Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Objective: To understand the epidemiological and spatial clustering characteristics of hand-foot-mouth disease in Pingxiang City, Jiangxi Province from 2013 to 2023, so as to provide the evidence for improving hand-foot-mouth disease prevention and control measures. Methods: Data of hand-foot-mouth disease cases in Pingxiang City from 2013 to 2023 were collected from the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. Demographic, temporal, and regional distribution characteristics were described. The trend in incidence was analyzed using the average annual percent change (AAPC). The spatial clustering and aggregation patterns of hand-foot-mouth disease were identified using global and local spatial autocorrelation analyses. Results: A total of 58 020 hand-foot-mouth disease cases were reported in Pingxiang City from 2013 to 2023, with an average annual incidence of 289.71/105. No significant trend in the reported incidence of hand-foot-mouth disease was observed (AAPC=-7.398%, P>0.05). Among them, 33 892 were males and 24 128 were females, with infants aged 0-<3 years accounting for 70.59% of the total (40 958 cases). The peak incidence occurred mainly from May to June and from September to December. Luxi County had the highest average annual reported incidence of 677.10/105. Spatial autocorrelation analysis indicated significant spatial clustering of hand-foot-mouth disease in 2018, 2019, 2021, and 2022 (Moran's I=0.314, 0.339, 0.381, and 0.668, all P<0.05). High-high clustering areas were primarily identified in 7 townships (streets) of Anyuan District, 2 in Xiangdong District, 4 in Shangli County, and 1 in Luxi County. Conclusions The reported incidence of hand-foot-mouth disease in Pingxiang City from 2013 to 2023 remained stable overall, with higher susceptibility among young children and peak incidence during summer and autumn. Spatial clustering of hand-foot-mouth disease was observed, expanding northward and southwestward from Anyuan District as the core area.

Objective To establish a sandwich enzyme-linked immunosorbent assay (ELISA) method for the quantitative detection of Chromogranin A (CHGA) in saliva, and to explore its preliminary application in the testing of saliva samples. Methods Recombinant human CHGA protein was used to immunize BALB/c mice, and monoclonal antibodies (mAbs) were prepared and screened using conventional hybridoma technology. A double-antibody sandwich ELISA detection method was constructed, and the matrix effect of saliva samples was optimized. This method was then applied to detect the concentration of CHGA in the saliva of stressed individuals. Results Twenty-one stable hybridoma cell lines secreting high affinity anti-human CHGA antibodies were obtained. A pair of detection antibodies with the best effect was selected, and the optimal coating concentration was determined to be 10 μg/mL, with the optimal dilution of detection antibodies being 1:32 000. The accuracy and reproducibility of this method were verified, with both intra-batch and inter-batch variation coefficients less than 15×, and the recovery rate between 80× and 120×. The matrix effect was further optimized to make it suitable for saliva sample detection. Saliva samples from individuals in different stress states were collected, and the CHGA levels were detected using the method established in this study, indicating its potential to reflect the intensity of stress. Conclusion A reliable saliva CHGA ELISA detection method has been successfully established, and its potential as a biomarker in stress-related research has been preliminarily explored.
Saliva/metabolism* ; Enzyme-Linked Immunosorbent Assay/methods* ; Humans ; Animals ; Mice, Inbred BALB C ; Mice ; Chromogranin A/immunology* ; Antibodies, Monoclonal/immunology* ; Female ; Male ; Reproducibility of Results ; Adult

Objective:To investigate the relationship between the BCL2 family protein BIM and ibrutinib resistance in chronic lymphocytic leukemia (CLL) and to analyze its regulatory mechanisms on apoptosis and autophagy.Methods:RNA sequencing (RNA-seq) was used to examine changes in the expression of BCL2 family proteins in samples from patients with CLL, MEC1 cell lines, and ibrutinib-resistant cell lines (MR). Western blot was used to analyze changes in BIM protein expression during apoptosis in MR. shRNA knockdown was used to assess the effects of BIM on cell proliferation and apoptosis. RNA-seq and the autophagy inhibitor chloroquine treatment were used to study autophagy-related changes in MR.Results:BIM expression was significantly downregulated before and after drug resistance in CLL primary cells and MEC1 cell lines ( P<0.0001). Knockdown of BIM in CLL cells inhibited ibrutinib-induced apoptosis and promoted cell proliferation ( P<0.05 for both). In addition, protective autophagy was increased in MR and apoptosis was increased after administration of chloroquine and small interfering RNA. The increased expression of LC3-Ⅱ protein in BIM-knockdown cell lines ( P<0.01) suggested that reduction of BIM may mediate autophagy activation. Conclusion:Downregulation of BIM may be a key factor in promoting ibrutinib resistance in CLL by activating protective autophagy. These findings provided a potential target for improving CLL treatment.

Objective This study aims to investigate the effects of acupuncture on the spatial learning and memory capacities,the morphological characteristics of hippocampal neurons,the components of extracellular matrix,as well as the structure of the blood-brain barrier in SAMP8 mice.Moreover,it endeavors to explore the underlying mechanism through which the"Tongdu Qishen"(activating governor vessel and awakening spirit)acupuncture method ameliorates the cognitive function and modulates cerebral blood flow in SAMP8 mice.Methods Twenty 6-month-old male SAMP8 mice were randomly allocated into a model group and an electroacupuncture group,with ten mice in each group.Additionally,ten homologous 6-month-old male SAMR1 mice were designated as the normal control group.In the electroacupuncture group,the acupoint"Renzhong"(GV 26)was punctured using a quick insertion technique,while"Baihui"(GV 20)and"Yintang"(EX-HN 3)were punctured via a transverse insertion method.Subsequently,the needle handles were connected to an electroacupuncture apparatus,which was set to operate with a dense-sparse wave at a frequency of 100 Hz/2 Hz and an electric current of 2 mA.Each session of acupuncture lasted for 20 minutes and was conducted once a day for a consecutive period of 28 days.The normal group,the model group,and the electroacupuncture group all underwent identical fixation and restraint procedures to ensure consistent experimental conditions.The Morris water maze was employed to evaluate the spatial learning and memory abilities of the mice.The Nissl staining technique was utilized to assess the alterations in hippocampal neurons of SAMP8 mice.The laser speckle imaging system was adopted to measure the cerebral blood flow of the mice in each group.Transmission electron microscopy was applied to observe the ultrastructure of the blood-brain barrier within the frontal cortex tissue of the SAMP8 mice's brains.The Western blotting method was used to detect the expressions of Collagen-Ⅳ and Fibronectin in the brain tissues of SAMP8 mice.Results In comparison with the model group,the"Tongdu Qishen"acupuncture method demonstrated a significant efficacy in improving the spatial learning and memory abilities of SAMP8 mice(P<0.05).It also effectively alleviated the degeneration of hippocampal neurons,remarkably increased the cerebral blood flow perfusion volume of SAMP8 mice(P<0.05),ameliorated the damage to the blood-brain barrier structure,significantly upregulated the content of Collagen-Ⅳ(P<0.05),and significantly downregulated the content of Fibronectin(P<0.0001).Conclusion The"Tongdu Qishen"acupuncture method is capable of favorably regulating the extracellular matrix of SAMP8 mice,thereby improving cerebral blood flow and ultimately enhancing their learning and memory abilities.

Objective:To investigate the mechanisms of baicalin in treating septic acute liver injury through a combination of network pharmacology and animal experiments.Methods:Thirty male C57BL/6 mice (6 weeks old) were divided into five groups ( n=6): control group (normal saline), model group [lipopolysaccharide (LPS) 10 mg/kg, intraperitoneal injection], low-dose baicalin group (10 mg/kg), high-dose baicalin group (20 mg/kg), and baicalin-only group (20 mg/kg, without LPS). Baicalin was administered orally for 14 consecutive days prior to modeling. Mice were sacrificed 24 h after LPS injection. Alanine transaminase, aspartate transaminase liver tissue histopathology were measured; neutrophil infiltration was visualized using immunofluorescence; mRNA expression levels of interleukin (IL)-1β, IL-17, IL-6, and tumor necrosis factor (TNF)-α were detected by RT-qPCR; and the expression of Toll-like receptor 4 (TLR4) and phosphorylated nuclear factor (NF)-κB proteins were analyzed by Western blotting. Results:In the LPS model group, the ALT, AST, and histopathological injury score were (148.60±22.02) U/L, (81.58±11.59) U/L, and 8.50(7.75, 9.25), respectively. These indicators were significantly reduced in the high-dose baicalin group with (77.90±16.79) U/L, (49.92±14.89) U/L, and 1.00(1.00, 2.25) (all P<0.05). Compared with the LPS group, neutrophil infiltration in the liver of high-dose baicalin group was also significantly reduced [1.18%(0.98%, 1.22%) vs. 6.13%(5.41%, 8.69%), P<0.05]. RT-qPCR results showed that the relative mRNA expression levels of inflammatory cytokines IL-1β [(1.03±0.06) vs. (2.60±0.34)], IL-17 [(1.21±0.12) vs. (2.94 ± 0.39)], IL-6 [(1.37±0.26) vs. (2.73±0.18)], and TNF-α [(1.18±0.10) vs. (3.30±0.92)] were significantly decreased in the high-dose baicalin group compared with the LPS group (all P<0.05). Western blot analysis revealed that the relative protein expression levels of TLR4 [(1.25±0.13) vs. (1.73±0.06)] and phosphorylated NF-κB [(1.25±0.25) vs. (1.79±0.12)] were also significantly lower in the high-dose baicalin group (both P<0.05). Conclusion:Baicalin reduces liver injury in septic mice by downregula-ting the expression of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, and IL-17, potentially through the inhibition of the TLR4/NF-κB signaling pathway.

Objective:To establish and evaluated a logistic regression model for predicting the acute biliary pancreatitis (ABP) based on liver-injury related indexes.Methods:Clinical data of 210 patients diagnosed with acute pancreatitis (AP) at the Affiliated Hospital of Jiangnan University from October 2020 to December 2022 were retrospectively analyzed, including 113 males and 97 females, with a median age of 52 years (range, 43 to 58). Among these, 88 were diagnosed with ABP and 122 with acute non-biliary pancreatitis (ANBP). Additionally, a test cohort was created using data from 101 AP patients diagnosed between January and December 2023, including 60 males and 41 females, with a median age of 53 years (range, 43 to 63). Based on the original dataset, univariate and multivariate logistic regression analyses were conducted to identify the factors influencing ABP. A prediction probability formula (Pre) was then established based on the multivariate results. The effectiveness of each indicator in predicting ABP was evaluated using the receiver operating characteristic (ROC) curve. The ROC curve analysis determined the optimal cutoff value of Pre, which was subsequently used to diagnose ABP and ANBP in the test cohort.Results:Multivariate logistic regression analysis showed the factors influencing ABP include direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (CHE), and fibrinogen (FIB). Based on the multivariate analysis results, the prediction probability formula (Pre) for ABP was established as follows: P=1/{1+ exp[-(4.807+ 0.134×DBIL-1.859×AST/ALT-0.0003×CHE-0.387×FIB)]}. ROC curve analysis revealed that the area under the curve (AUC) for Pre in predicting ABP was 0.858, with an optimal cutoff value of 0.56, at which the sensitivity was 69.3% and the specificity was 91.0%. Using the cutoff value of 0.56 for Pre, ABP was diagnosed when Pre≥0.56 and ANBP was diagnosed when Pre<0.56. This criterion was applied to diagnose patients in the test cohort, where the sensitivity and specificity of Pre for diagnosing ABP were 86.1% and 92.3%, respectively.Conclusion:The logistic regression model based on liver injury-related indicators is a valuable tool for clinically assessing the incidence of ABP.

Objective:To analyze the changes of serum metabolites in patients with acute pancreatitis (AP) by non-targeted metabolomics method.Methods:Serum samples and clinical data of 15 AP patients hospitalized in the Affiliated Hospital of Jiangnan University from August to September 2024 were collected and included in the AP group, including 9 males and 6 females, aged (55.4±15.3) years. The serum and clinical data of 25 patients with colon polyps in the same hospital during the same period of time were collected, including 15 males and 10 females, aged (61.2±11.5) years, and were included in the control group. Serum metabolomic detection was performed using the ultra-high performance liquid chromatography tandem Fourier transform mass spectrometer. The modeling method was orthogonal partial least square discriminant analysis, and principal component analysis was performed on the data matrix to screen the differential metabolites in serum of AP patients. The Kyoto Encyclopedia database of Genes and Genomes was used to annotate differential metabolites, and the pathway of differential metabolite enrichment was analyzed by software.Results:The principal component analysis showed that the contribution ratio of the first principal component was 15.1%, the proportion of the second principal component was 10.8%, and the total proportion of the two was 25.9%. In principal component analysis, two groups of samples can be clearly distinguished and show obvious clustering characteristics. According to the analysis of OPLS-DA model, there were significant differences in serum metabolic profiles between AP group and control group. There were 683 differentially expressed metabolites between the two groups, with 367 differentially expressed metabolites up-regulated compared with the control group and 316 differentially expressed metabolites down-regulated compared with the control group. It is mainly Phosphatidic Acid (Lte4/8: 0) (+ 218%), Omeprazole Sulphone (-38%), and 2-(Propylthio) Nicotinic Acid (2-propyl thionicotinic acid) (-58%), Gein (salicyricetin) (-47%) and so on. Pathway enrichment analysis showed that the differential metabolites in AP patients were mainly concentrated in citric acid cycle, arginine biosynthesis and glycerophospholipid metabolism pathways.Conclusion:Serum metabolites in AP patients change significantly, including citric acid cycle, arginine biosynthesis, glycerophospholipid metabolism.

Objective:To explore the aperiodic components(1/f slopes)and their associations with cognitive impairment in patients with schizophrenia.Methods:Nineteen patients with schizophrenia according to the Interna-tional Statistical Classification of Diseases and Related Health Problem,Tenth Revision(ICD-10)and 21 normal controls were administrated the total Brief Assessment of Cognition in Schizophrenia(BACS)to measure the cogni-tive performance.The 5-minute eyes-closed and eyes-open resting EEG signals were collected and parameterized in-to aperiodic components(1/f slope).Finally,Pearson correlation was used to examine the relationships between the 1/f slope and cognition assessment scores.Results:The patients with schizophrenia had higher 1/f slope compared to HC on central location of scalp(P＜0.05).The vocal memory scores showed a significantly positive relation with 1/f slopes in patients with schizophrenia(anterior location:r=-0.68,P＜0.05;central location:r=-0.44,P＜0.05),but a significantly negative relation in normal controls(anterior location:r=0.57,P＜0.05;posterior lo-cation:r=0.54,P＜0.05).Conclusion:The 1/f slopes of EEG in schizophrenia were steeper than normal control,suggesting its strong cognitive functional significance and complex mechanisms in schizophrenia.