Eight butyl-phthalides, senkyunolide K(1), senkyunolide N(2), butylphthalide(3), senkyunolide I(4), senkyunolide H(5),(Z)-butylidenephthalide(6),(Z)-ligustilide(7), and 3-butylidene-7-hydroxyphthalide(8) were isolated from the aerial part of Ligusticum sinense by column chromatography on silica gel column, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic and chemical data, especially NMR and MS. Compound 1 was a new butyl-phthalide and compounds 2-8 were isolated from the aerial part of L. sinense for the first time. Furthermore, the inhibitory activities of compounds 1-8 against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse RAW264.7 macrophages in vitro were evaluated. The results showed that compounds 1-8 exerted inhibitory activities on NO production with IC_(50) of 19.34-42.16 μmol·L~(-1).
Animals ; Mice ; Nitric Oxide/biosynthesis* ; Ligusticum/chemistry* ; Benzofurans/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; RAW 264.7 Cells ; Molecular Structure

To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective To explore the abnormal changes of resting state functional connectivity of pain networks in patients with cervical discogenic pain(CDP).Methods The resting-state functional magnetic resonance imaging(rs-fMRI)data of 40 patients with CDP and 40 age-and gender-matched healthy controls(HC)were collected.The seed of posterior insula(PI)was used to define the pain network,and seed-based whole-brain functional connectivity analyses were performed to explore the difference of functional connectivity between CDP patients and HC,the associations between functional connectivity and clinical measures were analyzed.Results The functional connectivity between bilateral PI and bilateral thalamus(THA)was increased,and the functional connectivity between left PI and middle cingulate cortex(MCC),left postcentral gyrus(PoCG)and MCC were decreased in CDP patients.Moreover,the func-tional connectivity between right PI and left THA was positively correlated with visual analogue scale(VAS),and the functional connectivity between left PoCG and MCC was negatively correlated with VAS.Conclusion Functional connectivity abnormalities exist in pain network resting state of CDP patients,which may provide an imaging basis for revealing the neuropathological mechanism of pain in CDP patients.

BACKGROUND:Satisfactory clinical results have been achieved in the treatment of Sanders Ⅲ calcaneal fractures by percutaneous compression fixation with three-dimensional frame screws.However,whether the stability of minimally invasive plate internal fixation can be achieved in terms of biomechanics,and the advantages and disadvantages after comparison are still unknown. OBJECTIVE:To investigate the fixation effect of different internal fixation devices on Sanders Ⅲ calcaneal fractures by finite element analysis. METHODS:A finite element model of Sanders Ⅲ calcaneal fracture was made based on CT data of a 26-year-old healthy male volunteer.The calcaneal fracture models were fixed by minimally invasive three-dimensional frame screws and minimally invasive Y-plate.The longitudinal loads of 350 and 700 N were applied respectively.The displacement and stress distribution of the two models were analyzed,and the stability of each model was compared. RESULTS AND CONCLUSION:(1)The peak stress of bone block and implant in the minimally invasive three-dimensional frame screw model was significantly lower than that in the minimally invasive minimally invasive plate model.The average stress of bone block and implant in the three-dimensional frame screw model was also significantly lower than that in the minimally invasive plate model.(2)The maximum displacement of the two models was located at the medial side of the articular surface of the posterior talus,and the maximum displacement of the three-dimensional frame screw model was smaller than that of the minimally invasive plate model.(3)The longitudinal displacement between the anterior fragment and the medial fragment of the minimally invasive plate model was smaller,and the transverse and vertical displacement between the medial fragment and the middle fragment of the three-dimensional group screw model was smaller.(4)It is concluded that both of the two internal fixation models can provide satisfactory fixation effect.The three-dimensional frame screw model can provide better transverse and vertical stability with more uniform stress distribution and smaller comprehensive displacement of bone fragments,while the minimally invasive plate has more advantages in maintaining longitudinal stability.

Objective To develop a time-resolved fluorescent immunoassay kit for the rapid,accurate and quantitative detection of S100B protein in serum and to evaluate its performance.Methods The test strip was prepared using time-resolved fluorescent microsphere-labeled anti-S100B polyclonal antibody and rabbit IgG antibody,labeling pads,sample pads,S100B nitrocellulose films and absorbent paper,and an S100B time-resolved fluorescence immunoassay kit was obtained by assembling the cartridge.The performance of the kit developed was evaluated by standard curve,accuracy,minimum detection limit,linear interval,specificity,reproducibility and stability.The reference intervals of 199 pieces of healthy human serum and plasma samples from a certain region were detected with the kit,and the clinical performance of the kit and Roche Elecsys S100 kit was tested by synchronous blind method to assess the consistency of the results of the two kits for 142 samples.Results The S100B time-resolved fluorescence immunoassay kit had the standard curve beingy=(1.133 02+1.752 24)/[1+(x/1.082 20)×(-0.603 52)]-1.752 24,R2=0.999 08 and the linear range being[0.05,30]ng/mL,which met the requirements of the relative deviation of the accuracy within±15％,the minimum detection limit not hgier than 0.05 ng/mL,the relative deviation of specificity within±15％and the coefficient of variation of intra-and inter-batch difference less than 15％.The stability test results indicated that the kit was valid for 12 months at 2-30 ℃ conditions.The reference intervals of serum and plasma samples measured by the kit were both lower than 0.3 ng/mL.Clinical trials showed that the results by the kit and Roche Elecsys S100 Assay Kit were in high agreement(Kappa=0.906 1＞0.80)and met the requirements.Conclusion The kit developed detects the concentration of S100B protein in serum quickly,accurately and quantitatively,and provides references for the diagnosis and treatment of neurological diseases,autoimmune diseases,cerebrovascular diseases and etc.[Chinese Medical Equipment Journal,2024,45(1):47-55]

Objective To detect the changes of mitophagy level in rats with endplate cartilage degeneration induced by spinal instability,and explore the role of PINK1/Parkin-mediated mitophagy in endplate cartilage and intervertebral disc degeneration.Methods The rat spinal instability model was established by surgically removing the superspinal and interspinal ligaments of L2 to L5,and cleaning the bilateral articular processes of the L2 to L5.Eighteen SD rats were divided into the normal group,the degenerative group,and the carbonyl cyanide 3-chlorophenylhydrazone(CCCP)group,with 6 rats in each group.The rats in the normal group had no special treatment,the rats in the degenerative group constructed a rat spinal instability model,and the rats in the CCCP group were injected with 5 μL of CCCP(10 μmol/L)in the intervertebral disc after the construction of spinal instability model.The changes of histomorphology in the endplate cartilage and intervertebral disc were abserved by HE staining,and the change of extracellular matrix of endplate cartilage was observed by safranin O-fast green staining.RT-PCR detected the mRNA expression of type Ⅱ collagen(COL-2A),aggrecan(ACAN),PINK1 and Parkin in each group.The changes of the protein expression levels of COL-2A,ACAN,PINK1,Parkin and mitochondrial membrane proteins of Tomm20 and Timm23 were detected by Western blot.Results Compared with the normal group,the intervertebral disc nucleus pulposus of rats in the degenerative group was significantly destroyed and the secretion of extracellular matrix of endplate chondrocytes decreased;while the structure of intervertebral discs for rats in the CCCP group was more intact,and the secretion of extracellular matrix of endplate chondrocytes was significantly increased compared with that in the degenerative group.Compared with the normal group,the expression of COL-2A and ACAN in endplate cartilage tissues of rats in the degenerative group were significantly down-regulated(P<0.05),the expression of mitochon-drial autophagy-related genes of PINK1 and Parkin were significantly decreased(P<0.05),and the expression of mitochondrial membrane proteins of Tomm20 and Timm23 were increased(P<0.05).Compared with the degenerative group,the expression of COL-2A,ACAN,PINKI and Parkin in the endplate cartilage tissue of rats in the CCCP group were significantly up-regulated(P<0.05),and the protein levels of Tomm20 and Timm23 were significantly down-regulated(P<0.05).Conclusion Rat spinal instability leads to a decrease level of mitophagy mediated by PINK1/Parkin signaling pathway in endplate cartilage,thereby inducing endplate cartilage and intervertebral disc degeneration,and the activation of mitophagy can significantly reduce endplate cartilage and intervertebral disc degeneration.