Ultrasound-guided serratus anterior plane block to prevent neurocognitive impairment in elderly patients after thoracoscopic lobectomy: protocol for a single-centre, double-blind, randomised controlled trial.

INTRODUCTION: Postoperative neurocognitive dysfunction (PND), including postoperative delirium (POD), is a common complication in elderly patients after major surgeries, often leading to poor postoperative recovery. Although the pathological mechanism underlying PND is still unclear, postoperative pain is strongly associated with the development of PND. The ultrasound-guided serratus anterior plane block (SAPB) has been reported to relieve postoperative pain in thoracic surgery. Therefore, this prospective trial hypothesises that SAPB may reduce the incidence of PND in the elderly undergoing thoracoscopic lobectomy. METHODS AND ANALYSIS: This study is designed as a single-centre, double-blind, randomised controlled clinical trial. A total of 256 elderly patients scheduled to undergo thoracoscopic lobectomy at Shanghai Pulmonary Hospital will be randomly assigned to general anaesthesia group or SAPB group. The primary outcome is the incidence of PND 7 days postoperatively or before discharge from hospital. The secondary outcomes include the occurrence of POD, the postoperative pain scores, Quality of Recovery at 1-2 days postoperatively and incidence of PND at 3 months postoperatively. The levels of fasting blood glucose in peripheral blood will be examined before and 1-2 days postoperatively. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research Ethics Committee of Shanghai Pulmonary Hospital (identifier: K20-290). All participants will be required to provide written informed consent before any protocol-specific procedures. Findings will be disseminated in a peer-reviewed journal and in national and/or international meetings to guide future practice. TRIAL REGISTRATION NUMBER: ChiCTR2100052633.

4-octyl itaconate ameliorates alveolar macrophage pyroptosis against ARDS via rescuing mitochondrial dysfunction and suppressing the cGAS/STING pathway.

Acute respiratory distress syndrome (ARDS) is a high-mortality pulmonary disorder characterized by an intense inflammatory response and a cytokine storm. As of yet, there is no proven effective therapy for ARDS. Itaconate, an immunomodulatory derivative accumulated during inflammatory macrophage activation, has attracted widespread attention for its potent anti-inflammatory and anti-oxidative properties. This study pointed to explore the protective impacts of 4-octyl itaconate (4-OI) on ARDS. The results showed that lung injury was attenuated markedly after 4-OI pre-treatment, as represented by decreased pulmonary edema, inflammatory cell infiltration, and production of inflammatory factors. LPS stimulation induced NLRP3-mediated pyroptosis in vitro and in vivo, as represented by the cleavage of gasdermin D (GSDMD), IL-18 and IL-1ß release, and these changes could be prevented by 4-OI pretreatment. Mechanistically, 4-OI eliminated mitochondrial reactive oxygen species (mtROS) and mtDNA escaping to the cytosol through the opening mitochondrial permeability transition pore (mPTP) in alveolar macrophages (AMs) under oxidative stress. In addition, 4-OI pretreatment markedly downregulated cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING) expression, and interferon regulatory factor 3 (IRF3) phosphorylation in vitro and in vivo. Meanwhile, inhibition of STING/IRF3 pathway alleviated NLRP3-mediated pyroptosis induced by LPS in vitro. Taken together, this study indicated that 4-OI ameliorated ARDS by rescuing mitochondrial dysfunction and inhibiting NLRP3-mediated macrophage pyroptosis in a STING/IRF3-dependent manner, which further revealed the potential mechanism of itaconate in preventing inflammatory diseases.

[Research progress in obesity-induced low fertility in males].

The prevalence of obesity in men of reproductive age is globally increasing. Obesity alters the ratio of testosterone to estradiol and the homeostasis of leptin and other hormone levels by interfering with the hypothalamus-pituitary-gonadal axis. In addition, it may change epigenetic modifications and intergenerational transmission, which would affect the health of the offspring. Both of the pathways reduce male fertility, which may be associated with the obesity-induced change in the levels of some hormones and consequently the alteration of epigenetic modifications. This review focuses on the adverse effects of obesity on male fertility by influencing endocrine hormones and epigenetic modifications, and further discusses the effects of endocrine hormones on male fertility by epigenetic modification, aiming to provide some basic data for the prevention and treatment of obesity-related male fertility in clinical practice.

Therapeutic effects of mifepristone combined with Gestrinone on patients with endometriosis.

OBJECTIVE: To evaluate the clinical therapeutic effects of mifepristone combined with gestrinone on patients with endometriosis. METHODS: A total of 150 endometriotic patients treated in our hospital between January 2014 and December 2015 were randomly divided into a control group and a treatment group (n=75). The control group began to orally take gestrinone capsules on the second day after menstruation started (2.5 mg/time, twice/week). The treatment group orally took mifepristone tablets (12.5 mg/time, once/day), and the dosage and administration of gestrinone capsules were the same as those of the control group. After 24 weeks of consecutive treatment, the clinical therapeutic effects of the two groups were assessed, and the pelvic symptom score, clinical sign score, serum sex hormone levels and pregnancy outcomes were compared. RESULTS: The total effective rates of control and treatment groups were 77.3% and 90.7% respectively, between which the difference was statistically significant (P<0.05). After treatment, the scores of pelvic symptoms (dysmenorrhea, dyspareunia, pelvic pain) and clinical signs (pelvic tenderness, induration) significantly reduced (P<0.05). Each score of the treatment group decreased more significantly than that of the control group did (P<0.05). The serum follicle hormone, luteinizing hormone, estrogen and progesterone levels were significantly lower than those before treatment (P<0.05). Each level of the treatment group dropped more significantly than that of the control group did (P<0.05). The pregnancy rates in the 6th and 12th months of follow-up were 28.0% and 13.3% in the control group respectively, and 42.7% and 29.3% in the treatment group respectively. Such rates of the two groups were significantly different at each follow-up time point (P<0.05). CONCLUSION: Mifepristone combined with gestrinone had satisfactory clinical therapeutic effects on endometriosis by reducing hormone levels and improving pregnancy outcomes. Therefore, this regimen is worthy of promotion and application in clinical practice.

Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is an increasingly common autoimmune disorder mediated by antibodies to certain subunit of the N-methyl-D-aspartate receptor. Recent literatures have described anti-thyroid and infectious serology in this encephalitis but without follow-up. CASE PRESENTATION: A 17-year-old Chinese female patient presented with psychiatric symptoms, memory deficits, behavioral problems and seizures. She then progressed through unresponsiveness, dyskinesias, autonomic instability and central hypoventilation during treatment. Her conventional blood work on admission showed high titers of IgG antibodies to thyroglobulin, thyroid peroxidase and IgM antibodies to Epstein-Barr virus viral capsid antigen. An immature ovarian teratoma was found and removal of the tumor resulted in a full recovery. The final diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was made by the identification of anti-N-methyl-D-aspartate receptor antibodies in her cerebral spinal fluid. Pathology studies of the teratoma revealed N-methyl-D-aspartate receptor subunit 1 positive ectopic immature nervous tissue and Epstein-Barr virus latent infection. She was discharged with symptoms free, but titers of anti-thyroid peroxidase and anti-thyroglobulin antibodies remained elevated. One year after discharge, her serum remained positive for anti-thyroid peroxidase and anti-N-methyl-D-aspartate receptor antibodies, but negative for anti-thyroglobulin antibodies and IgM against Epstein-Barr virus viral capsid antigen. CONCLUSIONS: Persistent high titers of anti-thyroid peroxidase antibodies from admission to discharge and until one year later in this patient may suggest a propensity to autoimmunity in anti- N-methyl-D-aspartate receptor encephalitis and support the idea that neuronal and thyroid autoimmunities represent a pathogenic spectrum. Enduring anti-N-methyl-D-aspartate receptor antibodies from admission to one year follow-up but seroreversion of Epstein-Barr virus viral capsid antigen IgM may raise the important issue of elucidating the triggers and boosters of anti- N-methyl-D-aspartate receptor encephalitis.

Feasibility of ozone absorption by H2O2 solution in rotating packed beds.

This work examined the feasibility of ozone (O(3)) absorption by H(2)O(2) solution in a rotating packed bed (RPB). The O(3) removal efficiency was determined at various operating variables including RPB speed, gas flow rate, and liquid flow rate in three RPBs. For each RPB, the results demonstrated that the RPB speed positively affected the O(3) removal efficiency. Also, the O(3) removal efficiency increased with the liquid flow rate but decreased with the gas flow rate. Moreover, the obtained results indicated that the O(3) removal efficiency increased as the inner radius of the bed was increased and the outer radius of the bed was decreased. Furthermore, the developed method for O(3) absorption using H(2)O(2) solution could provide the removal efficiency of more than 95%. Consequently, the novel method would have a great potential in the removal of O(3) from the exhausted gases.

Generation and characterization of C305, a murine neutralizing scFv antibody that can inhibit BLyS binding to its receptor BCMA.

B-lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor (TNF) family and a key regulator of B cell response. Neutralizing single-chain fragment variable (scFv) antibody against BLyS binding to its receptor BCMA has the potential to play a prominent role in autoimmune disease therapy. A phage display scFv library constructed on pIII protein of M13 filamentous phage was screened using BLyS. After five rounds of panning, their binding activity was characterized by phage-ELISA. Nucleotide sequencing revealed that at least two different scFv gene fragments (C305 and D416) were obtained. The two different scFv gene fragments were expressed to obtain the soluble scFv antibodies, then the soluble scFv antibodies were characterized by means of competitive ELISA and in vitro neutralization assay. The results indicated that C305 is the neutralizing scFv antibody that can inhibit BLyS binding to its receptor BCMA.

Application of phage-displayed single chain antibodies in western blot.

A phage display single chain fragment variable library constructed on pIII protein of M13 filamentous phage was screened using B-lymphocyte stimulator and FP248 as selective molecules. After four rounds of panning, there was a remarkable enrichment in the titer of bound phages. Twenty phage clones were selected from the last round and screened by means of phage-ELISA. With the antibody phages as primary antibodies in Western blot, we developed a method for detecting the specific antigen. The dilutions of antibody phages depend on the affinity between antibody-displayed phage particles and antigens.

Recombinant scFv antibodies against E protein and N protein of severe acute respiratory syndrome virus.

Three single chain antibodies (scFv) against the proteins of severe acute respiratory syndrome coronavirus (SARS-CoV) were isolated by phage display from an scFv antibody library. Bio-panning was carried out against immobilized purified envelope (E) and nucleocapsid (N) proteins of SARS-CoV. Their binding activity and specificity to E or N protein of SARS-CoV were characterized by phage-ELISA. Two of them, B10 and C20, could recognize non-overlapping epitopes of the E protein according to the two-site binding test result. Clone A17 could recognize N protein. The sequence of the epitope or overlapping epitope of scFv antibody A17 was PTDSTDNNQNGGRNGARPKQRRPQ. The affinity (equilibrium dissociation constant, K(d)) of SARS-CoV E protein was 5.7 x 10(-8) M for B10 and 8.9 x 10(-8) M for C20. The affinity of A17 for N protein was 2.1 x 10(-6) M. All three scFv antibodies were purified with affinity chromatography and determined by Western blot.