ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

Objective: To explore the relationship between beverage dependence and sleep quality among college students, providing empirical evidence for improving their sleep quality. Methods: From December 2024 to January 2025, a convenience sampling method was used to conduct a questionnaire survey among 3 974 college students from four universities in Anhui Province. The Beverage Addiction Scale for College Students (BASCS) was used to assess beverage dependence, and the Self rating Scale of Sleep(SRSS) was used to evaluate sleep quality. A multivariate Logistic regression model was employed to analyze the relationship between beverage dependence and sleep quality, and a restricted cubic spline model was used to examine the dose response relationship between the two. Results: The positive rate of beverage dependence symptoms among college students was 7.6%, with positive rates of 9.6%, 13.8%, and 7.4% for the withdrawal symptoms, health effects, and dependence symptoms dimensions, respectively. The detection rate of sleep disorders was 23.6%. Multivariate Logistic regression analysis showed that after adjusting for covariates such as grade, gender, and body mass index, compared with the no beverage dependence group, students with positive beverage dependence symptoms had a higher risk of sleep disorders( OR =3.71, 95% CI =2.87-4.80, P <0.01). The OR (95% CI ) for sleep disorders among students with positive symptoms in the withdrawal symptoms, health effects, and dependence symptoms dimensions were 2.80(2.22-3.53), 2.38(1.95-2.91), and 2.45(1.89-3.18)(all P <0.01). Further analysis using a restricted cubic spline model revealed that the overall beverage dependence score and its three dimensional scores were approximately linearly related to the risk of sleep disorders among college students (all nonlinear P >0.05). Conclusions Beverage dependence is associated with sleep quality among college students. Schools should take multiple approaches, such as health education on beverage awareness, to improve students sleep quality.

Working memory is an executive memory process that includes encoding, maintenance, and retrieval. These processes can be modulated by transcranial alternating current stimulation (tACS) with sinusoidal waves. However, little is known about the impact of the rate of current change on working memory. In this study, we aimed to investigate the effects of two types of tACS with different rates of current change on working memory performance and brain activity. We applied a randomized, single-blind design and divided 81 young participants who received triangular wave tACS, sinusoidal wave tACS, or sham stimulation into three groups. Participants performed n-back tasks, and electroencephalograms were recorded before, during, and after active or sham stimulation. Compared to the baseline, working memory performance (accuracy and response time) improved after stimulation under all stimulation conditions. According to drift-diffusion model analysis, triangular wave tACS significantly increased the efficiency of non-target information processing. In addition, compared with sham conditions, triangular wave tACS reduced alpha power oscillations in the occipital lobe throughout the encoding period, while sinusoidal wave tACS increased theta power in the central frontal region only during the later encoding period. The brain network connectivity results showed that triangular wave tACS improved the clustering coefficient, local efficiency, and node degree intensity in the early encoding stage, and these parameters were positively correlated with the non-target drift rate and decision starting point. Our findings on how tACS modulates working memory indicate that triangular wave tACS significantly enhances brain network connectivity during the early encoding stage, demonstrating an improvement in the efficiency of working memory processing. In contrast, sinusoidal wave tACS increased the theta power during the later encoding stage, suggesting its potential critical role in late-stage information processing. These findings provide valuable insights into the potential mechanisms by which tACS modulates working memory.
Humans ; Memory, Short-Term/physiology* ; Male ; Female ; Young Adult ; Transcranial Direct Current Stimulation/methods* ; Brain/physiology* ; Adult ; Electroencephalography ; Single-Blind Method

Objective : To investigate whole genome information of a newly isolatedBifidobacterium animalissubsp. lactic B4 strain from healthy human feces was analyzed and its probiotic properties. Methods : The antimicrobial resistance, hemolytic, gastric acid tolerance and biochemical characteristics of B. animalis B4 were evaluated byin vitroexperiments, and its whole genome was sequentially sequenced and functional annotation was performed by next and three-generation sequencing technology. Results: Whole genome sequencing of B. animalis B4 showed that its genome size was 1 944 146 bp, with GC content of 60.49%, no plasmid, and a total of 1 642 genes. The results ofin vitroanalysis showed that the B. animalis B4 had good probiotic properties, including non-hemolytic and stomach acid resistance. At the same time, the genome results showed that the B. animalis B4 strain did not have toxin and disease-related genes, drug resistance genes were few and the transmission ability was not high, so it had high safety. Gene annotation of KEGG, COG and GO showed that it contained many biological active enzymes, such as β-galactosidase, L-lactate dehydrogenase and other probiotic genes. Conclusion The B. animalis B4 has good probiotic properties, showing excellent safety at the genetic level, with a probiotic gene sequence.

Objective:To analyze the differences in emergency rescue service capacities between county-level hospitals in Zhejiang and Jiangsu provinces, and propose targeted improvement suggestions.Methods:Cluster sampling was employed, with representative county-level hospitals recommended by provincial hospital alliances in Zhejiang and Jiangsu. Emergency departments voluntarily submitted data, resulting in 24 hospitals from Zhejiang and 34 from Jiangsu. Data were collected through the China County-Level Hospital Emergency Service Capability Evaluation System. Differences between provinces were analyzed. Spearman correlation analysis explored relationships between multidimensional indicators, and multivariate logistic regression identified factors influencing hospital grade B++ and above.Results:In terms of department scale, Jiangsu had a larger emergency department area (4 853 m 2vs. 1 927 m 2, P<0.001), more beds of comprehensive inpatient wards in the emergency department (25.5 beds vs. 5.5 beds, P=0.011), and higher scores for the ratio of emergency department area to beds (4.8 vs. 3.4, P=0.005) than Zhejiang. In terms of staffing, Jiangsu had a higher proportion of doctors with master's degrees or above (13.8% vs. 0.0%, P<0.001), a higher proportion of frontline emergency medical staff with over three years of clinical experience (100.0% vs. 91.5%, P=0.001), and more doctors (19 vs. 15, P=0.039) and nurses (46 vs. 32, P=0.039). In terms of quality and safety and medical service capacity, Zhejiang had a higher severe trauma resuscitation success rate (92.9% vs. 83.75%, P=0.003), annual emergency surgery volume (1 002 vs. 428, P=0.015), and number of emergency surgery procedures (125 vs. 42, P=0.027), but Jiangsu had a shorter emergency room stay time (87.5 min vs. 136.2 min, P=0.029). In terms of informatization, Zhejiang outperformed Jiangsu in all indicators, especially in patient information interconnection and sharing (100.0% vs. 82.4%, P=0.030) and in-hospital diagnosis and treatment timeline (91.7% vs. 73.5%, P=0.043). Correlation analysis showed that the total specialty scale score was significantly positively correlated with the in-hospital emergency rescue service capacity score ( r=0.576) and the staffing score ( r=0.455). The total evaluation score was significantly positively correlated with the informatization total score ( r=0.397) and the pre-hospital emergency rescue service capacity score ( r=0.322). Binary Logistic regression analysis showed that the emergency rescue service capacity score was significantly positively correlated with hospital grade ( B=1.431, P=0.03, OR=4.185, 95% CI:1.152-15.205). For every 1-unit increase in the emergency department area ( B=0.002, P=0.05), the probability of a hospital being upgraded to B++ or above increased by 0.2% ( OR=1.002, 95% CI:1.000-1.004). Conclusions:Both provinces exhibit distinct advantages in emergency department development. Departmental scale and configuration significantly impact emergency service capabilities, while staffing and quality management constitute core elements for improvement. Informatization construction notably enhances emergency service efficiency and quality.

ObjectiveTo observe the mechanism of chronic psychological stress aggravating idiopathic pulmonary fibrosis （IPF） in rats and the regulatory effect of Xiaoyaosan. MethodSixty SD rats were acclimatized for one week and then randomly divided into five groups： sham operation group， IPF group， IPF and depression model group， pirfenidone group， and pirfenidone + Xiaoyaosan group， with 12 rats in each group. The IPF group was induced by intratracheal instillation of bleomycin （5 mg·kg^-1） and administered 0.9% sodium chloride solution intragastrically. The model group was induced with bleomycin （5 mg·kg^-1） combined with chronic unpredictable mild stress to establish a rat model of IPF and depression and administered 0.9% sodium chloride solution intragastrically. Concurrently， the pirfenidone group was administered pirfenidone aqueous solution （50 mg·kg^-1） intragastrically， and the pirfenidone + Xiaoyaosan group was administered pirfenidone aqueous solution （50 mg·kg^-1） and Xiaoyaosan decoction （19.27 g·kg^-1） intragastrically. The experiment lasted for four weeks. Various parameters， including body weight， food intake， sucrose consumption rate， open field behavior， lung function， lung coefficient， pathological changes in lung tissue， and hydroxyproline （HYP） content were compared among the groups. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum cortisol （CORT）， corticotropin-releasing hormone （CRH）， adrenocorticotropic hormone （ACTH） levels， and serotonin （5-HT） levels in serum and hippocampus. The levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in serum and lung tissue were also measured. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA expression of IL-1β， TNF-α， IL-6， p38 mitogen-activated protein kinase （p38 MAPK）， and nuclear transcription factor-κB p65 （NF-κB p65） in lung tissue. Western blot was used to detect the expression of proteins related to the p38 MAPK/NF-κB signaling pathway. ResultCompared with the normal group， IPF and depression model group showed slow weight gain， reduced food intake， decreased sucrose consumption rate， reduced total distance and average speed of movement in the open field test， weakened lung function， increased lung coefficient （P<0.01）， significant inflammatory cell infiltration in lung tissue by hematoxylin-eosin （HE） staining， collagen fiber deposition by Masson staining， and increased HYP content （P<0.01）. There were elevated levels of serum CORT， CRH， and ACTH （P<0.05， P<0.01）， increased protein and mRNA levels of IL-1β， IL-6， and TNF-α in serum and lung tissue， decreased 5-HT levels in serum and hippocampus， and increased relative expression of p-p38 MAPK and p-NF-κB p65 proteins in lung tissue （P<0.01）. Compared with the IPF and depression model group， the depression and IPF of rats in the pirfenidone + Xiaoyaosan group were effectively ameliorated， as evidenced by faster weight gain， increased food intake and sucrose consumption rate， increased total distance and average speed of movement in the open field test， enhanced lung function， reduced lung coefficient （P<0.01）， decreased inflammatory cell infiltration by HE staining， reduced collagen fiber deposition by Masson staining in lung tissue， and decreased HYP content （P<0.01）. Decreased serum CORT， CRH， and ACTH levels （P<0.05， P<0.01）， decreased protein and mRNA levels of IL-1β， IL-6， and TNF-α in serum and lung tissue （P<0.05， P<0.01）， increased 5-HT levels in serum and hippocampus （P<0.05， P<0.01）， and decreased relative expression of p-p38 MAPK and p-NF-κB p65 proteins in lung tissue were also noted （P<0.05， P<0.01）， with the effects of Xiaoyaosan + pirfenidone being more significant. ConclusionChronic unpredictable stress exacerbates the progression of IPF in rats. The combination of Xiaoyaosan and pirfenidone not only improves depressive-like behavior but also alleviates pulmonary fibrosis， potentially through the regulation of the p38 MAPK/NF-κB signaling pathway and inhibition of excessive expression of inflammatory factors.

Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Objective Studies on the expression and location of zinc finger protein A20 (A20) and connective tissue growth factor (CTGF) in liver tissues of patients with chronic hepatitis B were conducted, and the relationship between them and liver fibrosis was determined by FibroScan. Methods Studies on A20 and CTGF in liver tissues of 160 patients with chronic hepatitis B were conducted in accordance with the stage of pathological fibrosis and inflammation of the liver, and quantitative immunohistochemistry test was conducted, and statistical analysis was conducted by FibroScan. Results The expressions of A20 and CTGF in liver tissues increased with the aggravation of liver pathological fibrosis and inflammation, and there were significant differences between each stage and the control group (P<0.05), and there were significant differences between adjacent groups (P<0.05). Studies have shown that FibroScan increases along with pathological fibrosis and inflammation in the liver. There are significant differences between the stage and the control group (P<0.05), and no significant differences between the adjacent groups (P>0.05). There was positive correlation between liver A20 and CTGF, r=0.796 (P<0.05). Conclusions In patients with chronic hepatitis B, A20, CTGF and FibroScan are positively correlated with the degree of liver fibrosis, and A20 and CTGF are also positively correlated with the degree of liver inflammation, which can be used as indicators to evaluate the degree of liver inflammation and fibrosis, and further guide the anti-inflammatory and anti-fibrosis treatment of patients.