Objective: To investigate the protective effects and underlying mechanisms of sodium pyruvate (SP) on RBC storage lesions using an oxidative damage model. Methods: Six units of leukocyte-depleted suspended RBCs (discarded for non-infectious reasons within three days post-collection) were randomly assigned to four groups: negative control (NS), positive control (PS), experimental group 1 (SP1), and experimental group 2 (SP2). Oxidative stress was induced in the PS group by the addition of hydrogen peroxide (H O ), while SP1 and SP2 received SP supplementation at different concentrations (25 mM and 50 mM, respectively) in the presence of H O . After 1 hour of incubation, RBC morphology was assessed microscopically, and biochemical indicators including glutathione (GSH), malondialdehyde (MDA), methemoglobin (MetHb), adenosine triphosphate (ATP), and Na /K -ATPase activity were measured. Results: RBCs in the PS group exhibited pronounced morphological damage, including cell shrinkage and echinocyte formation, whereas both SP-treated groups showed significantly reduced structural injury. SP treatment led to elevated GSH levels and decreased concentrations of MDA and MetHb, suggesting attenuation of oxidative stress. Additionally, SP enhanced intracellular ATP levels and Na /K -ATPase activity, thereby contributing to membrane stability. Notably, the SP2 group (50 mM) demonstrated superior protective effects compared to SP1 (25 mM). Conclusion: Sodium pyruvate effectively attenuates oxidative storage lesions in RBCs, primarily through its antioxidant properties, energy metabolism supporting ability, and celluar membrane stabilizing function. These findings suggest SP as a promising additive for enhancing the quality and safety of stored RBCs.

Objective To investigate the effect and mechanism of Efferocytosis Relatived LncRNA (EFRL) on homocysteine-induced atherosclerosis in macrophage efferocytosis. Methods RAW264.7 cells were cultured in vitro, and the Control group (0 μmol/L Hcy) and Hcy intervention group (100 μmol/L Hcy) were set up. After GapmeR transfection of macrophages with Hcy intervention, EFRL knockdown negative control group (Hcy combined with LNA-NC) and EFRL knockdown group (Hcy combined with LNA-EFRL) were set up. High-throughput sequencing was applied for different expression of LncRNA MSTRG. 88917.16 (EFRL), UCSC was used to analyze its conservation, CPC and CPAT were used to analyze its ability to encode proteins, and GO and KEGG were used to analyze related biological functions. The localization of LncRNA EFRL in macrophages was analyzed by nucleoplasmic separation and RNA-FISH. Quantitative real-time PCR was used to detect the expression levels of LncRNA EFRL and its target gene SPAST in Hcy-treated macrophages. The apoptosis rate of Jurkat cells induced by UV was detected by flow cytometry. In vitro efferocytosis assay combined with immunofluorescence technique was used to analyze macrophage efferocytosis. ELISA was used to detect the levels of interleukin 1β(IL-1β) and IL-18. Results The new LncRNA MSTRG.88917.16 was identified and named EFRL(Efferocytosis Relatived LncRNA). UCSC, CPC and CPAT analyses showed that LncEFRL is highly conserved and does not have the ability to encode proteins. GO and KEGG analyses suggested that LncEFRL may be involved in macrophage efferocytosis. LncRNA EFRL was localized in the nucleus of macrophages as determined by nucleoplasmic separation and RNA-FISH. In comparison to the Control group, the expression levels of LncRNA EFRL and its target gene SPAST in the Hcy group were increased. In comparison to the Control group (0 min), the apoptosis rate of the experimental group (15, 30 min) Annexin V is more than 85%. Compared with Hcy combined with LNA-NC group, Hcy combined with LNA-EFRL group had enhanced macrophage efferocytosis and reduced levels of inflammatory factors. Compared with Hcy combined with LNA-NC group, the expression level of SPAST in Hcy combined with LNA-EFRL group was decreased. Conclusion Inhibition of EFRL expression can alleviate the process of Hcy inhibiting macrophage efferocytosis, and the mechanism is related to the regulation of the downstream target gene SPAST by EFRL.
RNA, Long Noncoding/physiology* ; Animals ; Homocysteine ; Mice ; Macrophages/drug effects* ; Humans ; RAW 264.7 Cells ; Atherosclerosis/chemically induced* ; Apoptosis/genetics* ; Phagocytosis/genetics* ; Jurkat Cells ; Interleukin-1beta/genetics* ; Efferocytosis

Objective Sleep-related head jerks （SRHJ） are a newly recognized sleep-onset motor phenomenon that has not yet been incorporated into the ICSD-3 classification of sleep disorders， and this study aims to provide a descriptive analysis of the clinical and video polysomnography （VPSG） features of SRHJ patients. Methods A retrospective analysis was performed for the VPSG recordings collected over a 2-year period in Sleep Laboratory of Department of Neurology， Peking Union Medical College Hospital， and the patients with a neck myoclonus index of >15 events per hour during REM sleep were diagnosed with SRHJ. The clinical and VPSG features of these patients with SRHJ were analyzed， as well as the proportion of patients with SRHJ-related arousals and micro-arousals or comorbidity with other types of sleep disorders. Results There were eight patients in the SRHJ group， and the occurrence rate of SRHJ during REM sleep was 77%. The head jerk index ranged from 15 to 91.5 events/h during REM sleep and from 0.5 to 4 events/h during NREM sleep. The patients with SRHJ-related arousals and micro-arousals accounted for 44%， among whom 44% were comorbid with jerks involving other body parts （such as the upper limbs， the lower limbs， and the shoulders）. Comorbid sleep disorders included obstructive sleep apnea-hypopnea syndrome in two patients， REM sleep behavior disorder in two patients， narcolepsy in one patient， and propriospinal myoclonus in one patient. Conclusion SRHJ is a paroxysmal motor event mainly observed during REM sleep and often has a low frequency of attack， possibly due to physiological causes. However， frequent episodes may disrupt sleep stability. There are currently no diagnostic criteria for SRHJ， and its diagnosis should consider the frequency of attacks， the impact on sleep stability， and potential adverse consequences.

Objective:To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.Methods:This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells. Results:The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS ( PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS ( P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS ( P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS ( P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells ( P>0.05). Conclusions:From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.

Objective:To elucidate the clinical and genetic characteristics of PLA2G6-related parkinsonism. Methods:The clinical, imaging and genetic data of 6 patients with PLA2G6-related parkinsonism admitted to Peking Union Medical College Hospital from January 2015 to December 2022 were retrospectively collected and analyzed. The prognosis was followed up through phone call. Results:There were 3 male and 3 female patients, and the age of disease onset was (24.3±5.4) years. Phenotypically, 5 of them had dystonia-parkinsonism (DP) with obvious atrophy of cerebellum and 1 presented as early-onset Parkinson′s disease (EOPD) with no brain structural abnormality. Only 1 patient presented with abnormal brain iron deposition. All of the patients were partially responsive to levodopa. Three cases underwent levodopa challenge test with the objective levodopa responsiveness varied from 10.3% and 10.6% in 2 DP patients, to 77.0% in 1 EOPD patient. Levodopa-induced dyskinesias were present in 4 of them, and all appeared within the first year since the initiation of dopaminergic treatment. Two patients underwent bilateral deep brain stimulation (DBS) of subthalamic nucleus and globus pallidus internus respectively, albeit revealed poor outcome. Genetically, 8 PLA2G6 variants were identified. Two of them were found to be novel (c.1973A>G and exon2 heterozygous deletion), and the most frequent variant was the c.991G>T mutation which was detected in 4 patients. Conclusions:The phenotype of PLA2G6-related parkinsonism is complex. Cerebellar atrophy is a frequent magnetic resonance imaging feature. Levodopa responsiveness tends to depend on the clinical phenotype, and EOPD is better than DP. DBS might not be promising in DP patients with obvious cerebral atrophy. The c.991G>T mutation is the most frequent mutation, suggesting a common founder effect.

Objective : To investigate the protective effect and mechanism of Hudi Enteric capsules in ionizing radiation injury to small intestinal crypt cells (IEC⁃6 cells) in rats. Methods : IEC⁃6 cells were irradiated with 6 mega electron volt X ⁃rays (2 , 4 , 6 , 8 and 10 Gy) , cell clone formation assay was used to detect cell proliferation , and the 6 Gy ionizing radiation was selected to establish a cellular radiation damage model according to the cell survival rate. The effect of each concentration ( 12. 5 , 25 , 50 , 100 and 200 μg/ml) of Hudi enteric extract on the viability of IEC⁃6 cells was examined by cell counting kit⁃8(CCK⁃8) method , and the effect on the viability of IEC⁃6 cells after irradiation at ( 10 , 20 , 40 and 80 μg/ml) concentrations was examined according to the results. After obtaining the optimal irradiation dose and extract concentration , the cells were divided into control group , model group and Hudi extract group (80 μg/ml) , the control group was pseudo⁃irradiated and the other two groups received 6 Gy of ionizing radiation , and the Hudi enteric extract group was pre⁃treated with drugs 2 h before irradiation. Apoptosis was detected by Annexin V ⁃PI double staining; cell senescence was detected by β ⁃galactosidase (β⁃Gal) staining; reactive oxygen species was detected by DCFH⁃DA fluorescent probe ; the corresponding protein expression of p16 , p21 , Catalase (CAT) and Superoxide dismutase ( SOD2) was detected by Western blot. Results : The proliferation of IEC⁃6 cells was inhibited by radiation doses ranging from 4 Gy to 10 Gy(P < 0. 001) ; (P < 0. 001) , and the apoptosis rate , β ⁃Gal positivity rate and DCFH⁃DA fluorescence intensity in the Hudi enteric extract group were lower than those in the model group (P < 0. 05) . The protein expressions of CAT and SOD2 in the Hudi extract group were higher than those in the model group ( P < 0. 05) , and the protein expressions of p16 and p21 were lower than those in the model group (P < 0. 05) . Conclusion The mechanism of action of Hudi enteric capsules that attenuate radiation damage in IEC⁃6 cells may be related to the inhibition of reactive oxygen species production , reduction of oxidative stress , and attenuation of cellular senescence and apoptosis.

Objective:To compare the clinical efficacy of unilateral biportal endoscopy (UBE) and uniportal endoscopy (UE) for unilateral laminotomy for bilateral decompression (ULBD) in the treatment of lumbar spinal stenosis.Methods:Data of 82 patients with lumbar spinal stenosis treated by ULBD under UBE or UE from January 2020 to June 2021 in Dalian Central Hospital affiliated to Dalian Medical University and the First Hospital affiliated to Wenzhou Medical University were retrospectively analyzed, including 36 males and 46 females, aged 63.3±7.5 years (range, 47-81 years). According to the surgical procedure, they were divided into UBE group (42 cases), including 20 males and 22 females; aged 63.2±7.6 years (range, 47-81 years) and UE group (40 cases), including 16 males and 24 females; aged 63.5±7.5 years (range, 48-80 years). Operation time, hospital stay and surgical complications were compared between the two groups. Visual analogue scale (VAS) of low back and leg pain before surgery, 1 day, 7 d, 1 month and 6 months after surgery, and Oswestry disability index (ODI) before surgery, 1 month and 6 months after surgery were compared. Dural sac area before and after surgery, resection angle of ipsilateral facet joint, decompression rate of disc space and bone lateral recess were calculated.Results:All patients were operated successfully. In the UBE group, the operation time was 63.1±7.0 min, and the hospital stay was 3.9±0.9 d. The UE group was 61.2±6.2 min and 3.7±0.9 d, respectively ( t=1.31, P=0.195; t=1.24, P=0.217). The VAS of back and legs pain in UBE group decreased from 7.19±0.97 before operation to 3.43±0.63 points at postoperative 1 day, 1.71±0.60 at postoperative 7 d, 1.33±0.48 at postoperative 1 month and 1.36±0.48 points at postoperative 6 months ( F=352.29, P<0.001). The VAS score of the UE group decreased from 6.85±0.89 points before operation to 2.45±0.75 points at postoperative 1 day, 1.75±0.59 points at postoperative 7 d, 1.33±0.47 points at postoperative 1 month and 1.28±0.45 points at postoperative 6 months ( F=291.44, P<0.001). The VAS of low back and leg pain was higher in the UBE group than in the UE group at 1 day postoperatively ( t=6.41, P<0.001), and the difference was not statistically significant at 7 d postoperatively ( t=-0.27, P=0.786). The ODI of UBE group decreased from 66.62%±4.98% before operation to 21.81%±2.61% at postoperative 1 month and 11.62%±2.31% at postoperative 6 months ( F=1991.35, P<0.001). The ODI score of UE group decreased from 64.35%±5.16% before operation to 22.85%±3.26% at postoperative 1 month and 11.15%±2.86% at postoperative 6 months ( F=1931.18, P<0.001). The postoperative dural sac area of the UBE and UE groups was 135.1±10.0 mm 2 and 120.9±10.4 mm 2 ( t=6.30, P<0.001). The resection angle of ipsilateral facet joint was 69.3°±4.9° and 94.3°±4.1° in the two groups, respectively, with a statistically significant difference ( t=-25.00, P<0.001). The decompression rate of ipsilateral disk-flavum space was 39.0%±3.0% and 38.7%±3.3% in the two groups ( t=1.52, P=0.314). On the contralateral side was 41.6%±3.3% and 22.8%±3.2% ( t=26.32, P<0.001), respectively. The ipsilateral osseous side fossa decompression rate in the two groups were 70.0%±4.8% and 59.3%±3.9% ( t=15.64, P<0.001), the contralateral were 73.0%±3.4% and 48.4%±4.3% ( t=28.86, P<0.001). There was no significant difference in the decompression rate of ipsilateral disco-flavum space or bony lateral recess between the UBE group and the contralateral group ( t=-1.40, P=0.174; t=-1.72, P=0.096), while the decompression rate of discoflavum space and bony side recess on the ipsilateral side of UE group were higher than those on the contralateral side ( t=28.51, P<0.001; t=13.95, P<0.001). Conclusion:Both UE-ULBD and UBE-ULBD have good short-term clinical efficacy in patients with lumbar spinal stenosis. UB is better than UBE in early postoperative pain relief. However, UBE shows better imaging performance in decompression effect and better retention of facet joints.

Objective:To investigate the expression and clinical significance of plasma methylated SEPT9 (mSEPT9) gene in patients with primary liver cancer.Methods:393 cases who visited our hospital from May 2016 to October 2018 were selected. Among them, 75 cases were in the primary liver cancer (PLC) group, 50 cases were in the liver cirrhosis (LC) group, and 268 cases were in the healthy control group (HC). The three groups' positive rates of mSEPT9 expression in the peripheral plasma were detected by the polymerase chain reaction (PCR) fluorescent probe method. The correlational clinical features of liver cancer were analyzed. At the same time, the electrochemiluminescence detection method was used to compare the AFP positive rate. Statistical analysis was conducted using chi-square tests or continuity-corrected chi-square tests.Results:367 cases actually had valid samples. There were 64, 42, and 64 cases in the liver cancer group, cirrhosis group, and healthy control group, respectively. Among them, 34 cases of liver cancer were verified from pathological tissues. The positive rate of plasma mSEPT9 was significantly higher in the liver cancer group than that in the liver cirrhosis and healthy control groups [76.6% (49/64), 35.7% (15/42), and 3.8% (10/261), respectively], and the differences were statistically significant ( χ2 = 176.017, P < 0.001). The sensitivity of plasma mSEPT9 detection (76.6%) was significantly better in liver cancer (76.6%) than that of AFP patients (54.7%), and the difference was statistically significant ( χ2 = 6.788, P < 0.01). Compared with the single detection, the sensitivity and specificity of plasma mSEPT9 combined with AFP were significantly improved (89.7% vs. 96.3%, respectively). Patients with liver cancer aged≥50 years, with clinical stage II or above, and those with pathological signs of moderate to low differentiation had higher levels of plasma mSEPT9 positive expression, and the differences were statistically significant ( χ2 = 6.41, 9.279, 6.332, P < 0.05). During the follow-up period, the survival time of liver cancer patients with positive plasma mSEPT9 expression was significantly shorter than that of those with negative expression (310 ± 26 days vs. 487 ± 59 days, respectively), with statistically significant differences (Log Rank P = 0.039). Conclusion:In China, the positive rate of plasma mSEPT9 detection in liver cancer patients is higher than that of AFP in relation to age, clinical stage, and degree of tissue differentiation; additionally, it has certain survival predictive values. As a result, detecting this gene has important clinical significance and potential clinical application value in the non-invasive diagnosis and prognosis assessment of patients with primary liver cancer.

Early screening based on computed tomography (CT) pulmonary nodule detection is an important means to reduce lung cancer mortality, and in recent years three dimensional convolutional neural network (3D CNN) has achieved success and continuous development in the field of lung nodule detection. We proposed a pulmonary nodule detection algorithm by using 3D CNN based on a multi-scale attention mechanism. Aiming at the characteristics of different sizes and shapes of lung nodules, we designed a multi-scale feature extraction module to extract the corresponding features of different scales. Through the attention module, the correlation information between the features was mined from both spatial and channel perspectives to strengthen the features. The extracted features entered into a pyramid-similar fusion mechanism, so that the features would contain both deep semantic information and shallow location information, which is more conducive to target positioning and bounding box regression. On representative LUNA16 datasets, compared with other advanced methods, this method significantly improved the detection sensitivity, which can provide theoretical reference for clinical medicine.
Algorithms ; Humans ; Lung Neoplasms/diagnostic imaging* ; Neural Networks, Computer ; Radiographic Image Interpretation, Computer-Assisted/methods* ; Tomography, X-Ray Computed/methods*

Objective:To summarize the clinical manifestation and imaging of superficial siderosis of the central nervous system and explore the potential etiology.Methods:The clinical and imaging data of 7 patients diagnosed as superficial siderosis of the central nervous system in Peking Union Medical College Hospital from May 2013 to November 2019 were retrospectively reviewed. The etiology and follow-up prognosis through phone call were analyzed.Results:There were 7 patients included (3 male and 4 female) with an average age of 53 years (41-58 years). The cardinal manifestations were sensorineural deafness (all 7 cases), cerebellar ataxia (all 7 cases) and pyramidal signs (all 7 cases). Dizziness (6 cases), bladder disturbance (5 cases), headache (3 cases), double vision (2 cases) and congnitive impairment (1 case) could also happen. Magnetic resonance imaging showed symmetrical well-defined curvilinear homogeneous low signal on T 2 or blood-sensitive sequences (T 2* gradient echo or susceptibility-weighted imaging) over the superficial surface of cerebellar, brain stem, and spinal cord or cranio-cervical junction. All the 7 patients showed cerebellar atrophy especially the upper vermis. The potential causes included trauma history in 3 cases, intraspinal fluid-filled collection which indicated dural defect or duropathologies in 3 cases, intraspinal mass in 1 case and vertebral and disc degeneration in all 7 patients. The 5 patients who successsfully got follow-up showed exacerbation of variable degree. Conclusions:Classical superficial siderosis of the central nervous system is a rare disease with cardinal manifestation of progressive ataxia, sensorineural deafness and pyramidal signs. T 2WI of magnetic resonance imaging showing low signal over the superficial surface of cerebellar, brain stem, and spinal cord could indicate the diagnosis, and blood-sensitive sequences such as T 2* gradient echo or susceptibility-weighted imaging were more sensitive. Duropathologies or dural defect may be the most probable causes of the disease and should be examined and treated carefully.