High-flow nasal cannula oxygen therapy during anesthesia recovery for older orthopedic surgery patients: A prospective randomized controlled trial.

BACKGROUND: Hypoxemia is a common complication in older patients during postoperative recovery and can cause pulmonary complications. Therefore, reducing the incidence of postoperative hypoxemia is a clinical concern. AIM: To investigate the clinical efficacy of high-flow nasal cannula oxygen (HFNCO) in the resuscitation period of older orthopedic patients. METHODS: In this prospective randomized controlled trial, 60 older patients who underwent orthopedic surgery under general anesthesia were randomly divided into two groups: those who used conventional face mask and those who used HFNCO. All patients were treated with 60% oxygen for 1 h after extubation. Patients in the conventional face mask group were treated with a combination of air (2 L) and oxygen (2 L) using a traditional mask, whereas those in the HFNCO group were treated with HFNCO at a constant temperature of 34 °C and flow rate of 40 L/min. We assessed the effectiveness of oxygen therapy by monitoring the patients' arterial blood gas, peripheral oxygen saturation, and postoperative complications. RESULTS: The characteristics of the patients were comparable between the groups. One hour after extubation, patients in HFNCO group had a significantly higher arterial partial pressure of oxygen (paO2) than that of patients in conventional face mask group (P < 0.001). At extubation and 1 h after extubation, patients in both groups showed a significantly higher arterial partial pressure of carbon dioxide (paCO2) than the baseline levels (P < 0.001). There were no differences in the saturation of peripheral oxygen, paO2, and paCO2 between the groups before anesthesia and before extubation (P > 0.05). There were statistically significant differences in paO2 between the two groups before anesthesia and 1 h after extubation and immediately after extubation and 1 h after extubation (P < 0.001). However, there were no significant differences in the oxygen tolerance score before leaving the room, airway humidification, and pulmonary complications 3 d after surgery between the two groups (P > 0.05). CONCLUSION: HFNCO can improve oxygen partial pressure and respiratory function in elderly patients undergoing orthopedic surgery under general endotracheal anesthesia. Thus, HFNCO can be used to prevent postoperative hypoxemia.

Mutational profiling of melanomas in patients from the southeast coast of China.

BACKGROUND: Melanoma is one of the most lethal cancers in China, and the genomic landscape of melanoma in the Asian population is different from Caucasians. METHODS: To better understand the genomic profile of distinct kinds of melanomas in China, we used an NGS platform to analysis of 62 melanomas from the southeast coast of China. RESULTS: The recurrently mutated genes are BRAF (29%), RAS (29%), CTNNB1 (11.3%), KIT (9.7%) and NF1 (8.1%) in the whole group. Among the different types of melanoma, cutaneous melanoma has a high frequency of BRAF mutation (70.6%), NRAS (57.1%) is the top one gene found in the mucosal group. For acral melanoma, except for the RAS family, CTNNB1 mutation (13.2%) first found to be frequently mutated in our cohort and patients with CTNNB1 activating mutation. These results may be related to a more reduced response to immunotherapy, according to the earlier report. CONCLUSIONS: Our study profiled the mutational landscape of melanoma in patients from the southeast coast of China. In addition to the most frequently mutated genes (BRAF, RAS, KIT) reported in other studies, we found some new recurrent gene mutations, such as CTNNB1 mutation in acral melanoma, that had not been reported in other studies.

Gene expression profile of the hippocampus of rats subjected to traumatic brain injury.

Traumatic brain injury (TBI) is a serious public health problem as well as a leading cause of severe posttraumatic disability. Numerous studies indicate that the differentially expressed genes (DEGs) of neural signaling pathways are strongly correlated with brain injury. To further analyze the roles of the DGEs in the central nervous system, here we systematically investigated TBI on the hippocampus and its injury mechanism at the whole genome level. On the basis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Analyses, we revealed that the DEGs were involved in many signaling pathways related to the nervous system, especially neuronal survival-related pathways. Finally, we verified the microarray results and detected the gene expression of neuronal survival-related genes in the hippocampus by using real-time quantitative polymerase chain reaction. With Western blot and axon growth assay, the expression of P2rx3 was upregulated in rats subjected to TBI, and overexpression of P2rx3 promoted neurite growth of NG108 cells. Our results suggested that the DEGs (especially P2rx3) and several signaling pathways might play a pivotal role in TBI. We also provided several targeted genes related to TBI for future investigation.

Intramolecular dehydrogenative C-S bond coupling of thioamides to form 1,3-benzothiazines under metal-free conditions.

A novel HTIB-promoted direct intramolecular dehydrogenative C-S bond coupling reaction of thioamides has been developed to provide 1,3-benzothiazine derivatives in good yields. The reaction proceeds smoothly to reach completion at room temperature within 1 min under metal-free conditions. This protocol provides a mild and efficient strategy for the synthesis of six-membered N,S-containing heterocycles. Preliminary mechanistic studies indicate that a spirocyclic intermediate might be involved.

Negative-Pressure Hydrocephalus: A Case Report on Successful Treatment Under Intracranial Pressure Monitoring with Bilateral Ventriculoperitoneal Shunts.

BACKGROUND: Negative-pressure hydrocephalus (NegPH), a very rare condition of unknown etiology and optimal treatment, usually presents postneurosurgery with clinical and imaging features of hydrocephalus, but with negative cerebrospinal fluid pressure. CASE DESCRIPTION: We describe a NegPH case of -3 mm Hg intracranial pressure that was successfully treated to achieve 5 mm Hg under continuous intracranial pressure monitoring with horizontal positioning, head down and legs elevated to 10°-15°, neck wrapping for controlled venous drainage, chest and abdomen bandages, infusion of 5% dextrose fluid to lower plasma osmolarity (Na+, 130-135 mmol/L), daily cerebrospinal fluid drainage >200 mL, and arterial blood gas partial pressure of carbon dioxide >40 mm Hg.

Genetic landscape of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.

CEACAM5 has different expression patterns in gastric non-neoplastic and neoplastic lesions and cytoplasmic staining is a marker for evaluation of tumor progression in gastric adenocarcinoma.

OBJECTIVE: The aim of this study was to investigate the expression patterns of CEACAM5 in non-neoplastic and neoplastic gastric lesions, as well as its application in the differential diagnosis and its relationship with tumor progression. METHODS: CEACAM5 expression was detected by immunohistochemical staining in the serial sections of the gastric neoplastic and non-neoplastic lesions. The impacts of CEACAM5 expression patterns on tumor progression were evaluated by statistics, the clinical and pathological data included sex, age, tumor extension, lymph node involvement and tumor staging. RESULTS: There was no CEACAM5 expression in normal gastric epithelial cells. In hyperplastic polyps, CEACAM5 was expressed with apical membranous staining in the hyperplastic and prolonged gastric pit adjacent to the surface. Intestinal metaplasia (IM) expressed CEACAM5 mainly with membranous pattern, and some cases showed membranous staining mixed with cytoplasmic staining. GIN expressed CEACAM5 mainly with membranous staining, but the mixed staining of cytoplasmic and membranous patterns increased, and especially in the high grade GIN, cytoplasmic staining of CEACAM5 began to occur. Compared with IM and GIN, CEACAM5 expression patterns of hyperplastic polyp showed a significant difference (P=0.000). IM, low grade GIN and the whole GIN showed no significant difference in CEACAM5 expression patterns (P=0.355), but IM and high grade GIN showed a significant difference (P=0.027). There was a significant difference between low and high grade GIN (P=0.002). GIN and well-differentiated carcinomas showed no significant difference (P=0.070), but low grade GIN and well differentiated carcinomas showed a significant difference (P=0.006). In gastric adenocarcinomas, CEACAM5 expression patterns showed a significant difference in tumor grading (P=0.010) and Laurén classification (P=0.001). In histological grading, well differentiated carcinomas showed more membranous staining than moderately and poorly differentiated, and more cytoplasmic CEACAM5 staining was detected in moderately and poorly differentiated carcinomas. Similar to that, in Laurén classification, intestinal carcinomas showed more membranous staining, and diffuse carcinomas showed more cytoplasmic staining. Moreover, CEACAM5 expression patterns showed a significant difference in tumor extension (P=0.012), lymph node involvement (P=0.015) and tumor staging (P=0.002), suggesting that CEACAM5 should be involved in tumor progression. In advanced carcinomas, CEACAM5 was expressed with more cytoplasmic staining regardless of the histological classification. CONCLUSION: CEACAM5 had different expression patterns in gastric non-neoplastic and neoplastic lesions. The CEACAM5 expression patterns were associated with tumor progression. Membranous staining of CEACAM5 might be a marker of premalignancy in gastric lesions, and cytoplasmic CEACAM5 might enhance tumor invasion and migration and be an evaluated marker for progressive and advanced gastric cancer. Also, it might be useful for the differential diagnosis of gastric premalignant lesions.

Molecular modeling, docking and dynamics simulations of GNA-related lectins for potential prevention of influenza virus (H1N1).

The Galanthus nivalis agglutinin (GNA)-related lectin family exhibit significant anti-HIV and anti-HSV properties that are closely related to their carbohydrate-binding activities. However, there is still no conclusive evidence that GNA-related lectins possess anti-influenza properties. The hemagglutinin (HA) of influenza virus is a surface protein that is involved in binding host cell sialic acid during the early stages of infection. Herein, we studied the 3D-QSARs (three-dimensional quantitative structure-activity relationships) of lectin- and HA-sialic acid by molecular modeling. The affinities and stabilities of lectin- and HA-sialic acid complexes were also assessed by molecular docking and molecular dynamics simulations. Finally, anti-influenza GNA-related lectins that possess stable conformations and higher binding affinities for sialic acid than HAs of human influenza virus were screened, and a possible mechanism was proposed. Accordingly, our results indicate that some GNA-related lectins, such as Yucca filamentosa lectin and Polygonatum cyrtonema lectin, could act as drugs that prevent influenza virus infection via competitive binding. In conclusion, the GNA-related lectin family may be helpful in the design of novel candidate agents for preventing influenza A infection through the use of competitive combination against sialic acid specific viral infection.

Plant lectins: targeting programmed cell death pathways as antitumor agents.

Lectins, a group of highly diverse, carbohydrate-binding proteins of non-immune origin that are ubiquitously distributed in plants, animals and fungi, are well-characterized to have numerous links a wide range of pathological processes, most notably cancer. In this review, we present a brief outline of the representative plant lectins including Ricin-B family, proteins with legume lectin domains and GNA family that can induce cancer cell death via targeting programmed cell death pathways. Amongst these above-mentioned lectins, we demonstrate that mistletoe lectins (MLs), Ricin, Concanavalin A (ConA) and Polygonatum cyrtonema lectin (PCL) can lead to cancer cell programmed death via targeting apoptotic pathways. In addition, we show that ConA and PCL can also result in cancer cell programmed death by targeting autophagic pathways. Moreover, we summarize the possible anti-cancer therapeutic implications of plant lectins such as ConA, Phaseolus vulgaris lectin (PHA) and MLs that have been utilized at different stages of preclinical and clinical trials. Together, these findings can provide a comprehensive perspective for further elucidating the roles of plant lectins that may target programmed cell death pathways in cancer pathogenesis and therapeutics. And, this research may, in turn, ultimately help cancer biologists and clinicians to exploit lectins as potential novel antitumor drugs in the future.