ObjectiveTo investigate the mechanism of action of remifentanil （RMZL） in alleviating lung ischemia-reperfusion injury （LIRI） in rats by inhibiting pyroptosis through modulating hypoxia inducible factor-1α （HIF-1α）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. MethodsRats were stochastically assigned into Control group， LIRI group， RMZL low-dose group， RMZL medium-dose group， RMZL high-dose group， and RMZL high-dose+HIF-1α activator dimethyloxallyl glycine （DMOG） group， with 18 rats in each group. Rats in Control group only had their left pulmonary hilum free and did not undergo ischemia-reperfusion treatment. Except for the Control group， LIRI models were constructed in all other groups. Rats in LIRI group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before constructing LIRI model； rats in Control group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before freeing left pulmonary hilum； rats in other groups were intraperitoneally injected with corresponding dose of drug 15 minutes before constructing LIRI model. The wet/dry weight ratio of lungs was calculated. HE staining was used to study lung tissue pathology. Immunofluorescence staining was used to detect the relative fluorescence intensity of gasdermin D （GSDMD） and NLRP3 double positive cells in lung tissue. ELISA was used to detect interleukin-1β and IL-18 in lung tissue. Western blot was used to detect HIF-1α， NLRP3， cysteine-aspartic protease-1 （Cleaved caspase-1）， and gasdermin D-N （GSDMD-N） proteins in lung tissue. ResultsCompared to the Control group， the LIRI group showed disordered alveolar structure， thickened alveolar septa， and abundant inflammatory cell infiltration in rats. The lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， IL-1β， IL-18 levels， and HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N proteins increased （P0.05）. For the LIRI group， rats in the RMZL low， medium， and high-dose groups displayed attenuated alveolar septal thickening and reduced inflammatory cell infiltration. The lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， IL-1β， IL-18 levels， and HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N proteins declined， and the RMZL high-dose group showed the most prominent trend （P0.05）. Compared with the RMZL high-dose group， rats in the RMZL high-dose+DMOG group exhibited thickened alveolar septa and more inflammatory cell infiltration， along with increased lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， levels of IL-1β and IL-18， and protein expression of HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N （P0.05）. ConclusionRMZL may inhibit pyroptosis in LIRI rats by suppressing HIF-1α/NLRP3 pathway.

Objective To investigate the radon activity concentrations in subways of Nanning City and assess the average annual effective doses for subway staff and passengers due to radon exposure. Methods Sixty-three stations across the subway lines 2, 3, and 5 were selected as study sites. Radon activity concentrations were measured using the scintillation counting method with scintillation vials. Results The radon activity concentrations in subway lines 2, 3, and 5 were 7.9-24.4, 12.0-26.2, and 12.6-18.2 Bq/m³, respectively. The average radon activity concentrations for these three lines were (17.4 ± 4.6), (19.1 ± 4.1), and (14.6 ± 1.7) Bq/m³, respectively. Statistical analysis using SPSS 26.0 software revealed a significant difference in radon activity concentrations among these stations (P<0.01). Considering the data in previous research, the average radon activity concentration across all stations in the subway lines of Nanning City was determined to be 17.4 Bq/m³. The estimated average annual effective dose due to radon exposure was 0.131 mSv for subway staff and 0.033 mSv for passengers. Conclusion The radon activity concentrations in the subway lines of Nanning City were significantly lower than the national standard limit (400 Bq/m³). The annual effective doses from radon exposure for both subway staff and passengers were below the limits specified in the Basic Standards for Protection Against Ionizing Radiation and for the Safety of Radiation Sources (GB18871—2002). The health impact of radon and its progeny on subway staff and passengers in the subway lines of Nanning City was extremely low and can be considered negligible.

Diabetic nephropathy（DN） is a common and severe microvascular complication of diabetes. In recent years， the classical herbal formula Shenqi dihuang decoction has demonstrated unique advantages in the clinical treatment of DN. This article conducts a systematic review of the mechanisms of action and clinical applications of Shenqi dihuang decoction in the treatment of DN. It reveals that the mechanism by which this formula improves DN involves multi-target synergistic regulation. For instance, Shenqi dihuang decoction exerts multiple pharmacological effects by regulating signaling pathways including phosphatidy linostiol 3-kinase/protein kinase B， AMP-activated protein kinase/silent information regulator 1/forkhead box O1， and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathways.These effects include regulating glucose and lipid metabolism， inhibiting oxidative stress， reducing inflammation， improving insulin resistance， modulating cell death （apoptosis/autophagy/ferroptosis/pyroptosis）， and preventing renal fibrosis. Existing clinical studies indicate that Shenqi dihuang decoction and its modified formulas， alone or in combination with other therapeutic methods， can significantly improve glucose and lipid metabolism， reduce proteinuria， and delay renal function decline in patients with DN. These effects are superior to those of Western medicines such as irbesartan， valsartan， and empagliflozin， and the treatment demonstrates good safety. Future research should leverage systems biology and artificial intelligence technologies to further elucidate the integrated mechanisms in the treatment of DN by Shenqi dihuang decoction， thereby advancing the precision and standardization of its clinical application.

Objective To explore the impact of the duration of protracted abstinence(PA)treatment on the level of impulsivity among heroin addicts and to analyze the mediating effect of impulsive cognition between abstinence duration and impulsive behavior.Methods Thirty-six heroin addicts undergoing PA treatment(PA group)and forty matched healthy controls(HC)(HC group)were recruited.Demographic information was collected via questionnaires,and impulsive cognition assessments were conducted.Participants completed the GO/NOGO task to collect data on impulsive behavior.Intergroup differences were compared using the independent sample t-test,and multiple linear regression analysis and mediating effect analysis were performed on the PA group.Results The PA group exhibited significantly higher scores on motor impulsivity,non-planning impulsivity,and total impulsivity compared to the HC group.Additionally,the PA group demonstrated significantly increased NOGO error rate during the GO/NOGO task compared to the HC group(P＜0.001).Multiple linear regression analysis revealed that abstinence duration had a significant negative impact on total impulsivity and non-planning impulsivity(P＜0.001).Mediating effect analysis found a partial mediation effect of total impulsivity between abstinence duration and NOGO error rate(P＜0.001).Conclusion The PA treatment has a significant impact on the level of impulsivity among heroin addicts.Impulsive cognition play a partial mediating role between abstinence duration and impulsive behavior.These results provide an important theoretical and practical basis for optimizing PA treatment programs.

Objective To explore the impact of the duration of protracted abstinence(PA)treatment on the level of impulsivity among heroin addicts and to analyze the mediating effect of impulsive cognition between abstinence duration and impulsive behavior.Methods Thirty-six heroin addicts undergoing PA treatment(PA group)and forty matched healthy controls(HC)(HC group)were recruited.Demographic information was collected via questionnaires,and impulsive cognition assessments were conducted.Participants completed the GO/NOGO task to collect data on impulsive behavior.Intergroup differences were compared using the independent sample t-test,and multiple linear regression analysis and mediating effect analysis were performed on the PA group.Results The PA group exhibited significantly higher scores on motor impulsivity,non-planning impulsivity,and total impulsivity compared to the HC group.Additionally,the PA group demonstrated significantly increased NOGO error rate during the GO/NOGO task compared to the HC group(P＜0.001).Multiple linear regression analysis revealed that abstinence duration had a significant negative impact on total impulsivity and non-planning impulsivity(P＜0.001).Mediating effect analysis found a partial mediation effect of total impulsivity between abstinence duration and NOGO error rate(P＜0.001).Conclusion The PA treatment has a significant impact on the level of impulsivity among heroin addicts.Impulsive cognition play a partial mediating role between abstinence duration and impulsive behavior.These results provide an important theoretical and practical basis for optimizing PA treatment programs.

Objective:To evaluate the role of inositol 1, 4, 5 triphosphate receptor 1 (IP3R1)-regulated changes in mitochondria-associated endoplasmic reticulum membrane (MAM) structure in the long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal mice.Methods:Sixty SPF-grade healthy neonatal C57BL/6J mice of either sex, aged 6 days, weighing 6-10 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), multiple sevoflurane anesthesia group (group S), and IP3R antagonist 2-APB+ multiple sevoflurane anesthesia group (group I+ S). Group S and group I+ S inhaled 3% sevoflurane anesthesia for 2 h starting from 6, 8 and 10 days after birth. In group I+ S, 2-APB 3 mg/kg was intraperitoneally injected before each sevoflurane anesthesia. The open field test was performed at day 31 after birth to assess the spontaneous mobility. The Morris water maze test was performed at days 31-36 after birth to assess the cognitive function. Mice were sacrificed at the end of the water maze test, hippocampal CA1 region was isolated and hippocampal tissues were obtained for determination of the intracellular calcium ion concentration ([Ca 2+ ] i) and rate of necroptosis (using Flow cytometry) and expression of IP3R1, G protein-coupled receptor 75 (GRP75), receptor-interacting protein kinase 1 (RIPK1), RIPK3, and phosphorylated human mixed-series protein kinase-like structural domains (p-MLKL) (by Western blot). Transmission electron microscopy was performed to observe and record the partial length of MAMs, endoplasmic reticulum circumference and mitochondrial circumference. Results:There were no statistically significant differences in the speed, distance, and time of staying at the center in open field tests among the three groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged on postnatal days 33-35, the number of crossing the original platform was reduced, the necroptosis rate in the hippocampal CA1 region and [Ca 2+ ] i were increased, the expression of IP3R, GRP75, RIPK1, RIPK3 and p-MLKL was up-regulated, and the ratio of MAMs partial length/endoplasmic reticulum perimeter and ratio of MAMs partial length/mitochondria perimeter in hippocampal neurons were elevated in group S ( P<0.05). Compared with group S, the escape latency was significantly shortened on postnatal days 32-35, the number of crossing the original platform was increased, the necroptosis rate in the hippocampal CA1 region and [Ca 2+ ] i were decreased, the expression of IP3R, GRP75, RIPK1, RIPK3 and p-MLKL was down-regulated, and the ratio of MAMs partial length/endoplasmic reticulum perimeter and ratio of MAMs partial length/mitochondria perimeter in hippocampal neurons were decreased in group I+ S ( P<0.05). Conclusions:Structural changes in MAMs in the hippocampal CA1 region mediated by the up-regulation of IP3R1 expression are involved in the process of long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal mice.

Objective:To evaluate the relationship between sevoflurane preconditioning-induced reduction of cognitive impairment and hippocampal necroptosis after cardiopulmonary bypass (CPB) in rats.Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 6 months, weighing 400-450 g, were divided into 4 groups ( n=15 each) using the random number table method: control group (group C), sevoflurane group (Sev group), CPB group and CPB+ sevoflurane preconditioning group (CPB+ Sev group). The rats were exposed to 0.4% sevoflurane for 2 h in CPB+ Sev group and Sev group. The CPB model was established at 30 min after the end of sevoflurane preconditioning in CPB+ Sev group. The open field test was performed to assess the autonomic movement ability on the 2nd day after CPB. The Morris water maze test was used to assess the cognitive function on the 3rd day after CPB. The hippocampal tissues were removed after the end of the Morris water maze test for determination of the necroptosis rate and cytosolic calcium concentration of hippocampal neuron ([Ca 2+ ] i) (by flow cytometry) and the expression of phosphorylated receptor-interacting protein kinase 1 (p-RIPK1), phosphorylated RIPK3 and phosphorylated mixed-lineage kinase-like domain (p-MLKL) (by Western blot) and for microscopic examination of the ultrastructure of hippocampal neurons (by transmission electron microscopy). Results:There was no statistically significant difference in the parameters of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was decreased, the time of staying at the original platform quadrant was shortened, the hippocampal necroptosis rate and [Ca 2+ ] i were increased, the expression of p-RIPK1, p-RIPK3 and p-MLKL was up-regulated ( P<0.05), the organelles of hippocampal neurons swelled, lysosomes broke, and some chromatin in nuclei dissoluted in CPB group. Compared with CPB group, the escape latency was significantly shortened, the number of crossing the original platform was increased, the time of staying at the original platform quadrant was prolonged, the hippocampal necroptosis rate and [Ca 2+ ] i were decreased, the expression of p-RIPK1, p-RIPK3 and p-MLKL was down-regulated ( P<0.05), and the damage to the ultrastructure of hippocampal neurons was sinificantly reduced in CPB+ Sev group ( P<0.05). Conclusions:The mechanism by which sevoflurane preconditioning attenuates cognitive impairment may be related to the inhibition of calcium overload-mediated hippocampal necroptosis in a rat model of CPB.

Objective:To evaluate the role of RhoA/ROCK2 pathway in electroacupuncture (EA) preconditioning-induced reduction of the perioperative neurocognitive disorder (PND) in aged rats.Methods:Eighty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 600-650 g, were divided into 4 groups ( n=20 each) using the random number table method: sham operation group (group S), PND group, EA preconditioning group and EA preconditioning plus RhoA agonist arachidonic acid group (EA+ AA group). The PND model was prepared using exploratory laparotomy performed under 3% sevoflurane anesthesia. In PND, EA and EA+ AA groups, EA preconditioning was initiated 5 days before operation as follows: Bilateral acupoints Zusanli, Hegu and Neiguan were stimulated with sparse-dense waves at 2/15 Hz and an electric current intensity of 1 mA, applied for 30 min a day for 5 consecutive days. Arachidonic acidin 10 mg/kg was intraperitoneally injected at 30 min before surgery in group AA. The open field test was conducted at 3 days postoperatively to measure the autonomous motor function, and the Morris water maze test was conducted at 3-7 days postoperatively to evaluate the cognitive function. After the end of Morris water maze test, the rats were sacrificed, and the hippocampal tissue in CA1 region was obtained for determination of the apoptosis rate of cells and concentrations of cytoplasmic calcium ion ([Ca 2+ ] i) (by flow cytometry) and the expression of phosphorylated RhoA (p-RhoA), ROCK2, and cleaved caspase-3 (by Western blot) and for examination of the ultrastructure of hippocampal neurons (with a transmission electron microscope). Results:There was no statistically significant difference in each parameter of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was marked in PND group. Compared with PND group, the escape latency was significantly shortened, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was significantly attenuated in EA group. Compared with EA group, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was aggravated in EA+ AA group. Conclusions:The mechanism by which EA preconditioning reduces PND is related to inhibiting the activation of hippocampal RhoA/ROCK2 signaling pathway and reducing calcium overload-mediated apoptosis in cells of aged rats.

Objective To explore the effects of different daily doses of methadone maintenance treatment(MMT)on subjective craving and brain function under drug cues among heroin addicts,providing an objective basis for the formulation of methadone medi-cation plan in clinical practice.Methods Twenty-nine heroin addicts were included and grouped according to the daily dose of metha-done 40 mg,≤40 mg/d group 15 participants(group A),>40 mg/d group 14 participants(group B).The functional magnetic reso-nance imaging(fMRI)data of brain response induced by drug cues were collected using a 3.0T MR scanner,and the craving data induced by drug cues in the subjects were collected.Brain activity and behavioral data processing were analyzed using SPM8 and SPSS 20.0 software.Results There were no statistically significant differences in craving scores between the two groups of subjects exposed to drug cues(t=-0.69,P>0.05).The brain regions with differences in brain response included the left caudate nucleus(group A showed signifi-cantly enhanced response),and the strength of its response was negatively correlated with the daily dose of methadone(r=-0.465,P=0.025).Conclusion Higher doses of MMT may help control the value cognitive processing of drug cues in heroin addicts through the caudate nucleus,which can better prevent relapse.In the future,the degree of activation of the caudate nucleus under drug cues may serve as an indicator for evaluating the effectiveness of methadone treatment.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.