Bioinformatics analysis identifies potential ferroptosis key genes in the pathogenesis of diabetic peripheral neuropathy.

Background: Diabetic peripheral neuropathy (DPN) is a serious complication in Diabetes Mellitus (DM) patients and the underlying mechanism is yet unclear. Ferroptosis has been recently intensively researched as a key process in the pathogenesis of diabetes but there yet has been no related bioinformatics-based studies in the context of DPN. Methods: We used data mining and data analysis techniques to screen differentially expressed genes (DEGs) and immune cell content in patients with DPN, DM patients and healthy participants (dataset GSE95849). These DEGs were then intersected with the ferroptosis dataset (FerrDb) to obtain ferroptosis DEGs and the associated key molecules and miRNAs interactions were predicted. Results: A total of 33 ferroptosis DEGs were obtained. Functional pathway enrichment analysis revealed 127 significantly related biological processes, 10 cellular components, 3 molecular functions and 30 KEGG signal pathways. The biological processes that were significantly enriched were in response to extracellular stimulus and oxidative stress. Key modules constructed by the protein-protein interaction network analysis led to the confirmation of the following genes of interest: DCAF7, GABARAPL1, ACSL4, SESN2 and RB1. Further miRNA interaction prediction revealed the possible involvement of miRNAs such as miR108b-8p, miR34a-5p, mir15b-5p, miR-5838-5p, miR-192-5p, miR-222-3p and miR-23c. Immune-environment content of samples between DM and DPN patients revealed significant difference in the levels of endothelial cells and fibroblasts, which further speculates their possible involvement in the pathogenesis of DPN. Conclusion: Our findings could provide insight for investigations about the role of ferroptosis in the development of DPN.

W-Band Beam-Tilted H-Plane Horn Array Antenna with Wideband Integrated Waveguide Feed Network Based on MMPTE.

A W-band H-plane horn array antenna with tilted radiation beam based on waveguide structure is proposed in this paper. The designed antenna array consists of four H-plane antenna elements and a broadband feed network. The distribution of excitations is determined by the theory of maximum power transmission efficiency (MMPTE). A multiple branch coupler, two T-junctions and three fixed phase shifters are employed to construct the feed network, which can generate the required amplitude and phase in broadband frequency range from 80 GHz to 100 GHz. The computer numerical control (CNC) milling machines technology is employed to machine the feed network and antenna. All measured and simulated results are in good agreement, which verify the feasibility of the theory of MMPTE to generate a radiation beam directed to any angle from -35° to 35° with suitable excitation provided by the proposed feed network in this paper.

Effects of propofol on sleep architecture and sleep-wake systems in rats.

Previous studies have shown that the synchronization of electroencephalogram (EEG) signals is found during propofol-induced general anesthesia, which is similar to that of slow-wave sleep (SWS). However, a complete understanding is lacking in terms of the characteristics of EEG changes in rats after propofol administration and whether propofol acts through natural sleep circuits. Here, we examined the characteristics of EEG patterns induced by intraperitoneal injection of propofol in rats. We found that high (10 mg/kg) and medium (5 mg/kg) doses of propofol induced a cortical EEG of low-frequency, high-amplitude activity with rare electromyographic activity and markedly shortened sleep latency. The high dose of propofol increased deep slow-wave sleep (SWS2) to 4 h, as well as the number of large SWS2 bouts (>480 s), their mean duration and the peak of the power density curve in the delta range of 0.75-3.25 Hz. After the medium dose of propofol, the total number of wakefulness, light slow-wave sleep (SWS1) and SWS2 episodes increased, whereas the mean duration of wakefulness decreased. The high dose of propofol significantly increased c-fos expression in the ventrolateral preoptic nucleus (VLPO) sleep center and decreased the number of c-fos-immunoreactive neurons in wake-related systems including the tuberomammillary nucleus (TMN), perifornical nucleus (PeF), lateral hypothalamic nucleus (LH), ventrolateral periaqueductal gray (vPAG) and supramammillary region (SuM). These results indicated that the high dose of propofol produced high-quality sleep by increasing SWS2, whereas the medium dose produced fragmented and low-quality sleep by disrupting the continuity of wakefulness. Furthermore, sleep-promoting effects of propofol are correlated with activation of the VLPO cluster and inhibition of the TMN, PeF, LH, vPAG and SuM.

Chinese Association for the Study of Pain: Experts consensus on ultrasound-guided injections for the treatment of spinal pain in China (2020 edition).

Spinal pain (SP) is a common condition that has a major negative impact on a patient's quality of life. Recent developments in ultrasound-guided injections for the treatment of SP are increasingly being used in clinical practice. This clinical expert consensus describes the purpose, significance, implementation methods, indications, contraindications, and techniques of ultrasound-guided injections. This consensus offers a practical reference point for physicians to implement successfully ultrasound-guided injections in the treatment of chronic SP.

DJ-1 plays a neuroprotective role in SH-SY5Y cells by modulating Nrf2 signaling in response to lidocaine-mediated oxidative stress and apoptosis.

To investigate the effects of DJ-1 on lidocaine-induced cytotoxicity in neurons and the link with Nrf2 signaling, SH-SY5Y cells were treated with 1, 4, 8, and 16 mM lidocaine. Cell viability was measured by MTT assay, and apoptosis was measured by flow cytometry analysis. The mitochondrial membrane potential, reactive oxygen species (ROS) levels, lipid peroxidation (MDA), and GSH/GSSG ratio were determined with specific kits. Expression of DJ-1, Nrf2, and Nrf2 downstream signaling proteins (glutathione peroxidase [GPx], heme oxygenase-1 [HO-1], catalase [CAT], and glutathione reductase [GR]), was determined by western blot and qRT-PCR. The cell viability was dramatically decreased, while levels of apoptosis, ROS and Cys106-oxidized DJ-1 were significantly enhanced following treatment with lidocaine (concentration 4-16 mM), and increases were observed in a dose-dependent manner. After treatment with 8 mM lidocaine, DJ-1, and nuclear Nrf2, as well as antioxidative stress-related proteins, GPx, GR, HO-1, and CAT, were all significantly inhibited. Overexpression of DJ-1 suppressed lidocaine-induced apoptosis and oxidative stress in SH-SY5Y cells and activated Nrf2 signalling at the same time, and these effects were reversed by the inhibition of Nrf2. DJ-1 could protect SH-SY5Y cells from lidocaine-induced apoptosis through inhibition of oxidative stress via Nrf2 signaling.

Rac2 deficiency attenuates CCl4-induced liver injury through suppressing inflammation and oxidative stress.

Oxidative stress is a leading cause to liver injury. Rac2 is a Ras-associated guanosine triphosphatase, an important molecule modulating a large number of cells and involved in the regulation of reactive oxygen species (ROS). For the study described here, we supposed that Rac2 knockout protects mice against CCl4-induced acute liver injury. We found that Rac2 expressed highly in CCl4-induced liver tissues. CCl4-treated Rac2 knockout (Rac2-/-) mice had reduced CD24 levels and steatosis. In addition, CCl4-induced high expression of pro-inflammatory cytokines and chemokine were reversed by Rac2 deficiency compared to CCl4-treated wild type (WT) mice. We also found that fibrosis-related signals of MMP-9, MMP-2 and TGF-ß1 were also down-regulated in Rac2 knockout mice induced by CCl4. Significantly, oxidative stress induced by CCl4 was also suppressed owing to the lack of Rac2, evidenced by enhanced superoxide dismutase (SOD) activity, and reduced malondialdehyde (MDA) levels, superoxide radical, H2O2, xanthine oxidase (XO), xanthine dehydrogenase (XDH) and XO/XDH ratio. Moreover, c-Jun N-terminal protein kinase mitogen-activated protein kinases (JNK MAPK) was activated by CCl4, which was reversed in the liver of Rac2-/- mice through western blot and immunohistochemical analysis. In vitro, endotoxin (LPS) was treated to hepatocytes isolated from WT mice and Rac2-/- mice. The data further confirmed the role of Rac2 deficiency suppressed pro-inflammatory cytokines and chemokine, as well as fibrosis-related signals. Of note, production of ROS induced by LPS was reduced in Rac2-/- cells, accompanied with enhanced SOD1, SOD2 and reduced XO and phosphorylated-JNK expressions. Our results indicated that Rac2 played an essential role in acute liver injury induced by CCl4, providing the compelling information of the effects of Rac2 on liver injury, and revealing a novel regulatory mechanism for acute liver injury.

Optimal effective concentration of ropivacaine for postoperative analgesia by single-shot femoral-sciatic nerve block in outpatient knee arthroscopy.

OBJECTIVE: To compare analgesic and mobility effects of different ropivacaine concentrations in femoral-sciatic nerve block, for postoperative analgesia in knee arthroscopy. METHODS: Outpatients (American Society of Anesthesiologists physical classification status of I or II), scheduled for elective knee arthroscopy, were randomly allocated to one of seven groups, prospectively investigating different concentrations of ropivacaine (0.12%; 0.14%; 0.16%; 0.18%; 0.20%; 0.22% or 0.50%), for ultrasound-guided femoral-sciatic nerve block procedures for postoperative analgesia. Visual analogue scale (VAS) pain scores and motor block evaluation scales were observed at 4, 8, 16 and 24 h postsurgery. RESULTS: In total, 105 patients were enrolled; results were analysed for 103. VAS scores for the 0.12%, 0.14% and 0.16% groups were significantly different from the 0.50% group. There were no significant differences between the 0.18%, 0.20%, 0.22% and 0.50% groups: half maximal effective concentrations and 95% maximal effective concentrations of ropivacaine were 0.158 (95% confidence intervals [CI] 0.149, 0.167) and 0.198 (95% CI 0.186, 0.221), respectively. Rates of motor blockade (Bromage score or hip motor function scale > 0) were significantly different between the 0.50% group and all other ropivacaine doses. CONCLUSION: The 0.20% ropivacaine dose for femoral-sciatic nerve block in knee arthroscopy provided satisfactory postoperative analgesia, while preserving ability of motion.

Percutaneous cardiopulmonary support for catastrophic pulmonary fat embolism in pigs.

OBJECTIVE: The purpose of this study was to evaluate the effect of percutaneous cardiopulmonary support (PCPS) for fatal fat embolism. METHODS: Twelve piglets were randomly assigned into either a conventional treatment group (CT group, n = 6) or a PCPS group (n = 6) after receiving 0.3 mL/kg of fat intravenously. The piglets in the CT group received conventional treatments including mechanical ventilation with 100% oxygen, steroid, fluids, anticoagulant, and positive inotropic agents. In addition to conventional treatments, the piglets in the PCPS group received PCPS after fat injection. Mean arterial pressure, central venous pressure, pressure of end tidal carbon dioxide, oxygen saturation, partial pressure of oxygen in arterial blood, arterial carbon dioxide pressure or tension, plasmic lactic acid, and free fatty acid were monitored. The survival rate and the consumption of positive inotropic agents were also recorded. RESULTS: The survival rate of piglets 10 hours after fat injection was much higher in the PCPS group than that in the CT group (100% vs. 0%, p < 0.01). The dosages of positive inotropic agents in the PCPS group were much lower than that in the CT group (p < 0.01). Oxygen saturation, partial pressure of oxygen in arterial blood, and arterial carbon dioxide pressure or tension were significantly improved in the PCPS group in the first 3 hours after fat injection when compared with those in the CT group (p < 0.05 or 0.01), but there were no statistical differences between the two groups in mean arterial pressure, central venous pressure, free fatty acid, and lactic acid at the period. CONCLUSION: PCPS can increase the survival rate of piglets with fatal fat embolism by providing effective cardiopulmonary support. This study suggests that PCPS might be an effective treatment for a patient with severe fat embolism if conventional treatments have not worked.

Sex-related differences in DNA copy number alterations in hepatitis B virus-associated hepatocellular carcinoma.

BACKGROUND: Males have a higher prevalence of hepatocellular carcinoma (HCC) than females in general, but the reasons for the sex disparity are still obscure. DNA copy number alteration (CNA) is a major feature of solid tumors including HCC, but whether CNA plays a role in sex-related differences in HCC development has never been evaluated. METHODS: High-resolution array comparative genomic hybridization (CGH) was used to examine 17 female and 46 male HCC patients with chronic hepatitis B virus (HBV) infection in Shanghai, China. Two-tailed Fisher's exact or chi2 tests was used to compare CNAs between females and males. RESULTS: The overall frequencies and patterns of CNAs in female and male cases were similar. However, female HCC tumors presented more copy number gains compared to those in males on 1q21.3-q22 (76.5% vs. 37.0%, P = 0.009), 11q11 (35.3% vs. 0.0%, P = 0.0002) and 19q13.31-q13.32 (23.5% vs. 0.0%, P = 0.004), and loss on 16p11.2 (35.3% vs. 6.5%, P = 0.009). Relative to females, male cases had greater copy number loss on 11q11 (63.0% vs. 17.6%, P = 0.002). Further analyses showed that 11q11 gain correlated with 19q13.31-q13.32 gain (P = 0.042), 11q11 loss (P = 0.011) and 16p11.2 loss (P = 0.033), while 1q21.3-q22 gain correlated with 19q13.31-q13.32 gain (P = 0.046). CONCLUSIONS: These findings suggest that CNAs may play a role in sex-related differences in HBV-associated HCC development.

A comparative study of the mortality rate of rats receiving a half lethal dose of fat intravenously: under general anaesthesia versus under spinal anaesthesia.

BACKGROUND: There is no data that demonstrates what anaesthesia is suitable for patients who have a high risk of fat embolism syndrome (FES). We investigated the mortality rates of rats that received a half lethal dose (LD(50)) of fat by intravenous injection after induction of general or spinal anaesthesia. METHODS: An LD(50) of fat for rats was determined by using a toxicological method. Three hundred and seventy five rats were randomly assigned to receive general anaesthesia (group GA, n=125), or spinal block (group SA, n=125), or no anaesthesia (group C, n=125). The rats were injected with the LD(50) of fat at 20 min after anaesthesia induction. The mortality rates were recorded at 2, 8, 12, and 24h after fat injection. RESULTS: The LD(50) of fat was 0.706 ml/kg and its 95% CI was 0.622 ml/kg-0.801 ml/kg. The mortality rate was lower in the group GA than in the group SA (p<0.01), whilst there was no statistical difference between the group SA and the group C (p=0.442). CONCLUSION: It is feasible to assess the efficacy of various treatments for FES by comparing the mortality rates of animals after injection of an LD(50) of fat. The mortality rate of rats was lower when FES was induced under general anaesthesia than under spinal anaesthesia which implies that general anaesthesia is superior to spinal anaesthesia for patients who have a high risk of FES.

Association of genetic polymorphisms in STAT1 gene with increased risk of hepatocellular carcinoma.

OBJECTIVE: Although signal transducer and activator of transcription 1 (STAT1), a transcription factor, plays a critical role in carcinogenesis and has been implicated as a tumor suppressor, few studies have investigated the associations between polymorphisms of this gene and the risk of cancer development. The aim of this study was to examine whether STAT1 gene polymorphisms are associated with the risk of hepatocellular carcinoma (HCC). METHODS: Ten single nucleotide polymorphisms in the STAT1 gene were genotyped by TaqMan assays in 469 HCC cases and 558 age-, sex- and HBsAg-matched controls in a Chinese population. RESULTS: Minor allele homozygous genotypes at rs867637 (9,046 bp 3' of STP A>G), rs3771300 (IVS24-153T>G), and rs2280235 (IVS20-103G>A), compared with their homozygote genotypes of common alleles, were associated with 1.6- (95% CI 1.1-2.3), 1.6- (95% CI 1.1-2.4), and 1.4-fold (95% CI 0.95-1.9) increased risk of HCC, respectively. The GGA haplotype, comprised of risk alleles at rs867637, rs3771300 and rs2280235, conferred a 1.2-fold (95% CI 1.0-1.5) increased risk of HCC, as compared to the most common haplotype of ATG. Diplotype GGA/GGA conferred a 1.6-fold (95% CI 1.0-2.5) increased risk of HCC compared with diplotype ATG/ATG. CONCLUSION: Our results demonstrate for the first time that polymorphisms in the STAT1 gene are associated with HCC susceptibility.

Ultrasound-guided continuous femoral nerve block for analgesia after total knee arthroplasty: catheter perpendicular to the nerve versus catheter parallel to the nerve.

BACKGROUND AND OBJECTIVES: This study tested the hypothesis that, in continuous femoral nerve block (CFNB) under ultrasound guidance, placing a catheter perpendicular to the nerve can shorten the time of catheter insertion while providing a similar quality of analgesia compared with placing a catheter parallel to the nerve. METHODS: Fifty patients undergoing total knee arthroplasty were randomly assigned to receive ultrasound-guided CFNB either with the catheter parallel to the nerve technique (parallel group, n = 25) or with the catheter perpendicular to the nerve technique (perpendicular group, n = 25). Patient-controlled morphine analgesia pumps were available to all the patients after surgery. The time of catheter insertion, failure rates, pain scores, morphine consumption, nausea and vomiting, and maximal degree of knee flexion were recorded. RESULTS: The time of catheter insertion was shorter in the perpendicular group than in the parallel group (12 +/- 3 versus 22 +/- 6 mins, P < 0.01). Failed catheter insertion occurred in 3 (12%) of 25 patients in the parallel group and in none of 25 patients in the perpendicular group (P = 0.2347). There were no significant differences in pain scores, opioid consumption, incidence of nausea and vomiting, and maximal degree of knee flexion between the 2 groups. CONCLUSIONS: In CFNB under ultrasound guidance, using the catheter perpendicular to the nerve technique can shorten the time of catheter insertion while providing a similar quality of analgesia after total knee arthroplasty as compared with the catheter parallel to the nerve technique.