Aim To investigate the role and underlying mechanisms of transient receptor potential cation chan-nel 6(TRPC6)in epileptogenesis using a kainic acid(KA)-induced mouse model.Methods C57BL/6 and TRPC6-KO(KO)mice were divided into two groups and implanted with cannulas for microinjection of KA(0.03 g·L-1,5 μL)into the lateral ventricle to establish the acute epilepsy model group,with saline injection serving as the control group.The Racine score was used to record the uninterrupted seizure grade of mice within two hours after KA administration.Immunohistochemistry was used to detect neuronal loss and tissue damage in the hippocampus brain region of mice.Immunofluorescence staining,Western blot and qPCR were used to detect the expressions of TRPC6,NLRP3,ASC,Caspase-1,p62,Atg7,Atg5,Beclin-1,LC3b-Ⅱ/LC3b-Ⅰ.in the hippocampus.Results KA induced significant neuronal loss and tissue damage in the hippocampal CA3 brain region of epilep-sy mice,while the expression levels of TRPC6,NL-RP3,ASC and Caspase-1 and other proteins in the hippocampus brain area of epilepsy mice increased,and the protein expression of autophagy-related proteins Atg7,Atg5,Beclin-1,LC3b-Ⅱ/LC3b-Ⅰ increased,while the expression of p62 protein decreased.TRPC6 knockout exacerbated KA-induced epileptogenesis,neuronal injury,inflammatory response and autophagy activation.Conclusion TRPC6 is involved in KA-in-duced epileptigenesis,and the mechanism may be re-lated to the activation of NLRP3 inflammasome-autoph-agy signaling caused by TRPC6 deletion.

A subset of patients with multiple myeloma(MM)present with reduced serum vitamin B12 levels at initial diagnosis;however,its clinical significance and underlying mechanisms remain unclear.Vitamin B12 plays a crucial role in hematopoiesis and immune regulation.This study aims to elucidate its association with extramedullary diseases,immune function,and prognosis in MM patients.A retrospec-tive analysis was conducted of 92 newly diagnosed MM patients,who received treatment at the Second Af-filiated Hospital of Soochow University between January 2020 and December 2023.Patients were classi-fied into a low vitamin B12 group(n=37)and a normal vitamin B12 group(n=55)based on their ser-um vitamin B12 levels.The findings revealed that the incidence of extramedullary infiltration was signifi-cantly higher in the low vitamin B12 group than in the normal group(26.5％vs.17.0％,P=0.031).Survival analysis demonstrated that patients with low vitamin B12 levels had significantly shorter overall survival(OS)and progression-free survival(PFS)(OS:P=0.0123;PFS:P=0.0136).Additionally,these patients showed a decreasing trend in peripheral blood total T cell,CD4+T cell,and CD8+T cell counts,with serum vitamin B12 levels showing a significant positive correlation with the total T cell count(R=0.2717,P=0.0135)and CD4+T cell count(R=0.2175,P=0.0497).In conclusion,reduced serum vitamin B12 levels at initial diagnosis are significantly associated with poor prognosis in MM pa-tients and may serve as a potential prognostic biomarker.Furthermore,vitamin B12 deficiency may con-tribute to immune dysfunction,particularly impaired T cell immunity,and a higher incidence of extr-amedullary diseases.

Aim To investigate the role and underlying mechanisms of transient receptor potential cation chan-nel 6(TRPC6)in epileptogenesis using a kainic acid(KA)-induced mouse model.Methods C57BL/6 and TRPC6-KO(KO)mice were divided into two groups and implanted with cannulas for microinjection of KA(0.03 g·L-1,5 μL)into the lateral ventricle to establish the acute epilepsy model group,with saline injection serving as the control group.The Racine score was used to record the uninterrupted seizure grade of mice within two hours after KA administration.Immunohistochemistry was used to detect neuronal loss and tissue damage in the hippocampus brain region of mice.Immunofluorescence staining,Western blot and qPCR were used to detect the expressions of TRPC6,NLRP3,ASC,Caspase-1,p62,Atg7,Atg5,Beclin-1,LC3b-Ⅱ/LC3b-Ⅰ.in the hippocampus.Results KA induced significant neuronal loss and tissue damage in the hippocampal CA3 brain region of epilep-sy mice,while the expression levels of TRPC6,NL-RP3,ASC and Caspase-1 and other proteins in the hippocampus brain area of epilepsy mice increased,and the protein expression of autophagy-related proteins Atg7,Atg5,Beclin-1,LC3b-Ⅱ/LC3b-Ⅰ increased,while the expression of p62 protein decreased.TRPC6 knockout exacerbated KA-induced epileptogenesis,neuronal injury,inflammatory response and autophagy activation.Conclusion TRPC6 is involved in KA-in-duced epileptigenesis,and the mechanism may be re-lated to the activation of NLRP3 inflammasome-autoph-agy signaling caused by TRPC6 deletion.

Objective To explore the factors affecting the enhancement quality of head and neck computed tomography angiography(CTA)images based on bolus-tracking technology,and provide a basis for quantitatively controlling image quality.Methods The general information,injection parameters,scanning parameters and analysis data of enhancement quality of images of 500 subjects who underwent head and neck CTA examinations in our hospital from January to June 2024 were prospectively collected.A comprehensive evaluation of enhancement quality of head and neck CTA images of the examinees was conducted,and the relevant examination data of the examinees with qualified and unqualified enhancement quality of images were compared.Multivariate Logistic regression analysis was used to analyze the independent factors influencing the enhancement quality of image.Results Among 500 CTA images of head and neck,262 cases had qualified enhancement quality of images and 238 cases were unqualified.There were statistically significant differences in gender,height,body weight,tube voltage,scanning direction,trigger threshold,diagnostic delay time,iodine contrast agent concentration,iodine contrast agent dosage,and iodine contrast agent flow rate between the examinees with qualified and unqualified enhancement quality of images(P<0.05).Multivariate Logistic analysis showed that the examinees were male(95%CI:0.22 to 0.75,P=0.004),body weight(95%CI:0.92 to 0.97,P<0.01),and head-foot direction scanning(95%CI:0.03 to 0.43,P=0.002),diagnostic delay time(95%CI:0.44 to 0.92,P=0.017),iodine contrast agent dosage(95%CI:1.21 to 1.34,P<0.001),iodine contrast agent flow rate(95%CI:0.14 to 0.59,P<0.001)were all the independent influencing factors of enhancement quality of image;Among them,the iodine contrast agent dosage(β=0.24,OR=1.27)was positively correlated with the enhancement quality of image,the examinees were male(β=-0.89,OR=0.41),body weight(β=-0.06,OR=0.94),head-foot direction scanning(β=-2.23,OR=0.11),diagnostic delay time(β=-0.45,OR=0.64),and iodine contrast agent flow rate(β=-1.26,OR=0.28)were negatively correlated with the enhancement quality of image.Conclusion In the application of bolus-tracking technology for head and neck CTA,individual factors,scanning parameters,and injection regimens are the key control elements that affect the positive results of enhancement quality of head and neck CTA images.In clinical practice,technicians can establish personalized scanning protocols by integrating artificial intelligence-assisted decision-making systems to achieve precise,standardized and personalized imaging.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry/mass spectrometry(UPLC-Q-TOF-MS/MS), network pharmacology, and animal experiments were integrated o explore the blood glucose-lowering effects and mechanisms of Poria aqueous extract. Firstly, the active components of Poria aqueous extract were identified by UPLC-Q-TOF-MS/MS. Subsequently, network pharmacology was employed to predict the blood glucose-lowering components and mechanisms of Poria aqueous extract. Finally, a rat model of diabetes mellitus, 16S rDNA sequencing, and Western blot were employed to investigate the blood glucose-lowering effect and mechanism of Poria aqueous extract. A total of 39 triterpenoids were identified in the Poria aqueous extract, among them, 25-hydroxypachymic acid, 25α-hydroxytumulosic acid, 16α-hydroxytrametenolic acid, polyporenic acid C, and tumulosic acid may be the main active ingredients for treating diabetes. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis revealed that Poria might exert its therapeutic effects through multiple pathways such as NOD-like receptor signaling pathway, nuclear factor-kappa B(NF-κB) signaling pathway, and tumor necrosis factor(TNF) signaling pathway. The results of animal experiments demonstrated that Poria aqueous extract significantly reduced the levels of blood glucose and lipids and regulated the intestinal flora in diabetic rats. The main affected taxa included g＿Escherichia-Shigella, g＿Corynebacterium, g＿Prevotella＿9, g＿Prevotellaceae＿UCG-001, and g＿Bacteroidota＿unclassified. In addition, Poria aqueous extract lowered the levels of D-lactic acid and lipopolysaccharide, alleviated colonic mucosal damage, significantly down-regulated the protein levels of NOD-like receptor pyrin domain-containing protein 3(NLRP3), NF-κB, and TNF-α, and significantly up-regulated the protein levels of zonula occludens 1 and occludin in diabetic rates. Poria aqueous extract may play a role in treating diabetes mellitus by repairing the intestinal flora disturbance, protecting the intestinal barrier function, and inhibiting the NF-κB/NLRP3 signaling pathway. The results provide a scientific basis for clinical application and expansion of indications of Poria.
Animals ; Rats ; Network Pharmacology ; Tandem Mass Spectrometry ; Male ; Drugs, Chinese Herbal/pharmacology* ; Chromatography, High Pressure Liquid ; Blood Glucose/drug effects* ; Rats, Sprague-Dawley ; Hypoglycemic Agents/administration & dosage* ; Poria/chemistry* ; Diabetes Mellitus, Experimental/metabolism* ; NF-kappa B/genetics* ; Gastrointestinal Microbiome/drug effects* ; Humans

Objective To establish a rapid,sensitive,and specific multiplex PCR detection method for the simultaneous detection of Cryptosporidium,Eimeria,and bovine parvovirus.Methods Specific primers targeting the SSU rRNA genes of Cryptosporidium and Eimeria,as well as the VP2 gene of bovine parvovirus were designed and the corresponding recombinant plasmid standards were constructed.To establish the multiplex PCR method,the reaction conditions were optimized using temperature gradient PCR and single-variable control methods.The sensitivity,specificity,reproducibility,and clinical application of the protocol were evaluated.Results The optimal annealing temperature was found to be 60.5℃,and the forward and reverse primer concentrations were determined to be 0.2 μmol/L for Eimeria,and 0.4 μmol/L for Cryptosporidium and bovine parvovirus.The assay demonstrated high sensitivity,with detection limits of 243,260,and 3 110 copies for the recombinant plasmid standards of Cryptosporidium,Eimeria,and bovine parvovirus,respectively.Specificity testing showed no cross-reactivity with ten common bovine pathogens,including Salmonella,bovine viral diarrhea virus,and bovine rotavirus.Consistent intra-and inter-batch results confirmed the strong reproducibility of the method.Clinical application to 81 diarrhea samples from various regions in the Ganzi Prefecture,Sichuan,revealed positivity rates of 18.52%(15/81)for Cryptosporidium,34.57%(28/81)for Eimeria,and 18.52%(15/81)forbovineparvovirus,withamixedinfectionrateof3.7%(3/81).Conclusions Themultiplex PCR method established in this study offers a reliable tool for differential diagnosis and epidemiological investigation of the three common diarrheal pathogens in yaks.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective:To investigate the protection effect of a new 360-degree radiation protection and position fixation device on the pelvic cavity during chest CT examination.Methods:Three shielding methods were applied to the pelvic cavity of the standard simu-lated human model,i.e.,no shielding(group A),traditional 180-degree front protection with a lead square towel(group B),and 360-degree protection with a new protection device(group C).Philips IQon Spectral CT was used to perform chest CT scan at a tube voltage of 80 kVp,100 kVp,and 120 kVp,respectively,and the cumulative radiation doses from the front,side,and back of the pelvic cavity were measured and analyzed statistically.Results:Compared with groups A and B,group C had significantly lower cumulative radiation doses of the front,side,and back of the pelvic cavity in the simulated human model(all P<0.05);at the tube voltages of 80,100,and 120 kVp,the cumulative dose of the pelvic cavity in group C was reduced by 85%,84%,and 67%,respectively,compared with that in group B,and was reduced by 88%,87%,and 76%,respectively,compared with that in group A.Compared with group A,group B had significant reductions in the radiation doses of the side and back of the pelvic cavity(P<0.05)and a significantly higher radiation dose of the front of the pelvic cavity,which was increased by 19%,23%,and 10%,respectively,at the tube voltages of 80,100,and 120 kVp,and there were significant differences in all tube voltage conditions(P<0.05)except under the tube voltage condition of 120 kVp(P=0.190).In addition,after the application of the device for protection,the reduction rate of pelvic radiation dose under the tube voltages of 80 and 100 kVp was higher than that under the tube voltage of 120 kVp.Conclusion:The new 360-degree radiation protection and position fixation device can significantly reduce the cumulative radiation dose of pelvic organs during chest CT scan,and it holds promise for clinical application due to its characteristics of conve-nient wearing and fixed patient position.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.