Background Pesticides like organophosphorus and pyrethroids are extensively utilized, and associated potential human health risks arising from multi-route exposure, including environmental sources and dietary intake, cannot be overlooked. Conducting human exposure studies using pesticide exposure biomarkers is essential for an objective evaluation of human pesticide exposure levels. Objective To develop a rapid and precise liquid chromatography-tandem mass spectrometry method for the detection of 12 pesticide metabolites in urine, including 5 metabolites of organophosphorus pesticide, 4 metabolites of pyrethroid pesticide, 2 metabolites of herbicides, and 1 metabolite of insecticide. Methods After overnight enzymatic hydrolysis, urine samples were subjected to extraction and purification using Oasis HLB 96-well solid-phase extraction. Subsequently, the samples were analyzed by liquid chromatography-tandem mass spectrometry and quantified using the isotope internal standard method. The developed method was employed to analyze 143 urine samples from a general population to assess its effectiveness and to evaluate pesticide exposure levels. Results All 12 target compounds exhibited good linear ranges, with their correlation coefficients of calibration curves exceeding 0.999. The limits of detection (LOD) ranged from 0.02 to 0.19 μg·L⁻¹, while the limits of quantitation (LOQ) ranged from 0.06 to 0.27 μg·L⁻¹. The recoveries at three spiked levels ranged from 84% to 112%, and the inter- and intra- day precisions of targeted analystes were 0.43%-9.6% and 1.6%-9.7% respectively. Using this method, 143 urine samples from residents in Jiangsu region were analyzed, and 11 pesticides were detected except N,N-diethyl-m-toluamide (DEET). Conclusion The established method of solid-phase extraction combined with liquid chromatography-tandem mass spectrometry has the characteristics of low detection limit, good repeatability, and high throughput, which is suitable for quantitative detection of selected 12 pesticides in large batches of human urine samples, and provides technical support for pesticide internal exposure monitoring and health risk assessment.

OBJECTIVE To explore the mechanism of Baihe Dihuang decoction in the treatment of Alzheimer's disease(AD) based on network pharmacology, molecular docking and animal experiment. METHODS TCMSP were used to predict the active components and targets of Baihe Dihuang decoction and disease-related targets were collected from GeneCards, OMIM and DRUGBANK databases, respectively. Target protein interactions were analyzed with STRING database and biological function and pathway were analyzed with Metascape database. Lastly relevant results were analyzed with Cytoscape 3.8.0. AutoDock vina software was used for molecular docking to analyze the binding energy of the active components and key targets of Baihe Dihuang decoction. PyMOL software were used to visualize the optimal docking results. ICR male mice were randomly divided into control group, model group, Rolipram group, low, medium and high dose group of Baihe Dihuang decoction. After 14 days of administration, the neurobehavioral scores of mice in each group were collected, and the expression of related proteins in brain tissue was detected, ELISA and Western blotting were used to detect the expression of the key protein cAMP, PKA, p-CREB and BDNF. At last, the adverse reaction of Baihe Dihuang decoction was observed by vomiting experiment. RESULTS A total of 13 active components and 39 key targets were collected from network pharmacology. The docking results showed that the first 10 core targets all performed well and their effects were closely related to PRKACA. Compared with the control group, the model group mice's recognition rate of new objects and the spontaneous alternation reaction rate were significantly reduced, the escape latency was significantly prolonged, and the target quadrant stay time, the number of crossing platforms were significantly reduced; cAMP, PKA, p-CREB and BDNF in the hippocampus of mice was significantly decreased. Baihe Dihuang decoction could reverse the behavior of AD mice and the expression of cAMP, PKA, p-CREB and BDNF. In the vomiting experiment, the anesthesia recovery time of the Rolipram group was significantly prolonged, while that of the Baihe Dihuang decoction group was not significantly affected. CONCLUSION The mechanism of Baihe Dihuang decoction in the treatment of AD may be related to its influence on cAMP-PKA and regulation of cAMP-PKA-CREB-BDNF signal pathway, and the adverse reactions are milder than those of clopramide.

Objective To use metabolomics method to study the metabolic profiles of amino acids and lysophosphatidylcholine(LPC)in the serum of rats with nonalcoholic fatty liver disease(NAFLD),to identify biomarkers for NAFLD,and to speculate on the possible mechanism responsible for its occurrence.Methods NAFLD rats were prepared by feeding a high-fat diet and intraperitoneal injection of carbon tetrachloride.Levels of 15 LPCs and 18 amino acids in the serum were determined in control and NAFLD rats by liquid chromatography-mass spectrometry.Changes in serum LPC and amino acid metabolic profiles in NAFLD rats were analyzed by principal component analysis and orthogonal partial least squares discriminant analysis.Correlations between biomarkers and NAFLD were analyzed by Pearson's correlation analysis.Results The metabolic profiles of serum LPC and amino acids differed significantly between the NAFLD group and the control group and were completely distinct.LPC(20∶1),arginine,and glutamic acid had significant contributions to NAFLD and were identified as biomarkers.Furthermore,LPC(20∶1)and arginine were significantly correlated with serum biochemical indicators such as aspartate transaminase,alanine transaminase,low-density lipoprotein,and total bilirubin.Conclusions The metabolic profiles of serum LPC and amino acids may be closely related to NALFD.

We investigated the prevalence and genetic variation of porcine pseudorabies virus(PRV)in Hunan Province.A total of 18 861 serum samples and 1 725 suspected PRV-infected tissue sam-ples were collected from Hunan Province from 2021 to 2022.ELISA and qPCR assays were used to detect PRV-gE antibodies in serum samples and the PRV-gE nucleic acids in tissue samples.The positive rates of samples in different years and seasons were analyzed correspondingly.Moreover,the gC gene sequences of 15 PRV-positive samples were amplified,sequenced,and analyzed.The results showed that 2 004 serum and 56 tissue samples tested positive,with an average positive rate of 10.74％and 3.25％,respectively.The sequence analysis showed that the nucleotide and ami-no acid sequence identities of the gC gene among 15 PRV-positive samples were 98.4％-100.0％and 98.8％-100.0％,respectively.Further genetic evolution analysis showed that 13 PRV strains belonged to the same branch with the PRV variants,while two strains were clustered into the same branch with the classical PRV strains.The above results indicate that PRV remains widely prevalent in different regions of Hunan Province,and the variant strain is the dominant epi-demic subtype,which provided a scientific basis for exploring the epidemiological characteristics of PRV and the development of vaccines against PR in Hunan Province.

No case of moyamoya syndrome with bilateral posterior cerebral artery (PCA) occlusion has been reported in China so far as this disease is extremely rare. The case shown in this article is a middle-aged women who has a history of atrial fibrillation, hypertension and type 2 diabetes acutely attacked by this syndrome. The main clinical manifestations included binocular blindness, right limb weakness. Imaging findings showed bilateral acute cerebral infarction in the parietal occipital lobe, bilateral anterior cerebral artery and middle cerebral artery smoke angiogenesis, bilateral PCA occlusion with distal smoke angiogenesis. Considering the medical history of the patient, the cause of the disease was diagnosed as embolic stroke of undetermined source. The patient′s consciousness has been recovered and the limb weakness has been improved after active symptomatic treatment. However, the blindness did not see any improvements. This case report aims to improve clinicians′ understanding of bilateral PCA embolization in patients with moyamoya syndrome so the occurrence of cerebral infarction can be effectively prevented.

Objective:To promote the evidence application of the "Expert Consensus on Nursing Care for Prevention of Adult Oral Tracheal Intubation Unplanned Extubation" and verify its effectiveness.Methods:This was a quasi-experimental study. A total of 31 ICU nurses from Tianjin Teda Hospital were trained by workshops, in order to help promote the evidence transformation. With the evidence application model of the JBI Evidence-Based Health Care Center, we reviewed the measures for mechanically ventilated patients before and after intervention (51 cases at baseline and 77 cases at second review).Results:No unplanned extubation occurred during the period of two rounds of evidence review, the implementation rate of 9 review indicators had improved, and 6 of them showed statistically significant differences. indicator 1 increased from 3.92% (2/51) to 100.00% (77/77),indicator 3 increased from 86.27% (44/51) to 100.00% (77/77), indicator 5 increased from 27.45% (14/51) to 100.00% (77/77), indicator 7 increased from 45.10% (23/51) to 70.13% (54/ 77), indicator 8 increased from 50.98% (26/51) to 100.00% (77/77), indicator 9 increased from 45.10% (23/51) to 77.92 % (60/77), the difference was all statistically significant ( χ2 values were 8.02-119.87, all P<0.05). Conclusions:The "Expert Consensus on Nursing Care for Prevention of Adult Oral Tracheal Intubation Unplanned Extubation" can provide guidelines for clinical nursing practice. While preventing unplanned extubation, it can standardize nurses' behavior and promote medical-nursing cooperation.

BACKGROUND: Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender. METHODS: Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method. RESULTS: Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades. CONCLUSIONS One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.
Young Adult ; Humans ; Male ; Proteome ; Cardiovascular Diseases ; Proteomics ; Ischemia ; Blood Coagulation

OBJECTIVE To study the protective effect and mechanism of Shiyifang medicinal wine （SYF） on knee osteoarthritis（KOA）of rabbit induced by papain . METHODS Thirty-five rabbits were randomly divided into blank group ，model group，positive group （Diclofenac diethylamine emulsion 200 mg/kg），SYF high -dose group （386 mg/kg）and SYF low -dose group（97 mg/kg），with 7 rabbits in each group （all had 4 males and 3 females）. Except for the blank group ，the other groups ’ rabbits were injected 0.5 mL papain mixture （containing 2% papain and 0.03 mol/L L -cysteine）into the right knee cavity on day 1， 4 and 7，to replicate KOA model . Blank group was given constant volume of normal saline . From the 15th day ，drugs were applied to right hind knee joints of rabbits in each group ，twice a day for 20 days. At the same time ，the diameter of right knee joints of rabbits was measured by vernier calipers at day 0，8，14 and 35 to calculate swelling degree . After the experiment ，the levels of IL-1β，TNF-α and PGE 2 in synovial tissue were determined by enzyme -linked immunosorbent assay . Hematoxylin-eosin（HE） staining was used to prepare the sections of synovial tissue ，and the pathological changes were observed . The relative mRNA expressions of TLR 4，MyD88 and NF - кB p 65 in the TLR 4/MyD88/NF- кB signaling pathway were detected by real -time quantitative polymerase chain reaction . The relative protein expressions of TLR 4，MyD88，NF-кB p 65 and p -NF-кB p 65 were detect by Western blot . RESULTS Compared with blank group，the degree of knee swelling could be increased in model group ，the pathological damage of synovial tissue was more serious ，and the levels of IL -1β，TNF-α and PGE 2 were increased significantly in synovial tissue （P＜0.05）. The relative expression levels of TLR 4，MyD88，NF-кB p 65 mRNAs and TLR 4，MyD88，p-NF-кB p 65 proteins were significantly increased（P＜0.05）. Compared with model group ，swelling degree of right hind knee and the pathological injury degree of synovial tissue were significantly improved in each treatment group ，while the levels of IL -1β，TNF-α and PGE 2 in synovial tissue were significantly decreased （P＜0.05）. The relative mRNA expressions of TLR 4，MyD88 and NF -кB p 65 and relative protein expressions of TLR 4，MyD88（except for SYF low -dose group ）and p -NF-кB p 65 were all significantly decreased （P＜0.05）. CONCLUSIONS SYF shows protective effect on KOA induced by papain ，the mechanism of which is associated with decreasing the levels of IL -1β，TNF-α and PGE 2 and down -regulating TLR 4/MyD88/NF-кB signaling pathway .

OBJECTIVE To explore the regulatory mechanism of compatibility of ginseng and gecko dispensing granule on kidney yang deficiency model rats. METHODS Male SD rats were randomly divided into normal group （no modeling ，no administration），model group （modeling，no administration ），Jinkui shenqi pill group （modeling，dose of 2.33 g/kg），ginseng group（modeling，dose of 0.53 g/kg），gecko group （modeling，dose of 0.21 g/kg）and compatibility group （modeling，ginseng 0.53 g/kg and gecko 0.21 g/kg）. The body mass and anal temperature of rats were measured at different time points ；the serum levels of cAMP ，cGMP，CRH，ACTH，CORT，T，T3，T4，E2，IgG and IgM were measured ；the pathomorphological changes of adrenal gland ，thyroid gland and testis were observed ；mRNA expression of CRH ，thyroid stimulating hormone releasing hormone （TRH）and gonadotropin releasing hormone （GnRH）in hypothalamus were detected. RESULTS Compared with model group ，the anal temperature ，the levels of cAMP ，CRH，ACTH，CORT，T3，T and cAMP/cGMP ，T/E2 in serum and mRNA expressions of TRH and GnRH in hypothalamus were significantly increased in the compatibility group （P＜0.05 or P＜0.01）；the levels of cGMP，E2 and IgG in serum and mRNA expression of CRH in hypothalamus decreased significantly （P＜0.05 or P＜0.01）； the pathological injuries of adrenal gland ，thyroid gland and testis were all improved. Compared with ginseng or gecko dispensing granules alone ，the anal temperature and T/E 2 of rats in the compatibility group increased significantly ，and mRNA expression of CRH in hypothalamus decreasedsignificantly （P＜0.05 or P＜0.01）. CONCLUSIONS Thecompatibility of ginseng and gecko dispensing granule has a synergistic regulatory effect on kidney yang deficiency model rats ， the mechanism of which may be associated with hypothalamus-pituitary-adrenal axis ， hypothalamus-pituitary-thyroid axis ， hypothalamus-pituitary-gonad axis and neuroendocrine immune network formed by immune function. Compatible drugs are better than single drugs.

Objective:To investigate the correlation between white matter hyperintensities (WMHs) and collateral circulation in patients with stroke caused by anterior circulation large vessel occlusion (aLVO).Methods:Patients with stroke caused by aLVO treated with endovascular mechanical thrombectomy in the Department of Neurology, Zhengzhou People's Hospital from December 2017 to April 2021 were retrospectively enrolled. Their demography, vascular risk factors, baseline clinical data and Fazekas scale score were collected. Multivariate logistic regression analysis was used to determine the independent correlation between WMHs and the collateral circulation status in patients with aLVO. Results:During the study, 166 patients with aLVO were included (77 males, 46.39%; aged 69.62±5.91 years). Their baseline National Institutes of Health Stroke Scale (NIHSS) score was 9.33±4.42. There were 120 patients (72.29%) in the good collateral circulation group and 46 (27.71%) in the poor collateral circulation group. Univariate analysis showed that there were significant differences in baseline NIHSS score, total Fazekas score and periventricular Fazekas score between the good collateral circulation group and the poor collateral circulation group (all P<0.05). Multivariate logistic regression analysis showed that total Fazekas score (odds ratio 2.583, 95% confidence interval 1.445-4.619; P=0.001) and periventricular Fazekas score (odds ratio 2.190, 95% confidence interval 1.022-4.692; P=0.044) were the independent risk factors for the poor collateral circulation. Conclusion:The severity of WMHs is associated with the poor collateral circulation in patients with aLVO.