Intraoperative dexmedetomidine on postoperative sleep disturbance in older patients undergoing major abdominal surgery: A randomized controlled trial protocol.

Background: Postoperative sleep disturbance (PSD) occurs frequently in patients who undergo major abdominal surgical procedures. Dexmedetomidine is a promising agent to improve the quality of sleep for surgical patients. We designed this trial to investigate the effects of two different doses of intraoperative dexmedetomidine on the occurrence of PSD in elderly patients who have major abdominal surgery. Methods: In this randomized, double-blind, controlled trial, 210 elderly patients aged ≥65 years will be randomized, with an allocation ratio of 1:1:1, to two dexmedetomidine groups (intraoperative infusion of 0.3 or 0.6 µg/kg/h) and a normal saline placebo group. The primary endpoint is the occurrence of PSD on the first night after surgery, assessed using the Athens Insomnia Scale. The secondary endpoints are (1) the incidence of PSD during the 2nd, 3rd, 5th, 7th, and 30th nights postoperatively; (2) pain at rest and on movement at 24 and 48 h postoperatively, assessed using the Numerical Rating Scale; (3) the incidence of postoperative delirium during 0-7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method; (4) depressive symptoms during 0-7 days postoperatively or until hospital discharge, assessed using the 15-items Geriatric Depression Scale; and (5) quality of recovery on postoperative days 1, 2, and 3, assessed using the 15-items Quality of Recovery Scale. Patients' sleep data will also be collected by Xiaomi Mi Band 7 for further analysis. Discussion: The findings of this trial will provide clinical evidence for improving the quality of sleep among elderly patients undergoing major abdominal surgery. Ethics and dissemination: This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University (No. 2023-160). The results will be published in a peer-reviewed journal. Trial registration: Chinese Clinical Trial Registry (ChiCTR2300073163).

Postoperative C-Reactive Protein Predicts Postoperative Delirium in Colorectal Cancer Following Surgery.

Background: Postoperative delirium (POD) is a common complication in operative patients. Neuroinflammation has been reported to be a potential mechanism associated with the development of POD. Identifying available inflammatory markers such as C-reactive protein (CRP) would aid clinicians in early detection of POD. Previous studies have demonstrated that CRP may be a promising predictive marker for POD. Thus, this study aimed to explore the association between CRP and POD among those elderly colorectal cancer (CRC) patients. Methods: 643 patients with CRC were included in this study. CRP levels were measured before operation and on postoperative day 1. The univariate and multivariate regression analyses were used to identify risk factors for POD. Results: Of 643 patients with CRC, 112 cases (17.4%) had POD. CRC patients with POD showed older age, higher CRP level on postoperative day 1, and higher percentage of smoking, diabetes mellitus, and chronic obstructive pulmonary disease (COPD) than CRC patients without POD. Preoperative CRP level was not associated with the POD. Univariate and multivariate regression analyses showed that older age (> 70 years), diabetes mellitus, COPD, and higher CRP level on postoperative day 1 (> 48 mg/L) were risk factors for POD in CRC patients. Conclusion: Postoperative CRP level is an independent indicator for POD among CRC patients, suggesting the predictive role of postoperative CRP levels for POD in elderly CRC patients undergoing surgery.

Oleanolic acid regulates the Treg/Th17 imbalance in gastric cancer by targeting IL-6 with miR-98-5p.

BACKGROUND: Gastric cancer (GC) was a type of malignant tumor with a very high fatality rate. Oleanolic acid (OA) was a class of pentacyclic triterpenes which was proved to have anti-cancer activity. While the specific molecular mechanism of OA's role in inhibiting GC was not fully understood. This study aimed to explore how OA played an anti-cancer role in GC. METHODS: Expression of miR-98-5p was examined using qPCR, and expression levels of Treg/Th17-related factors were evaluated using qPCR and western blot. Flow cytometry was conducted to assess the proportion of Treg cells and Th17 cells. Besides, dual luciferase reporter assay was performed to verify that IL-6 was a target of miR-98-5p. RESULTS: Downregulation of miR-98-5p and upregulation of Treg/Th17-related factors were observed in GC tissues. What's more, the Treg/Th17 imbalance was found in PBMCs of GC patients. Overexpression of miR-98-5p promoted balance of Treg/Th17 cells via directly targeting IL-6 to downregulate expression of IL-6. Finally, OA could promote balance of Treg/Th17 cells by upregulating expression of miR-98-5p. DISCUSSION: All our results proved that OA could promote balance of Treg/Th17 cells in GC by targeting IL-6 with miR-98-5p, indicating a potential drug for treatment of GC.

Twelve New Genomic Loci Associated With Bone Mineral Density.

Aiming to identify more genomic loci associated with bone mineral density (BMD), we conducted a joint association analysis of 2 genome-wide association study (GWAS) by the integrative association method multi-trait analysis of GWAS (MTAG). The first one is the single GWAS of estimated heel BMD (eBMD) in the UK biobank (UKB) cohort (N = 426,824), and the second one is the GWAS meta-analysis of total body BMD (TB-BMD) in 66,628 participants from 30 studies. Approximate conditional association analysis was performed in the identified novel loci to identify secondary association signal. Statistical fine-mapping was conducted to prioritize plausible credible risk variants (CRVs). Candidate genes were prioritized based on the analyses of cis- expression quantitative trait locus (cis-eQTL) and cis-protein QTL (cis-pQTL) information as well as the functional category of the SNP. By integrating the information carried in over 490,000 participants, this largest joint analysis of BMD GWAS identified 12 novel genomic loci at the genome-wide significance level (GWS, p = 5.0 × 10-8), nine of which were for eBMD and four were for TB-BMD, explaining an additional 0.11 and 0.23% heritability for the two traits, respectively. These loci include 1p33 (lead SNP rs10493130, peBMD = 3.19 × 10-8), 5q13.2 (rs4703589, peBMD = 4.78 × 10-8), 5q31.3 (rs9324887, pTB-BMD = 1.36 × 10-9), 6p21.32 (rs6905837, peBMD = 3.32 × 10-8), 6q14.1 (rs10806234, peBMD = 2.63 × 10-8), 7q21.11 (rs10806234, pTB-BMD = 3.37 × 10-8), 8q24.12 (rs11995866, peBMD = 6.72 × 10-9), 12p13.31 (rs1639122, peBMD = 4.43 × 10-8), 12p12.1 (rs58489179, peBMD = 4.74 × 10-8), 12q24.23 (rs75499226, peBMD = 1.44 × 10-8), 19q13.31 (rs7255083, pTB-BMD = 2.18 × 10-8) and 22q11.23 (rs13056137, pTB-BMD = 2.54 × 10-8). All lead SNPs in these 12 loci are nominally significant in both original studies as well as consistent in effect direction between them, providing solid evidence of replication. Approximate conditional analysis identified one secondary signal in 5q13.2 (rs11738874, pconditional = 5.06 × 10-9). Statistical fine-mapping analysis prioritized 269 CRVs. A total of 65 candidate genes were prioritized, including those with known biological function to bone development (such as FGF1, COL11A2 and DEPTOR). Our findings provide novel insights into a better understanding of the genetic mechanism underlying bone development as well as candidate genes for future functional investigation.

Two novel pleiotropic loci associated with osteoporosis and abdominal obesity.

Aiming to uncover a shared genetic basis of abdominal obesity and osteoporosis, we performed a bivariate GWAS meta-analysis of femoral neck BMD (FNK-BMD) and trunk fat mass adjusted by trunk lean mass (TFMadj) in 11,496 subjects from 6 samples, followed by in silico replication in the large-scale UK Biobank (UKB) cohort. A series of functional investigations were conducted on the identified variants. Bivariate GWAS meta-analysis identified two novel pleiotropic loci 12q15 (lead SNP rs73134637, p = 3.45 × 10-7) and 10p14 (lead SNP rs2892347, p = 2.63 × 10-7) that were suggestively associated and that were replicated in the analyses of related traits in the UKB sample (osteoporosis p = 0.06 and 0.02, BMI p = 0.03 and 4.61 × 10-3, N up to 499,520). Cis-eQTL analysis demonstrated that allele C at rs73134637 was positively associated with IFNG expression in whole blood (N = 369, p = 0.04), and allele A at rs11254759 (10p14, p = 9.49 × 10-7) was negatively associated with PRKCQ expression in visceral adipose tissue (N = 313, p = 0.04) and in lymphocytes (N = 117, p = 0.03). As a proof-of-principle experiment, the function of rs11254759, which is 235 kb 5'-upstream from PRKCQ gene, was investigated by the dual-luciferase reporter assay, which clearly showed that the haplotype carrying rs11254759 regulated PRKCQ expression by upregulating PRKCQ promoter activity (p = 4.60 × 10-7) in an allelic specific manner. Mouse model analysis showed that heterozygous PRKCQ deficient mice presented decreased fat mass compared to wild-type control mice (p = 3.30 × 10-3). Mendelian randomization analysis demonstrated that both FNK-BMD and TFMadj were causally associated with fracture risk (p = 1.26 × 10-23 and 1.18 × 10-11). Our findings may provide useful insights into the genetic association between osteoporosis and abdominal obesity.

Association of genetic variations in IL-6/IL-6R pathway genes with gastric cancer risk in a Chinese population.

Interleukin-6 (IL-6) and its receptor (IL-6R) were regarded to be responsible for the occurrence of gastric cancer for their regulation roles in the inflammation. The genetic variations in these two genes (IL-6: rs6949149, rs1800796, rs10499563 and IL-6R: rs2228145) have been suggested to be associated with gastric cancer risk. However, the published results were inconsistent among subjects of different ethnicity. To evaluate such an association in Chinese population, we carried out this case-control study based on 473 patients with gastric cancer and 474 healthy controls, whose genotypes were detected by the Sequenom MassARRAY platform, and Helicobacter pylori infection was assessed by immunogold testing kit. This study showed that rs1800796 CG genotype was associated with decreased risk of gastric cancer (adjusted OR=0.75, 95% CI: 0.57-0.99, p=0.043). The stratified analysis revealed that, in the Helicobacter pylori negative infection subgroup, rs2228145 AC (adjusted OR=0.64, 95% CI: 0.42-0.97) and AC/CC (adjusted OR=0.66, 95% CI: 0.45-0.99) genotypes were associated with decreased risk of gastric cancer, respectively. In contrast, in the Helicobacter pylori positive infection subgroup, rs10499563 TC (adjusted OR=0.64, 95% CI: 0.43-0.95), CC (adjusted OR=0.35, 95% CI: 0.14-0.90), TC/CC (adjusted OR=0.59, 95% CI: 0.40-0.87) genotype were associated with decreased gastric cancer risk, respectively. Moreover, in the male subgroup, rs1800796 CG (adjusted OR=0.61, 95% CI: 0.44-0.84) and CG/GG (adjusted OR=0.67, 95% CI: 0.49-0.91) genotype were associated with decreased risk of gastric cancer, respectively. In short, this study suggested that IL-6R rs2228145 and IL-6 rs10499563 genotype were associated with decreased risk of gastric cancer for the individuals with negative and positive Helicobacter pylori infection.

Hyperbaric oxygen therapy in acute ischemic stroke: a review.

Stroke, also known as cerebrovascular disease, is a common and serious neurological disease, which is also the fourth leading cause of death in the United States so far. Hyperbaric medicine, as an emerging interdisciplinary subject, has been applied in the treatment of cerebral vascular diseases since the 1960s. Now it is widely used to treat a variety of clinical disorders, especially hypoxia-induced disorders. However, owing to the complex mechanisms of hyperbaric oxygen (HBO) treatment, the therapeutic time window and the undefined dose as well as some common clinical side effects (such as middle ear barotrauma), the widespread promotion and application of HBO was hindered, slowing down the hyperbaric medicine development. In August 2013, the US Food and Drug Administration declared artery occlusion as one of the 13 specific indications for HBO therapy. This provides opportunities, to some extent, for the further development of hyperbaric medicine. Currently, the mechanisms of HBO therapy for ischemic stroke are still not very clear. This review focuses on the potential mechanisms of HBO therapy in acute ischemic stroke as well as the time window.