[Treatment of Tile type C pelvic ring fracture using orthopedic robot combined with Starr pelvis reduction frame].

OBJECTIVE: To investigate the clinical effect of orthopedic robot combined with Starr pelvic reduction frame in the treatment of Tile type C pelvic ring fracture. METHODS: From October 2019 to May 2021, 14 patients with type C pelvic ring fracture were treated with robotic combined with Starr pelvic reduction frame, including 9 males and 5 females. The age ranged from 33 to 69 years. All the 14 patients had fresh closed fractures without femur, tibia and fibula fracture. Surgery was completed from 4 to 7 d after hospital admission. During the operation, the X-ray carbon bed was used, the pelvic ring was reduced by Starr pelvis reduction frame, and pelvic ring fracture was treated by orthopedic robot. Operation time, bleeding volume, fluoroscopy times of single screw placement, fracture reduction quality, affected limb function and complications were observed. Radiological reduction was evaluated using Matta scoring standard, and clinical efficacy was evaluated by Majeed pelvic function scoring system at the final follow-up. RESULTS: All of 14 patients successfully completed the operation, the operation time was 84 to 141 min, the bleeding volume was 20 to 50 ml, and the fluoroscopy times of single screw insertion was 4 to 9 times. All of 14 patients were followed up for 12 to 24 months. The healing time was 3 to 7 months. No complications such as fracture of internal fixation, screw loosening, infection and nerve injury were found. According to the evaluation criteria of Matta imaging reduction, 9 cases were excellent, 4 cases were good, and 1 case was fair. At the final follow-up, Majeed pelvic function scoring system was used:10 cases were excellent, 4 cases were good. CONCLUSION: The treatment of type C pelvic ring fracture with robotic combined Starr pelvis reduction frame is simple, time-saving, less trauma, less complications and effective.

The clinical significance and prognostic value of serum beta-2 microglobulin in adult lymphoma-associated hemophagocytic lymphohistiocytosis: a multicenter analysis of 326 patients.

To investigate the prognostic impact of serum beta-2 microglobulin (B2M) in adult lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). The clinical and laboratory characteristics of 326 adult patients in a multicenter cohort with lymphoma-associated HLH with available baseline serum B2M levels were retrospectively analyzed. A total of 326 cases were included in this study, and the median serum B2M level was 5.19 mg/L. The optimal cut-off of serum B2M was 8.73 mg/L, and the cases with serum B2M level >8.73 mg/L were older and had a more advanced stage, lower levels of platelets, albumin, and fibrinogen, and higher creatinine level. The serum B2M >8.73 mg/L, creatinine ≥133 µmol/L, fibrinogen ≤1.5 g/L, agranulocytosis (<0.5 × 109/L), severe thrombocytopenia (<50 × 109/L), and high Epstein-Barr virus DNA copy number were found to have independent prognostic values in all patients, and the serum B2M >8.73 mg/L was also an independent prognostic factor in patients with creatinine <133 µmol/L. Finally, a prognostic scoring system was established based on independent prognostic factors of all patients and categorized the patients into three groups with significant prognostic differences. This study confirmed that the serum B2M level can be an independent prognostic factor in lymphoma-associated HLH and established a prognostic scoring system to predict patients' survival.

OXCT1 regulates hippocampal neurogenesis and alleviates cognitive impairment via the Akt/GSK-3ß/ß-catenin pathway after subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a life-threatening neurological disease that usually has a poor prognosis. Neurogenesis is a potential therapeutic target for brain injury. Ketone metabolism also plays neuroprotective roles in many neurological disorders. OXCT1 (3-Oxoacid CoA-Transferase 1) is the rate-limiting enzyme of ketone body oxidation. In this study, we explored whether increasing ketone oxidation by upregulating OXCT1 in neurons could promote neurogenesis after SAH, and evaluated the potential mechanism involved in this process. METHODS: The ß-hydroxybutyrate content was measured using an enzymatic colorimetric assay. Adeno-associated virus targeting neurons was injected to overexpress OXCT1, and the expression and localization of proteins were evaluated by western blotting and immunofluorescence staining. Adult hippocampal neurogenesis was evaluated by dual staining with doublecortin and 5-Ethynyl-2'-Deoxyuridine. LY294002 was intracerebroventricularly administered to inhibit Akt activity. The Morris water maze and Y-maze tests were employed to assess cognitive function after SAH. RESULTS: The results showed that OXCT1 expression and hippocampal neurogenesis significantly decreased in the early stage of SAH. Overexpression of OXCT1 successfully increased hippocampal neurogenesis via activation of Akt/GSK-3ß/ß-catenin signaling and improved cognitive function, both of which were reversed by administration of LY294002. CONCLUSIONS: OXCT1 regulated hippocampal ketone body metabolism and increased neurogenesis through mechanisms mediated by the Akt/GSK-3ß/ß-catenin pathway, improving cognitive impairment after SAH.

The temporal effect of uncertain context on the perceptual processing of painful and non-painful stimulation.

Uncertainty has been demonstrated to influence the perception of noxious stimuli, but little is known about the effects of prolonged uncertain contexts on the perception of painful and non-painful stimuli. To address this knowledge gap, the present study utilized a cue-based NPU-threat task, where uncertain and certain trials were separated into distinct blocks. The objective was to investigate the impact of uncertain contexts on the temporal dynamics of electroencephalogram (EEG) activity during the processing of painful and non-painful stimuli. The results revealed that the influence of uncertain contexts on neural responses extends beyond painful trials and is also evident in non-painful trials. In uncertain contexts, it has been observed that painful stimuli elicit larger P2 amplitudes and late beta band (13-30 Hz) event-related desynchronization (ERD) around 500-700 ms. However, in certain contexts, painful stimuli evoke stronger late gamma band (50-70 Hz) event-related synchronization (ERS) around 600-700 ms. For non-painful trials, in uncertain contexts, significantly higher amplitudes of the late positive potential (LPP) component and delta-theta band (2-7 Hz) ERS were observed compared to certain non-painful stimuli. These findings demonstrate that uncertain contexts exert a significant impact on the processing of both painful and non-painful stimuli, and this influence is mediated by distinct neural mechanisms.

[Clinical analysis of posterior axillary approach internal fixation for Idebergâ a andâ ¡glenoid fractures].

OBJECTIVE: To investigate the efficacy of posterior axillary approach internal fixation for Ideberg Ⅰa andⅡ glenoid fractures. METHODS: From December 2018 to September 2021, 9 patients with lower part of glenoid fractures were treated by posterior axillary approach, including 3 males and 6 females, aged from 50 to 78 years old. All the fractures were closed fractures. According to Ideberg type of scapular glenoid fracture was type Ⅰa in 6 cases and type Ⅱ in 3 cases. AP and lateral X-ray films of scapula were taken at 6, 12 weeks and 6 and 12 months postoperatively. Constant-Murley and disabilities of the arm shoulder and hand (DASH), and other complications were recorded at the latest follow-up. RESULTS: Nine patients were followed up, ranged from 6 to 15 months. And bone healing was achieved in all 9 patients at the final follow-up, the healing time 3 to 6 months, Constant-Murley score at the final follow-up ranged from 55 to 96, and DASH score ranged from 3.33 to 33.33. Both of them were better than preoperative. CONCLUSION: The posterior axillary approach internal fixation for Ideberg Ⅰa and Ideberg Ⅱ Glenoid fractures scapular fracture is satisfactory and worthy of clinical application.

Measuring Sleep Stages and Screening for Obstructive Sleep Apnea with a Wearable Multi-Sensor System in Comparison to Polysomnography.

Objective: To assess the performance of a wearable multi-sensor system (SensEcho) in comparison to polysomnography (PSG) in measuring sleep stages and searching for obstructive sleep apnea (OSA). Methods: Participants underwent overnight simultaneous monitoring using SensEcho and PSG in a sleep laboratory. SensEcho analyzed the recordings spontaneously, and PSG was assessed as per standard guidelines. The degree of snoring was evaluated according to the guidelines for the diagnosis and treatment of OSA hypopnea syndrome (2011 revision). The Epworth Sleepiness Scale (ESS) was used to assess general daytime sleepiness. Results: This study included 103 Han Chinese, 91 of whom (age 39.02 ± 13.84 years, body mass index 27.28 ± 5.12 kg/m2, 61.54% male) completed the assessments. The measures of total sleep time (P = 0.198); total wake time (P = 0.182); shallow sleep (P = 0.297), deep sleep (P = 0.422), rapid eye movement sleep (P = 0.570), and awake (P = 0.336) proportions were similar between SensEcho and PSG. Using an apnea-hypopnea index (AHI) cutoff of ≥ 5 events/h, the SensEcho had 82.69% sensitivity and 89.74% specificity. Almost the same results were obtained at an AHI threshold of ≥ 15 events/h. Although the specificity increased to 94.67%, it decreased to 43.75% at an AHI cutoff of ≥ 30 events/h. Conclusion: This study demonstrated that SensEcho can be used to evaluate sleep status and screen for OSA. Nevertheless, improving the accuracy of its assessment of severe OSA and further testing its effectiveness in community and home environments is necessary.

Increased NOX2 expression in astrocytes leads to eNOS uncoupling through dihydrofolate reductase in endothelial cells after subarachnoid hemorrhage.

Introduction: Endothelial nitric oxide synthase (eNOS) uncoupling plays a significant role in acute vasoconstriction during early brain injury (EBI) after subarachnoid hemorrhage (SAH). Astrocytes in the neurovascular unit extend their foot processes around endothelia. In our study, we tested the hypothesis that increased nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression in astrocytes after SAH leads to eNOS uncoupling. Methods: We utilized laser speckle contrast imaging for monitoring cortical blood flow changes in mice, nitric oxide (NO) kits to measure the level of NO, and a co-culture system to study the effect of astrocytes on endothelial cells. Moreover, the protein levels were assessed by Western blot and immunofluorescence staining. We used CCK-8 to measure the viability of astrocytes and endothelial cells, and we used the H2O2 kit to measure the H2O2 released from astrocytes. We used GSK2795039 as an inhibitor of NOX2, whereas lentivirus and adeno-associated virus were used for dihydrofolate reductase (DHFR) knockdown in vivo and in vitro. Results: The expression of NOX2 and the release of H2O2 in astrocytes are increased, which was accompanied by a decrease in endothelial DHFR 12 h after SAH. Moreover, the eNOS monomer/dimer ratio increased, leading to a decrease in NO and acute cerebral ischemia. All of the above were significantly alleviated after the administration of GSK2795039. However, after knocking down DHFR both in vivo and in vitro, the protective effect of GSK2795039 was greatly reversed. Discussion: The increased level of NOX2 in astrocytes contributes to decreased DHFR in endothelial cells, thus aggravating eNOS uncoupling, which is an essential mechanism underlying acute vasoconstriction after SAH.

Neuroprotective mechanisms of OXCT1 via the SIRT3-SOD2 pathway after traumatic brain injury.

BACKGROUND: Ketones are not only utilized to produce energy but also play a neuroprotective role in many neurodegenerative diseases. However, whether this process has an impact on secondary brain damage after traumatic brain injury (TBI) remains unknown. OXCT1 (3-Oxoacid CoA-Transferase 1) is the rate-limiting enzyme in the intra-neuronal utilization of ketones. In this study, we investigated whether reduced expression of OXCT1 after TBI could impact neuroprotective mechanisms and exacerbate neurological dysfunction. MATERIALS AND METHODS: Experimental TBI was induced by a modified version of the weight drop model, it is a model of severe head trauma. Expression of OXCT1 in the injured hippocampus of mice was measured at different time points using immunoblotting assays. The release of abnormal mitochondrial cytochrome c from neurons of the mouse injured lateral hippocampus was measured 1 week after TBI using immunoblotting assays. Neuronal death was assessed by Nissl staining and the level of reactive oxygen species (ROS) within the neurons of the injured lateral hippocampus was assessed by Dihydroethidium staining. RESULTS: OXCT1 was overexpressed in hippocampal neurons by injection of adeno-associated virus into the lateral ventricle. OXCT1 expression levels decreased significantly 1 week post-TBI. After comparing the data obtained from different groups of mice, OXCT1 was found to significantly increase the expression of SIRT3 and reduce the proportion of acetylated SOD2, thus decreasing the production of ROS in the injured hippocampal neurons, reducing neuronal death, and improving cognitive function. CONCLUSIONS: OXCT1 has a critical previously unappreciated protective role in neurological impairment following TBI via the SIR3-SOD2 pathway. These findings highlight the potential of OXCT1 as a simple treatment for patients with TBI.

Reliability and validity of the Chinese version of the Nightmare disorder index in adolescents.

The Nightmare Disorder Index Questionnaire (NDI) was developed to measure the impact of nightmares. The purpose of this study was to investigate the psychometric properties of NDI among Chinese adolescents. This study investigated the validity and internal consistency of the Nightmare Disorder Index Chinese (NDI-CV) among 6014 Chinese adolescents who completed the NDI-CV, Nightmare Distress Questionnaire-Chinese Version (NDQ-CV), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Chinese Adolescent Daytime Sleepiness Scale (CADSS), Generalized Anxiety Disorder-7 Questionnaire (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). In addition, we investigated the test-retest reliability of the NDI-CV among 423 adolescents who completed a retest of the NDI-CV after a 2-week interval. Finally, NDI-CV demonstrated good psychometric properties in a sample of Chinese adolescents (Cronbach's α coefficient of 0.876), and the 95% confidence interval for the 2-week retest correlation coefficient was 0.675-0.977 (p < 0.001).

TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs.

The pregnane X receptor (PXR) is an important regulator of hepatocellular carcinoma cellular resistance to antitumor drugs. Activation of PXR was modulated by the co-regulators. The target protein for the Xenopus plus end-directed kinesin-like protein (Xklp2) known as TPX2 that was previously considered as a tubulin regulator, also functions as the regulator of some transcription factors and pro-oncogenes in human malignances. However, the actions of TPX2 on PXR and HCC cells are still unclear. In the present study, our results demonstrate that the high expression of endogenous mRNA level of TPX2 not only correlated with the poor prognosis of advanced HCC patients who received sorafenib treatment but also with expression of PXR's downstream genes, cyp3a4 and/or mdr-1. Results from luciferase and real-time polymerase chain reaction (qPCR) showed that TPX2 leads to enhancement of the transcription factor activation of PXR. Protein-protein interactions between PXR and TPX2 were identified using co-immunoprecipitation. Mechanically, overexpression of TPX2 led to enhancement of PXR recruitment to its downstream gene cyp3a4's promoter region (the PXRE region) or enhancer region (the XREM region). Treatment of HCC cells with paclitaxel, a microtubule promoter, led to enhancement of the effects of TPX2, whereas vincristine, a microtubule depolymerizing agent caused a decrease in TPX2-associated effects. TPX2 was found to cause acceleration of the metabolism or clearance of sorafenib, a typical tyrosine kinase inhibitor (TKI) in HCC cells and in turn led to the resistance to sorafenib by HCC cells. By establishing novel actions of TXP2 on PXR in HCC cells, the results indicate that TPX2 could be considered a promising therapeutic target to enhance HCC cells sensitivity to antitumor drugs.

Eukaryotic initiation factor 6 repression mitigates atherosclerosis progression by inhibiting macrophages expressing Fasn.

Atherosclerosis, a chronic inflammatory disease that often leads to myocardial infarction and stroke, is mainly caused by lipid accumulation. Eukaryotic initiation factor 6 (Eif6) is a rate-limiting factor in protein translation of transcription factors necessary for lipogenesis. To determine whether Eif6 affects atherosclerosis, Eif6+/- mice were crossed into Apoe-/- background. Apoe-/-/Eif6+/- mice on high fat diet showed significant reduction in atherosclerotic lesions and necrotic core content in aortic root sections in comparison with Apoe-/- mice. RNA-Seq was used to investigate the effect of Eif6 in aorta. Deficiency of Eif6 shows broad effect on cell metabolism. Expression of genes for fatty acid synthesis including Fatty acid synthase (Fasn), Elovl3, Elovl6 and Acaca are down-regulated in aortas. Importantly, Fasn is decreased in macrophages. Results suggest that Eif6 deficiency may decrease atherosclerosis through inhibition of Fasn and lipids metabolism in macrophages.

Endothelial NOX4 aggravates eNOS uncoupling by decreasing dihydrofolate reductase after subarachnoid hemorrhage.

Endothelial malfunction is a major contributor to early or delayed vasospasm after subarachnoid hemorrhage (SAH). As a representative form of endothelial dysfunction, endothelial nitric oxide synthase (eNOS) uncoupling leads to a reduction in nitric oxide (NO) generated by endothelial cells. In this study, we investigated how the interaction between endothelial NOX4 (nicotinamide adenine dinucleotide phosphate oxidase 4) and DHFR (dihydrofolate reductase) contributes to eNOS uncoupling after SAH. Setanaxib and the adeno-associated virus (AAV) targeting brain vascular endothelia were injected through the tail vein and the expression and localization of proteins were examined by western blot and immunofluorescence staining. The NO content was measured using the NO assay kit, and laser speckle contrast imaging was used to assess cortical perfusion. ROS (reactive oxygen species) level was detected by DHE (dihydroethidium) staining, DCFH-DA (2',7'-dichlorofluorescin diacetate) staining and H2O2 (hydrogen peroxide) measurement. The Garcia score was employed to examine neurological function. Setanaxib is widely used for its preferential inhibition for NOX1/4 over other NOX isoforms. After endothelial NOX4 was inhibited by Setanaxib in a mouse model of SAH, the endothelial DHFR level was significantly elevated, which attenuated eNOS uncoupling, increased cortical perfusion, and improved the neurological function. The protective role of inhibiting endothelial NOX4, however, disappeared after knocking down endothelial DHFR. Our results suggest that endothelial DHFR decreased significantly because of the elevated level of endothelial NOX4, which aggravated eNOS uncoupling after SAH, leading to decreased cortical perfusion and worse neurological outcome.

Nightmare Distress as a Risk Factor for Suicide Among Adolescents with Major Depressive Disorder.

Purpose: Nightmare is common and is also independently implicated in suicide risk among the adolescent population. Adolescents with major depressive disorder (MDD) are at an increased risk of suicide. Therefore, comorbid nightmares may amplify suicide risk among this clinical population. This study aimed to explore the effects of nightmares on suicide risk among adolescents with MDD. Patients and Methods: Subjects were 499 outpatients aged 12-18 in four large psychiatric hospitals clinic of China, from January 1 to October 31, 2021. Simultaneously, we matched 499 healthy controls according to gender and age. All participants underwent affective state (depressive and anxiety symptoms) and sleep variable (nightmare frequency/distress, insomnia symptoms, and daytime sleepiness) evaluation as well as MDD diagnoses and determination of suicide risk by a fully structured diagnostic clinical interview. Results: Adolescents with MDD reported a higher incidence of frequent nightmares (at least one night per week) and level of nightmare distress than healthy controls (22.0% vs 6.1%; 28.85 ± 11.92 vs 17.30 ± 5.61). Over half of the patients with suicide risk (51.6%) experienced frequent nightmares compared with approximately one-third of those at a risk for suicide (30.7%). Patients with suicide risk scored scientifically higher on sleep variables, depressive and anxiety symptoms than those without the risk. Further logistic regression analysis indicated that female gender, junior grade, recurrent depressive episode, severe nightmare distress and severe depressive symptoms were independently and significantly associated with suicide risk. Conclusion: Our study provided evidence that adolescents with MDD experienced a higher prevalence of frequent nightmares and suffered more nightmare distress. Nightmare distress is an independent risk factor for suicide risk.

[Staged operation for complex closed Pilon fracture].

OBJECTIVE: To explore clinical efficacy of staged surgery in treating complex closed Pilon fracture. METHODS: From June 2019 to January 2021, 29 patients with complex closed Pilon fracture were treated by staging surgery, including 18 males and 11 females, aged ranged from 31 to 68 years old with an average of (43.50±6.62) years old;7 cases were typeⅡand 22 cases were type Ⅲ according to Ruedi-Allgower classification. All patients had fresh closed fractures without talus and calcaneal fractures. The time from injury to closed reduction and external fixation, the interval between two stages of surgery, fracture healing time and complications were recorded. American Orthopedic Foot and Ankle Society(AOFAS) was used to assess clinical effects. Burwell-Charnley system was used to evaluate radiological reduction. RESULTS: All 29 patients were followed up from 13 to 30 months with an aver age of (15.43±5.31) months. All fractures healed well from 2 to 6 months with an average of (3.77±1.22) months. No internal fixation fracture, screw loosening, infection, internal fixation irritation, ankle stiffness occurred. The time from injury to closed reduction and cross-ankle fixation ranged from 1.22 to 7.34 h with an average of(2.31±3.52) h, the interval between two stages ranged from 5 to 9 days with an average of (5.98±2.11) days. AOFAS score was improved from 34.11±6.89 before operation to 90.10±10.11 after oepration at 12 months(P<0.05). According to AOFAS grading, 16 patients got excellent result, 9 good and 4 moderate. Fifteen patients got anatomic reduction, 12 patients were good reduction, and 2 cases were poor reduction according to Burwell-Charnley system. CONCLUSION: Staged surgery for complex closed Pilon fracture has advantages of less complications, statisfied reduction, stable fixation, which could obtain good recovery of ankle joint.

The Combination of AFP and "Up-To-Seven" Criteria May Be a Better Strategy for Liver Transplantation in Chinese Cirrhotic HCC Patients.

Background: Orthotopic liver transplantation (OLT) is a life-saving option for patients with hepatocellular carcinoma (HCC), but the expanded OLT criteria remain controversial. Objective: The study aimed to explore whether expanded OLT criteria can be applied to Chinese cirrhotic patients with HCC. Methods: This retrospective study analyzed risk factors for HCC recurrence and death and compared patients' tumor characteristics and outcomes in groups of Milan, "Up-to-seven," and Hangzhou criteria, and groups between met and unmet the combinative criteria of "Up-to-seven" and AFP of < 1000 ng/mL. Results: Among 153 patients who underwent OLT for HCC from January 2015 to February 2019 in 4 years of follow-up, 20 (13.1%) patients had HCC recurrence, and 11 (7.2%) had HCC-related death. Multivariate Cox regression analysis showed that preoperative alpha-fetoprotein (AFP) of > 1000 ng/mL (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 2.45-41.13, P = 0.001) was an independent risk factor for HCC recurrence and HCC-related death (HR: 6.63, 95%CI: 1.31-33.52, P = 0.022). Patients who did not meet Milan criteria but satisfied the "Up-to-seven" criteria had no differences in overall survival (OS) (P = 0.69) and disease-free survival (DFS) (P = 0.35) than patients who met the Milan criteria. The combination of "Up-to-seven" criteria and AFP of < 1000 ng/mL differed significantly (HR: 18.9; 95% CI: 4.0-89.2; P < 0.001). Patients with HCC who met the "Up-to-seven" criteria and AFP of < 1000 ng/mL (n = 121) had excellent survival with 4-year OS of 91.6% (P < 0.001) and DFS of 90.8% (P < 0.001), which is significantly better compared to the other group (n = 32) (OS of 67.5% and DFS of 46.5%) and patients who met the Milan criteria (n = 108, OS of 89.8%, DFS of 89.6%), allowing 28.9% (13/45) of patients who did not meet the Milan criteria to benefit from OLT. Conclusion: Chinese cirrhotic patients with HCC who met the combinative criteria of "Up-to-seven" and AFP of < 1000 ng/mL had better survival than those who met the Milan criteria, and these combinative criteria benefited more patients and may become a better option for OLT.

Lactobacillus improves the effects of prednisone on autoimmune hepatitis via gut microbiota-mediated follicular helper T cells.

BACKGROUND: Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver dysfunction. The gut microbiota and T follicular helper (Tfh) cells play critical roles in the immunopathogenesis and progression of AIH. We aimed to investigate the effect of gut microbiota combined with prednisone therapy on Tfh cell response in AIH. METHODS: Samples from AIH patients and mouse model of experimental autoimmune hepatitis (EAH) were analyzed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, flow cytometry, and hematoxylin-eosin staining to determine the role of gut microbiota on AIH. RESULTS: Lactobacillus significantly increased the levels of Bacteroides fragilis, Clostridium, Clostridium leptum, Bifidobacterium, and Lactobacillus and significantly enhanced the suppressive effects of prednisone on the levels of AIH clinical indexes in AIH patients. Lactobacillus exerts the same prptective effects as prednisone in EAH mice and enhanced the effects of prednisone. Lactobacillus also reinforced the inhibitory effects of prednisone on the levels of serum IL-21 and the proportions of Tfh cells in peripheral blood mononuclear cells. Mechanistically, prednisone and Lactobacillus regulated Tfh cell response in EAH mice in an MyD88/NF-κB pathway-dependent manner. CONCLUSION: Our results suggested a therapeutic potential of Lactobacillus in the prednisone-combined treatment of AIH. Video Abstract.

Histone Methyltransferase SETDB1 Promotes Immune Evasion in Colorectal Cancer via FOSB-Mediated Downregulation of MicroRNA-22 through BATF3/PD-L1 Pathway.

Tumors may develop a variety of immune evasion mechanisms during the progression of colorectal cancer (CRC). Here, we intended to explore the mechanism of histone methyltransferase SETDB1 in immune evasion in CRC. The expression of SETDB1, microRNA-22 (miR-22), BATF3, PD-L1, and FOSB in CRC tissues and cells was determined with their interactions analyzed also. Gain-of-function and loss-of-function approaches were employed to evaluate the effects of the SETDB1/FOSB/miR-22/BATF3/PD-L1 axis on T cell function, immune cell infiltration, and tumorigenesis. Aberrant high SETDB1 expression in CRC was positively associated with PD-L1 expression. SETDB1 negatively regulated miR-22 expression by downregulating FOSB expression, while miR-22 downregulated PD-L1 expression via targeting BATF3. Furthermore, SETDB1 silencing promoted the T cell-mediated cytotoxicity to tumor cells via the FOSB/miR-22/BATF3/PD-L1 axis and hindered CRC tumor growth in mice while leading to decreased immune cell infiltration. Taken together, SETDB1 could activate the BATF3/PD-L1 axis by inhibiting FOSB-mediated miR-22 and promote immune evasion in CRC, which provides a better understanding of the mechanisms underlying immune evasion in CRC.

[Expression Analysis of miRNA Profiles in Apheresis Platelets during Storage].

OBJECTIVE: To study the expression profiles changes of miRNA in apheresis platelets after 1, 3 and 5 days of storage. METHODS: The apheresis platelets were collected from 20 volunteer blood donors. After mixing fully, the platelets were stored in a shaker with (22±2) ℃ horizontal oscillation. The samples were taken on the 1st, 3rd and 5th day, and used to sequence for miRNAs by DNA nanoball (DNB) sequencing technology, which were named as C_1, C_3 and C_5, respectively. The expression level of platelets miRNA was standardized by transcripts per kilobase million (TPM) algorithm. MiRNAs with P-value < 0.001 and the expression difference of more than two times were considered as significant difference between two groups. The expression of miRNAs was verified by real-time fluorescence quantitative PCR (RT-qPCR). RESULTS: By DNB sequencing, there were 688, 730, and 679 platelet miRNAs expressed in C_1, C_3 and C_5 group, respectively. Cluster analysis showed that the expression profile of miRNAs changed significantly. The expression level of the first 20 high abundance miRNAs was about 4/5 of the total amounts of expressed miRNAs in each group, which the top five miRNAs were miR-21-5p, miR-26a-5p, miR-199a-3p, miR-126-3p, and let-7f-5p. The correlation of high abundance platelet miRNAs among the three groups was high (R2=0.876, R2=0.979, R2=0.937, respectively) and the differences were not statistically significant (P>0.05). Compared with the differential expression of platelet miRNAs with more than 1 000 TPM in the C_3 and C_1 group, there were 6 differentially expressed miRNAs, including 3 up-regulated (miR-146a-5p, miR-379-5p, and miR-486-5p) and 3 down-regulated (miR-652-3p, miR-142-5p, and miR-7-5p). While in the C_5 and C_1 group, there were 4 differentially expressed miRNAs, including 2 up-regulated (miR-146a-5p and let-7b-5p) and 2 down-regulated (miR-30d-5p and miR-142-5p). Compared with the differentially expression of platelet miRNAs between 1-1 000 TPM in the C_3 and C_1 group, there were 133 differentially expressed miRNAs, in which 99 were up-regulated and 34 were down-regulated. While in the C_5 and C_1 group, there were 77 differentially expressed miRNAs, in which 31 were up-regulated and 46 were down-regulated. The six selected differentially expressed miRNAs verified by RT-qPCR were consistent with those of sequencing. CONCLUSION: The expression profiles of platelets miRNAs change significantly among 1, 3, and 5 d of storage in vitro.

Dobutamine promotes the clearance of erythrocytes from the brain to cervical lymph nodes after subarachnoid hemorrhage in mice.

Background: Erythrocytes and their breakdown products in the subarachnoid space (SAS) are the main contributors to the pathogenesis of subarachnoid hemorrhage (SAH). Dobutamine is a potent ß1-adrenoreceptor agonist that can increase cardiac output, thus improving blood perfusion and arterial pulsation in the brain. In this study, we investigated whether the administration of dobutamine promoted the clearance of red blood cells (RBCs) and their degraded products via meningeal lymphatic vessels (mLVs), thus alleviating neurological deficits in the early stage post-SAH. Materials and methods: Experimental SAH was induced by injecting autologous arterial blood into the prechiasmatic cistern in male C57BL/6 mice. Evans blue was injected into the cisterna magna, and dobutamine was administered by inserting a femoral venous catheter. RBCs in the deep cervical lymphatic nodes (dCLNs) were evaluated by hematoxylin-eosin staining, and the hemoglobin content in dCLNs was detected by Drabkin's reagent. The accumulation of RBCs in the dura mater was examined by immunofluorescence staining, neuronal death was evaluated by Nissl staining, and apoptotic cell death was evaluated by TUNEL staining. The Morris water maze test was used to examine the cognitive function of mice after SAH. Results: RBCs appeared in dCLNs as early as 3 h post-SAH, and the hemoglobin in dCLNs peaked at 12 h after SAH. Dobutamine significantly promoted cerebrospinal fluid (CSF) drainage from the SAS to dCLNs and obviously reduced the RBC residue in mLVs, leading to a decrease in neuronal death and an improvement in cognitive function after SAH. Conclusion: Dobutamine administration significantly promoted RBC drainage from cerebrospinal fluid in the SAS via mLVs into dCLNs, ultimately relieving neuronal death and improving cognitive function.