Correlation analysis between HLA-DQA1*0102/DQB1*0602 genotypes and narcolepsy patients in China.

Background and objective: At present, the etiology of narcolepsy is not fully understood, and it is generally believed to be an autoimmune reaction caused by interactions between environmental and genetic factors. Human leukocyte antigen (HLA) class II genes are strongly associated with this gene, especially HLA-DQB1*0602/DQA1*0102. In this study, we mainly analyzed the correlation between different genotypes of HLA-DQB1*0602/DQA1*0102 and clinical manifestations in Chinese patients with narcolepsy. Experimental method: Narcolepsy patients who were treated at the Department of Neurology, The First Affiliated Hospital of Shandong First Medical University from January 2021 to September 2023 were selected. General information, sleep monitoring data, cerebrospinal fluid (CSF) orexin levels, and human leukocyte antigen gene typing data were collected. The statistical analysis was performed using SPSS 26.0, and the graphs were drawn using GraphPad Prism 9.5. Main results: A total of 78 patients were included in this study. The DQA1 and DQB1 gene loci were detected in 54 patients, and only the DQB1 gene locus was detected in 24 narcoleptic patients. The most common allele at the HLA-DQB1 locus was *0602 (89.7%), and the most common genotype at this locus was *0602*0301 (19.2%), followed by *0602*0602 (17.9%). The most common phenotype of the HLA-DQA1 locus is *0102 (92.6%), and the most common genotype of this locus is *0102*0102 (27.8%), followed by *0102*0505 (14.8%). There were significant differences (p < 0.05) between HLA-DQB1*0602-positive and HLA-DQB1*0602-negative patients in terms of orexin-A levels, presence or absence of cataplexy, UNS, PSG sleep latency, REM sleep latency, N1 sleep percentage, oxygen depletion index, and average REM latency on the MSLT. The HLA-DQA1*0102-positive and HLA-DQA1*0102-negative patients showed significant differences (p < 0.05) in disease course, presence or absence of sudden onset, PSG REM sleep latency, N1 sleep percentage, and average REM latency on the MSLT. There were significant differences in the average REM latency of the MSLT between HLA-DQB1*0602/DQA1*0102 homozygous and heterozygous patients p < 0.05, and no differences were found in the baseline data, orexin-A levels, scale scores, or other sleep parameters. Conclusion: Different genotypes of HLA-DQA1*0102/DQB1*0602 are associated with symptoms of cataplexy in Chinese narcoleptic patients. Homozygous individuals have a shorter mean REM latency in the MSLT, greater genetic susceptibility, and relatively more severe sleepiness.

Piezocatalytically-induced controllable mineralization scaffold with bone-like microenvironment to achieve endogenous bone regeneration.

Orderly hierarchical structure with balanced mechanical, chemical, and electrical properties is the basis of the natural bone microenvironment. Inspired by nature, we developed a piezocatalytically-induced controlled mineralization strategy using piezoelectric polymer poly-L-lactic acid (PLLA) fibers with ordered micro-nano structures to prepare biomimetic tissue engineering scaffolds with a bone-like microenvironment (pcm-PLLA), in which PLLA-mediated piezoelectric catalysis promoted the in-situ polymerization of dopamine and subsequently regulated the controllable growth of hydroxyapatite crystals on the fiber surface. PLLA fibers, as analogs of mineralized collagen fibers, were arranged in an oriented manner, and ultimately formed a bone-like interconnected pore structure; in addition, they also provided bone-like piezoelectric properties. The uniformly sized HA nanocrystals formed by controlled mineralization provided a bone-like mechanical strength and chemical environment. The pcm-PLLA scaffold could rapidly recruit endogenous stem cells, and promote their osteogenic differentiation by activating cell membrane calcium channels and PI3K signaling pathways through ultrasound-responsive piezoelectric signals. In addition, the scaffold also provided a suitable microenvironment to promote macrophage M2 polarization and angiogenesis, thereby enhancing bone regeneration in skull defects of rats. The proposed piezocatalytically-induced controllable mineralization strategy provides a new idea for the development of tissue engineering scaffolds that can be implemented for multimodal physical stimulation therapy.

ADSC-Exos enhance functional recovery after spinal cord injury by inhibiting ferroptosis and promoting the survival and function of endothelial cells through the NRF2/SLC7A11/GPX4 pathway.

BACKGROUND: Spinal cord injury (SCI) is a devastating disease that causes major motor, sensory and autonomic dysfunctions. Currently, there is a lack of effective treatment. In this study, we aimed to investigate the potential mechanisms of Exosomes from adipose-derived stem cells (ADSC-Exos) in reducing ferroptosis and promoting angiogenesis after spinal cord injury. METHODS: We isolated ADSC-Exos, the characteristics of which were confirmed. In vitro, we tested the potential of ADSC-Exos to promote the survival and function of human brain microvascular endothelial cells (HBMECs) and analyzed the ferroptosis of HBMECs. In vivo, we established rat models of SCI and locally injected ADSC-Exos to verify their efficacy. RESULTS: ADSC-Exos can reduce reactive oxygen species (ROS) accumulation and cell damage induced by an excessive inflammatory response in HBMECs. ADSC-Exos inhibit ferroptosis induced by excessive inflammation and upregulate the expression of glutathione peroxidase 4(GPX4) in HBMECs. It can also effectively promote proliferation, migration, and vessel-like structure formation. In vitro, ADSC-Exos improved behavioral function after SCI and increased the number and density of blood vessels around the damaged spinal cord. Moreover, we found that ADSC-Exos could increase nuclear factor erythroid-2-related factor 2(NRF2) expression and nuclear translocation, thereby affecting the expression of solute carrier family 7 member 11(SLC7A11) and GPX4, and the NRF2 inhibitor ML385 could reverse the above changes. CONCLUSION: Our results suggest that ADSC-Exos may inhibit ferroptosis and promote the recovery of vascular and neural functions after SCI through the NRF2/SLC7A11/GPX4 pathway. This may be a potential therapeutic mechanism for spinal cord injury.

The value of circadian heart rate variability for the estimation of obstructive sleep apnea severity in adult males.

OBJECTIVES: Heart rate variability (HRV) is becoming more prevalent as a measurable parameter in wearable sleep-monitoring devices, which are simple and effective instruments for illness evaluation. Currently, most studies on investigating OSA severity and HRV have measured heart rates during wakefulness or sleep. Therefore, the objective of this study was to investigate the circadian rhythm of HRV in male patients with OSA and its value for the estimation of OSA severity using group-based trajectory modeling. METHODS: Patients with complaints of snoring were enrolled from the Sleep Center of Shandong Qianfoshan Hospital. Patients were divided into 3 groups according to apnea hypopnea index (AHI in events/h), as follows: (<15, 15≤AHI<30, and ≥30). HRV parameters were calculated using 24 h Holter monitoring, which included time-domain and frequency-domain indices. Circadian differences in the standard deviation of normal to normal (SDNN) were evaluated for OSA severity using analysis of variance, trajectory analysis, and multinomial logistic regression. RESULTS: A total of 228 patients were enrolled, 47 with mild OSA, 48 moderate, and 133 severe. Patients with severe OSA exhibited reduced triangular index and higher very low frequency than those in the other groups. Circadian HRV showed that nocturnal SDNN was considerably higher than daytime SDNN in patients with severe OSA. The difference among the OSA groups was significant at 23, 24, 2, and 3 o'clock sharp between the severe and moderate OSA groups (all P<0.05). The heterogeneity of circadian HRV trajectories in OSA was strongly associated with OSA severity, including sleep structure and hypoxia-related parameters. Among the low-to-low, low-to-high, high-to-low, and high-to-high groups, OSA severity in the low-to-high group was the most severe, especially compared with the low-to-low and high-to-low SDNN groups, respectively. CONCLUSIONS: Circadian HRV in patients with OSA emerged as low daytime and high nocturnal in SDNN, particularly in men with severe OSA. The heterogeneity of circadian HRV revealed that trajectories with low daytime and significantly high nighttime were more strongly associated with severe OSA. Thus, circadian HRV trajectories may be useful to identify the severity of OSA.

Relationship between ODI and sleep structure of obstructive sleep apnea and cardiac remodeling.

PURPOSE: The purpose of the study was to evaluate the quantitative relationship between Oxygen Desaturation Index (ODI) and sleep structure of obstructive sleep apnea (OSA) and cardiac remodeling. METHODS: In this study, patients were enrolled from January 2015 to October 2022, and were divided into 3 groups according to AHI: patients with AHI < 15, patients with 15 ≤ AHI < 30, and 260 patients with AHI ≥ 30. Stratified linear regression was used to analyze independent risk factors for cardiac remodeling in OSA. RESULTS: A total of 479 patients were enrolled. We found that compared with AHI < 15 group (n = 120), the group with AHI > 30 (n = 260) had increased left atrial anteroposterior diameter, left ventricular end-diastolic internal diameter, left ventricular posterior wall thickness, right ventricular anteroposterior diameter, and interventricular septal thickness (P < 0.05). The group with 15 ≤ AHI ≤ 30 (n = 99) had increased left atrial anteroposterior diameter (P < 0.05). Multivariate linear regression revealed that N2 sleep was an independent risk factor for left ventricular posterior wall thickness, with positive correlation (p < 0.05). N3 sleep was an independent risk factor for transverse right atrial diameter and right ventricular anteroposterior diameter, with negative correlation (P < 0.05). ODI was an independent risk factor for interventricular septal thickness, with positive correlation (P < 0.05). The arousal index was an independent risk factor for increased left atrial anteroposterior diameter, with positive correlation (P < 0.05). CONCLUSIONS: Increased ODI is an independent risk factor for interventricular septal thickness, while decreased slow wave sleep is an independent risk factor for right heart remodeling in OSA.

The effect of obstructive sleep apnea on fatty liver disease may be obscured by alcohol consumption: An ordinal logistic regression analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is closely associated with non-alcoholic fatty liver disease (NAFLD). The current definition of NAFLD cannot exclude the involvement of alcohol consumption in the development of fatty liver disease (FLD), but alcohol can aggravate OSA and participate in steatosis. There is limited evidence on the relationship between OSA and alcohol and its effect on FLD severity. OBJECTIVE: To determine the effect of OSA on FLD severity based on ordinal responses, and its relationship with alcohol consumption, in order to develop strategies for the prevention and treatment of FLD. METHODS: Patients with chief complaints of "snoring" who underwent polysomnography and abdominal ultrasound between January 2015 and October 2022 were selected. A total of 325 cases were divided into three groups according to abdominal ultrasound results: no FLD (n = 66), mild FLD (n = 116), and moderately severe FLD (n = 143) group. Patients were also categorized into alcoholic and nonalcoholic groups. Univariate analysis was used to examine the correlation between OSA and FLD severity. Multivariate ordinal logistic regression analysis was further used to identify the determinants of FLD severity and differences between the alcoholic and nonalcoholic groups. RESULTS: A higher proportion of moderately severe FLD was observed in the group with an apnea/hypopnea index (AHI) > 30 compared to the AHI<15 group in all participants and in the nonalcoholic population (all p < 0.05). There was no significant difference among these groups in the alcoholic population. Ordinal logistic regression analysis found that in all participants, age [OR = 0.966(0.947-0.986)], BMI [OR = 1.293 (1.205-1.394)], diabetes mellitus [OR = 1.932(1.132-3.343)], hyperlipidemia [OR = 2.432(1.355-4.464)], severe OSA [OR = 2.36(1.315-4.259)] (all p < 0.05) were the independent risk factors for more severe FLD. However, different risk factors applied according to alcohol consumption. In addition to age and BMI, the independent risk factors for the alcoholic group also included diabetes mellitus [OR = 3.323(1.494-7.834)] while in the non-alcoholic group risk factors included hyperlipidemia [OR = 4.094(1.639-11.137)], and severe OSA[OR = 2.956(1.334-6.664)] (all p < 0.05). CONCLUSION: Severe OSA is an independent determinant for developing more severe NAFLD in nonalcoholic population, and alcohol consumption may obscure the effect of OSA on the progression of FLD.

The Impact of Sleep Pattern in School/Work Performance During the COVID-19 Home Quarantine in Patients With Narcolepsy.

Objectives: Narcolepsy patients were observed improvements in their academic performance during the COVID-19 home quarantine. Therefore, we aim to investigate the influence of sleep behavioral changes on school/work performance in narcolepsy patients during the home quarantine. Methods: Patients admitted to Shandong Provincial Qianfoshan Hospital from Jan 1, 2017 to Jan 1, 2021 who were diagnosed with narcolepsy were studied by online questionnaires in two different periods (during and 1 year after the COVID-19 home quarantine), including five aspects: (1) changes in school/work performance (percentile ranking in class/Sheehan Disability Scale 1, SDS1); (2) daytime functions; (3) clinical symptoms; (4) psychological moods; (5) medication situations. Results: A total of 46 narcolepsy patients 34 (73.9%) narcolepsy type 1, 12 (26.1%) narcolepsy type 2 with average age of 20.76 ± 8.99 years and an equal number of age and gender matched control subjects were enrolled. During the COVID-19 home quarantine, the narcolepsy patients were found that they altered sleep patterns, including later get up time (P < 0.001), longer total sleep time (TST, P = 0.001), better sleep quality (PSQI, P = 0.001), and lower anxiety level (P = 0.005). Their school/work performance improved parallelly [with better percentile ranking (P = 0.001) and lower SDS1 scores (P = 0.002)]. The results of multiple linear stepwise regression analysis showed a linear regression relationship between TST [efficient (95%) -7.356 (-13.570 to 1.143)], SDS1 score [efficient (95%) 6.580 (2.346-10.815), P = 0.004] and the percentile ranking after adjusting for potential effects. Both the improvements of sleep behavior and school/work performance disappeared after the end of COVID-19 home quarantine. No similar fluctuation was found in the control group. Discussion: Changes in sleep pattern during the COVID-19 home quarantine, such as longer sleep time and later wake-up time, can reduce the degree of daytime sleepiness and increase the degree of daytime wakefulness of narcolepsy patients, which can alleviate the impact of the disease on school/work performance.

Percutaneous Transforaminal Endoscopic Debridement and Drainage with Accurate Pathogen Detection for Infectious Spondylitis of the Thoracolumbar and Lumbar Spine.

OBJECTIVE: In this study, we aimed to analyze the clinical outcomes of percutaneous transforaminal endoscopic debridement and drainage (PTEDD) with accurate pathogen detection for patients with infectious spondylitis of the thoracolumbar and lumbar spines. METHODS: From January 2017 to February 2019, a consecutive series of 43 patients with infectious spondylitis of the thoracolumbar and lumbar spine were surgically treated with PTEDD. Organism culture, next-generation DNA sequencing, and pathological examination of the sample extracted from the infectious site were performed for accurate microbiological diagnosis. All patients were followed up for 24-36 months. Clinical and radiological outcomes were analyzed preoperatively and postoperatively. RESULTS: Surgeries were completed successfully on all 43 patients under local infiltration anesthesia. Positive culture of the responsible organism was obtained in 33 cases (76.7%). Among the 43 patients who underwent next-generation DNA sequencing, 42 (97.7%) had positive results. Corresponding antibiotic medication was given based on the pathogen detection. The modified Macnab criteria were found to be excellent in 32 patients (74.4%) and good in 11 (25.6%). Postoperative magnetic resonance imaging showed that the abscess and infectious area were reduced significantly at 3 months and had disappeared or almost disappeared at the final follow-up. Spontaneous fusion was obtained in 30 patients (69.8%). No patients required revision or conversion to open debridement and reconstruction. CONCLUSIONS: For patients with infectious spondylitis of the thoracolumbar and lumbar spine, PTEDD is an effective and safe treatment. Next-generation DNA sequencing is a much more sensitive method for detecting the responsible organisms.

Progranulin Promotes Functional Recovery in Rats with Acute Spinal Cord Injury via Autophagy-Induced Anti-inflammatory Microglial Polarization.

Since microglia-associated neuroinflammation plays a critical role in the progression of acute spinal cord injury, modulation of microglial activation has been suggested as a potential therapeutic strategy. Progranulin has been reported to exert neuroprotective effects by attenuating neuroinflammation, but whether these effects are due to the modulation of microglial polarization and the underlying mechanism remain unclear. Here, we investigated the effect of progranulin on microglial polarization and analyzed the crosstalk between microglial autophagy and polarization. We found that progranulin could reduce proinflammatory cytokine production at the lesion site and promote locomotor functional recovery after acute spinal cord injury. In vitro, we found that progranulin could activate microglia to acquire an anti-inflammatory phenotype and express IL-10. Moreover, progranulin-mediated enhancement of anti-inflammatory microglial polarization was attributed to the protection of lysosomal function and the enhancement of autophagic flux. Above all, progranulin exerts anti-inflammatory effects by protecting lysosomal function to enhance microglial autophagy, induce M2 microglial polarization, and ultimately improve neurological function after acute spinal cord injury. These results suggest that targeting the autophagy-lysosomal pathway to modulate microglial polarization and reduce neuroinflammation is a potential treatment for spinal cord injury.

Epidemiological Study of Lung Cancer and Clinical Medication in England from 2001 to 2019.

We aimed to explore the epidemiological characteristics and changes of lung cancer and the clinical medication in England from 2001 to 2019. We searched related research using search engine systems such as MEDLINE, PubMed, and PsychINFO. Lung cancer is a serious disease and the prognosis is usually very poor. The overall mortality rate of lung cancer decreased year by year in England from 2001 to 2019, but men, the elderly, and people exposed to polluted air are still more likely to be infected with lung cancer or die as a result, the prevalence and mortality rate of lung cancer in the north of England is significantly higher than that in the south, and the gap is increasing year by year. Lung cancer has changeable risk factors such as quitting smoking and improving air quality, which can effectively reduce the related risk. Paclitaxel, docetaxel, gemcitabine, and vinorelbine are the main drugs for the treatment of lung cancer in England and the treatment of these drugs is beneficial to the survival and quality of life of patients. Men and the elderly are at high risk of lung cancer, which means that lung cancer has obvious gender inequality and age inequality. At the same time, based on the statistical data of lung cancer risk in different regions, it can be concluded that lung cancer also has strong geographical and economic inequality. Changing risk factors and using drugs can effectively reduce the risk of lung cancer and provide effective treatment.

Unraveling the Proteomic Landscape of Intestinal Epithelial Cell-Derived Exosomes in Mice.

Purpose: This study aimed to identify the biological functions of small intestine intestinal epithelial cell derived exosomes (IEC-Exos) and further distinguished the difference proteins in IEC-Exos between ileum and jejunum related to function of the digestive system and occurrence of several diseases. Materials and Methods: IECs of Male C57BL/6J mice were isolated. IEC-Exos were extracted from jejunum and ileum epithelial cell culture fluid by ultracentrifugation. In addition, isobaric tags for relative and absolute quantitation (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to detect IEC-Exo proteins and conduct biological information analysis. Results: The results showed that compared with jejunum IEC-Exos from ileum IEC-Exos, there were 393 up-regulated proteins and 346 down-regulated proteins. IECs-Exos, especially derived from jejunum, were rich in angiotensin-converting enzyme 2 (ACE2). The highly expressed proteins from ileum IEC-Exos were mostly enriched in genetic information processing pathways, which mainly mediate the processes of bile acid transport, protein synthesis and processing modification. In contrast, the highly expressed proteins from jejunum IEC-Exos were mainly enriched in metabolic pathways involved in sugar, fatty acid, amino acid, drug, and bone metabolism, etc. The differentially expressed proteins between ileum and jejunum IEC-Exos were not only related to the function of the digestive system but also closely related to the occurrence of infectious diseases, endocrine diseases and osteoarthritis, etc. Conclusion: IEC-Exos there were many differentially expressed proteins between ileum and jejunum, which played different roles in regulating intestinal biological functions. ACE2, the main host cell receptor of SARS-CoV-2, was highly expressed in IEC-Exos, which indicated that IEC-Exos may be a potential route of SARS-CoV-2 infection.

Effects of Escin on Oxidative Stress and Apoptosis of H9c2 Cells Induced by H2O2.

OBJECTIVE: Myocardial infarction (MI) is a serious heart health problem in the world with a high mortality rate. Our study is mainly aimed at validating the antioxidative stress and antiapoptotic effects of escin in a H2O2-induced cardiomyocyte injury model. METHODS: H9c2 cells were divided into control group, H2O2 treatment group, and H2O2+escin group. We studied the effect of escin on H9c2 cells and its mechanism by flow cytometry, real-time PCR, CCK-8 assay and Western blot. Cell morphology was observed by cell staining and optical microscopy. RESULTS: We found that the level of reactive oxygen species (ROS) in the H2O2 treatment group was significantly elevated, while the high level of ROS was significantly reversed after treatment with escin. The protein levels of SOD1, SOD2, Bcl-2, and IκB-α in the H2O2 treatment group were significantly decreased compared with the H2O2+escin group, and the Bax, TNF-α, IL-1ß, p65, and IκKα protein expressions were greatly higher than those in the H2O2+escin group. And the results of PCR were also consistent with those. TUNEL-positive cells also decreased significantly when treated with escin. Flow cytometry showed that the percentage of apoptotic cells decreased greatly after treatment of escin. Through IL-1ß immunofluorescence, the fluorescence intensity of the H2O2 treatment group was greatly higher compared with that of the control group, but escin reversed this effect. CONCLUSIONS: These results indicated that escin inhibits H2O2-induced H9c2 cell apoptosis, oxidative stress, and inflammatory responses via the NF-κB signaling pathway.

Identification and Validation of an Annexin-Related Prognostic Signature and Therapeutic Targets for Bladder Cancer: Integrative Analysis.

Abnormal expression and dysfunction of Annexins (ANXA1-11, 13) have been widely found in several types of cancer. However, the expression pattern and prognostic value of Annexins in bladder cancer (BC) are currently still unknown. In this study, survival analysis by our in-house OSblca web server revealed that high ANXA1/2/3/5/6 expression was significantly associated with poor overall survival (OS) in BC patients, while higher ANXA11 was associated with increased OS. Through Oncomine and GEPIA2 database analysis, we found that ANXA2/3/4/13 were up-regulated, whereas ANXA1/5/6 were down-regulated in BC compared with normal bladder tissues. Further LASSO analysis built an Annexin-Related Prognostic Signature (ARPS, including four members ANXA1/5/6/10) in the TCGA BC cohort and validated it in three independent GEO BC cohorts (GSE31684, GSE32548, GSE48075). Multivariate COX analysis demonstrated that ARPS is an independent prognostic signature for BC. Moreover, GSEA results showed that immune-related pathways, such as epithelial-mesenchymal transition and IL6/JAK/STAT3 signaling were enriched in the high ARPS risk groups, while the low ARPS risk group mainly regulated metabolism-related processes, such as adipogenesis and bile acid metabolism. In conclusion, our study comprehensively analyzed the mRNA expression and prognosis of Annexin family members in BC, constructed an Annexin-related prognostic signature using LASSO and COX regression, and validated it in four independent BC cohorts, which might help to improve clinical outcomes of BC patients, offer insights into the underlying molecular mechanisms of BC development and suggest potential therapeutic targets for BC.

Genetically modified mesenchymal stem cells promote spinal fusion through polarized macrophages.

Spinal fusion is an effective treatment for low back pain and typically applied with prosthetic fixation devices. Spinal fusion can be improved by transplantation of mesenchymal stem cells (MSCs) into the paraspinal muscle. However, in contrast to the direct contribution of MSCs to spinal fusion, the indirect effects of MSCs on spinal infusion have not been studied and were thus addressed here. The correlation between the outcome of spinal fusion and the local macrophage number, polarization and the levels of placental growth factor (PlGF) in patients was analyzed. MSCs were genetically modified to overexpress PlGF, and its effects on macrophage proliferation and polarization were analyzed in vitro in a transwell co-culture system, as well as in vivo in a mouse model for spinal fusion, for which the cells were bilaterally injected into paravertebral muscles of the mouse lumbar spine. The effects on spinal fusion were assessed by microcomputed tomography and a custom four-point bending apparatus for structural bending stiffness. Local macrophages were analyzed by flow cytometry. We found that posterior spinal fusion could be improved by PlGF-expressing MSCs, compared to the control MSCs, evident by significant improvement of bone bridging of the targeted vertebrae. Mechanistically, PlGF-expressing MSCs appeared to attract macrophages and induce their M2 polarization, which in turn promotes the bone formation. Together, our data suggest that PlGF-expressing MSCs may improve spinal fusion through macrophage recruitment and polarization.

Bilateral triceps tendon approach is flexible and efficient in the treatment of type C distal humerus fractures.

PURPOSE: The purpose of this study was to assess and compare elbow range of motion, triceps extension strength and functional results of type C (AO/OTA) distal humerus fractures treated with bilateral triceps tendon (BTT) approach and olecranon osteotomy (OO). At the same time, we are also trying to know whether BTT approach can provide sufficient vision for comminuted intra-articular fractures of the distal humerus, and whether it is convenient to convert to the treatment to total elbow arthroplasty (TEA) or OO. METHODS: Patients treated with OO and BTT approaches for type C distal humerus fractures between July 2014 and December 2017 were retrospectively reviewed. Inclusion criteria include: (1) patients' age were more than 18 years old, (2) follow-up was no less than 6 months, and (3) patients were diagnosed with type C fractures (based on the AO/OTA classification). Exclusion criteria include: (1) open fractures (Gustillo type 2 or type 3), (2) treated by other approaches, and (3) presented with combined injuries of ipsilateral upper extremities, such as ulnar nerve. Elbow range of motion and triceps extension strength testing were completely valuated, when the fractures had healed. Assessment of functional results using the Mayo elbow performance score and complications were conducted in final follow-up. The data were compared using the two tailed Student's t-test. All data were presented as mean ± standard deviation. RESULTS: Eighty-six patients of type C distal humerus fractures, treated by OO and BTT approach were retrospectively reviewed between July 2014 and December 2017. Fifty-five distal humerus fractures (23 males and 32 females, mean age 52.7 years) treated by BTT approach or OO were included in this study. There were 10 fractures of type C1, 16 type C2 and 29 type C3 according to the AO/OTA classification. Patients were divided into two surgical approach groups chosen by the operators: BTT group (28 patients) and OO group (27 patients). And the mean follow-up time of all patients was 15.6 months (range, 6-36 months). Three cases in BTT group were converted to TEA, and one converted to OO. Only one case in BTT group presented poor articular reduction with a step more than 2 mm. There were not significantly different in functional outcomes according to the Mayo elbow performance score, operation time and extension flexion motion are values between BTT group and OO group (p > 0.05). Complications and reoperation rate were also similar in the two groups. Triceps manual muscle testing were no significant difference in the two groups, even subdivided in elder patients (aged >60 years old). CONCLUSION: BTT is a safe approach to achieve similar functional result comparing with OO. BTT were not suitable for every case with severe comminuted pattern, but it avoids the potential complications related to OO, and has no complications concerning with triceps tendon. It is convenient for open reduction internal fixation and flexible to be converted to OO, as well as available to be converted to TEA in elder patients.

Exploration of sleep function connection and classification strategies based on sub-period sleep stages.

Background: As a medium for developing brain-computer interface systems, EEG signals are complex and difficult to identify due to their complexity, weakness, and differences between subjects. At present, most of the current research on sleep EEG signals are single-channel and dual-channel, ignoring the research on the relationship between different brain regions. Brain functional connectivity is considered to be closely related to brain activity and can be used to study the interaction relationship between brain areas. Methods: Phase-locked value (PLV) is used to construct a functional connection network. The connection network is used to analyze the connection mechanism and brain interaction in different sleep stages. Firstly, the entire EEG signal is divided into multiple sub-periods. Secondly, Phase-locked value is used for feature extraction on the sub-periods. Thirdly, the PLV of multiple sub-periods is used for feature fusion. Fourthly, the classification performance optimization strategy is used to discuss the impact of different frequency bands on sleep stage classification performance and to find the optimal frequency band. Finally, the brain function network is constructed by using the average value of the fusion features to analyze the interaction of brain regions in different frequency bands during sleep stages. Results: The experimental results have shown that when the number of sub-periods is 30, the α (8-13 Hz) frequency band has the best classification effect, The classification result after 10-fold cross-validation reaches 92.59%. Conclusion: The proposed algorithm has good sleep staging performance, which can effectively promote the development and application of an EEG sleep staging system.

The Conditioned Medium of Lactobacillus rhamnoides GG Regulates Microglia/Macrophage Polarization and Improves Functional Recovery after Spinal Cord Injury in Rats.

Lactobacillus rhamnoides, a human intestinal colonizer, can act through various pathways to induce microglia/macrophages to produce cytokines and to polarize microglia/macrophages to different phenotypes to reduce the inflammatory response. In this article, we evaluated the treatment potential of the Lactobacillus rhamnoides GG conditioned medium (LGG-CM) in rat model with SCI (acute spinal cord injury), including functional, neurophysiological, and histological outcomes and the underlying neuroprotective mechanisms. In our experiment, LGG-CM (30 mg/kg) was injected directly into the injury site in rats immediately after SCI. Measured by the BBB scale (Basso, Beattie, and Bresnahan locomotor rating scale) and inclined plane test, rats in the LGG-CM-treated group showed better locomotor scores. Moreover, compared to the vehicle treatment group, LGG-CM increased the mRNA level of the M2 marker (CD206), and decreased that of the M1 marker (iNOS). Western blot assays showed that LGG-CM-treated SCI rats had a higher grayscale ratio of p65 and a lower ratio of p-IκBα/IκBα. Our study shows that local injection of LGG-CM after acute SCI can inhibit inflammatory responses and improve motor function recovery. These effects may be related with the inhibition to the NF-κB (The nuclear factor-kappa B) signal pathway which leads to M2 microglia/macrophage polarization.

Macrophage-mediated degradable gelatin-coated mesoporous silica nanoparticles carrying pirfenidone for the treatment of rat spinal cord injury.

The treatment of spinal cord injury is still a challenge worldwide; there is still no effective method. Our strategy is to devise a macrophage-mediated degradable gelatin coated mesoporous silica nanoparticles, which could carry pirfenidone and realize spatiotemporal control of pirfenidone release in the lesion site. For the in vivo experiment, three groups of SD rats subjected to spinal cord contusion injury were injected with GNS-PFD, PFD or PBS. Spinal cord functions were observed. In vitro, we investigated the expression of inflammatory and anti-inflammatory factors. Spinal cord function and recovery were better in the GSN-PFD and PFD than the control group. In the in vitro study, the MMPs after SCI in lesion site were lower in the experimental group. Moreover, the expression of anti-inflammatory and inflammatory factors showed better in the experimental group. The inflammatory response of the PFD to time and space can be achieved with the loading of macrophage-mediated degradable gelatin coated mesoporous silica nanoparticles.

Peripheral Macrophage-derived Exosomes promote repair after Spinal Cord Injury by inducing Local Anti-inflammatory type Microglial Polarization via Increasing Autophagy.

Treatment for spinal cord injury (SCI) remains a challenge worldwide, and inflammation is a major cause of secondary injury after SCI. Peripheral macrophages (PMs) have been verified as a key factor that exert anti-inflammatory effects after SCI, but the mechanism is unidentified. As local macrophages, microglia also exert significant effects after SCI, especially polarization. Exosomes show source cell-like biological functions to target cells and have been the subject of much research in recent years. Thus, we hypothesized the PM-derived exosomes (PM-Exos) play an important role in signal transmission with local microglia and can be used therapeutic agents for SCI in a series of in vivo and in vitro studies. For the in vivo experiment, three groups of Sprague-Dawley (SD) rats subjected to spinal cord contusion injury were injected with 200 µg/ml PM-Exos, 20 µg/ml PM-Exos or PBS via the tail vein. Recovery of the rats and of spinal cord function were observed. In vitro, we investigated the potential anti-inflammatory mechanism of PM-Exos and evaluated microglial autophagy, anti-inflammatory type microglia polarization and the upstream signaling pathway. The results showed that spinal cord function and recovery were better in the PM-Exo groups than the control group. In the in vitro study, microglial autophagy levels and the expression of anti-inflammatory type microglia were higher in the experimental groups than the control group. Moreover, the expression of proteins related to the PI3K/AKT/mTOR autophagic signaling pathway was suppressed in the PM-Exo groups. PM-Exos have a beneficial effect in SCI, and activation of microglial autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway, enhancing the polarization of anti-inflammatory type microglia, that may play a major role in the anti-inflammatory process.