The association between perioperative pupillary parameters and postoperative acute pain: A pilot cross-sectional study.

OBJECTIVE: We aim to explore the capacity of perioperative pupillary variables to predict acute pain in the post-anesthesia care unit (PACU). METHODS: Patients scheduled to undergo thoracic or abdominal surgery under general anesthesia between April 2021 and June 2021 were enrolled. We measured the pupil diameter, pupillary light reflex (PLR), and pupillary reflex dilatation 5 min before anesthesia induction (T1), 5 min after intubation (T2), at the end of anesthesia (T3), immediately before extubation (T4), and 5 min after extubation (T5). We assessed the early postoperative pain intensity in the PACU using Numeric Rating Scales (NRS) at recovery, 5 min after recovery, and 10 min after recovery. Logistic regression models were used to evaluate the association between perioperative pupillary variables and postoperative pain intensity. RESULTS: Fifty-one patients were enrolled, 50 of whom were included in the final analysis. A total of 13 patients (26%) needed remedial analgesia in the PACU. Pupil parameters at T1, T2, T3, and T5 were not associated with NRS in the PACU. Multiple logistic regression models and receiver operating characteristic (ROC) curves indicated that only latency of PLR at T4 can predict postoperative acute pain. The ROC analysis showed that the cutoff value for latency of PLR at T4 was 0.29 s to discriminate between no pain and pain, and the area under the curve was 0.778 (95% CI 0.634-0.922, p = 0.002) with sensitivity 50.0% and specificity 91.7%. CONCLUSION: The latency of PLR immediately before extubation may be a useful predictor for postoperative acute pain in the PACU.

Isolation, synthesis and absolute configuration of 4,5-dihydroxypiperines improving behavioral disorder in AlCl3-induced dementia.

A pair of stereoisomers of new 4,5-dihydroxypiperine was isolated from P. retrofractum and showed profound activity on AlCl3-induced dementia. In order to determine their absolute configurations and biological activities, all four possible stereoisomers of 4,5-dihydroxypiperine were synthesized from piperidine by Sharpless asymmetric dihydroxylation and Mitsunobu reaction. Their absolute configurations were established as (4R,5R) (1), (4S,5S) (2), (4S,5R) (3) and (4R,5S) (4) by NMR, optical rotation and CD spectra. It is note that only compound 4 improved behavioral disorder in AlCl3-induced dementia. Accordingly, the pair of stereoisomers isolated from P. retrofractum was determined to be (4S,5S) and (4R,5S)-isomers (2 and 4). The ratio of the epimers was present as 1:0.7 (4:2).

[Construction of three HLA-A*0201-peptide tetramers and their preliminary application in detection of vitiligo-specific cytotoxic T lymphocytes].

OBJECTIVE: To construct vitiligo-specific HLA-A*0201-peptide tetramers and to apply the constructed tetramers in detection of vitiligo-specific cytotoxic T lymphocytes (CTL). METHODS: Proteins HLA-A0201*-BSP and ß2M were obtained by effective prokaryotic expression. The purified proteins were refolded with vitiligo antigen peptides MelanA 26-35, gp100 209-217, and tyrosinase 1-9, respectively to form HLA-A*0201-peptide complex. The complex was biotinylated by BirA enzyme and purified by gel-filtration chromatography. The tetramers were generated by mixing the complex with phycoerythrin (PE)-streptavidin at a ratio of 4∶1 and identified by Dot-blot assay. The capacity of tetramer to detect vitiligo-specific CTL was analyzed by flow cytometry. RESULTS: The biotinylation of vitiligo-specific HLA-A*0201-peptide tetramers were successfully performed by Dot-blot. Flow cytometry analysis indicated that the tetramer effectively bound to specific CTL from peripheral blood of patients with vitiligo. CONCLUSION: Three kinds of biotinylated vitiligo-specific HLA-A*0201-peptide tetramers have been constructed successfully. The tetramer can detect antigen specific CTL from patients with vitiligo.

[Single mini-incision combined with honeycomb titanium plate in treatment of acute acromioclavicular joint dislocation].

OBJECTIVE: To explore clinical effect of single small incision with honeycomb titanium plate in treating acute acromioclavicular dislocation. METHODS: The clinical data of 40 patients with acute acromioclavicular dislocation admitted from December 2019 to December 2021 were retrospectively analyzed and divided into two groups according to different surgical methods. Among them, 20 patients were fixed with single small incision with honeycomb titanium plate (titanium plate group), including 11 males and 9 females, aged from 23 to 65 years old with an average of (47.40±12.58) years old;12 patients on the left side, 8 patients on the right side;11 patients with type Ⅲ, 3 patients with type Ⅳ, and 6 patients with type Ⅴ according to Rockwood classification. Twenty patients were fixed with clavicular hook plate (clavicular hook group), including 8 males and 12 females, aged from 24 to 65 years old with an average of (48.40±12.08) years old;12 patients on the left side, 8 patients on the right side;10 patients with type Ⅲ, 2 patients with type Ⅳ, and 8 patients with type Ⅴ according to Rockwood classification. Operative time, incision length, intraoperative blood loss, hospital stay, visual analogue scale (VAS) and Constant-Murley score of shoulder joint function were compared between two groups. Anteroposterior radiographs of the affected shoulder joint were recorded before, immediately and 6 months after surgery, and the coracoclavicular distance was measured and compared. RESULTS: Both groups of patients were successfully completed operation without serious complications. All patients were followed up for 6 to 15 months with an average of (11.9±4.8) months. There were no incisional infection, internal plant fracture or failure, bone tunnel fracture and other complications occurred. The incision length of titanium plate group (35.90±3.14) mm was significantly shorter than that of clavicular hook group (49.30±3.79) mm (P<0.05). There were no significant difference in operative time, intraoperative blood loss and hospital stay between two groups (P>0.05). At 1 and 3 months after operation, VAS of titanium plate group was lower than that of clavicular hook group (P<0.05). Connstant-Murley scores in titanium plate group at 1, 3 and 6 months after operation were (86.80±1.36), (91.60±2.32) and (94.90±2.22), respectively;and in clavicular hook group were (78.45±5.47), (85.55±2.01) and (90.25±1.92), which were higher than that of clavicular hook group (P<0.05). There was no significant difference in coracoclavicular distance between two groups immediately and 6 months after operation(P>0.05). CONCLUSION: For the treatment of acute acromioclavicular joint dislocation, single small incision combined with honeycomb titanium plate have advantages of shorter incision, fast recovery of shoulder joint function without the second operation, and has good satisfaction of patient.

Identification of particle distribution pattern in vertical profile via unmanned aerial vehicles observation.

Below the boundary layer, the air pollutants have been confirmed to present the decreasing trend with the height in most situaitons. However, the disperiosn rate of air pollutants in the vertical profile is rarely investigated in detail, especially through in-situ measurement. With this consideration, we employed an unmanned aerial vehicle equipped with portable monitoring equipments to scrutinize the vertical distribution of PM2.5. Based on the original data, we found that PM2.5 concentration decreases gradually with altitude below the boundary layer and demonstrated an obvious linear correlation. Therefore, the vertical distribution of PM2.5 was quantified by representing the distribution of PM2.5 with the slope of PM2.5 vertical distribution. We used backward trajectories to reveal the causes of outliers (PM2.5 increasing with altitude), and found that PM2.5 in the high altitude came from the southwest. Besides, the relationship between the vertical distribution of PM2.5 and various meteorological factors was investigated using stepwise regression analysis. The results show that the four meteorological factors most strongly correlated with the slope values are: (a) the difference in relative humidity between the ground and the air; (b) the difference in temperature between the ground and the air; (c) the height of the boundary layer; and (d) the wind speed. The slope values increase with increasing the difference in relative humidity between ground and air and the difference in temperature between the ground and the air, and decrease with increasing boundary layer height and wind speed. According to the Random Forest calculations, the ground-to-air relative humidity difference is the most important at 0.718; the wind speed is the least important at 0.053; and the ground-to-air temperature difference and boundary layer height are 0.140 and 0.088, respectively.

Exosomal RBP4 potentiated hepatic lipid accumulation and inflammation in high-fat-diet-fed mice by promoting M1 polarization of Kupffer cells.

Exosomes containing various biological cargoes have potential to be novel diagnostic biomarkers for metabolic diseases. In this study, retinol-binding protein 4 (RBP4) was found to be enriched in serum exosomes, and its increased levels could be considered as an independent risk factor for the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Exosomal RBP4 (exo-RBP4), primarily derived from hepatocytes, significantly enhanced the M1-like polarization of Kupffer cells (KCs) via promoting the activation of NOX2 and NF-κB and reactive oxygen species (ROS) accumulation, resulting in the over-production of inflammatory cytokines including TNF-α. Subsequently, those excess cytokines remarkably increased the levels of intracellular free fatty acid uptake and lipogenesis-related genes (FAS and SREBP-1c) but decreased fatty acid degradation-related genes (CPT-1 and PPARα) in palmitic acid-treated LO2 cells. More notably, TNF-α significantly elevated RBP4 transcription by activating STAT3 in hepatocytes, playing a positive role in NAFLD development. Intravenous injection with RBP4 (50 µg/kg) potentiated hepatic lipid accumulation, M1-type KC proportion, and serum pro-inflammatory cytokine levels in the hepatic tissues of high-fat-diet-fed mice. Collectively, these data indicated that exo-RBP4 converted KCs to M1 subtype by mediating the NOX2/ROS/NF-κB pathway, subsequently promoting de novo lipogenesis in hepatocytes by TNF-α secretion to activate the JAK2/STAT3 signaling pathway. Therefore, this study uncovered a novel intercellular communication between the inflammatory microenvironment and lipid metabolism for fostering NAFLD progression and found the potential of exo-RBP4 as a novel diagnostic biomarker and therapeutic target for NAFLD.

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

Effects of sulfur dosage on continuous bioleaching of heavy metals from contaminated sediment.

The bioleaching technology has been considered as a promising green technology for remediation of contaminated sediments in recent years. Bioleaching technology was generally conducted in the batch bioreactor; however, the continuous bioreactor should be developed for the application of bioleaching technology in the future. The purposes of this study were to establish a continuous bioleaching process, and to evaluate the effects of sulfur dosage on the efficiency of metal removal during this continuous bioleaching process. The obtained results show that the pH decrease, sulfate production and metal removal efficiency all increased with increasing sulfur dosage in the continuous bioleaching process due to high substrate concentration for sulfur-oxidizing bacteria. After 30 days of operation time, the maximum solubilization efficiencies for Zn, Ni, Cu and Cr were found to be 78%, 90%, 88% and 68%, respectively, at 5% of sulfur dosage. After the bioleaching process, heavy metals bound in the carbonates, Fe-Mn oxides and organics/sulfides in the sediment were effectively removed and the potential ecological and toxic risks of treated sediment were greatly reduced. The results of bacterial community analyses demonstrated that this continuous bioleaching process were dominated by several acidophilic sulfur-oxidizing bacteria; S. thermosulfidooxidans, At. thiooxidans/At. ferrooxidans, S. thermotolerans and At. albertensis, whereas the percentage of less-acidophilic sulfur-oxidizing bacteria (T. thioparus and T. cuprina) was lower than 15% of total bacteria. In addition, the cell numbers of sulfur-oxidizing bacteria increased as the sulfur dosage was increased in the continuous bioleaching process.

The Role of Respiratory Flora in the Pathogenesis of Chronic Respiratory Diseases.

Large quantities of bacteria, including Firmicutes, Actinobacteria, and Bacteroidetes, colonize the surface of the respiratory mucosa of healthy people. They interact and coexist with the local mucosal immune system of the human airway, maintaining the immune stability and balance of the respiratory system. While suffering from chronic respiratory diseases, the microbial population in the airway changes and the proportion of Proteobacteria is increased in patients with asthma. The abundance of the microbial population in patients with chronic obstructive pulmonary disease (COPD) is decreased, and conversely, the proportion of Firmicutes and Proteobacteria increased. The diversity of airway microorganisms in cystic fibrosis (CF) patients is decreased, while pathogenic bacteria and conditional pathogenic bacteria are proliferated in large numbers. The proportion of Firmicutes and Proteobacteria is increased in patients with upper airway cough syndrome (UACS), which replaces the dominance of Streptococcus and Neisseria in the pharynx of a normal population. Therefore, a clear understanding of the immune process of the airway flora and the immune dysfunction of the flora on the pathogenesis of chronic respiratory diseases can provide new ideas for the prevention and treatment of human respiratory diseases.

Radiomics nomogram for prediction disease-free survival and adjuvant chemotherapy benefits in patients with resected stage I lung adenocarcinoma.

BACKGROUND: Robust imaging biomarkers are needed for risk stratification in stage I lung adenocarcinoma patients in order to select optimal treatment regimen. We aimed to construct and validate a radiomics nomogram for predicting the disease-free survival (DFS) of patients with resected stage I lung adenocarcinoma, and further identifying candidates benefit from adjuvant chemotherapy (ACT). METHODS: Using radiomics approach, we analyzed 554 patients' computed tomography (CT) images from three multicenter cohorts. Prognostic radiomics features were extracted from computed tomography (CT) images and selected using least absolute shrinkage and selection operator (LASSO) Cox regression model to build a radiomics signature for DFS stratification. The biological basis of radiomics was explored in the Radiogenomics dataset (n=79) by gene set enrichment analysis (GSEA). Then a nomogram that integrated the signature with these significant clinicopathologic factors in the multivariate analysis were constructed in the training cohort (n=238), and its prognostic accuracy was evaluated in the validation cohort (n=237). Finally, the predictive value of nomogram for ACT benefits was assessed. RESULTS: The radiomics signature with higher score was significantly associated with worse DFS in both the training and validation cohorts (P<0.001). The GSEA presented that the signature was highly correlated to characteristic metabolic process and immune system during cancer progression. Multivariable analysis revealed that age (P=0.031), pathologic TNM stage (P=0.043), histologic subtype (P=0.010) and the signature (P<0.001) were independently associated with patients' DFS. The integrated radiomics nomogram showed good discrimination performance, as well as good calibration and clinical utility, for DFS prediction in the validation cohort. We further found that the patients with high points (point ≥8.788) defined by the radiomics nomogram obtained a significant favorable response to ACT (P=0.04) while patients with low points (point <8.788) showed no survival difference (P=0.7). CONCLUSIONS: The radiomics nomogram could be used for prognostic prediction and ACT benefits identification for patient with resected stage I lung adenocarcinoma.

Clinical epidemiology of gastric cancer in Hehuang valley of China: a 10-year epidemiological study of gastric cancer.

AIM: To investigate the clinical epidemiological characteristics of gastric cancer in the Hehuang valley, China, to provide a reference for treatment and prevention of regional gastric cancer. METHODS: Between February 2003 and February 2013, the records of 2419 patients with gastric cancer were included in this study. The patient's characteristics, histological and pathological features, as well as the dietary habits of the patients, were investigated. RESULTS: The clinical data showed that adenocarcinoma was the leading histological type of gastric cancer in this area. Characteristics of gastric cancer in different ethnic groups and age showed that the 60.55-65.50 years group showed the high incidence of gastric cancer in all ethnic groups. There were more male gastric cancer patients than female. Intestinal was the most common type of gastric cancer in the Hehuang valley. There was no significant difference in the proportion of sex in terms of Helicobacter pylori infection. The impact of dietary habits on gastric cancer showed that regular consumption of fried or grilled food, consumption of high-salt, high-fat and spicy food and drinking strong Boiled brick-tea were three important factors associated with gastric cancer in males and females. CONCLUSION: Differences existed in race, sex, and age of patients according to the epidemiology of gastric cancer in the Hehuang valley. Moreover, dietary habits was also an important factor contributing to gastric cancer.