Effects of a multilevel intervention of resistance training with or without beta-hydroxy-beta-methylbutyrate in medical ICU patients during entire hospitalisation: a four-arm multicentre randomised controlled trial.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether resistance training and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients. METHODS: In this multicentre, four-arm, single-blind randomised control trial, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the resistance training group received protocol-based multilevel resistance exercise, the HMB group received 3 g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model, adhering to the principles of intention-to-treat analysis. RESULTS: Resistance training and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group and substantial improvements in 6WMD (99.768 and 88.577 m, respectively) (all with P < 0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the resistance training and combination groups (P < 0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects. CONCLUSIONS: Resistance training with or without beta-hydroxy-beta-methylbutyrate during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected. TRIAL REGISTRATION: ChiCTR2200057685 was registered on March 15th, 2022.

The Specifically Androgen-Regulated Gene (SARG) Promotes Papillary Thyroid Carcinoma (PTC) Lymphatic Metastasis Through Vascular Endothelial Growth Factor C (VEGF-C) and VEGF Receptor 3 (VEGFR-3) Axis.

The papillary thyroid carcinoma (PTC) metastasizes through lymphatic spread, but the follicular thyroid cancer (FTC) metastasis occurs by following hematogenous spread. To date, the molecular mechanism underlying different metastatic routes between PTC and FTC is still unclear. Here, we showed that specifically androgen-regulated gene (SARG) was significantly up-regulated in PTC, while obviously down-regulated in FTC through analyzing the Gene Expression Omnibus (GEO) database. Immunohistochemistry assay verified that the PTC lymph node metastasis was associated with higher levels of SARG protein in clinical PTC patient samples. SARG-knockdown decreased TPC-1 and CGTH-W3 cells viability and migration significantly. On the contrary, SARG-overexpressed PTC cells possessed more aggressive migratory ability and viability. In vivo, SARG overexpression dramatically promoted popliteal lymph node metastasis of xenografts from TPC-1 cells mouse footpad transplanting. Mechanistically, SARG overexpression and knockdown significantly increased and decreased the expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor 3 (VEGFR-3), respectively, thereby facilitating or inhibiting the tube formation in HUVECs. The tube formation experiment showed that SARG overexpression and knockdown promoted or inhibited the number of tube formations in HUVEC cells, respectively. Taken together, we showed for the first time the differential expression profile of SARG between PTC and FTC, and SARG promotes PTC lymphatic metastasis via VEGF-C/VEGFR-3 signal. It indicates that SARG may represent a target for clinical intervention in lymphatic metastasis of PTC.

A novel chiral inorganic mesoporous silica used as a stationary phase in GC.

Chiral mesoporous silica (CMS) has attracted widespread attention because of some unique properties, such as high surface area, uniformly structured nanoscale cavities, and excellent chemical and thermal stability. In this work, we report the utilization of a CMS as the stationary phase for the separation of racemates in gas chromatography (GC). A CMS-coated capillary column was fabricated by a dynamic coating method. Eighteen racemates belonging to different classes of organic compounds were separated on this column, including chiral alcohols, aldehydes, ketones, organic acids, halohydrocarbons, alkenes, alcohol amines, epoxides, and amino acid derivatives. In addition, linear alkanes, alcohols, and aromatic hydrocarbons have also been resolved.

Optical resolution and mechanism using enantioselective cellulose, sodium alginate and hydroxypropyl-ß-cyclodextrin membranes.

Chiral solid membranes of cellulose, sodium alginate, and hydroxypropyl-ß-cyclodextrin were prepared for chiral dialysis separations. After optimizing the membrane material concentrations, the membrane preparation conditions and the feed concentrations, enantiomeric excesses of 89.1%, 42.6%, and 59.1% were obtained for mandelic acid on the cellulose membrane, p-hydroxy phenylglycine on the sodium alginate membrane, and p-hydroxy phenylglycine on the hydroxypropyl-ß-cyclodextrin membrane, respectively. To study the optical resolution mechanism, chiral discrimination by membrane adsorption, solid phase extraction, membrane chromatography, high-pressure liquid chromatography ultrafiltration were performed. All of the experimental results showed that the first adsorbed enantiomer was not the enantiomer that first permeated the membrane. The crystal structures of mandelic acid and p-hydroxy phenylglycine are the racematic compounds. We suggest that the chiral separation mechanism of the solid membrane is "adsorption - association - diffusion," which is able to explain the optical resolution of the enantioselective membrane. This is also the first report in which solid membranes of sodium alginate and hydroxypropyl-ß-cyclodextrin were used in the chiral separation of p-hydroxy phenylglycine.

Solid-phase extraction with metal-organic frameworks for the analysis of chiral compounds.

Metal-organic frameworks (MOFs) are excellent porous materials with nanoscale cavities and high surface areas, which make them promising as novel adsorbents in solid-phase extraction (SPE). In this article we report a new application of the chiral MOF [Zn2 (D-Cam)2 (4,4'-bpy)]n in SPE used for the measurement of the enantiomeric excess (ee) of (±)-1,1'-bi-2-naphthol. Several important experimental parameters that may influence the extraction efficiency were investigated and optimized. Under the optimum conditions, a good linearity (R2  > 0.999) was found between the ee value and the reciprocal of the peak areas. When compared with the actual ee measured using chiral HPLC, the SPE-based assay also showed good accuracy and precision. The results showed that SPE based on chiral MOFs as adsorbents is a simple and effective method for the determination of the ee values of chiral compounds.

[Preparative separation of alkaloids from Cortex Phellodendri by high speed countercurrent chromatography].

High speed countercurrent chromatography was successfully applied to the separation of alkaloids from Cortex Phellodendri with a two-phase solvent system composed of CHCl3-CH3OH-0.5 mol/L HCl (2:1:1, volume ratio). Some alkaloid components were obtained, and identification of berberine was made by thin-layer chromatography.