OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

OBJECTIVE T o establish the automatic diagnosis system for varicella pneumonia based on multi-slice spiral computed tomography(MSCT)and verify its application value.METHODS The clinical data were collected from 295 patients with varicella who were treated in the hospital from Jan.2016 to Mar.2023 and assigned as the training set,the pulmonary imaging findings were acquired from the MSCT chest scanning.The automatic diagno-sis system for varicella pneumonia was established based on MSCT with the use of convolutional neural network technology.Totally 279 patients with varicella who were treated during the same period were chosen as the valida-tion set,the result of comprehensive diagnosis was set as gold standard,and the efficiency of the above system in diagnosis of varicella pneumonia was observed.RESULTS Totally 279 patients with varicella were included in the validation group,243 of whom had varicella pneumonia,and 36 had simple varicella infection.The sensitivity of the automatic diagnosis system established based on MSCT was 97.53％in diagnosis of the varicella pneumonia of the validation group,with the specificity 91.67％,the accuracy 96.77％,respectively higher than 93.83％,83.33％and 92.47％of MSCT,and it was highly consistent with the gold standard(Kappa=0.919,P＜0.001);there was consistency between MSCT and the gold standards(Kappa=0.675,P＜0.001).CONCLUSION The au-tomatic diagnosis system for varicella pneumonia established based MSCT can raise the sensitivity,specificity and accuracy in diagnosis of varicella pneumonia and have the advantages of automation and convenience,and serve as a new tool for clinical diagnosis of varicella pneumonia.

Background and Aims:Abdominal aortic aneurysm(AAA)is a common arterial dilation disease in vascular surgery,with aneurysm rupture being its most serious complication,often leading to fatal hemorrhage and posing a severe threat to patients'lives.Endovascular aneurysm repair(EVAR),due to its minimally invasive nature,safety,and rapid recovery,has become the preferred treatment for AAA.However,endoleak,a complication unique to EVAR,remains a major clinical challenge.Persistent endoleak can lead to sustained high pressure within the aneurysm sac,increasing the risk of continued expansion and rupture.It is one of the main causes of the high reintervention rate following EVAR.In particular,the treatment strategy for type Ⅱ endoleaks remains controversial.This study was conducted to evaluate the clinical value of selective sac embolization via the iliac approach combined with standard EVAR in managing intraoperative immediate endoleaks.Methods:The clinical data of AAA patients with a risk of endoleak who underwent standard EVAR at the First Hospital of China Medical University between March 2023 and September 2024 were retrospectively collected.Patients were divided into an intervention group(n=42)and a non-intervention group(n=32)based on whether selective sac embolization via the iliac approach was performed during operation.General clinical data,preoperative anatomical characteristics of the AAA,surgical details,and postoperative follow-up results were compared between the two groups.Results:There were no statistically significant differences between the two groups in terms of age,sex,anatomical features,rupture rate,or off-label use(all P>0.05).The technical success rate during surgery was 100%in both groups.One patient in the intervention group experienced transient sigmoid colon ischemia after operation,which resolved with conservative treatment.The mean follow-up period was(6.49±4.68)months.The proportions of aneurysm sac shrinkage,stability,and enlargement in the intervention group were 40.5%,57.1%,and 2.4%,respectively,compared to 59.4%,40.6%,and 0.0%in the non-intervention group,with no statistically significant differences(all P>0.05).The incidence of endoleak during follow-up was also comparable between the two groups(P>0.05).Conclusion:For intraoperative endoleaks during standard EVAR,selective sac embolization via the iliac approach is a technically simple and safe method that provides short-term outcomes comparable to those in patients without intraoperative endoleaks.Its long-term efficacy warrants further investigation through extended follow-up.

Objective To explore macrophage subpopulations in ischemic stroke (IS) by using single-cell RNA sequencing (scRNA-seq) data analysis and High-Dimensional Weighted Gene Co-Expression Network Analysis (hdWGCNA). Methods Based on single-cell sequencing data, transcriptomic information for different cell types was obtained, and macrophages were selected for subpopulation identification. hdWGCNA, cell-cell communication, and pseudotime trajectory analysis were used to explore the characteristics of macrophage subpopulations following IS. Key genes related to IS were identified using microarray data and validated for diagnostic potential through Receiver Operating Characteristic (ROC) analysis. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential functions of these genes. Results The scRNA-seq data analysis revealed significant changes in macrophage subpopulation composition after IS. A specific macrophage subpopulation enriched in the stroke group was identified and designated as MCAO-specific macrophages (MSM). Pseudotime trajectory analysis indicated that MSM cells were in an intermediate stage of macrophage differentiation. Cell-cell communication analysis uncovered complex interactions between MSM cells and other cells, with the CCL6-CCR1 signaling axis potentially playing a crucial role in neuroinflammation. Two gene modules associated with MSM were identified via hdWGCNA, significantly enriched in pathways related to NOD-like receptors and antigen processing. By integrating differentially expressed MSM genes with conventional transcriptomic data, three IS-related hub genes were identified: Arg1, CLEC4D, and CLEC4E. Conclusion This study reveals the characteristics and functions of macrophage subpopulations following IS and identifies three hub genes with potential diagnostic value, providing novel insights into the pathological mechanisms of IS.
Macrophages/metabolism* ; Computational Biology/methods* ; Single-Cell Analysis/methods* ; Transcriptome ; Ischemic Stroke/metabolism* ; Animals ; Gene Regulatory Networks ; Gene Expression Profiling ; Humans ; Male

Objective:To evaluate the prognostic value of 18F-fluorodeoxyglucose(FDG)positron emission tomography(PET)/com-puted tomography(CT)(18F-FDG PET/CT)metabolic parameters combined with clinical characteristics in treated patients with esophageal squamous cell carcinoma(ESCC).Methods:The clinical data of 75 patients(65 males and 10 females,age of 63.41±7.75 years)with pathologically confirmed ESCC in * Hospital from January 2015 to November 2021 were retrospectively analyzed.All pa-tients underwent 18F-FDG PET/CT examination after treatment.The relevant parameters of 18F-FDG PET/CT were determined:whole body SUVmax(SUVmaxwb);SUVmean and metabolic tumor volume(MTV)were measured with 40％SUVmax as the critical value,and whole body MTV(MTVwb)and whole body total lesion glycolysis(TLGwb)were calculated.Kaplan-Meier survival curves and Cox proportional hazards model were used to evaluate the relationship between PET parameters and overall survival(OS).Results:Fifty-two(69.3％)patients died.PET-positive patients exhibited a 6.029-fold increased risk of death compared with PET-negative patients(P<0.001),with the median survival time of 22.3 months and 43.2 months,respectively.PET-positive patients were catego-rized based on median parameters of PET:SUVmaxwb=11.09,MTVwb=27.07 cm3,and TLGwb=162.34 g.Kaplan-Meier survival curves and log-rank tests revealed the correlations of pathological classification,M stage,post-PET anti-tumor treatment,MTVwb,and TLGwb with OS.M stage emerged as an independent predictor for OS(hazard ratio=5.698,95％CI=1.791-18.123,P=0.003).Patients positive for both PET imaging and serology had a 6.112-fold higher death risk compared with those negative for PET imaging(P<0.001).Conclusion:18F-FDG PET/CT volume metabolism parameters are significant prognostic predictors for treated patients with ESCC,and patients positive for PET imaging and tumor markers are associated with a poor prognosis.

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Objective:To investigate the clinical and genetic characteristics of patients with amyotrophic lateral sclerosis (ALS) caused by FUS gene mutations. Methods:A retrospective analysis was conducted on 7 families diagnosed with FUS gene related ALS in the Department of Neurology of Henan Provincial People′s Hospital from January 2018 to June 2024. Clinical data and neuroelectrophysiological results of the probands and family members were collected. Next generation sequencing or whole exome sequencing was conducted on the probands. The detected variants of the FUS gene were confirmed by Sanger sequencing. Results:Among the 7 probands, 4 were with familial ALS and 3 with sporadic ALS, including 6 males and 1 female. The average age of onset was 24.6 years (ranging from 21 to 30 years). The onset site included bulbar muscles in 1 case, proximal upper limbs in 3 cases, proximal lower limbs in 2 cases, and both upper and lower limbs in 1 case. Four patients presented both upper and lower motor neurons involvement on examination, and 3 had only lower motor neuron syndrome. Muscle atrophy and fasciculation were observed in 6 patients respectively, and dyspnea in 3 patients. Bilateral muscle strength was asymmetric in 5 patients. Proximal muscle weakness was predominant in 6 of the 7 patients with upper limb weakness, and 3 of the 5 patients with lower limb weakness. Electromyography showed neurogenic damage in all 7 cases. Five heterozygous variants of the FUS gene were detected in 7 patients, including 2 patients with c.1574C>T(p.P525L), 2 with c.1552A>G(p.R518G), 1 with c.1561C>T(p.R521C), 1 with c.1441delC(p.R481Efs *48), and 1 with both c.1574C>T(p.P525L) and c.430_447del(p.G144_Y149del) variants. The variant c.1441delC(p.R481Efs *48) had not been previously reported. During follow-up, 6 patients died of respiratory failure 6-18 months after onset, with an average of 11.8 months. Conclusions:Patients with FUS gene related ALS have an early age of onset, rapid progression, short survival period, asymmetric limb weakness, and more severe involvement of proximal limbs. The c.1574C>T(p.P525L) is a hotspot mutation, and the novel variant c.1441delC(p.R481Efs *48) enriches the mutation spectrum of the FUS gene.

OBJECTIVE T o establish the automatic diagnosis system for varicella pneumonia based on multi-slice spiral computed tomography(MSCT)and verify its application value.METHODS The clinical data were collected from 295 patients with varicella who were treated in the hospital from Jan.2016 to Mar.2023 and assigned as the training set,the pulmonary imaging findings were acquired from the MSCT chest scanning.The automatic diagno-sis system for varicella pneumonia was established based on MSCT with the use of convolutional neural network technology.Totally 279 patients with varicella who were treated during the same period were chosen as the valida-tion set,the result of comprehensive diagnosis was set as gold standard,and the efficiency of the above system in diagnosis of varicella pneumonia was observed.RESULTS Totally 279 patients with varicella were included in the validation group,243 of whom had varicella pneumonia,and 36 had simple varicella infection.The sensitivity of the automatic diagnosis system established based on MSCT was 97.53％in diagnosis of the varicella pneumonia of the validation group,with the specificity 91.67％,the accuracy 96.77％,respectively higher than 93.83％,83.33％and 92.47％of MSCT,and it was highly consistent with the gold standard(Kappa=0.919,P＜0.001);there was consistency between MSCT and the gold standards(Kappa=0.675,P＜0.001).CONCLUSION The au-tomatic diagnosis system for varicella pneumonia established based MSCT can raise the sensitivity,specificity and accuracy in diagnosis of varicella pneumonia and have the advantages of automation and convenience,and serve as a new tool for clinical diagnosis of varicella pneumonia.

Objective:To investigate the clinical and genetic characteristics of spinal muscular atrophy (SMA) patients with SMN1 gene compound heterozygous mutations. Methods:Three SMA-Ⅲ pedigrees treated in Henan Provincial People′s Hospital from October 2019 to July 2020 were selected. The clinical data of 3 SMA-Ⅲ probands were retrospectively analyzed. Multiplex ligation-dependent probe amplification (MLPA) technology was used to detect the copy number of the SMN gene in the probands and their parents. Polymerase chain reaction amplification combined with microfluidic capillary electrophoresis were used to detect point mutations in the SMN1 gene of the probands. Sanger sequencing was used to validate candidate variant sites. Results:The 3 probands are all male, aged 19, 17 and 12 years, respectively. The main clinical manifestations were symmetrical muscle weakness mainly in the proximal lower limbs, mild to moderate elevation of serum creatine kinase, and neurogenic injury as determined by electromyography or muscle pathology. The genetic testing results showed that all 3 probands had heterozygous deletion in exon 7 of the SMN1 gene, and carried heterozygous variations c.275G>A (p.Trp92 *), c.689C>T (p.Ser230Leu), and c.708dupT (p.Pro237Serfs *19), respectively. The exon deletion and point mutation were inherited separately from their parents. c. 275G>A (p.Trp92 *) and c.708dupT (p.Pro237Serfs *19) variations had not been reported before. Conclusions:The clinical manifestations of SMA-Ⅲ patients are symmetrical muscle weakness, mainly in the proximal extremities of both lower limbs, and electromyography or muscle biopsy suggesting neurogenic lesions. The compound heterozygous variation of point mutation and heterozygous deletion in the SMN1 gene can lead to SMA-Ⅲ. Suspected SMA patients with SMN1 gene heterozygous deletion should take point mutation testing.

Objective:To analyze the clinical manifestations and muscular magnetic resonance imaging (MRI) features of 12 families with facioscapulohumeral muscular dystrophy (FSHD).Methods:Retrospective analysis was conducted on 12 FSHD families diagnosed by genetic testing at the Department of Neurology of Henan Provincial People′s Hospital from January 2017 to June 2021. Clinical data and lower limb muscle MRI results of the probands and related members of the families were collected, and the degree of muscle fatty degeneration shown in the MRI was scored using the modified Mercuri score.Results:There were 21 patients in 12 families, with the age of onset ranged from 10 to 47 years (mean 19.5 years). The course of disease ranged from 1 to 47 years (mean 23.1 years). The onset sites included unilateral upper extremity in 8 cases, bilateral proximal upper extremities in 9 cases, bilateral proximal lower extremities in 2 cases, unilateral proximal lower extremity in 1 case, and simultaneous onset in all 4 limbs in 1 case. Sixteen patients had limb weakness and bilateral asymmetry, and 11/16 cases were more severe on the right side than the left side. Winged scapular and facial muscle weakness were observed in all patients. The creatine kinase range was 85-1 038 U/L (461 U/L on average) in 12/21 cases. There were 10/21 cases of myogenic lesion in electromyography. Myodystroph-like pathological changes were found in 11/21 cases. The fragment length of the 4q35 subtelomere polymorphism EcoRI/p13E-11 was less than 38 kb in 20/21 cases; 1 case was confirmed based on clinical symptoms and family history. Fat infiltration occurred in at least one muscle of lower limbs in 9/10 cases, in thigh muscle in 9/10 cases and in calf muscle in 6/10 cases. The average score of fat infiltration in thigh muscle group was higher than that in calf muscle group. The muscles with higher fat infiltration scores were the vastus intermedius, the long head of the biceps femoris, the vastus medialis, the vastus lateralis, the semitendinosus, the semimembranosus, the vastus lateralis in the thigh (with score ≥2.15), the tibialis anterior, and the medial head of the gastrocnemius in the calf (with score ≥1.11). Fat infiltration in the medial and posterior thigh muscles was more common than in the anterior thigh muscles. There was asymmetry of bilateral muscle fat in 9/10 cases. There were edematous changes in thigh muscles in 1 case and in calf muscles in 3 cases.Conclusions:The age of onset of FSHD patients is mostly ≤30 years. Bilateral asymmetric involvement is the characteristic manifestation of FSHD. The FSHD patients ' muscles most affected by the disease in the thigh are the quadriceps femoris, the long head of the biceps femoris, the vastus medialis, the vastus lateralis, the semitendinosus, the semimembranosus, and the vastus intermedius. In the calf, the muscles most affected are the anterior tibial muscle and the medial head of the gastrocnemius. The MRI pattern of muscle involvement of patients with FSHD is bilateral asymmetrical lesions, with the right side having more severe lesions. The fatization of thigh muscles is more significant than that of calf muscles, and the asymmetry of fatization between bilateral muscles is also present.