Objective To investigate the effects and mechanisms of Huatan Quyu Decoction on learning and memory abilities in rats with vascular dementia(VD).Methods Totally 112 male SD rats were randomly selected with 16 rats as the sham-operation group,the remaining rats were used to prepare VD models by segmental ligation of the common carotid artery.The successfully modeled rats were randomly divided into model group,Huatan Quyu Decoction low-,medium-and high-dosage groups(6.1,12.1,24.2 g/kg),donepezil hydrochloride group(0.5 mg/kg)and combination group(Huatan Quyu Decoction 12.1 g/kg+donepezil hydrochloride 0.5 mg/kg),with 16 rats in each group.Each group was given the corresponding treatment measures for 4 weeks.The Morris water maze test was used to assess learning and memory abilities,neurological function was evaluated using Garcia score,HE staining was used to observe the morphology of the hippocampal tissue,ELISA was employed to detect the serum content of Aβ,immunohistochemistry was utilized to observe the β-catenin,LRP6 and GSK-3β protein expression in brain tissue.Results Compared with the sham-operation group,the escape latency of the model group rats was prolonged(P<0.01),the number of crossing platforms was reduced(P<0.01),and the neurological deficit score was decreased(P<0.01),the arrangement of hippocampal tissue cells was disorderly,and the tissue was severely damaged,the serum Aβ content increased(P<0.01),the expressions of β-catenin and LRP6 protein in brain tissue decreased,and the expression of GSK-3β protein increased(P<0.01).Compared with the model group,the escape latency of rats in each administration group was shortened,the number of crossing platforms increased,the neurological deficit score increased,the number of hippocampal cells was relatively more,the arrangement was more orderly,and the structure was relatively complete,the serum Aβ content decreased,the expressions of β-catenin and LRP6 proteins increased,and the expression of GSK-3β protein decreased.Among them,Huatan Quyu Decoction high-dosage group had a significantly better effect than Huatan Quyu Decoction low-and medium-dosage groups(P<0.01),and there was no statistical significance in various indicators compared with the donepezil hydrochloride group(P>0.05).Compared with the donepezil hydrochloride group,the combination group showed significant improvements in learning and memory abilities(P<0.01),the neurological deficit score significantly increased(P<0.01),the number of hippocampal cells significantly increased,arranged neatly,and structurally intact,the serum Aβ content significantly decreased(P<0.01),the expression of β-catenin and LRP6 proteins significantly increased,and the expression of GSK-3β protein significantly decreased(P<0.01).Conclusion Huatan Quyu Decoction can repair cognitive function in VD rats,improve learning and memory abilities,and alleviate VD symptoms by activating the Wnt/β-catenin signaling pathway to reduce serum Aβ content,decrease the apoptosis of nerve cells and alleviate the degree of pathological damage in hippocampal tissue.

Thirty SPF Kunming male mice aged 6-8 weeks were randomly divided into five groups:the control group,the model group,and the low,medium,and high dose groups of Dilong.Except for the control group,the other mice were continuously injected intraperitoneally with 80 mg/kg cyclophosphamide for 3 days to prepare an immunosuppressive model.After the model-ing was completed,the control group and the model group were given an equal amount of physio-logical saline by gavage,while the low,medium,and high dose Dilong groups were given 100,200,and 400 mg/kg of Dilong fermented material by gavage,respectively.The treatment lasted for 14 days,and thymus,spleen,blood,and intestinal contents were collected 2 hours after the last admin-istration.The results showed that cyclophosphamide caused a weight loss in mice during the exper-iment,reduced thymus index,white blood cells,lymphocytes,granulocytes,immunoglobulin levels in the blood,and disrupted gut microbiota.Dilong fermented material can effectively improve the decrease in body weight and thymus index of mice,increase the levels of immune cells and immu-noglobulin in the blood,improve the diversity and richness of intestinal microbiota,and increase the abundance of beneficial bacteria.Dilong fermented can effectively alleviate the immune suppres-sion and intestinal microbiota disorder caused by cyclophosphamide in mice.Considering all fac-tors,the optimal dosage is 200 mg/kg.

Pulmonary hypertension(PH)is a seri-ous disease characterized by abnormally high pul-monary arterial pressure(PAP),which leads to in-creased cardiac burden and may eventually lead to right heart failure.Levosimendan,as a calcium sen-sitizer,has the dual role of enhancing cardiac con-striction force and promoting vascular dilation.It shows a good prospect in the treatment of PH com-bined with right heart failure by reducing PAP,in-creasing RV contractile force and reducing anterior and posterior cardiac load without increasing myo-cardial oxygen consumption.Since it does not in-crease the intracellular Ca2+concentration,it avoids the arrhythmia-inducing,reduced coronary perfu-sion and other side effects of other positive inotro-pic drugs.At present,levosimandan is mainly trans-fused intravenically,which may lead to systemic hy-potension,arrhythmia and other side effects,while inhalation administration can reduce the occur-rence of adverse reactions,but its effectiveness and safety in the treatment of PH combined with right heart failure remains to be studied.The pur-pose of this review was to investigate the role of in-haled levosimendan in PH combined with right heart failure.

Thirty SPF Kunming male mice aged 6-8 weeks were randomly divided into five groups:the control group,the model group,and the low,medium,and high dose groups of Dilong.Except for the control group,the other mice were continuously injected intraperitoneally with 80 mg/kg cyclophosphamide for 3 days to prepare an immunosuppressive model.After the model-ing was completed,the control group and the model group were given an equal amount of physio-logical saline by gavage,while the low,medium,and high dose Dilong groups were given 100,200,and 400 mg/kg of Dilong fermented material by gavage,respectively.The treatment lasted for 14 days,and thymus,spleen,blood,and intestinal contents were collected 2 hours after the last admin-istration.The results showed that cyclophosphamide caused a weight loss in mice during the exper-iment,reduced thymus index,white blood cells,lymphocytes,granulocytes,immunoglobulin levels in the blood,and disrupted gut microbiota.Dilong fermented material can effectively improve the decrease in body weight and thymus index of mice,increase the levels of immune cells and immu-noglobulin in the blood,improve the diversity and richness of intestinal microbiota,and increase the abundance of beneficial bacteria.Dilong fermented can effectively alleviate the immune suppres-sion and intestinal microbiota disorder caused by cyclophosphamide in mice.Considering all fac-tors,the optimal dosage is 200 mg/kg.

Bisphenol A(BPA)is an environmental endocrine disruptor commonly found in industri-al products such as plastics,resin coatings,and paper coatings,and it poses potential reproductive hazards.Despite extensive research,studies examining its effects on the F1 generation of rabbits are limited.This study established a BPA exposure model in pregnant female rabbits to investigate its impact on reproductive hormones,apoptosis,oxidative stress,inflammatory responses,and tissue integrity in weaned female offspring.The results indicate that BPA exposure induces oxidative stress and inflammation in F1 rabbits,disrupts hormonal balance,and affects antioxidant enzymes and inflammatory mediators through the modulation of the Nrf2 and NF-κB signaling pathways,ultimately leading to apoptosis and tissue damage.

One-day-old AA broilers were divided into five groups(15 chickens each,5 replicates per group):control(basic diet),three groups with low,medium,and high doses of crude extract of Flos sophorae and Fructus sophorae(100,150,200 mg/kg),and one group with Macleaya cordata extract(300 mg/kg).The 42-day trial measured intestinal enzyme activity,morphology,antioxidant and immune capacity,barrier function,and microbiota structure and diversity.Compared to the control and Macleaya cordata groups,the high-dose crude extract of Flos sophorae and Fructus sophorae group significantly increased trypsin activity in the duodenum,jejunum,and ileum(P＜0.05).It also reduced reactive oxygen species and malondialdehyde levels,increased glu-tathione peroxidase activity,reduced tumor necrosis factor-α,increased interleukin-10,and elevated mRNA expression of tight junction protein-1 and mucin-2 in the jejunum(P＜0.05).Microbial di-versity analysis showed higher Shannon index,increased Firmicutes and Bacteroidetes,decreased Proteobacteria,and more beneficial bacteria in the high-dose group(P＜0.05).Supplementing 200 mg/kg of crude extract of Flos sophorae and Fructus sophorae enhances intestinal morpholo-gy and function,and promotes intestinal health,thereby increasing farming efficiency.

Objective To investigate the effects and mechanisms of Huatan Quyu Decoction on learning and memory abilities in rats with vascular dementia(VD).Methods Totally 112 male SD rats were randomly selected with 16 rats as the sham-operation group,the remaining rats were used to prepare VD models by segmental ligation of the common carotid artery.The successfully modeled rats were randomly divided into model group,Huatan Quyu Decoction low-,medium-and high-dosage groups(6.1,12.1,24.2 g/kg),donepezil hydrochloride group(0.5 mg/kg)and combination group(Huatan Quyu Decoction 12.1 g/kg+donepezil hydrochloride 0.5 mg/kg),with 16 rats in each group.Each group was given the corresponding treatment measures for 4 weeks.The Morris water maze test was used to assess learning and memory abilities,neurological function was evaluated using Garcia score,HE staining was used to observe the morphology of the hippocampal tissue,ELISA was employed to detect the serum content of Aβ,immunohistochemistry was utilized to observe the β-catenin,LRP6 and GSK-3β protein expression in brain tissue.Results Compared with the sham-operation group,the escape latency of the model group rats was prolonged(P<0.01),the number of crossing platforms was reduced(P<0.01),and the neurological deficit score was decreased(P<0.01),the arrangement of hippocampal tissue cells was disorderly,and the tissue was severely damaged,the serum Aβ content increased(P<0.01),the expressions of β-catenin and LRP6 protein in brain tissue decreased,and the expression of GSK-3β protein increased(P<0.01).Compared with the model group,the escape latency of rats in each administration group was shortened,the number of crossing platforms increased,the neurological deficit score increased,the number of hippocampal cells was relatively more,the arrangement was more orderly,and the structure was relatively complete,the serum Aβ content decreased,the expressions of β-catenin and LRP6 proteins increased,and the expression of GSK-3β protein decreased.Among them,Huatan Quyu Decoction high-dosage group had a significantly better effect than Huatan Quyu Decoction low-and medium-dosage groups(P<0.01),and there was no statistical significance in various indicators compared with the donepezil hydrochloride group(P>0.05).Compared with the donepezil hydrochloride group,the combination group showed significant improvements in learning and memory abilities(P<0.01),the neurological deficit score significantly increased(P<0.01),the number of hippocampal cells significantly increased,arranged neatly,and structurally intact,the serum Aβ content significantly decreased(P<0.01),the expression of β-catenin and LRP6 proteins significantly increased,and the expression of GSK-3β protein significantly decreased(P<0.01).Conclusion Huatan Quyu Decoction can repair cognitive function in VD rats,improve learning and memory abilities,and alleviate VD symptoms by activating the Wnt/β-catenin signaling pathway to reduce serum Aβ content,decrease the apoptosis of nerve cells and alleviate the degree of pathological damage in hippocampal tissue.

Bisphenol A(BPA)is an environmental endocrine disruptor commonly found in industri-al products such as plastics,resin coatings,and paper coatings,and it poses potential reproductive hazards.Despite extensive research,studies examining its effects on the F1 generation of rabbits are limited.This study established a BPA exposure model in pregnant female rabbits to investigate its impact on reproductive hormones,apoptosis,oxidative stress,inflammatory responses,and tissue integrity in weaned female offspring.The results indicate that BPA exposure induces oxidative stress and inflammation in F1 rabbits,disrupts hormonal balance,and affects antioxidant enzymes and inflammatory mediators through the modulation of the Nrf2 and NF-κB signaling pathways,ultimately leading to apoptosis and tissue damage.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Pulmonary hypertension(PH)is a seri-ous disease characterized by abnormally high pul-monary arterial pressure(PAP),which leads to in-creased cardiac burden and may eventually lead to right heart failure.Levosimendan,as a calcium sen-sitizer,has the dual role of enhancing cardiac con-striction force and promoting vascular dilation.It shows a good prospect in the treatment of PH com-bined with right heart failure by reducing PAP,in-creasing RV contractile force and reducing anterior and posterior cardiac load without increasing myo-cardial oxygen consumption.Since it does not in-crease the intracellular Ca2+concentration,it avoids the arrhythmia-inducing,reduced coronary perfu-sion and other side effects of other positive inotro-pic drugs.At present,levosimandan is mainly trans-fused intravenically,which may lead to systemic hy-potension,arrhythmia and other side effects,while inhalation administration can reduce the occur-rence of adverse reactions,but its effectiveness and safety in the treatment of PH combined with right heart failure remains to be studied.The pur-pose of this review was to investigate the role of in-haled levosimendan in PH combined with right heart failure.