Clinical characteristics and anaesthetic management of severe scoliosis patients with spinal muscular atrophy: case series.

Introduction and importance: There is no expert consensus or guidance on perioperative anaesthesia management for spinal surgery of spinal muscular atrophy (SMA) patients with severe scoliosis (Cobb≧90°). We provide a comprehensive summary of the perioperative characteristics observed in patients with SMA and propose an optimized perioperative management strategy for anaesthesia. Methods: This study is a retrospective single-centre research. Twenty-six SMA patients with severe scoliosis underwent posterior spinal fusion surgery from September 2019 to September 2022 were enroled. The main outcomes were to show the patients' characteristics in anaesthesia, intra- and post-operative periods. Outcomes: Nineteen patients underwent awake transnasal/transairway intubation. The median anaesthesia time of 25 patients treated under total intravenous anaesthesia was 425 min. After operation, the Cobb angle and correction rate in the coronal plane were median 54.0° and 54.4%. The length of mechanical ventilation with endotracheal intubation in ICU was median 17.5 h in 8 patients. The ICU length of stay of postoperative hospital was median 19 days. Postoperative pneumonia developed in nine patients, atelectasis in two patients, and pleural effusion in six patients. All patients did not need special oxygen therapy after discharge. Conclusion: Multidisciplinary consultation, lung-protective ventilation strategy, appropriate anaesthetic drugs and reasonable blood transfusion scheme and postoperative monitoring were important in anaesthesia, intraoperative and postoperative periods in the patients of severe scoliosis with spinal muscular atrophy.

Case Report: Monitoring Vancomycin Concentrations and Pharmacokinetic Parameters in Continuous Veno-Venous Hemofiltration Patients to Guide Individualized Dosage Regimens: A Case Analysis.

There are limited pharmacokinetic (PK) studies on vancomycin in patients treated with continuous renal replacement therapy (CRRT), and the results have been inconsistent. Because of individual differences, proposing a definite recommendation for the clinical regimen is not possible. Rapidly reaching target vancomycin concentrations will facilitate effective treatment for critically ill patients treated with CRRT. In this study, to understand the dynamic change in drug clearance rates in vivo, analyze the effect of PK changes on drug concentrations, and recommend loading and maintenance dosage regimens, we monitored the blood concentrations of vancomycin and calculated the area under the curve in two critically ill patients treated with vancomycin and continuous veno-venous hemofiltration (CVVH). On the basis of real-time therapeutic drug monitoring results and PK parameters, an individualized vancomycin regimen was developed for patients with CVVH. Good clinical efficacy was achieved, which provided support and reference for empirical vancomycin therapy in these patients.

Simple and sensitive colorimetric sensors for the selective detection of Cu(ii).

A simple, sensitive colorimetric probe for detecting Cu(ii) ions with fast response has been established with a detection limit of 2.82 µM. UV-Vis spectroscopy along with metal ion response, selectivity, stoichiometry, competition was investigated. In the presence of copper(ii), the UV-Vis spectrum data showed significant changes and the colorimetric detection showed a color change from colorless to yellow. After the selective binding of receptor L with Cu(ii), the UV-visible absorption at 355 nm decreased dramatically, a new absorbance band appeared at 398 nm and its intensity enhanced with the increase in the amount of Cu(ii). Moreover, it exhibited highly selective and sensitive recognition towards Cu(ii) ions in the presence of other cations over the pH range of 7-11. The complex structure was verified by FT-IR spectroscopy, elemental analysis and quantum mechanical calculations using B3LYP/6-31G(d) to illustrate the complex formation between L and Cu(ii). According to the Job plot and the quantum mechanical calculations, the stoichiometric ratio for the complex formation was proposed to be 1 : 1.

Phosphoproteome profiling provides insight into the mechanisms of ventilator-induced lung injury.

The incidence of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is a common health problem in the clinic and is projected to increase in prevalence in the future. Mechanical ventilation is commonly used to provide respiratory support and has become indispensable in emergency and critical medicine. However, ventilator use can result in lung tissue damage, collectively termed ventilator-induced lung injury (VILI). In the present study, phosphoprotein profiling of blood and tissue samples from ventilated and non-ventilated mice was performed and key changes in protein levels and cell signaling during VILI were identified. Activation of the PI3K/AKT and mitogen activated protein kinase signaling pathways, in addition to changes in expression of cancer, inflammatory and cell-death related proteins were detected in response to mechanical ventilation. Focal adhesion-related protein levels and signaling pathways were also significantly altered in an injury model compared with control. VILI can affect patient mortality in ALI and ARDS cases, and no targeted treatment options currently exist. Identifying biomarkers and understanding the signaling pathways associated with VILI is critical for the development of future therapies.

A green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinib.

BACKGROUND: Baricitinib, with a 2-(1-(ethylsulfonyl)azetidin-3-yl)acetonitrile moiety at N-2 position of the pyrazol skeleton, is an oral and selective reversible inhibitor of the JAK1 and JAK2 and displays potent anti-inflammatory activity. Several research-scale synthetic methods have been reported for the preparation of key quaternary heterocyclic intermediates of baricitinib. However, they were all associated with several drawbacks, such as the expensive materials, usage of pollutional reagents, and poor yields. RESULTS: In this manuscript, we established a green and cost-effective synthesis of 2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile and tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate for further scale-up production of baricitinib. This synthetic method employs commercially available and low-cost starting material benzylamine and an industry-oriented reaction of green oxidation reaction in microchannel reactor to yield important quaternary heterocyclic intermediates. CONCLUSION: Generally, this procedure is reasonable, green and suitable for industrial production.

Hydrogen sulfide prevents diaphragm weakness in cecal ligation puncture-induced sepsis by preservation of mitochondrial function.

Mitochondrial dysfunction plays an important role in the pathogenesis of diaphragm weakness during sepsis. Recently, hydrogen sulfide (H2S), a gaseous transmitter endogenously generated by cystathionine-ß-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST), is found to improve mitochondrial function. The present study aimed to examine whether H2S synthases are expressed in the diaphragm, and investigated the effect of H2S donor in sepsis-induced diaphragm weakness and its relationship with mitochondrial function. Immunohistochemical staining of the rat diaphragm revealed that positive immunoreactivity for CBS, CSE as well as 3-MST was predominately localized to muscle cells. Using a cecal ligation and puncture (CLP)-induced sepsis model, it was found that CBS and CSE, but not 3-MST, was significantly down-regulated in the diaphragm at 24 h post-CLP compared with sham group. To determine the effect of H2S on sepsis-induced diaphragm weakness, H2S donor NaHS was intraperitoneally administered 30 min after CLP operation. NaHS at a dose of 50 µmol/kg significantly decreased the mortality in septic rats. CLP markedly reduced diaphragm-specific force generation (force/cross-sectional area and maximal titanic force), which was improved by NaHS treatment. In addition, CLP caused mitochondrial damage in the diaphragm tissues as evidenced by increased mitochondrial superoxide production, decreased mitochondrial membrane potential and ATP production, as well as mitochondrial ultrastructural abnormalities, which was also attenuated by NaHS treatment. These findings indicate that H2S donor may prevent sepsis-induced diaphragm weakness by preservation of mitochondrial function, suggesting that modulation of H2S levels may be considered as a potential therapeutic approach for diaphragm dysfunction during sepsis.

Celastrol attenuates ventilator induced lung injury in mouse through inhibition of MAPK pathway.

PURPOSE: Previous studies have shown that celastrol has anti-inflammatory, anti-oxidative and anti-tumor activities, but little is known about its protective effects on ventilator induced lung injury (VILI). This study is aimed to investigate the effects of celastrol on VILI and explore its potential mechanism. METHODS: A total of 40 ICR male mice aged 7-9 weeks were randomly divided into 4 groups (n=10 per group): control group (Con), control + celastrol group (Con+Ce), mechanical ventilation group (Ven) and mechanical ventilation + celastrol group (Ven+Ce). The lungs were collected for histological examination, detection of W/D, and MPO, MDA, SOD, inflammatory cytokines (IL-1ß, IL-6, IL-10 and TNF-α) by ELISA, p-P38 and p-JNK 1/2 protein by Western blotting, and collagen-1 and TGF-ß mRNA expression by RT-PCR. RESULTS: The W/D in the Ven group was significantly higher than the W/D in the Con group and the Ven+Ce group (both P<0.01). Mechanical ventilation for 4 h markedly increased lung MPO and MDA activity, TNF-α, IL-1ß and IL-6, but dramatically reduced SOD and IL-10 (all P<0.01). However, celastrol pre-treatment compromised the increased MPO, MDA, TNF-α, IL-1ß, IL-6 (all P<0.01) and significantly increased SOD (P=0.035<0.05) and IL-10 (P<0.01). In addition, mRNA level of collagen-1 and TGF-ß as well as p-P38 and p-JNK 1/2 protein expression increased significantly (P<0.01) after mechanical ventilation, which however were markedly reduced in the presence of celastrol pre-treatment. CONCLUSION: Celastrol pre-treatment may exert anti-oxidative and anti-inflammatory effects and related lung fibrosis to attenuate VILI in mice, which may be related to the inhibition of p-P38 and p-JNK 1/2 by MAPK pathway.

Dehydrogenation inhibition on nano-Au/ZSM-5 catalyst: a novel route for anti-coking in methanol to propylene reaction.

A novel route for anti-deactivation of methanol-to-propylene catalyst has been established through supporting nano-gold on ZSM-5, which efficiently reinforces the catalytic stability due to the effect of gold nanoparticles on the stabilization of dehydrogenation intermediates within the coking process.

A facile route to synthesize endurable mesopore containing ZSM-5 catalyst for methanol to propylene reaction.

A novel route is proposed for the preparation of mesopore containing zeolite ZSM-5 via in situ hydrothermal treatment of a solution containing alkali-dissolved SBA-15 containing carbonized surfactant P123 in the mesopores; it exhibited prominent stability enhancement for methanol to propylene reaction.

Anti-inflammatory function of Nodosin via inhibition of IL-2.

In order to explore the anti-inflammatory effects of Nodosin from Isodon serra, a traditional Chinese herb medicine, mouse T lymphocytes were incubated with Nodosin. In the current study, Nodosin suppressed the overproduction of the T lymphocytes; moreover, cell mitosis cycle was modulated by interfering with DNA replication in G1 stages via inhibition of IL-2 cytokine secretion at the mRNA level by Nodosin. Interestingly, Xylene-induced mouse tumescence model results suggested Nodosin depressed the murine ear-swelling extent and the level of IL-2 in the blood serum. Finally, Nodosin possessed significant anti-inflammatory effects and is a potential candidate for further clinical trial.

A novel catalyst with high activity for polyhydric alcohol oxidation: nanosilver/zeolite film.

A novel catalyst of silver nanoparticles over a zeolite film-coated copper grid (SZFC) has been fabricated via an in situ electrolytic method; it exhibited high catalytic activity and selectivity at a relatively low temperature for the partial oxidation of 1,2-propylene glycol to methyl glyoxal.