ObjectiveTo investigate the independent risk factors for decompensation in patients with liver cirrhosis， to construct a nomogram-based risk assessment model， and to assess its risk assessment performance and clinical value by comparing it with Model for End-Stage Liver Disease （MELD）， MELD combined with serum sodium concentration （MELD-Na）， and MELD 3.0 scoring system. MethodsA retrospective analysis was performed for 514 patients with liver cirrhosis who attended The First Hospital of Shanxi Medical University from January 2020 to May 2025， and related data were collected， including demographic data and laboratory markers. According to the presence or absence of decompensation， the patients were divided into compensation group with 275 patients and decompensation group with 239 patients. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The least absolute shrinkage and selection operator regression analysis was used for screening of variables， and the multivariate logistic regression analysis was used to identify independent risk factors for decompensated liver cirrhosis and construct a nomogram model. The receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis were used to assess the discriminatory ability， calibration， and net clinical benefit of the model. ResultsThe multivariate logistic regression analysis showed that low hemoglobin （odds ratio ［OR］=0.984， 95% confidence interval ［CI］： 0.969　—　0.999， P<0.05）， low lymphocytes （OR=0.564， 95%CI： 0.383　—　0.830， P<0.05）， high international normalized ratio （OR=3.131， 95%CI： 1.242　—　7.891， P<0.05）， and low serum sodium （OR=0.922， 95%CI： 0.872　—　0.975， P<0.05） were independent risk factors for decompensation events in patients with liver cirrhosis. Construct the prediction model equation： Logit（P）=intercept value－0.016×hemoglobin－0.573×lymphocytes+1.141×INR－0.081×serum sodium. The nomogram constructed based on these factors had a good discriminatory ability， with an area under the ROC curve （AUC） of 0.787， a specificity of 77.8%， and a sensitivity of 67.4%， and it had significantly better predictive performance than MELD score （AUC=0.718）， MELD-Na score （AUC=0.719）， and MELD 3.0 score （AUC=0.725）. The calibration curve showed good consistency between the probability of risk assessed by the model and the observed probability. The decision curve analysis showed that compared with the MELD-based scores， this model provided higher net clinical benefit across a wide range of risk thresholds. ConclusionThis study successfully constructed and validated a nomogram risk assessment model incorporating hemoglobin， international normalized ratio， lymphocytes， and serum sodium. This model has good clinical practicability and can help to achieve early identification of high-risk patients with decompensated liver cirrhosis and optimize intervention strategies in clinical practice.

ObjectiveTo analyze the distribution of traditional Chinese medicine （TCM） syndrome elements in patients with immune-related adverse events （irAEs） associated with malignant tumor immunotherapy and to explore the influencing factors for the occurrence of irAEs. MethodsClinical data were retrospectively collected from malignant tumor patients treated with programmed death-1 （PD-1） inhibitors， including demographic information， tumor history， duration of immunotherapy， occurrence of irAEs， types and grades of irAEs （G1-G5）， and TCM four-diagnostic information. Patients were divided into irAEs group and the non-irAEs group based on the occurrence of irAEs. Propensity score matching （PSM） at a 1∶2 ratio was performed to balance baseline characteristics between groups. Syndrome elements before treatment and cumulative contributions of syndrome elements before and after irAEs onset were evaluated using the "Syndrome Elements Differentiation Scale". Logistic regression analysis was conducted to identify factors associated with the occurrence of irAEs. The use of glucocorticoids in the irAEs group was also analyzed. ResultsAfter 1∶2 matching， 59 patients were included in the irAEs group and 118 were in the non-irAEs group. No statistically significant differences were found between groups in terms of age， gender， primary tumor site， pathological type， or tumor stage （P＞0.05）. Patients in the non-irAEs group were more likely to have received targeted therapy， while the irAEs group had a longer duration of immunotherapy and a higher rate of positive programmed death-ligand 1 （PD-L1） expression （P＜0.05）. In total， 72 irAEs events occurred among 59 patients， with an overall incidence rate of 19.4% （59/304） and a grade 3~5 incidence rate of 6.8% （4/59）， mainly presenting as cardiotoxicity， nephrotoxicity， and pneumotoxicity.Before immunotherapy， the top three syndrome elements in the irAEs group were spleen （71.2%， 42/59）， kidney （42.4%， 25/59）， and lung （39.0%， 23/59）. For the pathogenic nature elements， yin deficiency （52.5%， 31/59）， phlegm （40.7%， 24/59）， and dampness （35.6%， 21/59） ranked highest. Compared to the non-irAEs group， the distribution of spleen， kidney， liver， yin deficiency， and qi deficiency elements showed significant differences in the irAEs group （P＜0.05）. After the occurrence of irAEs， the cumulative contributions of spleen， lung， stomach， heart， yin deficiency， qi deficiency， and yang hyperactivity elements increased significantly （P＜0.05）. Multivariate Logistic regression analysis indicated that duration of immunotherapy， spleen syndrome element， kidney syndrome element， liver syndrome element， yin deficiency element， and qi deficiency element were independent risk factors for irAEs （P＜0.05 or P＜0.01）. Among the irAEs patients， 15 received glucocorticoid combined with TCM treatment， while 6 received glucocorticoid therapy alone. Patients receiving combined treatment required lower doses and shorter courses of glucocorticoids compared to those treated with glucocorticoids alone （P＜0.05）. ConclusionIn malignant tumor patients， spleen， kidney， lung， yin deficiency， phlegm， dampness， and qi deficiency are the predominant syndrome elements before and after the occurrence of irAEs. However， elements such as heat and qi stagnation significantly increase after irAEs onset. Duration of immunotherapy， spleen， kidney， liver syndrome elements， yin deficiency， and qi deficiency are independent risk factors for the development of irAEs.

ObjectiveTo investigate the association between the maintenance treatment of modified Yiqi Huoxue Jiedu Formula （益气活血解毒方） or poly ADP ribose polymerase （PARP） inhibitors and the recurrence and metastasis of advanced ovarian cancer. MethodsA case-control study design was employed， dividing patients with advanced ovarian cancer into two groups based on the occurrence of recurrence and metastasis following first-line maintenance treatment. Patients with recurrence and metastasis comprised the case group， while those without recurrence and metastasis served as the control group. The previous first-line maintenance treatment method was set as the exposure factor in the study （with the use of modified Yiqi Huoxue Jiedu Formula defined as exposed and PARP inhibitors defined as unexposed）. Basic information was collected for both groups， including the achievement of satisfactory R0 surgery， age， stage， neoadjuvant chemotherapy， lymph node metastasis， germline BRCA1/2 mutations， homologous recombination deficiency positivity， first-line maintenance treatment method （modified Yiqi Huoxue Jiedu Formula or PARP inhibitors）， and CA125 levels after the last chemotherapy. The baseline data of the two groups were assessed for differences. If there exists difference， a 1∶1 nearest neighbor matching method was used for propensity score matching. Univariate and multivariate logistic regression analyses were employed to evaluate the association between the modified Yiqi Huoxue Jiedu Formula or PARP inhibitors and the recurrence and metastasis of ovarian cancer. ResultsA total of 201 patients with advanced ovarian cancer were included， with 97 in the case group and 104 in the control group. Both groups showed statistically significant differences in R0 surgery， stage， neoadjuvant chemotherapy， and CA125 levels after the last chemotherapy （P＜0.05）， indicating baseline imbalance. After propensity score matching， there were 71 patients in both the case and control groups， achieving baseline balance （P＞0.05）. Univariate logistic regression analysis indicated that the achievement of satisfactory R0 surgery （P = 0.006）， disease stage （P = 0.001）， the use of neoadjuvant chemotherapy （P = 0.024）， treatment modality （P = 0.006）， and CA125 levels after the last chemotherapy （P = 0.013） were associated with the recurrence and metastasis of ovarian cancer. Multivariate logistic regression analysis revealed that disease stage was an independent influencing factor for the recurrence and metastasis of ovarian cancer （P = 0.030）， whereas the P-value for the correlation between first-line maintenance treatment and ovarian cancer was 0.188. ConclusionFirst-line maintenance treatment of ovarian cancer patients with the use of modified Yiqi Huoxue Jiedu Formula or PARP inhibitors does not correlate with the recurrence and metastasis of ovarian cancer.

Objective:To study the effects of arsenic exposure on neurological function including voluntary motor ability, anxiety, and short-term memory ability of rats, as well as its impact on the expression levels of synaptic function related genes such as neuropeptide 1 (NLGN1), glutamate receptor 2A (NR2A), and postsynaptic density protein 95 (PSD95).Methods:Forty 3-week-old male specific pathogen free (SPF) grade Wistar rats [weighing (453.97 ± 35.68) g] were selected and divided into four groups using a random number table: 0 (control group) and 2, 10, and 50 mg/L arsenic exposure groups, with 10 rats in each group. They were given deionized water and 2, 10, and 50 mg/L sodium arsenite solutions for 12 weeks, respectively. The open field experiment and Y-maze experiment were used to test the voluntary motor ability, anxiety, and short-term memory ability of rats. Nissl staining was used to observe the pathological damage of the hippocampus in the brain. Real time fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of NLGN1, NR2A, and PSD95 in the hippocampus, respectively.Results:The results of the open field experiment revealed that the horizontal movement distances of rats in the 2 and 10 mg/L arsenic exposure groups were reduced compared to the control group, the movement distances in the central area in the 2, 10, and 50 mg/L arsenic exposure groups were reduced compared to the control group, and the residence time in the central area in the 10 and 50 mg/L arsenic exposure groups was reduced compared to the control group ( P < 0.05). The results of Y-maze experiment showed that the retention time of new arms in rats of the 2 and 10 mg/L arsenic exposure groups was shorter than that in the control group ( P < 0.05). The pathological examination results of Nissl staining showed that the control group had abundant Nissl bodies in hippocampal tissues of the cytoplasm with intact neuronal structures, tightly arranged cells, appearing blue purple in color and clear visible nuclei. However, the number of Nissl bodies decreased, intercellular gaps increased, disordered arrangement increased, cytoplasmic staining was lighter, and nuclear shrinkage phenomenon increased in the hippocampal tissues of rats in the 2, 10 and 50 mg/L arsenic exposure groups. The real-time fluorescence quantitative PCR detection results showed that there was a statistically significant difference in the mRNA expression levels of NLGN1, NR2A, and PSD95 in the hippocampal tissues of the four groups ( F = 13.85, 44.94, 4.63, P < 0.05). The results of Western blot analysis showed that the protein expression levels of NLGN1 and NR2A in the hippocampal tissues of rats in the 10 and 50 mg/L arsenic exposure groups were lower than those in the control group (0.65 ± 0.07, 0.69 ± 0.03 vs 1.00 ± 0.04, 0.51 ± 0.11, 0.51 ± 0.13 vs 1.00 ± 0.07, P < 0.05), and the expression level of PSD95 in the hippocampal tissues of rats in the 50 mg/L arsenic exposure group was lower than that in the control group (0.51 ± 0.09 vs 1.00 ± 0.05, P < 0.05). Conclusion:Arsenic may affect synaptic function and cause neurological dysfunction in rats by adjusting the expression levels of NLGN1, NR2A, and PSD95.

Objective:To explore the clinical efficacy, safety and possible neuroimaging mechanism of deep transcranial magnetic stimulation (dTMS) and repetitive transcranial magnetic stimulation (rTMS) in the treatment of refractory migraine.Methods:Thirty patients with refractory migraine were selected from the Department of Neurology, Affiliated Hospital of North Sichuan Medical College from October 2022 to August 2023. The patients were randomly divided into dTMS group ( n=10), rTMS group ( n=10) and sham stimulation group ( n=10). The dTMS group was treated with H7 coil and the rTMS group with "8" coil, and the sham stimulation group was treated with sham stimulation rTMS with the frequency of 10 Hz. The stimulation site was the contralateral primary motor cortex (M1) of headache, which was treated for 2 weeks (3 600 pulses per time, 5 times per week, 10 times in total). Visual Analogue Scale (VAS) and Headache Impact Test-6 (HIT-6) evaluations were performed before treatment, on the first day after treatment, and 1, 3 and 6 months after treatment. The resting-state functional magnetic resonance images of the 3 groups of patients before and after treatment were collected and analyzed by MATLAB2018b, SPM12 and RESTPLUS softwares, and the brain regions with different regional homogeneity (ReHo) before and after treatment were obtained. The general clinical data and scale scoring data were analyzed and processed by SPSS 26.0 version software. Results:There were significant differences in VAS scores among the dTMS group (before treatment 6.70±0.68, the first day after treatment 5.60±0.70, 1 month after treatment 5.00±0.82, 3 months after treatment 3.50±0.85, 6 months after treatment 3.90±1.45), the rTMS group (before treatment 6.90±0.74, the first day after treatment 5.90±0.74, 1 month after treatment 5.30±0.82, 3 months after treatment 5.30±0.82, 6 months after treatment 6.80±0.63) and the sham stimulation group (before treatment 6.60±0.97, the first day after treatment 6.70±0.95, 1 month after treatment 6.90±1.10, 3 months after treatment 6.70±0.68, 6 months after treatment 7.10±0.88; F=16.054, P<0.001), VAS scores among different time points ( F=34.292, P<0.001), and the interaction between groups and time ( F=24.136, P<0.001). Compared with those before treatment, VAS scores in the dTMS group and the rTMS group decreased on the first day after treatment, 1 month and 3 months after treatment (all P<0.05); VAS scores decreased in the dTMS group 6 months after treatment ( P<0.05). Compared with the sham stimulation group, the VAS scores of the dTMS group were lower at the same time points after treatment (all P<0.05), and the VAS scores of the rTMS group were lower on the first day after treatment, 1 month and 3 months after treatment (all P<0.05). Compared with the rTMS group, VAS scores were lower at 3 and 6 months after dTMS treatment (both P<0.05). There were significant differences in HIT-6 scores among groups ( F=13.173, P<0.001), HIT-6 scores among different time points ( F=60.788, P<0.001), and interaction between groups and time ( F=35.576, P<0.001). Compared with those before treatment, the HIT-6 scores in the dTMS group decreased on the first day after treatment ( P<0.05); the HIT-6 scores in the dTMS group and the rTMS group decreased 1 month and 3 months after treatment (both P<0.05); the HIT-6 scores decreased in the dTMS group 6 months after treatment ( P<0.05). Compared with the sham stimulation group, the HIT-6 scores were lower in the dTMS group at the same time points after treatment (all P<0.05), and the HIT-6 scores were lower in the rTMS group at 1 and 3 months after treatment (both P<0.05). Compared with the rTMS group, HIT-6 scores were lower at 3 and 6 months after dTMS treatment (both P<0.05). Analysis of ReHo results: compared with those before treatment, the ReHo values of the right cerebellar angle area 1 increased in the dTMS group and the sham stimulation group, decreased in the rTMS group. The ReHo values of the right middle occipital gyrus, left dorsolateral superior frontal gyrus and right cerebellar area 8 increased in the dTMS group, but decreased in the rTMS group and the sham stimulation group. The ReHo values of the left precentral gyrus and left superior temporal gyrus decreased in the dTMS group, while those in the rTMS group and the sham stimulation group increased. There were no obvious adverse reactions in the 3 groups during the treatment and follow-up period. Conclusions:dTMS and rTMS may help to improve the headache degree and quality of life of patients with refractory migraine, and they are safe, which may be related to the changes of brain network in the right cerebellar angle area 1, right middle occipital gyrus, left dorsolateral superior frontal gyrus, left precentral gyrus, left superior temporal gyrus and right cerebellar area 8.

Objective To investigate traditional Chinese medicine(TCM)syndrome characteristics associated with immunotherapy efficacy in cervical cancer using propensity score matching(PSM),aiming to identify the population benefiting from immunotherapy.Methods A retrospective analysis was conducted in 253 cervical cancer patients,who received the treatment with programmed death receptor 1(PD-1)inhibitors at Guang'anmen Hospital,China Academy of Chinese Medical Sciences from January 2020 to October 2024.Clinical data and TCM four-examination data were collected.After balancing the confounders via PSM(1∶1 matching)and with therapeutic efficacy as the dependent variable,multivariate logistic regression was performed to analyze the characteristics of TCM syndrome in the immunotherapy-response group and then a predictive model was constructed.Results(1)After matching with PSM,198 cases were included,99 cases in response group and 99 cases in non-response group.(2)Analysis of the distribution of TCM syndrome elements showed that the differences in the pathogenic syndrome elements of qi deficiency,qi stagnation,blood stasis,heat and phlegm between the two groups were statistically significant(P＜0.05 or P＜0.01),while there were no statistically significant differences in the disease-location syndrome elements of uterus,kidneys,lungs,spleen,liver,and heart,as well as in the pathogenic syndrome elements of blood deficiency,yin deficiency,yang deficiency,cold,and dampness(P＞0.05).The main pathogenic syndrome elements in the response group were qi deficiency,blood deficiency and heat,while those in the non-response group were qi stagnation,heat and phlegm.(3)The results of univariate regression analysis showed that targeted therapy(P=0.040),programmed cell death-ligand 1(PD-L1)expression level(P＜0.001),qi deficiency(P=0.009),blood deficiency(P＜0.001),yang deficiency(P＜0.001),yin deficiency(P＜0.001),qi stagnation(P=0.003),blood stasis(P＜0.001),cold(P＜0.001),cold(P＜0.001),heat(P＜0.001),phlegm(P＜0.001),and dampness(P＜0.001)were the factors associated with the efficacy of PD-1 inhibitors.(4)The results of multivariate logistic regression analysis showed that previous targeted therapy(OR=0.36,95%CI:0.16-0.83)and pathogenic syndrome elements of qi stagnation(OR=0.23,95%CI:0.10-0.49),phlegm(OR=0.28,95%CI:0.13-0.61)were the risk factors of associated with the efficacy of PD-1 inhibitors,while PD-L1 expression level(OR=15.27,95%CI:2.60-89.63),and pathogenic syndrome element qi deficiency(OR=2.90,95%CI:1.42-5.89)were the protective factors associated with the efficacy of PD-1 inhibitors in cervical cancer.(5)Receiver operating characteristic(ROC)curve analysis demonstrated that the area under the ROC curve(AUC)of the predictive model for evaluating PD-1 inhibitor efficacy in cervical cancer was 0.78(95%CI:0.71-0.84),indicating certain predictive value.Conclusion PD-L1 expression level and TCM pathogenic syndrome elements such as qi deficiency,qi stagnation,and phlegm are the independent factors influencing PD-1 inhibitor efficacy in cervical cancer,providing insights for optimizing integrated TCM-western medicine treatment strategies.

Objective:To explore the clinical efficacy, safety and possible neuroimaging mechanism of deep transcranial magnetic stimulation (dTMS) and repetitive transcranial magnetic stimulation (rTMS) in the treatment of refractory migraine.Methods:Thirty patients with refractory migraine were selected from the Department of Neurology, Affiliated Hospital of North Sichuan Medical College from October 2022 to August 2023. The patients were randomly divided into dTMS group ( n=10), rTMS group ( n=10) and sham stimulation group ( n=10). The dTMS group was treated with H7 coil and the rTMS group with "8" coil, and the sham stimulation group was treated with sham stimulation rTMS with the frequency of 10 Hz. The stimulation site was the contralateral primary motor cortex (M1) of headache, which was treated for 2 weeks (3 600 pulses per time, 5 times per week, 10 times in total). Visual Analogue Scale (VAS) and Headache Impact Test-6 (HIT-6) evaluations were performed before treatment, on the first day after treatment, and 1, 3 and 6 months after treatment. The resting-state functional magnetic resonance images of the 3 groups of patients before and after treatment were collected and analyzed by MATLAB2018b, SPM12 and RESTPLUS softwares, and the brain regions with different regional homogeneity (ReHo) before and after treatment were obtained. The general clinical data and scale scoring data were analyzed and processed by SPSS 26.0 version software. Results:There were significant differences in VAS scores among the dTMS group (before treatment 6.70±0.68, the first day after treatment 5.60±0.70, 1 month after treatment 5.00±0.82, 3 months after treatment 3.50±0.85, 6 months after treatment 3.90±1.45), the rTMS group (before treatment 6.90±0.74, the first day after treatment 5.90±0.74, 1 month after treatment 5.30±0.82, 3 months after treatment 5.30±0.82, 6 months after treatment 6.80±0.63) and the sham stimulation group (before treatment 6.60±0.97, the first day after treatment 6.70±0.95, 1 month after treatment 6.90±1.10, 3 months after treatment 6.70±0.68, 6 months after treatment 7.10±0.88; F=16.054, P<0.001), VAS scores among different time points ( F=34.292, P<0.001), and the interaction between groups and time ( F=24.136, P<0.001). Compared with those before treatment, VAS scores in the dTMS group and the rTMS group decreased on the first day after treatment, 1 month and 3 months after treatment (all P<0.05); VAS scores decreased in the dTMS group 6 months after treatment ( P<0.05). Compared with the sham stimulation group, the VAS scores of the dTMS group were lower at the same time points after treatment (all P<0.05), and the VAS scores of the rTMS group were lower on the first day after treatment, 1 month and 3 months after treatment (all P<0.05). Compared with the rTMS group, VAS scores were lower at 3 and 6 months after dTMS treatment (both P<0.05). There were significant differences in HIT-6 scores among groups ( F=13.173, P<0.001), HIT-6 scores among different time points ( F=60.788, P<0.001), and interaction between groups and time ( F=35.576, P<0.001). Compared with those before treatment, the HIT-6 scores in the dTMS group decreased on the first day after treatment ( P<0.05); the HIT-6 scores in the dTMS group and the rTMS group decreased 1 month and 3 months after treatment (both P<0.05); the HIT-6 scores decreased in the dTMS group 6 months after treatment ( P<0.05). Compared with the sham stimulation group, the HIT-6 scores were lower in the dTMS group at the same time points after treatment (all P<0.05), and the HIT-6 scores were lower in the rTMS group at 1 and 3 months after treatment (both P<0.05). Compared with the rTMS group, HIT-6 scores were lower at 3 and 6 months after dTMS treatment (both P<0.05). Analysis of ReHo results: compared with those before treatment, the ReHo values of the right cerebellar angle area 1 increased in the dTMS group and the sham stimulation group, decreased in the rTMS group. The ReHo values of the right middle occipital gyrus, left dorsolateral superior frontal gyrus and right cerebellar area 8 increased in the dTMS group, but decreased in the rTMS group and the sham stimulation group. The ReHo values of the left precentral gyrus and left superior temporal gyrus decreased in the dTMS group, while those in the rTMS group and the sham stimulation group increased. There were no obvious adverse reactions in the 3 groups during the treatment and follow-up period. Conclusions:dTMS and rTMS may help to improve the headache degree and quality of life of patients with refractory migraine, and they are safe, which may be related to the changes of brain network in the right cerebellar angle area 1, right middle occipital gyrus, left dorsolateral superior frontal gyrus, left precentral gyrus, left superior temporal gyrus and right cerebellar area 8.

Objective:To study the effects of arsenic exposure on neurological function including voluntary motor ability, anxiety, and short-term memory ability of rats, as well as its impact on the expression levels of synaptic function related genes such as neuropeptide 1 (NLGN1), glutamate receptor 2A (NR2A), and postsynaptic density protein 95 (PSD95).Methods:Forty 3-week-old male specific pathogen free (SPF) grade Wistar rats [weighing (453.97 ± 35.68) g] were selected and divided into four groups using a random number table: 0 (control group) and 2, 10, and 50 mg/L arsenic exposure groups, with 10 rats in each group. They were given deionized water and 2, 10, and 50 mg/L sodium arsenite solutions for 12 weeks, respectively. The open field experiment and Y-maze experiment were used to test the voluntary motor ability, anxiety, and short-term memory ability of rats. Nissl staining was used to observe the pathological damage of the hippocampus in the brain. Real time fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of NLGN1, NR2A, and PSD95 in the hippocampus, respectively.Results:The results of the open field experiment revealed that the horizontal movement distances of rats in the 2 and 10 mg/L arsenic exposure groups were reduced compared to the control group, the movement distances in the central area in the 2, 10, and 50 mg/L arsenic exposure groups were reduced compared to the control group, and the residence time in the central area in the 10 and 50 mg/L arsenic exposure groups was reduced compared to the control group ( P < 0.05). The results of Y-maze experiment showed that the retention time of new arms in rats of the 2 and 10 mg/L arsenic exposure groups was shorter than that in the control group ( P < 0.05). The pathological examination results of Nissl staining showed that the control group had abundant Nissl bodies in hippocampal tissues of the cytoplasm with intact neuronal structures, tightly arranged cells, appearing blue purple in color and clear visible nuclei. However, the number of Nissl bodies decreased, intercellular gaps increased, disordered arrangement increased, cytoplasmic staining was lighter, and nuclear shrinkage phenomenon increased in the hippocampal tissues of rats in the 2, 10 and 50 mg/L arsenic exposure groups. The real-time fluorescence quantitative PCR detection results showed that there was a statistically significant difference in the mRNA expression levels of NLGN1, NR2A, and PSD95 in the hippocampal tissues of the four groups ( F = 13.85, 44.94, 4.63, P < 0.05). The results of Western blot analysis showed that the protein expression levels of NLGN1 and NR2A in the hippocampal tissues of rats in the 10 and 50 mg/L arsenic exposure groups were lower than those in the control group (0.65 ± 0.07, 0.69 ± 0.03 vs 1.00 ± 0.04, 0.51 ± 0.11, 0.51 ± 0.13 vs 1.00 ± 0.07, P < 0.05), and the expression level of PSD95 in the hippocampal tissues of rats in the 50 mg/L arsenic exposure group was lower than that in the control group (0.51 ± 0.09 vs 1.00 ± 0.05, P < 0.05). Conclusion:Arsenic may affect synaptic function and cause neurological dysfunction in rats by adjusting the expression levels of NLGN1, NR2A, and PSD95.

Objective:To explore the mechanism of pterostilbene(PTE)in preventing and treating neuroinflamma-tion after cerebral ischemia-reperfusion injury(CIRI)in rats.Methods:Ninety male SD rats were randomly divided in-to a sham group,a model group(MCAO/R),a low-dose PTE group(PTE-L),a medium-dose PTE group(PTE-M),and a high-dose PTE group(PTE-H).CIRI model was prepared by middle cerebral artery occlusion reperfusion(MCAO/R)in rats.The neurological deficit in rats was evaluated by Zea Longa score.The volume of cerebral infarc-tion was detected by TTC staining.The morphological changes of ischemic cortex was observed HE staining.The ex-pressions of cyclooxygenase-2(COX-2),prostaglandin D2 receptor(DP2)and prostaglandin D1 receptor(DP1)were detected by RT-qPCR and Western Blot.The expressions of prostaglandin D2(PGD2),interleukin-1 β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by ELISA.Results:Compared with the sham group,the MCAO/R group showed a significant increase in neurological scores(P＜0.05),a significant increase in cerebral infarction vol-ume(P＜0.05),and aggravated cortical damage in the ischemic area.Additionally,there were significant increase in the expressions of COX-2,DP2 mRNA and protein(P＜0.05),along with increased expressions of PGD2,IL-1β and TNF-α(P＜0.05).Compared with the MCAO/R group,the PTE-L,PTE-M,and PTE-H groups showed a significant decrease in neurological scores(P＜0.05),a significant decrease in cerebral infarction volume(P＜0.05),and markedly alleviated cortical damage in the ischemic region.Additionally,there were significant decrease in the expres-sions of COX-2,DP2 mRNA and protein(P＜0.05),along with decreased expressions of PGD2,IL-1β and TNF-α(P＜0.05).Furthermore,a dose-effect relationship was observed for the neuroprotective effects of PTE on brain tissue(P＜0.05).However,there were no significant differences in the expressions of DP,mRNA and protein among all groups(P＞0.05).Conclusion:PTE can attenuate the neuroinflammation of CIRI in rats by inhibiting COX-2/PGD2/DP2 signaling pathway.

Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activ-ity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.