Exercise modalities for type 2 diabetes: A systematic review and network meta-analysis of randomized trials.

AIMS: We aimed to determine the effects of different exercise modalities in patients with type 2 diabetes mellitus (T2DM). METHODS: We searched PubMed, Embase, and the Cochrane Library from their inception until July 2020 to identify randomised controlled trials (RCTs) on exercise in adults with T2DM. Paired reviewers independently performed study selection, data extraction, and risk of bias assessment. The certainty of the evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. RESULTS: A total of 106 RCTs that enroled eight exercise modalities with 7438 patients were included. Six exercise modalities, except unsupervised aerobic/resistance exercise, significantly reduced glycosylated haemoglobin (HbA1c), with mean differences (MDs) ranging from 0.71 (95% confidence interval [CI]: 0.34-1.08) to 0.34 (95% CI: 0.17-0.52), low to high certainty, in comparison with no exercise. The evidence of low to moderate certainty showed that supervised aerobic/resistance exercise improved glycaemic control, body weight, blood pressure, and blood lipid profiles compared with no exercise. Flexibility exercise may be associated with glycaemic control (HbA1c: MD = 0.71, 95% CI: 0.34-1.08); fasting plasma glucose (MD = 1.48, 95% CI: 0.78-2.17), and weight loss (MD = 1.80, 95% CI: 0.85-2.75) compared with controls, but not blood pressure and lipid profiles. Balance exercise showed the largest benefit in improving total cholesterol (MD = 52.81, 95% CI: 28.47-77.16) and low certainty. We found no significant differences between exercises and the triacylglycerol (TG) level. CONCLUSIONS: Overall, our network meta-analyses support the recommendation for exercise in patients with T2DM, especially supervised exercises. Limited evidence supports the benefits of flexibility and balance exercises. The effectiveness of exercise modalities for TG reduction remains unclear.

Analgesic Effect of Perineural Injection of BoNT/A on Neuropathic Pain Induced by Chronic Constriction Injury of Sciatic Nerve in Rats.

This study was designed to investigate the analgesic effect of perineural injection of BoNT/A on neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) and possible mechanisms. SD rats were randomly divided into Sham group, CCI group and BoNT/A group. Paw mechanical withdrawal threshold (pMWT) and paw thermal withdrawal latency (pTWL) of each group were detected at different time points after surgery. The expression of myelin markers, autophagy markers and NLRP3 inflammasome-related molecules in injured sciatic nerves were examined at 12 days after surgery. Moreover, C-fiber evoked potential in spinal dorsal horn was recorded. The expression of SNAP-25, neuroinflammation and synaptic plasticity in spinal dorsal horn of each group were examined. Then rats treated with BoNT/A were randomly divided into DMSO group and Wnt agonist group to further explore the regulatory effect of BoNT/A on Wnt pathway. We found that pMWT and pTWL of ipsilateral paw were significantly decreased in CCI group compared with Sham group, which could be improved by perineural injection of BoNT/A at days 7, 9 and 12 after surgery. The peripheral analgesic mechanisms of perineural injection of BoNT/A might be related to the protective effect on myelin sheath by inhibiting NLRP3 inflammasome and promoting autophagy flow, while the central analgesic mechanisms might be associated with inhibition of neuroinflammation and synaptic plasticity in spinal dorsal horn due to inhibiting SNAP-25 and Wnt pathway. As a new route of administration, perineural injection of BoNT/A can relieve CCI induced neuropathic pain probably via both peripheral and central analgesic mechanisms.

Identification of a circRNA-miRNA-mRNA network to explore the effects of circRNAs on pathogenesis and treatment of systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by immune inflammation. It involves multiple organs. Many studies have demonstrated that circRNAs are closely associated with SLE. Nonetheless, the potential mechanism by which circRNAs impacts SLE is not fully understood. The aim of this study was to explore the regulatory roles of circRNAs, the key genes and pathways governing the pathophysiological processes of SLE, and to screen therapeutic agents. METHODS: The sequencing data of circRNA, miRNA and mRNA were obtained from Gene Expression Omnibus (GEO) datasets. Candidates were identified to construct a circRNA-miRNA-mRNA network based on circRNA-miRNA interactions and miRNA-mRNA interactions. Gene functional enrichments were performed on the DAVID database. Protein-protein interaction (PPI) network was constructed by STRING database and visualised in Cytoscape software. The hub genes were explored by the MCODE plugin app. The Connectivity Map L1000 platform was used to identify potential agents. RESULTS: A total of 1093 differentially expressed circRNAs (DEcircRNAs), 42 differentially expressed miRNAs (DEmiRNAs) and 1431 differentially expressed mRNAs (DEmRNAs) were identified. We integrated 3 overlapped circRNAs, 13 miRNAs and 352 target mRNAs into a circRNA-miRNA-mRNA network. We next identified 44 hub genes based on the PPI network. KEGG pathway analysis revealed that the DEGs were mainly associated with MAPK signalling pathway. In addition, we discovered several chemicals as potential treatment options for SLE. CONCLUSIONS: Through this bioinformatics analysis, we suggest a regulatory role for circRNAs in the pathogenesis and treatment of SLE from the view of a competitive endogenous RNA (ceRNA) network.

Complications and related risk factors of transradial access cannulation for hemodynamic monitoring in general surgery: a prospective observational study.

PURPOSE: To examine the short-term complications of arterial cannulation for intraoperative monitoring and their related risk factors. METHODS: We included adult inpatients (≥ 18 years old) who underwent an initial transradial access (TRA) cannulation and were scheduled for general surgery between April 8 and November 30, 2020. We used 20G arterial puncture needles for puncturing and manual compression for hemostasis. Demographic, clinical, surgical, anesthetic, and laboratory data were extracted from electronic medical records. Vascular, neurologic, and infectious complications of TRA cannulation were recorded and analyzed. Logistic regression analyses were used to identify risk factors related to TRA cannulation for intraoperative monitoring. RESULTS: Among 509 included patients, 174 developed TRA cannulation-related complications. Puncture site bleeding/hematoma and median nerve injury were observed in 158 (31.0%) and 16 (3.1%) patients, respectively. No patient developed cannula-related infections. Logistic regression analysis revealed increased odds of puncture site bleeding/hematoma in women (odds ratio 4.49, 95% CI 2.73-7.36; P < 0.001) and patients who received intraoperative red blood cell (RBC) suspension transfusion ≥ 4U (odds ratio 5.26, 95% CI 1.41-19.57; P = 0.01). No risk factors for nerve injury were identified. CONCLUSION: Bleeding/hematoma were a common complication of TRA cannulation for intraoperative hemodynamic monitoring during general surgery. Median nerve injury may be an under recognized complication. Female sex and extensive intraoperative RBC transfusion are associated with an increased risk of bleeding/hematoma; however, the risk factors for nerve injury remain unclear. TRIAL REGISTRATION: The study protocol was registered at https://www.chictr.org.cn (ChiCTR1900025140).

Deep learning and radiomics based automatic diagnosis of hippocampal sclerosis.

Accurate and rapid segmentation of the hippocampus can help doctors perform intractable temporal lobe epilepsy (TLE) preoperative evaluations to identify good surgical candidates. This study aims to establish a radiomics system for the automatic diagnosis of hippocampal sclerosis with the help of machine learning. A total of 240 cases were analysed to develop a diagnostic model. First, an automatic hippocampal segmentation process was established that exploits a priori knowledge of the relatively fixed location of the hippocampus in brain partitions, as well as a deep-learning segmentation network based on an Attention U-net. Then, we extracted 527 radiomics features from each side of the segmented hippocampus. The iterative sparse representation based on feature selection and a support vector machine classifier were finally used to establish the diagnostic model of hippocampal sclerosis. The diagnostic model consists of two consecutive steps: distinguish hippocampal sclerosis (HS) from normal control (NC) and detect whether the HS is located on the left or right side. When the automatic diagnosis model identified HS and NC, the sensitivity and specificity reached 0.941 and 0.917 in the 10-fold cross-validation set and 0.920 and 0.909 in the independent testing set. When the diagnostic model detected HS lateralization, the sensitivity and specificity reached 0.923 and 0.920 in cross-validation and 0.909 and 0.929 in independent testing. Our results show that the developed radiomics model can help detect TLE patients with hippocampal sclerosis and has the potential to simplify preoperative evaluations and select surgical candidates.

Reoperation for residual or recurrent hemifacial spasm after microvascular decompression.

PURPOSE: Microvascular decompression (MVD) surgery is the only potential curative method for hemifacial spasm (HFS). Little attention is paid to those recurrent/residual HFS cases. We want to study the potential etiology of those recurrent/residual HFS cases and evaluate the value of reoperation. METHODS: We retrospectively reviewed reoperation hemifacial spasm patients in our hospital. Intraoperative videos or images were carefully reviewed, and the etiology of recurrent/residual HFS is roughly divided into three categories. Intraoperative findings, surgical outcomes, and complications were carefully studied to assess the value of reoperation for recurrent/residual HFS patients. RESULTS: A total of 28 cases were included in our case series. Twenty-three of them are recurrent HFS cases, and 5 of them are residual HFS cases. The mean follow-up duration is 24.96 months. There are seventeen patients with missed culprit vessels or insufficient decompression of root exit zone (REZ), eight patients with Teflon adhesion, and three patients with improper application of decompression materials in our case series. The final reoperation outcome with 17 excellent, seven good, and four fair, respectively. Eight (28.57%) of them experienced long-term complications after reoperation. CONCLUSION: Re-operation for recurrent/residual HFS is an effective therapy and can achieve a higher cure rate. However, the complication rate is higher compared to the first MVD surgery. Accurately identifying REZ and proper decompression strategies to deal with the culprit vessels are very important for surgical success. TRIAL REGISTRATION NUMBER: UIN: researchregistry7603. Date of registration: Jan. 31st, 2022 "retrospectively registered".

An evolvable adversarial network with gradient penalty for COVID-19 infection segmentation.

COVID-19 infection segmentation has essential applications in determining the severity of a COVID-19 patient and can provide a necessary basis for doctors to adopt a treatment scheme. However, in clinical applications, infection segmentation is performed by human beings, which is time-consuming and generally introduces bias. In this paper, we developed a novel evolvable adversarial framework for COVID-19 infection segmentation. Three generator networks compose an evolutionary population to accommodate the current discriminator, i.e., generator networks evolved with different mutations instead of the single adversarial objective to provide sufficient gradient feedback. Compared with the existing work that enforces a Lipschitz constraint by weight clipping, which may lead to gradient exploding or vanishing, the proposed model also incorporates the gradient penalty into the network, penalizing the discriminator's gradient norm input. Experiments on several COVID-19 CT scan datasets verified that the proposed method achieved superior effectiveness and stability for COVID-19 infection segmentation.

Hypoxia-inhibited miR-338-3p suppresses breast cancer progression by directly targeting ZEB2.

Hypoxia plays an essential role in the development of various cancers. The biological function and underlying mechanism of microRNA-338-3p (miR-338-3p) under hypoxia remain unclarified in breast cancer (BC). Herein, we performed bioinformatics, gain and loss of function of miR-338-3p, a luciferase reporter assay, and chromatin immunoprecipitation (ChIP) in vitro and in a tumor xenograft model. We also explored the potential signaling pathways of miR-338-3p in BC. We detected the expression levels and prognostic significance of miR-338-3p in BC by qRT-PCR and in situ hybridization. MiR-338-3p was lowly expressed in BC tissues and cell lines, and BC patients with underexpression of miR-338-3p tend to have a dismal overall survival. Functional experiments showed that miR-338-3p overexpression inhibited BC cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) process, whereas miR-338-3p silencing abolished these biological behaviors. Zinc finger E-box-binding homeobox 2 (ZEB2) was validated as a direct target of miR-338-3p. ZEB2 overexpression promoted while ZEB2 knockdown abolished the promoted effects of miR-338-3p knockdown on cell biological behaviors through the NF-ĸB and PI3K/Akt signal pathways. HIF1A can transcriptionally downregulate miR-338-3p under hypoxia. In total, miR-338-3p counteracts hypoxia-induced BC cells growth, migration, invasion, and EMT via the ZEB2 and NF-ĸB/PI3K signal pathways, implicating miR-338-3p may be a promising target to treat patients with BC.

[Effects of benzo[a]pyrene subacute administrate on the cardiovascular of male Wistar rats].

OBJECTIVE: To explore subacute toxic effects of benzo[a]pyrene on the cardiovascular system of male Wistar rats. METHODS: Forty SPF grade male Wistar rats were randomly divided into blank control group, solvent control group, low, medium and high dose group(B[a]P concentrations were 1. 0, 2. 5 and 6. 25 mg/kg, respectively), eight in each group. The solvent group was given the same amount of olive oil and the blank group was not treated at all for 28 consecutive days. After the end of the exposure, the left ventricular structural function and hemodynamic changes were observed with Prospect 3. 0 small animal ultrasound imager and BL-410 biological function test system. Pathological changes of rat thoracic aorta and left ventricle were observed by HE staining. RESULTS: The total difference in ejection fraction(EF), fractional shortening(FS) and left ventricular end diastolic pressure(LVEDP) between the groups was statistically significant(H=11. 497, P=0. 022; H=11. 422, P=0. 022; H=10. 104, P=0. 039). The EF and FS of the middle dose group were lower than the solvent group(adjusted P<0. 05), the LVEDP of the high dose group was higher than that of the solvent group(adjusted P<0. 05). The HE staining of thoracic aorta in the medium and high dose groups showed the loss of endothelial cells, the shedding of some endothelial cells, the exposure of subintimal collagen, the large gap of the middle layer. In the medium and high dose group, left ventricular transverse striations were blurred, muscle fibers reduced or disappeared, the myocardial space widened, inflammatory cells or the myocardial interspace bleeding phenomenon was occasionally observed. CONCLUSION: Benzo[a]pyrene can cause cardiovascular and endothelial damage in male Wistar rats.

Membrane phospholipids remodeling upon imbibition in Brassica napus L. seeds.

Successful seed germination depends on the rapid repair of cell membrane damaged by dry storage. However, little is known about the reorganization of lipids during this process. In this study, the changes of intracellular redox environment, cell membrane integrity, lipid composition, and expression of genes related to phospholipid metabolism were assessed during imbibition of Brassica napus seeds. A total number of 443 lipids belonging to 7 categories were detected by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). In the 24 h-imbibed seeds, the relative content of triacylglycerol was lower than in dry seeds, while the relative content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS), especially PC (36:2, number of carbons in the acyl chains: number of double bonds), PC (36:3), and PE (36:3) were higher than those in dry seeds. Meanwhile, the content and unsaturation levels of phospholipids increased, indicating membrane lipids remodeling during seed imbibition. The plasma membrane integrity, which was measured by the relative electrolyte leakage (REL) of the membrane and FM4-64 fluorescent dye, was improved upon imbibition, confirming that cell membrane was repaired after 24 h-imbibition. The reduction of H2O2 content, redox potential, and malondialdehyde (MDA) content indicated that the degree of membrane lipid peroxidation was significantly decreased upon imbibition. Gene expression analysis showed that the differential expression of genes for key enzymes occurred in the plateau phase of the imbibition curve, i.e. after 8 h-to 24 h-imbibition. Moreover, the differential expression of genes such as those encoding phospholipase C (PLC), phospholipase D (PLD), triacylglycerol lipase (TAG lipase), choline/ethanolamine phosphotransferase (CEPT), and phosphatidylserine synthase (PTDSS2) during imbibition indicated that membrane lipid remodeling was related to complex metabolic pathways, among which the degradation of triacylglycerol and the synthesis of phospholipids using diacylglycerol might play an important role during membrane remodeling.

Conical intersections and the weak fluorescence of betalains.

Betalains are natural plant pigments found in certain plants belonging to the order Caryophyllales. This work presents theoretical calculations on the excited state properties of three betalains: betanin, an almost non-fluorescent natural betacyanin; indicaxanthin, a weakly fluorescent natural betaxanthin; and cBeet120, a synthetic betaxanthin fluorescence probe that is also weakly fluorescent. Calculations at the algebraic diagrammatic construction (ADC (2)) level of theory, combined with the conductor-like screening model (COSMO) to simulate solvent effects, predict absorption spectra in good agreement with experiment for all three of these betalains. Several distinct theoretical approaches identify torsions of the molecular geometry that can lead to conical intersections between the excited singlet (S1) and ground state (S0) potential surfaces and identify probable geometries at the minimum on the crossing seam (MXS). The present results thus emphasize the central role played by torsional modes in determining the fluorescence properties of natural betalains and of most synthetic betalain analogs as well. A direct implication of the results is that the fluorescence quantum yields of natural or synthetic betalains can potentially be enhanced by introducing structural modifications that permit the molecule to avoid these MXS geometries and/or by incorporation into a more rigid environment that hinders the specific bond rotations involved in the non-radiative relaxation of the excited state.

[Research Progress on Evaluation Method of Parkinson's Disease Bradykinesia Detection Based on Wearable Device].

Parkinson's Disease (PD) is a neurodegenerative disease that occurs in the middle-aged and elderly population and has dyskinesia as the main clinical symptom. Bradykinesia is a typical dyskinesia symptom of Parkinson's disease. The evaluation of bradykinesia based on wearable devices is an important support for individualized diagnosis and telemedicine. This paper focuses on the bradykinesia, expound the existing detection and evaluation techniques for wearable devices and data analysis methods. This paper also analyzes and discusses some current problems in the field and future research directions.

[Freezing of Gait Detection System for Parkinson's Patients Based on Inertial Measurement Unit].

In order to detect freezing of gait of Parkinson's patients automatically, a system based on inertial measurement unit to detect freezing of gait for Parkinson's patients is established. The two inertial measurement units are respectively fixed on the left and right ankles of the patient to be measured, the freezing index is calculated by windowed Fourier transform, the freezing threshold is calculated based on the freezing index during normal walking, and the freezing index and the freezing threshold are compared to complete the detection of freezing of gait. The experimental results show that the number of freezing of gait occurrences in Parkinson's patients is accurately detected, and it has high sensitivity and specificity, which can assist doctors to objectively assess the patient's condition.

Oxidative damage and antioxidative indicators in 48 h germinated rice embryos during the vitrification-cryopreservation procedure.

KEY MESSAGES: Cu/Zn SOD and other genes may be critical indicators of a stress response to reactive oxygen species (ROS) accumulation in 48 h germinated rice embryos subjected to vitrification cryopreservation. In the current study, reactive oxygen species (ROS) accumulation was investigated in 48 h germinated rice embryos during the vitrification-cryopreservation process. We found that vitrification-cryopreservation significantly affected ROS levels, especially superoxide anion levels, in 48 h germinated rice embryos. Malonaldehyde content in the apical meristems of germinated embryos was significantly positively correlated with the rate of superoxide anion generation and the highest levels of malonaldehyde content were reached after vitrification treatment. Cell viability in 48 h germinated embryos was significantly negatively correlated with the rate of superoxide anion generation, malonaldehyde content, and electrolyte leakage. Spatial and temporal patterns in ROS accumulation in these embryos existed during the vitrification procedure. Among the vitrification-cryopreservation treatments we assessed, the preculture treatment was found to stimulate superoxide anion generation and to activate the response system in the apical meristems of germinated embryos. Loading treatments motivated the catalase and ascorbate peroxidase activities. During the vitrification-dehydration treatment, oxidative stress reached the highest levels causing an antioxidative response. This response involved antioxidant enzymes promoting detoxification of ROS. Based on a comprehensive correlation analysis involving ROS accumulation, cell viability, the activities of antioxidant enzymes, and gene expression profiles, Cu/Zn SOD, CAT1, APX7, GR2, GR3, MDHAR1, and DHAR1 may be critical indicators of oxidative stress affected by the vitrification-cryopreservation treatments. The investigation of these antioxidative responses in 48 h germinated rice embryos may, therefore, provide useful information with respect to plant vitrification-cryopreservation.

[Inhibitory effect and mechanism of deoxyschizandrin on NLRP3 inflammasome].

This study was conducted to investigate the inhibitory effect and the molecular mechanism of deoxyschizandrin on the activity of NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome. Bone marrow-derived macrophages were used to study the effects of deoxyschizandrin on inflammasome activation using inflammasome inducers (ATP and nigericin). Cytotoxic effect was evaluated with CCK-8. The expression of IL-1ß, caspase-1 in the supernatant and the expression of pro-caspase-1, pro-IL-1ß, ASC, NLRP3 in cell was detected by Western blot for the inhibitory effect of deoxyschizandrin (25, 50, 100 and 200 µmol·L(−1)) on the activity of NLRP3 inflammasome. Immunofluorescence was applied to investigate NF-κB (p65) transportation to the nucleus. The results of CCK-8 showed that the optimum concentration of deoxyschizandrin was 6.25­400 µmol·L(−1). Deoxyschizandrin (25, 50, 100, and 200 µmol·L(−1)) could inhibit the activation of NLRP3 inflammasome caused by nigericin and ATP, and inhibit the secretion of IL-1ß, which was associated with inhibiting the cleavage of pro-caspase-1. The results of immunofluorescence and Western blot also suggest that the inhibitory activity of deoxyschizandrin on NLRP3 inflammasome was not dependent on NF-κB pathway and protein expression of NLRP3, ASC, pro-caspase-1 and pro-IL-1ß mediated by NF-κB. Our results confirmed that deoxyschizandrin could suppress the cleavage of pro-caspase-1 and inhibit the activity of NLRP3 inflammasome at 25­200 µmol·L−1 to reduce the inflammation response.This study was conducted to investigate the inhibitory effect and the molecular mechanism of deoxyschizandrin on the activity of NLRP3 (NOD-like receptor family,pyrin domain containing 3) inflammasome.Bone marrow-derived macrophages were used to study the effects of deoxyschizandrin on inflammasome activation using inflammasome inducers (ATP and nigericin). Cytotoxic effect was evaluated with CCK-8.The expression of IL-1ß,caspase-1 in the supernatant and the expression of pro-caspase-1,pro-IL-1ß,ASC,NLRP3 in cell was detected by Western blot for the inhibitory effect of deoxyschizandrin (25, 50, 100 and 200 µmol·L(-1)) on the activity of NLRP3 inflammasome. Immunofluorescence was applied to investigate NF-κB (p65) transportation to the nucleus. The results of CCK-8 showed that the optimum concentration of deoxyschizandrin was 6.25-400 µmol·L(-1). Deoxyschizandrin (25, 50, 100,and 200 µmol·L(-1)) could inhibit the activation of NLRP3 inflammasome caused by nigericin and ATP, and inhibit the secretion of IL-1ß, which was associated with inhibiting the cleavage of pro-caspase-1.The results of immunofluorescence and Western blot also suggest that the inhibitory activity of deoxyschizandrin on NLRP3 inflammasome was not dependent on NF-κB pathway and protein expression of NLRP3,ASC,pro-caspase-1 and pro-IL-1ßmediated by NF-κB. Our results confirmed that deoxyschizandrin could suppress the cleavage of pro-caspase-1 and inhibit the activity of NLRP3 inflammasome at 25-200 µmol·L(-1) to reduce the inflammation response.

Pretreatment lymphocyte to monocyte ratio as a predictor of prognosis in patients with early-stage triple-negative breast cancer.

Recent studies have shown that the lymphocyte to monocyte ratio (LMR) is a useful prognostic factor in various cancers. The purpose of the current study was to investigate the association between pretreatment LMR, disease-free survival (DFS), and overall survival (OS) in patients with early-stage (I to III) triple-negative breast cancer (TNBC). Pretreatment LMR with corresponding clinical features from 230 TNBC patients was noted. A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimal cutoff values for LMR, lymphocyte, and monocyte counts. The difference between variables was calculated using chi-square tests. The Kaplan-Meier method and univariate and multivariate Cox regression models were applied to assess OS and DFS. Based on the ROC analysis, the optimal cutoff point for LMR was 4.7. Associations between high LMR (≥4.7) and significantly small tumor size (P = 0.005) and TNM stage (P = 0.013) were found, although there was no significant association for other clinical pathological factors. In the multivariate analysis, LMR was a significant predictive factor for both OS (hazard ratio [HR] = 0.42; 95 % confidence interval [CI], 0.19-0.95; P < 0.001) and DFS (HR = 0.40; 95 % CI, 0.20-0.79; P < 0.001). In addition, the predictive values of the OS and DFS were also observed for absolute counts of lymphocytes (P < 0.001) and monocytes (P < 0.001). Our study suggests that pretreatment LMR may be a predictive factor for long-term survival in patients with early-stage TNBC.

CRYOPRESERVATION OF IN VITRO-GROWN SHOOT TIPS OF CHINESE MEDICINAL PLANT Atractylodes macrocephala KOIDZ. USING A DROPLET-VITRIFICATION METHOD.

BACKGROUND: Atractylodes macrocephala Koidz. is an important medicinal species from China that has been used for thousands of years for its special pharmacological antioxidant, hepatoprotective, anti-inflammatory, anti-allergic, antithrombotic, antiviral, and anticarcinogenic activities. OBJECTIVE: The aim of this research was to develop an efficient droplet-vitrification protocol for A. macrocephala shoot tips which could be used as a strategy for long-term conservation within gene banks. MATERIALS AND METHODS: The duration of preculture, loading, and PVS2 steps, as well as the recovery medium formulation, were optimized to achieve high levels of survival and regrowth for A. macrocephala shoot tips after liquid nitrogen exposure. RESULTS: Survival and regrowth levels after cryopreservation in the cultivar 'Baizhu' were as high as 76% and 62%, respectively. Thermal analysis using differential scanning calorimetry suggested that the PVS2 treatment plays a critical role for successful cryopreservation. CONCLUSION: The droplet-vitrification method established in this study could be used to cryopreserve A. macrocephala.

Investigation of ferroptosis-associated molecular subtypes and immunological characteristics in lupus nephritis based on artificial neural network learning.

BACKGROUND: Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) with poor treatment outcomes. The role and underlying mechanisms of ferroptosis in LN remain largely unknown. We aimed to explore ferroptosis-related molecular subtypes and assess their prognostic value in LN patients. METHODS: Molecular subtypes were classified on the basis of differentially expressed ferroptosis-related genes (FRGs) via the Consensus ClusterPlus package. The enriched functions and pathways, immune infiltrating levels, immune scores, and immune checkpoints were compared between the subgroups. A scoring algorithm based on the subtype-specific feature genes identified by artificial neural network machine learning, referred to as the NeuraLN, was established, and its immunological features, clinical value, and predictive value were evaluated in patients with LN. Finally, immunohistochemical analysis was performed to validate the expression and role of feature genes in glomerular tissues from LN patients and controls. RESULTS: A total of 10 differentially expressed FRGs were identified, most of which showed significant correlation. Based on the 10 FRGs, LN patients were classified into two ferroptosis subtypes, which exhibited significant differences in immune cell abundances, immune scores, and immune checkpoint expression. A NeuraLN-related protective model was established based on nine subtype-specific genes, and it exhibited a robustly predictive value in LN. The nomogram and calibration curves demonstrated the clinical benefits of the protective model. The high-NeuraLN group was closely associated with immune activation. Clinical specimens demonstrated the alterations of ALB, BHMT, GAMT, GSTA1, and HAO2 were in accordance with bioinformatics analysis results, GSTA1 and BHMT were negatively correlated with the severity of LN. CONCLUSION: The classification of ferroptosis subtypes and the establishment of a protective model may form a foundation for the personalized treatment of LN patients.

Construction of competing endogenous RNA networks in systemic lupus erythematosus by integrated analysis.

Objective: Systemic lupus erythematosus (SLE) is a disease characterised by immune inflammation and damage to multiple organs. Recent investigations have linked competing endogenous RNAs (ceRNAs) to lupus. However, the exact mechanism through which the ceRNAs network affects SLE is still unclear. This study aims to investigate the regulatory functions of the ceRNAs network, which are important pathways that control the pathophysiological processes of SLE. Methods: CircRNA microarray for our tested assays were derived from bone marrow samples from three healthy individuals and three SLE patients in our hospital. The other sequencing data of circRNA, miRNA and mRNA were obtained from Gene Expression Omnibus (GEO) datasets. Using the limma package of R program, the differential expression of mRNA and miRNA in the GEO database was discovered. Then predicted miRNA-mRNA and circRNA-miRNA were established using miRMap, miRanda, miRDB, TargetScan, and miTarBase. CircRNA-miRNA-mRNA ceRNA network was constructed using Cytoscape, and hub genes were screened using a protein-protein interaction network. Immune infiltration analysis of the hub gene was also performed by CIBERSORT and GSEA. Results: 230 overlapped circRNAs, 86 DEmiRNAs and 2083 DEmRNAs were identified in SLE patients as compared to healthy controls. We constructed a circRNA-miRNA-mRNA ceRNAs network contained 11 overlapped circRNAs, 9 miRNAs and 51 mRNAs. ESR1 and SIRT1 were the most frequently associated protein-protein interactions in the PPI network. KEGG analysis showed that DEGs was enriched in FoxO signaling pathway as well as lipids and atherosclerosis. We constructed a novel circRNA-miRNA-mRNA ceRNA network (HSA circ 0000345- HSA miR-22-3-P-ESR1/SIRT1) that may have a major impact on SLE. Conclusion: Through this bioinformatics and integrated analysis, we suggest a regulatory role for ceRNA network in the pathogenesis and treatment of SLE.

TRIM72 Alleviates Muscle Inflammation in mdx Mice via Promoting Mitophagy-Mediated NLRP3 Inflammasome Inactivation.

Chronic muscle inflammation exacerbates the pathogenesis of Duchenne muscular dystrophy (DMD), which is characterized by progressive muscle degeneration and weakness. NLRP3 (nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3) inflammasome plays a key role in the inflammatory process, and its abnormal activation leads to a variety of inflammatory or immune diseases. TRIM72 (MG53) is a protective myokine for tissue repair and regeneration. However, little is known about the potential impact of TRIM72 in the crosstalk between mitophagy and inflammatory process of DMD. Here, 10-week-old male mdx mice were injected intramuscularly with adeno-associated virus (AAV-TRIM72) to overexpress TRIM72 protein for 6 weeks. Then, skeletal muscle samples were collected, and relevant parameters were measured by histopathological analysis and molecular biology techniques. C2C12 cell line was transfected with lentivirus (LV-TRIM72) to overexpress or siRNA (si-TRIM72) to suppress the TRIM72 expression for the following experiment. Our data firstly showed that the TRIM72 expression was decreased in skeletal muscles of mdx mice. Then, we observed the increased NLRP3 inflammasome and impaired mitophagy in mdx mice compared with wild type mice. In mdx mice, administration of AAV-TRIM72 alleviated the accumulation of NLRP3 inflammasome and the consequent IL-18 and IL1ß maturation by inducing autophagy, while this protective effect was reversed by chloroquine. Mitochondrial reactive oxygen species (mtROS), as a recognized activator for NLRP3 inflammasome, was attenuated by TRIM72 through the induction of mitophagy in C2C12 cells. Additionally, we proposed that the TRIM72 overexpression might promote mitophagy through both the early stage by PI3K-AKT pathway and the late stage by autolysosome fusion. In conclusion, the current study suggests that TRIM72 prevents DMD inflammation via decreasing NLRP3 inflammasomes and enhancing mitophagy. Collectively, our study provides insight into TRIM72 as a promising target for therapeutic intervention for DMD.