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.

ObjectiveTo explore new targets and herbal medicines of total ginsenosides in ameliorating alcoholic hepatitis （AH） by data mining and experimental validation and to provide new directions for the clinical treatment of AH. MethodGSE28619 was selected as the test set from the GEO database and GSE83148 and GSE103580 were selected as the validation sets. The limma package and weighted gene co-expression network analysis （WGCNA） were employed to identify the AH-related differentially expressed genes and modular genes， and Venny was used to extract the common genes. The protein-protein interaction （PPI） network was constructed and the enrichment analysis was carried out. The hub genes were further screened and evaluated for their diagnostic value. After validation with the datasets， new potential targets of AH and traditional Chinese medicine were predicted. Molecular docking between the targets and active ingredients of traditional Chinese medicine was performed， and the results were validated by experiments. Eight out of 48 SD rats were randomly selected into a blank group and received an equal amount of normal saline. The rest rats were subjected to modeling with ethanol by gavage and then randomized into low- （10 mg·kg^-1）， medium- （20 mg·kg^-1）， and high-dose （40 mg·kg^-1） total ginsenosides， model， and positive control （metadoxine， 117 mg·kg^-1） groups. After 3 weeks of gavage， serum samples were collected for the measurement of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） levels， and liver samples were collected for hematoxylin-eosin （HE） staining. Western blot and Real-time PCR were employed to determine the protein and mRNA levels， respectively， of potential targets in the liver tissue. ResultData mining predicted the potential genes： Proto-oncogene FOS and collagen type Ⅰ alpha 2 （COL1A2）. Experimental validation showed that the liver injury was alleviated after drug administration compared with that after modeling. The serum AST and ALT levels were reduced after drug administration. The protein and mRNA levels of FOS were significantly up-regulated， while those of COL1A2 were down-regulated after drug administration. ConclusionTotal ginsenosides ameliorate HA via FOS and COL1A2.

Cardio-oncology is an emerging cross-discipline， which has received extensive attention and rapid development at home and abroad in recent years， while the construction of related disciplines in the field of traditional Chinese medicine （TCM） is still in its initial stage. By sorting out the construction of oncology and cardiology related disciplines at home and abroad at this stage， and clarifying the significance and main research contents of the discipline， it is proposed that the construction of TCM related disciplines should be oriented to the four main aspects， including clinical practice， scientific research， talent training and promotion of cultural characteristics. Therefore， actively carrying out multidisciplinary crossing， cultivating related professional talent team， and forming TCM diagnosis and treatment guidelines or consensus to support clinical practice is the essential foundation for the construction of TCM cardio-oncology discipline. Meanwhile， fully exploring the characteristics and advantages of TCM is the key to the construction process of the discipline， such as writing and summarising and analysing relevant high-quality clinical case reports of TCM for evidence-based optimisation， as well as widely applying the concept of "treating disease before it arises" of TCM characteristics to the clinical prevention and treatment of the relevant diseases and scientific research， etc.， so as to comprehensively guarantee the development of the discipline of TCM cardio-oncology.

Objective To explore the possible mechanisms of myocardial injury induced by simulated weightlessness in space flight and the recovery of myocardium in rats by aerobic exercise intervention.Methods The body weight of rats was weighed using an electronic balance;the cardiac function indexes of rats in each group were detected using echocardiography and isolated cardiac perfusion;and the expression of proteins related to the AMPK/ULK1/Beclin1 pathway in the myocardial tissues of rats in each group was detected using Western Blot.Results(1)When compared with the C1 group,the T1 group not statistically significant in body weight(P?>?0.05),and the wet weight of the flounder muscle,the wet weight-to-weight ratio of the flounder muscle,and the heart weight were all significantly decreased(P??0.05).After 4 weeks of aerobic exercise,when compared to group C2,group R showed a significant rise in the expression of AMPK and ULK1(P??0.05),and a rise in the expression of Beclin1,but not statistically significant(P?>?0.05);and group A showed a slight increase in the expression of AMPK,ULK1 and Beclin1 expression decreased slightly but not statistically significant(P?>?0.05),p-AMPK expression decreased significantly(P??0.05),and a significant decrease in the expression of ULK1(P??0.05);the expression of p-ULK1 decreased significantly(P?

Objective To observe the effect of Danshen injection (DSI) on pulmonary fibrosis in silicosis mice, and to analyze the differential metabolic pathway on pulmonary fibrosis in silicosis using DSI by urine metabolomics. Methods The specific pathogen free C57BL/6J mice were randomly divided into control group, silicosis model group, DSI prevention group and DSI treatment group. The mice in the last three groups were given 1 mL silica suspension with a mass concentration of 50 g/L by the one-time non-exposed tracheal method, and the mice in the control group were not given any treatment. Subsequently, mice in the DSI prevention group and the DSI treatment group were given intraperitoneal injection of DSI with a dose of 5 mL/kg body weight from 24 hours after exposure to dust and from the 29th day after exposure to dust, respectively, once per day until the 56th day after exposure. Mice in the other two groups were not treated. After DSI intervention, the lung histopathological changes of mice in all groups were evaluated. The components of mouse urine metabolites were analyzed using ultra-high performance liquid chromatography-quadrupole-time-of-fight mass spectrometry method. Human Metabolome Database was used to screen the potential differential metabolites (DMs). The related metabolic pathways were analyzed using MetaboAnanlyst 5.0 Web analytics platform. Results The result of hematoxylin-eosin staining and Van Gieson staining of mouse lung tissues showed that the pulmonary alveolar structure destroyed, typical fibrotic nodules appeared, collagen fiber deposition increased, and clumpy accumulation in the silicosis model group, compared with the control group. Compared with the silicosis model group, the degree of pulmonary alveolar inflammation and fibrosis in the lung tissues of mice in the DSI prevention group was obviously reduced to close to the control group, while pulmonary alveolar inflammation and fibrosis in the lung tissues of mice in the DSI treatment group were also reduced, although the outcome was not as good as that in the DSI prevention group. The result of urine metabolomics analysis identified four DMs in the model group and control group, seven DMs were identified in the DSI prevention group and silicosis model group, seven DMs were identified in the DSI treatment group and silicosis model group. A total of three DMs pathways related to pulmonary fibrosis in silicosis model group and the protective effect of DSI prevention group were identified, including D-arginine and D-ornithine metabolism, folic acid biosynthesis and metabolism, pantothenate and succinyl coenzyme A biosynthesis pathways (all P<0.01). Conclusion DSI treatment in any time point can interfere the process of pulmonary fibrosis in the silicosis mice, while the interference is more effective in the DSI group treated right after dust-exposure. DSI interferes with the urinary metabolism pathway of silicosis mice, and the D-arginine and D-ornithine metabolism, folic acid biosynthesis and metabolism, pantothenate and succinyl coenzyme A biosynthesis pathways may participate in the inhibiting process of early pulmonary fibrosis in silicosis mice by DSI.

【Objective】 To analyze ABO system hemolytic disease of the fetus and newborn (HDFN) and its influencing factors in Obstetrics Department of our hospital. 【Methods】 The blood samples of 1 040 neonates and their mothers in the obstetric department of our hospital were retrospectively analyzed from September 2022 to January 2023, including ABO and RhD blood group of the neonates and mothers, as well as 3 tests of HDFN, Hb, total bilirubin (TBIL) and indirect bilirubin(IBIL) of the neonates. Relevant clinical data of the neonates and mothers were collected, including maternal and neonatal age, neonatal sex, maternal pregnancy history, gestational age and delivery mode, and their influences on ABO-HDFN were analyzed. 【Results】 Among 1 040 HDFN samples, 298 were ABO incompatibility, among which 113 were HDFN positive, with a positive rate of 37.9% (113/298); the positive rate of HDFN in neonates born to mothers with type O was significantly higher than that in neonates born to mothers with type A and B (71.4% vs 8.2%, P<0.05); the positive rate of HDFN in neonates with antigen-A incompatibility was significantly higher than that in neonates with antigen-B incompatibility (48.7%vs 26.7%, P<0.05), which was the highest in neonates with O-A incompatibility [83.6% (61/73)], followed by O-B incompatibility [58.2% (39/67)]. There was no significant difference in Hb and bilirubin among the other groups except for the difference of Hb between the O-A incompatibility HDFN positive group and the HDFN negative group [(145.0±16.0) vs(153.4±13.2), P<0.05)]. The levels of Hb, TBIL and IBIL in the "direct antiglobulin test+ indirect antiglobulin test+release test+" group were significantly different from those in the HDFN negative group[(144.9±21.6) vs (153.3±13.2), P <0.05; (36.9±11.8) vs (29.6±6.1), P<0.05; (30.6±12.7) vs (23.0±6.9), P<0.05, respectively]. Logistic regression analysis showed that maternal delivery frequency, mother-neonate incompatible antigen and maternal blood type were independent risk factors for HDFN. 【Conclusion】 ABO-HDFN occurred mainly in neonates born to O-type mothers, and the positive rate was the highest in neonates with O-A incompatibility. The severity of HDFN had little relationship with the mother-neonate blood type, but had relationship with the result of 3 tests of HDFN. Maternal delivery frequency, mother-neonate incompatible antigen and maternal blood type were independent risk factors for HDFN.

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 investigate the expression level of soluble Programmed cell death ligand2 (sPD-L2) in the peripheral blood of patients with Brucella infection and their correlation with helper T cells (Th) subsets. Methods Data from eighty-three patients with confirmed Brucella infection, including 37 patients with acute phase Brucella infection and 46 patients with chronic phase Brucella infection, collected from the People's Hospital of Xinjiang Uygur Autonomous Region between January 2019 and December 2021, were analyzed. Fifty healthy individuals undergoing regular medical check-ups during the same period were included as the Healthy Control (HC) group. Flow cytometry was used to detect the percentage of Th1 and Th2 cells as CD4+ T cells in the peripheral blood of the three groups of samples. Quantitative real-time fluorescence PCR (qRT-PCR) was performed to measure the mRNA expression levels of Th1 and Th2 cell-associated transcription factors T-bet and GATA-3 in the peripheral blood of the three samples. The expression levels of cytokines sPD-L2, IFN-γ, and IL-4 in the serum of the three groups of samples were measured by the cytometric bead array (CBA) technique. Results Th1 cells in the acute phase brucellosis infection group (45.33±4.96)%, mRNA expression levels of T-bet (1.91±0.41), and IFN-γ expression levels (74.42±13.95) pg/mL were significantly higher in the acute phase Brucella disease group compared to the chronic phase group (21.78±4.42)%, (0.65±0.24), and (10.64±3.04) pg/mL, as well as the HC group (28.87±6.67)%, (1.12±0.25), and (7.48±2.92) pg/mL, respectively (P<0.05). Th2 cells (59.80±10.09)%, GATA-3 mRNA expression level (1.50±0.44), and IL-4 level (8.76±2.06) pg/mL were significantly higher in the chronic phase brucellosis infection group compared to the acute phase brucellosis patient group (40.61±9.32)%, (1.02±0.23), and (2.08±0.50) pg/mL, as well as the HC group (46.06±8.84)%, (1.18±0.28), and (2.70±0.75) pg/mL, respectively (P<0.05). Compared to the HC group (91.61±11.44) pg/mL, the sPD-L2 levels were significantly higher in the acute phase brucellosis patient group (156.77±24.69) pg/mL and slightly higher in the chronic phase brucellosis patient group (110.99±29.44) pg/mL, with a statistically significant difference between the acute and chronic phase brucellosis patient groups (P<0.05). Correlation analysis of the brucellosis patient group showed that sPD-L2 levels were positively correlated with the percentage of Th1 cells (r=0.540, P<0.01) and the levels of IFN-γ (r=0.692, P<0.01), and negatively correlated with the percentage of Th2 cells (r=-0.565, P<0.01) and the levels of IL-4 (r=-0.528, P<0.01). Conclusions In patients with acute brucellosis, sPD-L2 levels are significantly increased, which may resist brucellosis by promoting Th1 cells to secrete more pro-inflammatory factors to defend against Brucella infection. In chronic Brucella disease patients, the tilting of immune response types from Th1 to Th2 may be due to a decrease in sPD-L2 expression, which reduces the inhibitory effect of Th2, leading to incomplete clearance of Brucella and thus immune escape. Brucella may affect the conversion of Th1 to Th2 through the sPD-L2 pathway, exerting negative regulatory effects and resulting in difficulty in complete Brucella clearance, thus turning into a chronic phase.

Objective:To investigate the risk factors for hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS), and the predictive value of Neutrophil to lymphocyte ratio (NLR).Methods:Consecutive patients with AIS received IVT in Zhengzhou People’s Hospital from January 2021 to December 2022 were retrospectively enrolled. HT was defined as no intracranial hemorrhage was found on the first imaging examination after admission, and new intracranial hemorrhage was found on the imaging examination 24 h after IVT or when symptoms worsened. sHT was defined as HT and the National Institutes of Health Stroke Scale (NIHSS) score increased by ≥4 compared to admission or required surgical treatment such as intubation and decompressive craniectomy. The baseline clinical and laboratory data of the patients were collected, and NLR, lymphocyte to monocyte ratio (LMR), and platelet to neutrophil ratio (PNR) were calculated. Multivariate logistic regression analysis was used to identify the independent predictors of HT and sHT, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of NLR for HT and sHT after IVT. Results:A total of 196 patients were included (age 65.37±13.10 years, 124 males [63.3%]). The median baseline NIHSS score was 4 (interquartile range: 2-10). Twenty patients (10.2%) developed HT, and 12 (6.1%) developed sHT. Univariate analysis showed that there were statistically significant differences in age, baseline NIHSS score, creatinine, NLR, and stroke etiology type between the HT group and the non-HT group (all P<0.05); there were statistically significant differences in age, NLR, PNR, creatinine, baseline NIHSS score, and stroke etiological type between the sHT group and the non-sHT group (all P<0.05). Multivariate logistic regression analysis showed that NLR was an independent predictor of HT (odds ratio [ OR] 1.375, 95% confidence interval [ CI] 1.132-1.670; P=0.001) and sHT ( OR 1.647, 95% CI 1.177-2.304; P=0.004) after IVT. The ROC curve analysis showed that the area under the curve for predicting HT by NLR was 0.683 (95% CI 0.533-0.833; P=0.007), the optimal cutoff value was 5.78, the sensitivity and specificity were 55.0% and 84.1%, respectively. The area under the curve for predicting sHT by NLR was 0.784 (95% CI 0.720-0.839; P=0.001), the optimal cutoff value was 5.94, the sensitivity and specificity were 66.67% and 84.24%, respectively. Conclusions:A higher baseline NLR is associated with an increased risk of HT and sHT after IVT in patients with AIS, and can serve as a biomarker for predicting HT and sHT after IVT.

Background/Aims: Older adults are vulnerable to central obesity, while the association of changes in central fatness with risk of diabetes and metabolic control has not been investigated among this particular population. This study was aimed to address these issues. Methods: A total of 1,815 adults aged ≥ 60 years without diabetes at baseline were followed for 4 years. Incident diabetes was ascertained based on plasma glucose, hemoglobin A1c, medical history, and/or the use of anti-diabetic drugs. Central fatness was assessed by waist circumference (WC), waist-height ratio (WHtR), and body roundness index (BRI). Logistic regression analyses were used to assess the association of changes in central fatness with risk of diabetes, along with dose-response and mediation analyses. Results: During the 4-year follow-up, 177 participants developed diabetes. The risk of diabetes was increased by 42%, 41%, and 40% per 1 standard deviation increases in WC, WHtR, and BRI, respectively, in multivariable-adjusted models (all p < 0.01). Moreover, these relationships were all linearly-shaped (all pnonlinearity ≥ 0.11). Increases in WC, WHtR, and BRI correlated with increases in hemoglobin A1c, triglycerides-and-glucose index, triglycerides, white blood cell, and C-reactive protein (all p ≤ 0.04). Yet only changes in hemoglobin A1c and triglycerides-and-glucose index were identified as the possible mediators for risk of diabetes, with their mediating effect being about 35% and 21%, respectively. Conclusions Increases in central fatness were related to elevated risk of diabetes, and this association might be partly explained by the worsening of glycemic control and insulin resistance in older adults.