BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.

BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.

Objective:To compare the differences of three-dimensional computed tomography(3DCT),four-dimensional computed tomography(4DCT),and multi-parametric magnetic resonance(MR)sequences of the radiotherapy for liver cancer in delineation for target area,and analyze which MR sequence was more accurate in assisting CT image to delineate the target area,and design respectively reverse intensity modulated radiotherapy plan,and compare the dosimetric parameters of the target areas of receiving radiotherapy and normal liver tissue.Methods:This retrospective study was conducted to analyze radiotherapy data from case data of 18 patients with hepatocellular carcinoma(HCC)who admitted to the First Affiliated Hospital of Bengbu Medical University between August 2023 and June 2024.These data included 10 respiratory phases in 3DCT and 4DCT,and free-breathing sequence(MR-FB),diaphragm navigation sequence(MR-NAVI),and breath-hold(MR-BH)sequence of multi-parametric MRI,and the gross tumor volumes(GTVs)of them were delineated,which were respectively 5 modal images and liver contours included GTV3D,GTV4D,GTVMR-FB,GTVMR-NAVI,and GTVMR-BH.Pinnacle3 9.8 treatment plan system(TPS)was applied to conduct registration and fusion for image by using mutual information method.The 3DCT(GTV3D)was used as reference image to compare the volume of target area,and the displacement of mass center with other 4 kinds of images.The volume difference(VD),overlap ratio(OR),Dice similarity coefficient(DSC),and Jaccard index(JAC)were used to assess the differences among different target area.The indicators of plan evaluation included conformity index(CI),homogeneity index(HI),GTV doses(D2%,D98%,Dmean),and the exposure dose of normal tissue of liver.Results:In images of five modalities,the GTV median volumes were respectively 28.83,33.10,26.75,25.05,and 22.65 cm3.In images of five modalities,the median volume of liver were respectively 1293.46,1483.09,1213.81,1195.69,and 1141.02 cm3.Compared with other 3 target areas,the displacement of GTVMR-BH was the smallest on head-foot direction,with statistically significant differences among them(Z=-2.305,-2.307,-2.134,P<0.05).The OR,DSC,and JAC values of GTV4D were significantly better than these of GTVMR-FB,GTVMR-NAVI,and GTVMR-BH(ZOR=-2.911,-3.006,-3.195,ZDSC=-2.726,-2.215,-2.556,ZJAC=-2.556,-2.704,-2.953,P<0.05).The VD value of GTVMR-FB was better than that of GTV4D,GTVMR-NAVI,and GTVMR-BH,with statistically significant(Z=-2.675,-2.817,-2.580,P<0.05).Additionally,the OR,DSC,and JAC values of GTVMR-FB and GTVMR-NAVI were better than those of GTVMR-BH,with statistically significant(ZOR=-2.859,-2.817,ZDSC=-2.184,-2.783,ZJAC=-2.385,-2.783,P<0.05).All five plans met clinical dose requirements.Friedman test showed there was no statistically significant differences in dosimetric parameters of target area among different plans(P>0.05).However,compared to the PTV3D plan,the PTVMR-FB,PTVMR-NAVI,and PTVMR-BH plans resulted in lower levels in mean dose(Dmean)of liver and volume parameters(V5,V10,V20,V30)of various doses,with statistically significant differences(Dmean:Z=-2.433,-2.307,-2.807,ZV5=-2.512,-2.433,-2.652,ZV10=-2.433,-2.536,-2.968,ZV20=-2.536,-2.652,-2.807,ZV30=-2.611,-2.652,-2.968,P<0.05).Conclusion:In actually clinical application,MR-NAVI and 4DCT also can be adopted to assist 3DCT to delineate target area besides MR-FB sequence that is conventionally used in MR location,thus can enhance precision of delineation,and optimize radiotherapy plan,and decrease exposure dose of normal liver tissue.

Objective:To compare the differences of three-dimensional computed tomography(3DCT),four-dimensional computed tomography(4DCT),and multi-parametric magnetic resonance(MR)sequences of the radiotherapy for liver cancer in delineation for target area,and analyze which MR sequence was more accurate in assisting CT image to delineate the target area,and design respectively reverse intensity modulated radiotherapy plan,and compare the dosimetric parameters of the target areas of receiving radiotherapy and normal liver tissue.Methods:This retrospective study was conducted to analyze radiotherapy data from case data of 18 patients with hepatocellular carcinoma(HCC)who admitted to the First Affiliated Hospital of Bengbu Medical University between August 2023 and June 2024.These data included 10 respiratory phases in 3DCT and 4DCT,and free-breathing sequence(MR-FB),diaphragm navigation sequence(MR-NAVI),and breath-hold(MR-BH)sequence of multi-parametric MRI,and the gross tumor volumes(GTVs)of them were delineated,which were respectively 5 modal images and liver contours included GTV3D,GTV4D,GTVMR-FB,GTVMR-NAVI,and GTVMR-BH.Pinnacle3 9.8 treatment plan system(TPS)was applied to conduct registration and fusion for image by using mutual information method.The 3DCT(GTV3D)was used as reference image to compare the volume of target area,and the displacement of mass center with other 4 kinds of images.The volume difference(VD),overlap ratio(OR),Dice similarity coefficient(DSC),and Jaccard index(JAC)were used to assess the differences among different target area.The indicators of plan evaluation included conformity index(CI),homogeneity index(HI),GTV doses(D2%,D98%,Dmean),and the exposure dose of normal tissue of liver.Results:In images of five modalities,the GTV median volumes were respectively 28.83,33.10,26.75,25.05,and 22.65 cm3.In images of five modalities,the median volume of liver were respectively 1293.46,1483.09,1213.81,1195.69,and 1141.02 cm3.Compared with other 3 target areas,the displacement of GTVMR-BH was the smallest on head-foot direction,with statistically significant differences among them(Z=-2.305,-2.307,-2.134,P<0.05).The OR,DSC,and JAC values of GTV4D were significantly better than these of GTVMR-FB,GTVMR-NAVI,and GTVMR-BH(ZOR=-2.911,-3.006,-3.195,ZDSC=-2.726,-2.215,-2.556,ZJAC=-2.556,-2.704,-2.953,P<0.05).The VD value of GTVMR-FB was better than that of GTV4D,GTVMR-NAVI,and GTVMR-BH,with statistically significant(Z=-2.675,-2.817,-2.580,P<0.05).Additionally,the OR,DSC,and JAC values of GTVMR-FB and GTVMR-NAVI were better than those of GTVMR-BH,with statistically significant(ZOR=-2.859,-2.817,ZDSC=-2.184,-2.783,ZJAC=-2.385,-2.783,P<0.05).All five plans met clinical dose requirements.Friedman test showed there was no statistically significant differences in dosimetric parameters of target area among different plans(P>0.05).However,compared to the PTV3D plan,the PTVMR-FB,PTVMR-NAVI,and PTVMR-BH plans resulted in lower levels in mean dose(Dmean)of liver and volume parameters(V5,V10,V20,V30)of various doses,with statistically significant differences(Dmean:Z=-2.433,-2.307,-2.807,ZV5=-2.512,-2.433,-2.652,ZV10=-2.433,-2.536,-2.968,ZV20=-2.536,-2.652,-2.807,ZV30=-2.611,-2.652,-2.968,P<0.05).Conclusion:In actually clinical application,MR-NAVI and 4DCT also can be adopted to assist 3DCT to delineate target area besides MR-FB sequence that is conventionally used in MR location,thus can enhance precision of delineation,and optimize radiotherapy plan,and decrease exposure dose of normal liver tissue.

PD is a neurodegenerative disease characterized by degenerative death of dopaminergic neurons in the substantia nigra,exhibiting a range of motor and non-motor symptoms with serious effects on quality of life.circRNA is a covalently closed-loop non-coding RNA that plays a major role in PD progression.This article reviews the involvement of circRNA in oxidative stress,regulation of transcription,neuroinflammation,autophagy,and α-synuclein.

The global prevalence of gestational diabetes mellitus(GDM)is approximately 13.4%and is ex-pected to increase annually.However,the precise mechanism behind GDM remains to be established.Increasing evi-dence suggests that insulin resistance(IR)and β-cell impairment are key factors in the pathogenesis of GDM.Endoplas-mic reticulum stress(ERS)is characterized by the activation of the unfolded protein response through three key endoplas-mic reticulum transmembrane proteins:protein kinase RNA-like endoplasmic reticulum kinase(PERK),inositol-requiring enzyme 1α(IRE1α),and activating transcription factor 6(ATF6).ERS is implicated in IR in adipose tissue,liver,skeletal muscle,and placenta,and also plays a crucial role in β-cell impairment through processes such as apopto-sis,pyroptosis,and autophagy.Therefore,targeting ERS could be a potential therapeutic approach for the prevention and treatment of GDM.This review explores the potential role of ERS in IR and β-cell dysfunction in GDM,and provides evi-dence for the preventive and intervention effects of bioactive compounds on GDM based on the ERS pathway.This aims to enhance our understanding of the molecular pathological basis of GDM and offer new strategies for its prevention and treat-ment.

ObjectiveTo observe the effects of Tongmai Kaiqiao pills on the hypoxia-inducible factor-1α （HIF-1α）/adenovirus E1B 19 kD-interacting protein 3 （BNIP3） signaling pathway and mitochondrial autophagy in the hippocampus of the rat model of vascular dementia （VD）. MethodNinety male SD rats underwent adaptive feeding for one week before the study. Ten rats were randomly assigned to the sham group， where the common carotid artery was isolated without ligation. The remaining rats were subjected to sequential ligation of the common carotid artery for the modeling of VD. The successfully modeled rats were randomly assigned into the following groups： model， high-， medium-， and low-dose （27.6， 13.8， 6.9 g·kg^-1， respectively） Tongmai Kaiqiao pills， donepezil hydrochloride （0.45 mg·kg^-1）， and combination （27.6 g·kg^-1 Tongmai Kaiqiao pills + 2.5 mg·kg^-1 HIF-1α inhibitor YC-1） groups. After 4 weeks of treatment， samples were collected. Nissl staining and hematoxylin-eosin staining were performed to observe the loss of neurons and pathological changes， respectively， in the hippocampal region. Western blot was employed to determine the protein levels of HIF-1α， BNIP3， Beclin-1， and microtubule-associated protein 1 light chain 3B （LC3B） in the hippocampal tissue. Transmission electron microscopy was used to observe the mitochondrial ultrastructure and the number of autophagosomes in the hippocampal tissue. Immunofluorescence was employed to observe the fluorescence intensity of HIF-1α， BNIP3， and LC3B in the hippocampal tissue. ResultCompared with the sham group， the model group showed prolonged escape latency （P<0.01）， decreased number of platform crossings （P<0.01）， reduced and disarranged neuronal layers in the hippocampal region， decreased number of Nissl bodies， disrupted mitochondrial cristae， damaged mitochondrial double-membrane structures， increased number of autophagosomes， upregulated expression of HIF-1α， BNIP3， beclin1， and LC3B （P<0.05， P<0.01）， and enhanced fluorescence intensity of HIF-1α， BNIP3， and LC3B （P<0.05， P<0.01）. Compared with the model group， Tongmai Kaiqiao pills and donepezil hydrochloride shortened the searching time for the platform （P<0.01） and increased the number of platform crossings （P<0.01）. Moreover， the drugs increased the number of neurons with normal morphology and orderly arrangement and the number of Nissl bodies， alleviated the damage， increased the number of autophagosomes， upregulated the expression of HIF-1α， BNIP3， Beclin1， and LC3B （P<0.05， P<0.01）， and enhanced the fluorescence intensity of HIF-1α， BNIP3， and LC3B （P<0.05， P<0.01）. Compared with high-dose Tongmai Kaiqiao pills， the combination group prolonged the escape latency （P<0.01）， reduced the number of crossing platforms （P<0.01）， decreased the number of hippocampal neurons， aggravated the damage， decreased the number of Nissl bodies and autophagosomes， downregulated the expression of HIF-1α， BNIP3， beclin1， and LC3B （P<0.01）， and decreased the fluorescence intensity of HIF-1α， BNIP3， and LC3B （P<0.01）. ConclusionTongmai Kaiqiao pills may activate the HIF-1α/BNIP3 signaling pathway to promote the occurrence of mitochondrial autophagy， clear damaged mitochondria， provide energy for healthy cells， reduce neuronal cell death， and restore the brain function， thereby reducing ischemic damage to the hippocampal tissue， improving learning and memory abilities， and exerting therapeutic effects on VD in rats.

Vascular cognitive impairment (VCI) denotes a wide range of cognitive deficiencies resulting from cerebrovascular risk factors and cerebrovascular diseases. Sirtuin 1 (SIRT1), as a deacetylase, can mediate the deacetylation of histones and non-histone proteins. It is involved in regulating multiple pathophysiological processes of VCI, including neuroinflammation reduction, oxidative stress inhibition, cell apoptosis decrease, and blood-brain barrier protection, serving as a target for VCI treatment. This paper summarizes SIRT1 and the molecular mechanisms of targeting SIRT1 in order to provide a reference for the clinical treatment of VCI.

Parkinson's disease(PD)is a common neurodegenerative disease with a complex pathogenesis,and a large number of studies have shown that mitochondrial dysfunction is an important causative factor for PD,whereas dysregulation of mitochondrial quality control is a key factor leading to mitochondrial dysfunction,and that aberrant mitochondrial biogenesis,fusion/fission imbalance,and mitochondrial hyperautophagy are closely associated with the onset of PD,but the role of the mitochondrial quality control system in the progression of PD is unclear.Therefore,this paper reviews the mechanism of mitochondrial quality control system in PD,with the aim of providing new ideas and theoretical basis for the clinical prevention and treatment of PD.

Objective: To detect mutation of LBR gene in a pedigree affected with Pelger-Huёt anomaly (PHA) and to explore its clinical characteristics. Methods: Genomic DNA was extracted from the pedigree and healthy controls. The 14 exons of the LBR gene were subjected to PCR amplification and Sanger sequencing. Suspected mutations were verified in other family members and 100 healthy controls. Polyphen-2 and SIFT software were used to predict the effect of the mutation, and Swiss-model software was used to simulate the protein structure. Results: Three patients were found to carry a c. 893G>A mutation in exon 8 of the LBR gene, which resulted in substitution of the 298th amino acid residue glycine by glutamic acid (p.Gly298Glu). The same mutation was not found in healthy family members and 100 healthy controls. The mutation was predicted to be damaging. Bioinformatic simulation showed the mutation has altered the 3D structure of the LBR protein. Conclusion The c. 893G>A (p.Gly298Glu) mutation in the LBR gene probably underlies the PHA in this pedigree and has enriched the spectrum of LBR gene mutations.