could progress to the repair phase,resulting in 3 deaths(with the mortality rate of 21.43%),while 9 patients failed to pro-gress to the repair phase,resulting in 9 deaths(with the mortality rate of 100%),with significant differences(P＜0.05).The mortality rate of the first TPE intervention before the third stage of liver injury was 23.08%(3/13),while that of interven-tion after reaching or exceeding the third stage was 85.71%(6/7),and the difference was statistically significant(P＜0.05).Conclusion TPE should be executed actively in EHS patients combined with liver injury before the third phase to lock its pathological and physiological processes,thereby improving prognosis and reducing mortality.

Objective Hypertriglyceridemic waist(HW),hypertriglyceridemic waist-to-height ratio(HWHtR),and waist-to-hip ratio(WHR)have been shown to be indicators of cardiometabolic risk factors.However,it is not clear which indicator is more suitable for children and adolescents.We aimed to investigate the relationship between HW,HWHtR,WHR,and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods This was a national cross-sectional study.Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China.Demographics,physical activity,dietary intake,and family history of chronic diseases were obtained through questionnaires.ANOVA,x2 and logistic regression analysis was conducted. Results A significant sex difference was observed for HWHtR and WHR,but not for HW phenotype.The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents(HW:OR = 12.22,95%CI:9.54-15.67;HWHtR:OR = 9.70,95%CI:6.93-13.58).Compared with the HW and HWHtR phenotypes,the association between risk of cardiometabolic health risk factors(CHRF)clustering and high WHR was much weaker and not significant(WHR:OR = 1.14,95%CI:0.97-1.34). Conclusion Compared with HWHtR and WHR,the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived car-diomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a po-tential reagent for repairing damaged hearts.

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.
Chromatography, High Pressure Liquid ; Epimedium ; Tandem Mass Spectrometry ; Chromatography, Liquid ; Multivariate Analysis

ObjectiveTo investigate the mechanism of Jiedu Huoxue prescription in promoting the reendothelialization of injured vessels by regulating the nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3）/cysteine-aspartic acid protease （Caspase）-1-mediated pyroptosis. MethodA rat model of injured thoracic aorta was established by balloon injury， and 36 rats were assigned into shame surgery， model， low-， medium-， and high-dose Jiedu Huoxue prescription， and atorvastatin calcium tablet groups. The injured aortic segment was collected 28 days after surgery. Hematoxylin-eosin （HE） staining and Evans blue staining were conducted to reveal the changes of vascular structural morphology and the reendothelialization of blood vessels， respectively. The enzyme-linked immunosorbent assay （ELISA） was employed to determine the levels of tumor necrosis factor-α （TNF-α）， intercellular adhesion molecule-1 （ICAM-1）， interleukin （IL）-1β， and nitric oxide （NO） in the serum. Western blotting was employed to determine the expression of endothelial nitric oxide synthase （eNOS）， NF-κB p65， phospho-NF-κB p65 （p-NF-κB p65）， NLRP3， and Caspase-1 in the vascular tissue. ResultThe model group showed thickened endovascular membrane， proliferation and disarrangement of smooth muscle cells of the artery wall， obvious inflammatory cell infiltration， and narrowed luminal area. Jiedu Huoxue prescription and atorvastatin calcium tablets mitigated the pathological changes of the thoracic aorta in different degrees. After balloon injury， the endothelial coverage rate of the model group decreased significantly， while Jiedu Huoxue prescription and atorvastatin calcium tablets increased the reendothelialization rate （P<0.05）. Compared with the shame surgery group， the model group showed elevated levels of TNF-α， ICAM-1， and IL-1β （P<0.01） and lowered NO level （P<0.01） in the serum. In addition， the model group presented down-regulated protein level of eNOS （P<0.01） and up-regulated phosphorylation of pyroptosis-associated proteins NLPR3， Caspase-1， and NF-κB p65 in the vascular tissue （P<0.05， P<0.01）. Compared with the model group， Jiedu Huoxue prescription and atorvastatin calcium tablets lowered TNF-α， ICAM-1， and IL-1β levels （P<0.05， P<0.01） and elevated the NO level in the serum （P<0.05， P<0.01）. Moreover， the drugs up-regulated the expression of eNOS （P<0.01） and down-regulated the expression of NLRP3， Caspase-1， and NF-κB p65 （P<0.05， P<0.01） in the vascular tissue. ConclusionJiedu Huoxue prescription can promote the reendothelialization and inhibit the intimal hyperplasia of vessels after balloon injury by regulating the NF-κB/NLRP3/Caspase-1 pathway to inhibit pyroptosis and reduce endothelial inflammatory injury.

ObjectiveTo investigate whether Jiedu Huoxue prescription can induce macrophage autophagy and inhibit inflammatory response to stabilize vulnerable plaques of atherosclerosis （AS） by regulating phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodThirty ApoE^-/- mice fed with high-fat diet were randomly assigned into model， low-， medium-， and high-dose （5.35， 10.7， and 21.4 g·kg^-1·d^-1， respectively） Jiedu Huoxue prescription （Chinese medicine）， and rapamycin （2 mg·kg^-1·d^-1） groups. Six ApoE^-/- mice fed with common diet were used as the control group， and 6 C57BL/6J mice fed with common diet as the blank group. The drugs or equal volume of normal saline were administrated by gavage after 7 weeks of modeling， and the treatment lasted for 4 weeks. The serum levels of lipids and inflammatory cytokines ［monocyte chemoattractant protein-1 （MCP-1） and interleukin-6 （IL-6）］ were measured. Hematoxylin-eosin （HE） staining was employed to observe the pathological changes of the vascular wall of the aortic root. Immunohistochemistry was employed to detect the expression of macrophages/monocytes monoclonal antibody （MOMA-2） and α-smooth muscle actin （α-SMA）. Transmission electron microscopy was employed to count the autophagosomes in the aorta， and Western blot to determine the protein levels of Beclin-1， LC3， PI3K， Akt， and mTOR. ResultCompared with the control group， the model group showed elevated serum levels of lipids， MCP-1， and IL-6 （P<0.05）， inhibited expression of MOMA-2 and α-SMA （P<0.05， P<0.01）， up-regulated protein level of Beclin-1 （P<0.05）， and down-regulated protein levels of PI3K， Akt， and mTOR （P<0.05， P<0.01）. The model group presented obvious atherosclerotic plaques on the inner wall of the aorta， infiltration of inflammatory cells in the plaque， thickened and disarranged vascular intima where the plaque was attached， decreased autophagosomes and mitochondria， and destroyed mitochondrial structure. Chinese medicine and rapamycin groups showed lower levels of total cholesterol， triglycerides， low-density lipoprotein cholesterol， MCP-1， and IL-6 （P<0.05）， higher level of high-density lipoprotein cholesterol （P<0.05）， inhibited expression of MOMA-2 and α-SMA （P<0.05， P<0.01）， higher protein levels of Beclin-1 and LC3Ⅱ （P<0.05， P<0.01）， and lower protein levels of PI3K， Akt， and mTOR （P<0.05， P<0.01） than the model group. Moreover， Chinese medicine and rapamycin groups showed only a small number of atherosclerotic plaques on the inner wall of the aorta， reduced infiltration of inflammatory cells and thickness of the blood vessel wall， and increased autophagosomes and autophagic lysosomes. ConclusionJiedu Huoxue prescription can improve lipid metabolism， enhance macrophage autophagy， and reduce AS-induced inflammation to improve the stability of vulnerable plaques in AS mice by inhibiting the PI3K/Akt/mTOR signaling pathway.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 μm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.
Tandem Mass Spectrometry/methods* ; Multivariate Analysis ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Amino Acids/analysis*