Inhaled Nitric Oxide ReDuce postoperatIve pulmoNAry complicaTions in patiEnts with recent COVID-19 infection (INORDINATE): protocol for a randomised controlled trial.

BACKGROUND: A history of SARS-CoV-2 infection has been reported to be associated with an increased risk of postoperative pulmonary complications (PPCs). Even mild PPCs can elevate the rates of early postoperative mortality, intensive care unit (ICU) admission and prolong the length of ICU and/or hospital stays. Consequently, it is crucial to develop perioperative management strategies that can mitigate these increased risks in surgical patients who have recently been infected with SARS-CoV-2. Accumulating evidence suggests that nitric oxide (NO) inhalation might be effective in treating COVID-19. NO functions in COVID-19 by promoting vasodilation, anticoagulation, anti-inflammatory and antiviral effects. Therefore, our study hypothesises that the perioperative use of NO can effectively reduce PPCs in patients with recent SARS-CoV-2 infection. METHOD AND ANALYSIS: A prospective, double-blind, single-centre, randomised controlled trial is proposed. The trial aims to include participants who are planning to undergo surgery with general anaesthesia and have been recently infected with SARS-CoV-2 (within 7 weeks). Stratified allocation of eligible patients will be performed at a 1:1 ratio based on the predicted risk of PPCs using the Assess Respiratory Risk in Surgical Patients in Catalonia risk index and the time interval between infection and surgery.The primary outcome of the study will be the presence of PPCs within the first 7 days following surgery, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm and aspiration pneumonitis. The primary outcome will be reported as counts (percentage) and will be compared using a two-proportion χ2 test. The common effect across all primary components will be estimated using a multiple generalised linear model. ETHICS AND DISSEMINATION: The trial is approved by the Institutional Review Board of Xijing Hospital (KY20232058-F1). The findings, including positive, negative and inconclusive results, will be published in scientific journals with peer-review processes. TRIAL REGISTRATION NUMBER: NCT05721144.

High-strength hydrophilic N-halamines chitosan and cellulose nanofibers membranes with repeated bactericidal properties.

Direct addition of disinfectants and membrane separation techniques have been common methods to address microbial contamination in water. However, disinfectants may generate toxic by-products, and even minor damage or biofilm formation on filtration membranes can lead to a heightened risk of microbial contamination. Consequently, how to quickly and safely disinfect microbial contaminated water sources remains a huge challenge. In this study, the high-strength broad-spectrum antibacterial CNF/CS composite membrane was fabricated by utilizing cellulose nanofibers (CNF) to reinforce the structure of chitosan (CS). The resulting CNF/CS composite membrane exhibits an impressive tensile strength of 148 MPa and boasts an active chlorine content of 5.29 %. Notably, even after undergoing 50 washing cycles and 10 repeated chlorination procedures, the structural integrity and high active chlorine content of the composite membrane remain preserved, validating its exceptional strength, stability, and chlorine rechargeability. Additionally, the CNF/CS antibacterial materials demonstrate remarkable attributes in terms of rapid sterilization, sustained and consistent release of active chlorine, and efficient inhibition of biofilm formation, demonstrating great potential in efficient, green, and safe sterilization.

The role of titanium surface micromorphology in MG-63 cell motility during osteogenesis.

Different surface micromorphologies influence osteoblast movements and impact the osteogenesis around implants. In this study, a biomimetic chip that simulates the microenvironment of the implant and bone in vitro was developed (tissue-on-chip of group T and group C) to study the correlation of cell movement velocity (CMV), direction (CMD), acceleration (CMA), and cell attachment number (CA) with the surface micromorphology of the Titanium material. Computational fluid dynamics (CFD) was used for flow analysis. Changes in intraosseous pressure (IOP), local blood perfusion index (LBPI), new bone microstructure, microvessel density (MVD), and bone-implant contact (BIC) in beagle dogs were detected as implant surface alterations. Surface skewness (Ssk) and surface arithmetic mean height (Sa) were the most important negative factors for high CMV, accounting for 51% and 32%, respectively, of all the influencing factors. Higher Ssk (SskT > 0, SskC < 0) and Sa (SaT > SaC) resulted in lower CMV (CMVT:CMVC = 0.41:1), greater CA (CAT:CAC = 1.44:1), and higher BIC (BICT:BICC = 3.06:1) (P < 0.05). The surface micromorphology influenced the CMD of MG-63 cells within 20 µm from the material surface. However, it could not regulate the IOP, LBPI, MVD, new bone microstructure, or CMD (P > 0.05).

Effects of tetramethylpyrazine on neuronal apoptosis in the superficial dorsal horn in a rat model of neuropathic pain.

The Bennett and Xie (1988) model of chronic constriction injury (CCI) investigated the effects of tetramethylpyrazine (TMP) on neuropathic pain-associated behaviors and neuronal apoptosis in the spinal dorsal horn. Fifty-four male rats were randomly divided into sham (group S), CCI (group C) and TMP groups (group T). Each group was divided into subgroups (n = 6 in each group) according the time of sacrifice: 3 d, 7 d and 14 d. Rat sciatic nerves were unligated (group S), or the right sciatic nerve was loosely ligated (groups C and T) to produce CCI. Mechanical withdrawal thresholds (MWTs) and thermal withdrawal latencies (TWLs) were measured, and the rats were sacrificed at different time points post-operation. The L4-L6 sections of the spinal cord were removed. Apoptotic changes were evaluated using the TUNEL method. Immunohistochemistry assessed Bcl-2 and caspase-3 expression. TMP treatment increased MWT and TWL values and Bcl-2 expression, but it reduced neuronal apoptosis and caspase-3 expression in laminae I-II of the spinal dorsal horn. These results suggested that the inhibition of neuronal apoptosis via the modulation of Bcl-2 and caspase-3 proteins in the rat spinal dorsal horn contributed to TMP-induced analgesia.

[Clonidine and dexmedetomidine's effect on the altered expressions of growth associated protein-43 mRNA in rat dorsal root ganglion during the development of chronic neuropathic pain].

OBJECTIVE: To explore the effects of α(2) adrenergic receptor (α(2)AR) agonists clonidine and dexmedetomidine on the injury model of peripheral nerve chronic constriction in rats. METHODS: A total of 72 male SD rats weighing 180 - 250 g were randomly divided into 4 groups (n = 18 each). In sham operation group (S), the right sciatic nerves were exposed but not ligated. But, in other groups, four ligatures were placed around the right sciatic nerve according to the Bennett's method. From the instant after operation, 0.4 mg × kg(-1)× d(-1) clonidine and 50.0 µg × kg(-1)× d(-1) were injected intraperitoneally into the clonidine group (CL) and dexmedetomidine group (Dex) daily. And the same volume of normal saline was injected into the S and CCI groups (C) respectively. Mechanical and thermal pain thresholds were measured by paw withdrawal latencies at Day 1 pre-operation and Day 3, 7 and 14 post-operation. After that, the L(4-6) dorsal root ganglions to chronic constriction injured sciatic nerves were harvested. Reverse transcription-polymerase chain reaction (RT-PCR) and agarose gel electrophoresis were used to examine the expression of GAP-43 mRNA. RESULTS: Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of groups C, CL and Dex markedly decreased and the expression of GAP-43 mRNA in dorsal root ganglions significantly increased at Days 3, 7 and 14 post-operation versus those at pre-operation and group S (P < 0.05). TWL and MWT of groups CL and Dex at Days 7 and 14 post-operation significantly increased while the expression of GAP-43 mRNA in dorsal root ganglions markedly decreased versus those of group C (P < 0.05). TWL and MWT of group Dex were significantly higher while the expression of GAP-43 mRNA in dorsal root ganglions was lower than those of group CL (P < 0.05). Compared with Day 3, TWL and MWT of groups C, CL and Dex markedly decreased while the expression of GAP-43 mRNA significantly increased in dorsal root ganglions at Day 7 (P < 0.05). Compared with Day 7, TWL and MWT of groups CL and Dex markedly increased while the expression of GAP-43 mRNA in dorsal root ganglions significantly decreased at Day 14 (P < 0.05). CONCLUSION: Clonidine and dexmedetomidine both show evident analgesic effects on chronic neuropathic pain in rats probably through a reduction of nerve regeneration. But dexmedetomidine has a better efficacy due to of its high selectivity of α(2)AR.

Functions of acidic transmembrane residues in human melanocortin-3 receptor binding and activation.

The melanocortin-3 receptor (MC3R) is an important regulator of energy homeostasis, inflammation, and cardiovascular function. Inactivating mutations in MC3R gene are associated with childhood obesity. How MC3R binds to its ligands has rarely been studied. In the present study, we systematically mutated all ten acidic residues in transmembrane (TM) domains and measured the cell surface expression levels as well as ligand binding and signaling properties of these mutants. Our results showed that of the 19 mutants stably expressed in HEK293 cells, all were expressed on the cell surface, although some mutants had decreased levels of cell surface expression. We showed that with the superpotent analog [Nle(4), D-Phe(7)]-alpha-melanocyte stimulating hormone (MSH), E92, E131, D154, D158, D178, and D332 are important for ligand binding. D121 and D332 are important for binding and signaling. Further experiments using other ligands such as D-Trp(8)-gamma-MSH, alpha-MSH and gamma-MSH showed that different ligands induce or select different conformations. In summary, we showed that acidic residues in TMs 1 and 3 are important for ligand binding whereas the acidic residues in TMs 2 and 7 are important for both ligand binding and signaling.