Parkinson’s disease (PD) is a common neurodegenerative disorder with profound impact on patients’ quality of life and long-term health, and early detection and intervention are particularly critical. In recent years, the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD. In this paper, we systematically evaluated potential biomarkers, including proteins, metabolites, epigenetic markers, and exosomes, in the peripheral blood of PD patients. Protein markers are one of the main directions of biomarker research in PD. In particular, α‑synuclein and its phosphorylated form play a key role in the pathological process of PD. It has been shown that aggregation of α-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD. In terms of metabolites, uric acid, as a metabolite, plays an important role in oxidative stress and neuroprotection in PD. It has been found that changes in uric acid levels may be associated with the onset and progression of PD, showing its potential as an early diagnostic marker. Epigenetic markers, such as DNA methylation modifications and miRNAs, have also attracted much attention in Parkinson’s disease research. Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease, providing new research perspectives for the early diagnosis of PD. In addition, exosomes, as a potential biomarker carrier for PD, are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation. Studies have shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide a new breakthrough for early diagnosis. It has been shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide new breakthroughs in early diagnosis. In summary, through in-depth evaluation of biomarkers in the peripheral blood of PD patients, this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms. Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

[Objective] To evaluate the efficacy and safety of sacral neuromodulation (SNM) in the treatment of patients with benign prostatic hyperplasia (BPH) complicated with underactive bladder (UAB) who respond poorly to transurethral resection of the prostate (TURP). [Methods] A retrospective analysis was performed on 10 patients with BPH and UAB treated with TURP by the same surgeon in Zhongda Hospital Southeast University during Jan.2018 and Jan.2023.The residual urine volume was not significantly relieved after operation, and the maximum urine flow rate and urine volume per discharge were not significantly improved.All patients underwent phase I SNM, and urinary diaries were recorded before and after surgery to observe the average daily frequency of urination, volume per urination, maximum urine flow rate, and residual urine volume. [Results] The operation time was (97.6±11.2) min.During the postoperative test of 2-4 weeks, if the residual urine volume reduction by more than 50% was deemed as effective, SNM was effective in 6 patients (60.0%). Compared with preoperative results, the daily frequency of urination [(20.2±3.8) times vs. (13.2±3.2) times], volume per urination [(119.2±56.7) mL vs. (246.5±59.2) mL], maximum urine flow rate [(8.7±1.5) mL/s vs. (16.5±2.6) mL/s], and residual urine volume [(222.5±55.0) mL vs. (80.8±16.0) mL] were significantly improved, with statistical significance (P<0.05). There were no complications such as bleeding, infection, fever or pain.The 6 patients who had effective outcomes successfully completed phase II surgery, and the fistula was removed.During the follow-up of 1 year, the curative effect was stable, and there were no complications such as electrode displacement, incision infection, or pain in the irritation sites.The residual urine volume of the other 4 unsuccessful patients did not improve significantly, and the electrodes were removed and the vesicostomy tube was retained. [Conclusion] SNM is safe and effective in the treatment of BPH with UAB patients with poor curative effects after TURP.

BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.

BACKGROUND:Mesenchymal stem cells can regulate the tumor microenvironment by secreting extracellular vesicles containing cytokines,growth factors and exosomes for the precise regulation of biological behavior of tumor cells. OBJECTIVE:To investigate the effects of human umbilical cord-derived mesenchymal stem cell conditioned medium and their released exosomes on the biological properties of hepatocellular carcinoma cells. METHODS:Human umbilical cord mesenchymal stem cell supernatant was collected,centrifuged and filtered at high speed to obtain human umbilical cord mesenchymal stem cell conditioned medium.Human umbilical cord mesenchymal stem cell supernatant was collected and human umbilical cord mesenchymal stem cell exosomes were extracted by ultra-high speed gradient centrifugation.Human umbilical cord mesenchymal stem cell exosomes were labeled with PKH26 and co-cultured with hepatocellular carcinoma cell MHCC97-H.The uptake of exosomes by MHCC97-H cells was observed by fluorescence microscopy.The effects of human umbilical cord mesenchymal stem cell conditioned medium and human umbilical cord mesenchymal stem cell exosomes on biological functions of hepatocellular carcinoma cells were assessed by the CCK-8 proliferation assay,Transwell migration and invasion assay,and the apoptosis assay. RESULTS AND CONCLUSION:(1)Human umbilical cord mesenchymal stem cell exosomes could be uptaken by MHCC97-H cells and was mainly distributed in the cytoplasm.(2)After treatment with human umbilical cord mesenchymal stem cell conditioned medium,MHCC97-H cells showed a significant increase in proliferation,migration,and invasion(P<0.001,P<0.05,P<0.01),and a significant decrease in apoptosis(P<0.001),while after treatment with human umbilical cord mesenchymal stem cell exosomes,MHCC97-H cells showed a decrease in proliferation(P<0.001)and migration,invasion,and apoptosis were significantly enhanced(P<0.001).(3)The results indicated that human umbilical cord mesenchymal stem cell conditioned medium had the ability to promote the proliferation,migration,invasion,and inhibit apoptosis of MHCC97-H cells,while human umbilical cord mesenchymal stem cell exosomes had the properties of promoting the migration,invasion and apoptosis of MHCC97-H cells,inhibiting the proliferation.

BACKGROUND:Ilizarov bone transport is very effective in the treatment of open large tibial bone defects,but there are still complications,among which the difficulty of junction healing is one of the difficult points in treatment. OBJECTIVE:To investigate the effect of Ilizarov bone transport combined with antibiotic bone cement on junction healing after operation of open large tibial bone defect. METHODS:Totally 51 patients with open large tibial bone defect(bone defect>4 cm)admitted to Binzhou Medical University Hospital from August 2010 to January 2022 were selected,of which 28 received Ilizarov bone transport alone(control group)and 23 received Ilizarov bone transport combined with antibiotic bone cement treatment(trial group).External fixation time,bone healing time,bone healing index,visual analog scale score during bone removal,bone defect limb function,junction healing and complications at the final follow-up were statistically compared between the two groups. RESULTS AND CONCLUSION:(1)All the 51 patients were followed up for a mean of(22.53±5.77)months.External fixation time,bone healing time,bone healing index,postoperative infection rate,and non-healing rate of junction were less in the trial group than those in the control group(P<0.05).There was no significant difference between the two groups in visual analog scale scores at 6 months after the second surgery and in the functional excellence and good rate of limb with bone defect at the final follow-up(P>0.05).(2)These findings indicate that compared with the Ilizarov bone transport alone,Ilizarov bone transport combined with antibiotic bone cement treatment can promote the healing of open tibial fracture junction and increase the rate of bone healing.

BACKGROUND:Traditional Chinese medicine has rich experience and unique advantages in the empirical treatment of phlegm-heat and Fu-organs excess syndrome of ischemic stroke.In order to further explore the therapeutic targets and mechanisms of traditional Chinese medicine for this disease,it is crucial to establish a stable and reliable animal model of phlegm-heat and Fu-organs excess syndrome combined with empirical symptoms of ischemic stroke. OBJECTIVE:To explore the establishment method and evaluation system of the rat model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome. METHODS:Sixty male Sprague-Dawley rats were randomly divided into four groups:blank control group(n=12),ischemic stroke group(n=18),disease+syndrome group(n=18),phlegm-heat and Fu-organ excess syndrome group(n=12),all of which were given high-fat diet for 25 days.On the 26th day,the rats in the blank control group and ischemic stroke group were intragastrically given normal saline and high fat diet,while those in the other two groups were intragastrically given autologous feces suspension and high fat diet for 3 continuous days.After gavage,ischemic stroke models were established using the suture method in the ischemic stroke group and disease+syndrome group.The changes in diet,water intake,body mass,body temperature,fecal traits,nasal secretions,sputum in the throat,and tongue image were recorded.Neurological deficits,tongue image,blood lipid levels,morphological changes of brain tissue and carotid artery,and the serum levels of motilin and somatostatin were detected. RESULTS AND CONCLUSION:Compared with the control group,the rats in the disease+syndrome group had shortness of breath,listlessness,irritability,bradykinesia,a large number of secretions around the nose,audible and heavy sputum in the throat,decreased diet and water intake,increased body mass,body temperature,and slingual vein score,decreased fecal pellet count,Bristol score and fecal moisture content,increased serum total cholesterol,triglyceride,low-density lipoprotein and somatostatin levels,decreased motilin level,increased neurological deficit score,significant pathological changes of the carotid artery,and significant morphological changes of the brain tissue.The ischemic stroke group only showed pathological changes of ischemic brain tissue,without the characteristics of phlegm-heat and Fu-organ excess syndrome.The phlegm-heat and Fu-organ excess syndrome group could present with the typical characteristics of traditional Chinese medicine syndromes,without the pathological changes of brain tissue with ischemic stroke.To conclude,the compound modeling method of high-fat induction combined with suture method and autologous feces gavage can establish an animal model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome.

ObjectiveTo explore the changes in volatile components， total polysaccharides， enzyme activity， and chromaticity value of Myristicae Semen Koji（MSK） during the fermentation process， and conduct correlation analysis. MethodsBased on gas chromatography-mass spectrometry（GC-MS）， the changes of volatile components in MSK at different fermentation times were identified. The phenol sulfuric acid method， dinitrosalicylic acid method（DNS）， and carboxymethyl cellulose sodium salt method（CMC-Na） were used to investigate the total polysaccharide content， amylase activity， and cellulase activity during the fermentation process. Visual analysis technology was used to explore the changes in chromaticity values， revealing the fermentation process of MSK and the dynamic changes of various measurement indicators， partial least squares-discriminant analysis（PLS-DA） was used to explore the differential compounds of MSK at different fermentation degrees， and Pearson correlation analysis was used to explore the correlation between volatile components of MSK and total polysaccharides， enzyme activity， and chromaticity values. ResultsA total of 60 volatile compounds were identified from MSK， the relative contents of components such as （+）-α-pinene， β-phellandrene， β-pinene， （+）-limonene， and p-cymene obviously increased， while the relative contents of components such as safrole， methyl isoeugenol， methyleugenol， myristicin， and elemicin significantly decreased. During the fermentation process， the total polysaccharide content showed an upward trend， while the activities of amylase and cellulase showed an initial increase followed by a decrease， and reached their maximum value at 40 h. the overall brightness（L^*） and total color difference（ΔE^*） gradually increased， while the changes in red-green value（a^*） and yellow-blue value（b^*） were not obvious. PLS-DA results showed that MSK could be clearly distinguished at different fermentation times， and 13 differential biomarkers were screened out. Pearson correlation analysis results showed that the contents of α-terpinene， β-phellandrene， methyleugenol， β-cubebene and myristic acid had an obvious correlation with chromaticity values. ConclusionAfter fermentation， the volatile components， total polysaccharides， amylase activity， and cellulase activity of MSK undergo significant changes， and there is a clear correlation between them and chromaticity values， which reveals the dynamic changes in the fermentation process and related indicators of MSK， laying a foundation for the quality control.

AIM: To investigate the correlation of the expression of stromal cell-derived factor-1(SDF-1)and angiopoietin like protein 4(ANGPTL4)in serum with the severity of disease in patients with diabetic macular edema(DME).METHODS: From April 2020 to August 2023, 193 patients with diabetic retinopathy who were admitted to our hospital were prospectively separated into DME group(128 cases)(56 cases in mild group, 44 cases in moderate group, 28 cases in severe group)and non DME group(65 cases)according to whether the patients had macular edema and the severity of disease. Enzyme-linked immunosorbent assay(ELISA)was applied to determine the levels of ANGPTL4 and SDF-1 in serum. Multivariate Logistic regression was applied to analyze the factors that affected the severity of DME; receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of ANGPTL4 and SDF-1 levels in serum of DME patients for the severity of DME.RESULTS: The levels of ANGPTL4 and SDF-1 in serum of the DME group were obviously higher than those of the non DME group(P<0.01); the expression levels of ANGPTL4 and SDF-1 in serum of the mild, moderate, and severe groups increased obviously in sequence(P<0.05); multivariate Logistic regression analysis showed that the levels of ANGPTL4 and SDF-1 in serum were risk factors affecting the severity of DME(P<0.01); The area under the curve(AUC)of serum SDF-1 in the diagnosis of DME severity was 0.772(95%CI: 0.690-0.842), and the AUC of ANGPTL4 in the diagnosis of DME severity was 0.801(95%CI: 0.722-0.867). The AUC of ANGPTL4 combined with SDF-1 in the diagnosis of DME was 0.884(95%CI: 0.816-0.934), the sensitivity was 87.50%, and the specificity was 85.71%, which were significantly higher than ANGPTL4 or SDF-1 alone(Z=2.658, 2.469, all P<0.05).CONCLUSION: The levels of ANGPTL4 and SDF-1 in serum of DME patients are significantly increased, and their levels increase with the severity of the disease. They can be used as auxiliary indicators for diagnosing the severity of DME disease, and the combined diagnosis has a better effect.