Spherical Nucleic Acid-Mediated Spatial Matching-Guided Nonenzymatic DNA Circuits for the Prediction and Prevention of Malignant Tumor Invasion.

Detection of intracellular miRNAs, especially sensitive imaging of in vivo miRNAs, is vital to the precise prediction and timely prevention of tumorgenesis but remains a technical challenge in terms of nuclease resistance and signal amplification. Here, we demonstrate a gold nanoparticle-based spherical nucleic acid-mediated spatial matching-guided nonenzymatic DNA circuit (SSDC) for efficient screening of intracellular miRNAs and, in turn, finding cancerous tissues in living organisms before the appearance of clinical symptoms. Due to the substantially enhanced nuclease resistance, the false positive signal is avoided even in a complex biological medium. Target miRNA can straighten out the hairpin DNA probe to be linear, allowing the probe to penetrate into the internal region of a core/shell DNA-functionalized signal nanoampfilier and initiate a strand displacement reaction, generating an amplified fluorescence signal. The detection limit is as low as 17 pM, and miRNA imaging is in good accordance with the gold standard polymerase chain reaction method. The ability to image intracellular miRNAs is substantially superior to that of conventional fluorescence in situ hybridization techniques, making in vivo SSDC-based imaging competent for the precise prediction of tumorigenesis. By intratumoral chemotherapy guided by SSDC-based imaging, tumorigenesis and progression are efficiently controlled before the onset of clinical symptoms.

Inverse association between age and risk of lymph node metastasis in patients with early gastric cancer: a surveillance, epidemiology, and end results analysis.

Background: Recent studies have shown that young patients with gastric cancer are at a more advanced stage and have poor survival, but the cause is still unclear. The prognosis of gastric cancer is closely related to LNM, but the relationship between age and LNM in early gastric cancer (EGC) is currently unclear. Therefore, we aimed to study the relationship between age and the risk of LNM in EGC. Materials and Methods: We screened out patients with EGC who underwent surgery from the SEER research database from 1975 to 2016, and retrospectively analyzed the proportion of LNM in different age groups. We grouped age into 18-39, 40-49, 50-59, 60-69, 70-79, and ≥ 80 years old, and used univariate analysis and multivariate logistic regression to analyze the correlation between age and LNM. Results: We included 9231 patients with EGC, with LNM rates of 20.3%, 23.3%, 21.0%, 19.8%, 18.1%, and 13.2% in the age groups of 18-39 years old (2.3%), 40-49 (6.1%), 50-59 years old (15.7%), 60-69 years old (24.8%), 70-79 years old (27.2%) and ≥80 years old (23.9%), respectively. We found that when older than 39 years old, the risk of LNM and postoperative survival time of EGC patients decrease (p<0.001). Multivariate analysis results showed that age, tumor size, the number of retrieved lymph nodes (rN), tumor grade, and tumor location were related to LNM. Conclusions: This study found that age in patients with EGC was inversely related to the risk of LNM, and positively correlated with postoperative survival. For older patients with EGC, endoscopic treatment is more appropriate. For young patients with EGC, LNM should be considered when choosing endoscopic treatment.

Local resection via partial lamellar sclerouvectomy for ciliary body tumors - a case series.

BACKGROUND: Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China. METHODS: Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months. RESULTS: Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00-10.00) and the mean tumor thickness was 3.50 mm (range: 2.00-5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up. CONCLUSIONS: Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

The LANCET robotic system can improve surgical efficiency in total hip arthroplasty: A prospective randomized, multicenter, parallel-controlled clinical trial.

Objective: To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial. Methods: A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively. Results: None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications. Conclusion: The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications. The translational potential of this article: In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan for National Science and Technology Strategy.

Predictors of iatrogenic splenic injury in radical gastrectomy for gastric cancer.

Background: Iatrogenic splenic injury (ISI) is a recognized complication in radical gastrectomy that may result in incidental splenectomy (IS). However, the predictors of such events remain largely unknown. Methods: Medical records of the patients who underwent radical gastrectomy at our institution between January 2015 and December 2022 were retrospectively reviewed. Potential predictors of ISI and IS were collected and analyzed by multivariate logistic regression. Results were reported as an odds ratio (OR) with 95% confidence intervals (CI). Results: A total of 2916 patients were included, of whom 211 patients (7.2%) suffered from ISI and 75 patients (2.6%) underwent IS. Multivariate analysis demonstrated that BMI≥25 (OR: 3.198 (2.356-4.326), p<0.001), total gastrectomy (OR: 2.201 (1.601-3.025), p<0.001), and the existence of "criminal fold" (OR: 13.899 (2.824-251.597), p=0.011) were independent predictive risk factors for ISI; whereas laparoscopic surgical approach (OR: 0.048 (0.007-0.172), p<0.001) was a protective factor for ISI. Moreover, the existence of "criminal fold" (OR: 15.745 (3.106-288.470), p=0.008) and BMI≥25 (OR: 2.498 (1.002-6.046), p=0.044) were identified as independent risk factors of ISI under laparoscopic gastrectomy. There was no association between sex, age, previous abdominal surgery, neoadjuvant therapy, outlet obstruction, tumor stage, nodal stage, and total lymph node retrieved and ISI. Conclusions: BMI≥25 and total gastrectomy can predict high risk of ISI during radical gastrectomy. Laparoscopic surgery is superior to open gastrectomy in lowing the risk of ISI.

Joint trajectories of bullying victimization and sexual harassment victimization as predictors of adolescent alcohol use.

OBJECTIVE: The present study examined the independent and joint effects of bullying victimization and sexual harassment victimization on adolescent alcohol use over time within a community sample of adolescents. METHOD: Adolescents aged 13-15 years old at baseline (N = 800, Mage = 14.42, SD = 0.83; 57.5% female) recruited from Western New York State made five online survey reports of peer victimization and alcohol use over a 2-year period. Latent class growth analysis was used to identify trajectory classes of victimization from bullying and sexual harassment over time, and regression modeling was used to examine the associations with later alcohol use. RESULTS: Three developmental courses were identified for bullying victimization (moderate/decreasing, high/decreasing, never or low) and for sexual harassment victimization (moderate/decreasing, moderate/increasing, never or low). Adolescents in the moderate/decreasing group of bullying victimization subsequently consumed more alcoholic drinks when they drank. Belonging to the moderate/increasing group of sexual harassment was associated with increased later alcohol intoxication and number of drinks. Bullying victimization and sexual harassment victimization were concurrently correlated over time. Adolescents who followed the joint trajectory group of moderately decreasing bullying and increasing sexual harassment were more likely to report increased later alcohol intoxication and number of drinks. CONCLUSIONS: Moderate levels of bullying victimization along with increasing sexual harassment victimization are associated prospectively with greater alcohol use in adolescence. Findings highlight the importance of considering the cumulative, joint effects of multiple types of peer victimization on adolescent health outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Unveiling the Broad Substrate Specificity of Deoxynivalenol Oxidation Enzyme DepA and Its Role in Detoxifying Trichothecene Mycotoxins.

DepA, a pyrroloquinoline quinone (PQQ)-dependent enzyme isolated from Devosia mutans 17-2-E-8, exhibits versatility in oxidizing deoxynivalenol (DON) and its derivatives. This study explored DepA's substrate specificity and enzyme kinetics, focusing on DON and 15-acetyl-DON. Besides efficiently oxidizing DON, DepA also transforms 15-acetyl-DON into 15-acetyl-3-keto-DON, as identified via LC-MS/MS and NMR analysis. The kinetic parameters, including the maximum reaction rate, turnover number, and catalytic efficiency, were thoroughly evaluated. DepA-PQQ complex docking was deployed to rationalize the substrate specificity of DepA. This study further delves into the reduced toxicity of the transformation products, as demonstrated via enzyme homology modeling and in silico docking analysis with yeast 80S ribosomes, indicating a potential decrease in toxicity due to lower binding affinity. Utilizing the response surface methodology and central composite rotational design, mathematical models were developed to elucidate the relationship between the enzyme and cofactor concentrations, guiding the future development of detoxification systems for liquid feeds and grain processing. This comprehensive analysis underscores DepA's potential for use in mycotoxin detoxification, offering insights for future applications.

Comparison evaluation pretreatments on the quality characteristics, oxidative stability, and volatile flavor of walnut oil.

In this study, we applied various thermal pretreatment methods (e.g., hot-air, microwave, and stir-frying) to process walnut kernels, and conducted comparative analysis of the physicochemical properties, nutritional components, in vitro antioxidant activity, and flavor substances of the extracted walnut oil (WO). The results indicated that, thermal pretreatment significantly increased the extraction of total trace nutrients (e.g., total phenols, tocopherols, and phytosterols) in WO. The WO produced using microwave had 2316.71 mg/kg of total trace nutrients, closely followed by the stir-frying method, which yielded an 11.22% increase compared to the untreated method. The WO obtained by the microwave method had a higher Oxidative inductance period (4.05 h) and oil yield (2.48%). After analyzing the flavor in WO, we found that aldehydes accounted for 28.77% of the 73 of volatile compounds and 58.12% of the total flavor compound content in microwave-pretreated WO, these percentages were higher than those recorded by using other methods. Based on the comprehensive score obtained by the PCA, microwave-pretreatment might be a promising strategy to improve the quality of WO based on aromatic characteristics.

Precise Tuning of the D-Band Center of Dual-Atomic Enzymes for Catalytic Therapy.

Single-atom nanozyme-based catalytic therapy is of great interest in the field of tumor catalytic therapy; however, their development suffers from the low affinity of nanozymes to the substrates (H2O2 or O2), leading to deficient catalytic activity in the tumor microenvironment. Herein, we report a new strategy for precisely tuning the d-band center of dual-atomic sites to enhance the affinity of metal atomic sites and substrates on a class of edge-rich N-doped porous carbon dual-atomic sites Fe-Mn (Fe1Mn1-NCe) for greatly boosting multiple-enzyme-like catalytic activities. The as-made Fe1Mn1-NCe achieved a much higher catalytic efficiency (Kcat/Km = 4.01 × 105 S-1·M-1) than Fe1-NCe (Kcat/Km = 2.41 × 104 S-1·M-1) with an outstanding stability of over 90% activity retention after 1 year, which is the best among the reported dual-atom nanozymes. Theoretical calculations reveal that the synergetic effect of Mn upshifts the d-band center of Fe from -1.113 to -0.564 eV and enhances the adsorption capacity for the substrate, thus accelerating the dissociation of H2O2 and weakening the O-O bond on O2. We further demonstrated that the superior enzyme-like catalytic activity of Fe1Mn1-NCe combined with photothermal therapy could effectively inhibit tumor growth in vivo, with an inhibition rate of up to 95.74%, which is the highest value among the dual-atom artificial enzyme therapies reported so far.

Individualized atomoxetine response and tolerability in children with ADHD receiving different dosage regimens: the need for CYP2D6 genotyping and therapeutic drug monitoring to dance together.

Integrating CYP2D6 genotyping and therapeutic drug monitoring (TDM) is crucial for guiding individualized atomoxetine therapy in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this retrospective study was (1) to investigate the link between the efficacy and tolerability of atomoxetine in children with ADHD and plasma atomoxetine concentrations based on their CYP2D6 genotypes; (2) to offer TDM reference range recommendations for atomoxetine based on the CYP2D6 genotypes of children receiving different dosage regimens. This retrospective study covered children and adolescents with ADHD between the ages of 6 and <18, who visited the psychological and behavioral clinic of Children's Hospital of Nanjing Medical University from June 1, 2021, to January 31, 2023. The demographic information and laboratory examination data, including CYP2D6 genotype tests and routine TDM of atomoxetine were obtained from the hospital information system. We used univariate analysis, Mann-Whitney U nonparametric test, Kruskal-Wallis test, and the receiver operating characteristic (ROC) curve to investigate outcomes of interest. 515 plasma atomoxetine concentrations of 385 children (325 boys and 60 girls) with ADHD between 6 and 16 years of age were included for statistical analysis in this study. Based on genotyping results, >60% of enrolled children belonged to the CYP2D6 extensive metabolizer (EM), while <40% fell into the intermediate metabolizer (IM). CYP2D6 IMs exhibited higher dose-corrected plasma atomoxetine concentrations by 1.4-2.2 folds than those CYP2D6 EMs. Moreover, CYP2D6 IMs exhibited a higher response rate compare to EMs (93.55% vs 85.71%, P = 0.0132), with higher peak plasma atomoxetine concentrations by 1.67 times than those of EMs. Further ROC analysis revealed that individuals under once daily in the morning (q.m.) dosing regimen exhibited a more effective response to atomoxetine when their levels were ≥ 268 ng/mL (AUC = 0.710, P < 0.001). In addition, CYP2D6 IMs receiving q.m. dosing of atomoxetine were more likely to experience adverse reactions in the central nervous system and gastrointestinal system when plasma atomoxetine concentrations reach 465 and 509 ng/mL, respectively. The findings in this study provided promising treatment strategy for Chinese children with ADHD based on their CYP2D6 genotypes and plasma atomoxetine concentration monitoring. A peak plasma atomoxetine concentration higher than 268 ng/mL might be requisite for q.m. dosing. Assuredly, to validate and reinforce these initial findings, it is necessary to collect further data in controlled studies with a larger sample size.

Monomodular and multifunctional processive endocellulases: implications for swine nutrition and gut microbiome.

Poor efficiency of dietary fibre utilization not only limits global pork production profit margin but also adversely affects utilization of various dietary nutrients. Poor efficiency of dietary nutrient utilization further leads to excessive excretion of swine manure nutrients and results in environmental impacts of emission of major greenhouse gases (GHG), odor, nitrate leaching and surface-water eutrophication. Emission of the major GHG from intensive pork production contributes to global warming and deteriorates heat stress to pigs in tropical and sub-tropical swine production. Exogenous fibre enzymes of various microbial cellulases, hemicellulases and pectinases have been well studied and used in swine production as the non-nutritive gut modifier feed enzyme additives in the past over two decades. These research efforts have aimed to improve growth performance, nutrient utilization, intestinal fermentation as well as gut physiology, microbiome and health via complementing the porcine gut symbiotic microbial fibrolytic activities towards dietary fibre degradation. The widely reported exogenous fibre enzymes include the singular use of respective cellulases, hemicellulases and pectinases as well as their multienzyme cocktails. The currently applied exogenous fibre enzymes are largely limited by their inconsistent in vivo efficacy likely due to their less defined enzyme stability and limited biochemical property. More recently characterized monomodular, multifunctional and processive endoglucanases have the potential to be more efficaciously used as the next-generation designer fibre biocatalysts. These newly emerging multifunctional and processive endoglucanases have the potential to unleash dietary fibre sugar constituents as metabolic fuels and prebiotics, to optimize gut microbiome, to maintain gut permeability and to enhance performance in pigs under a challenged environment as well as to parallelly unlock biomass to manufacture biofuels and biomaterials.

Rare and common coding variants in lipid metabolism-related genes and their association with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is a complex disease that is influenced by environmental and genetic factors. In this study, we aimed to investigate the relationship between coding variants in lipid metabolism-related genes and CAD in a Chinese Han population. METHODS: A total of 252 individuals were recruited for this study, including 120 CAD patients and 132 healthy control individuals. Rare and common coding variants in 12 lipid metabolism-related genes (ANGPTL3, ANGPTL4, APOA1, APOA5, APOC1, APOC3, CETP, LDLR, LIPC, LPL, PCSK9 and SCARB1) were detected via next-generation sequencing (NGS)-based targeted sequencing. Associations between common variants and CAD were evaluated by Fisher's exact test. A gene-based association test of rare variants was performed by the sequence kernel association test-optimal (SKAT-O test). RESULTS: We found 51 rare variants and 17 common variants in this study. One common missense variant, LIPC rs6083, was significantly associated with CAD after Bonferroni correction (OR = 0.47, 95% CI = 0.29-0.76, p = 1.9 × 10- 3). Thirty-three nonsynonymous rare variants were identified, including two novel variants located in the ANGPTL4 (p.Gly47Glu) and SCARB1 (p.Leu233Phe) genes. We did not find a significant association between rare variants and CAD via gene-based analysis via the SKAT-O test. CONCLUSIONS: Targeted sequencing is a powerful tool for identifying rare and common variants in CAD. The common missense variant LIPC rs6083 confers protection against CAD. The clinical relevance of rare variants in CAD aetiology needs to be investigated in larger sample sizes in the future.

A nomogram incorporating treatment data for predicting overall survival in gastroenteropancreatic neuroendocrine tumors: a population-based cohort study.

BACKGROUND: Over the last few decades, the annual global incidence of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) has steadily increased. Because of the complex and inconsistent treatment of GEP-NETs, the prognosis of patients with GEP-NETs is still difficult to assess. The study aimed to construct and validate the nomograms included treatment data for prediction overall survival (OS) in GEP-NETs patients. METHODS: GEP-NETs patients determined from the Surveillance, Epidemiology, and End Results (SEER)-13 registry database (1992-2018) and with additional treatment data from the SEER-18 registry database (1975-2016). In order to select independent prognostic factors that contribute significantly to patient survival and can be included in the nomogram, multivariate Cox regression analysis was performed using the minimum value of Akaike information criterion (AIC) and we analyzed the relationship of variables with OS by calculating hazard ratios (HRs) and 95% CIs. In addition, we also comprehensively compared the nomogram using to predict OS with the current 7th American Joint Committee on Cancer (AJCC) staging system. RESULTS: From 2004 to 2015, a total of 42 662 patients at diagnosis years with GEP-NETs were determined from the SEER database. The results indicated that the increasing incidence of GEP-NETs per year and the highest incidence is in patients aged 50-54. After removing cases lacking adequate clinicopathologic characteristics, the remaining eligible patients ( n =7564) were randomly divided into training (3782 patients) and testing sets (3782 patients). In the univariate analysis, sex, age, race, tumour location, SEER historic stage, pathology type, TNM, stage, surgery, radiation, chemotherapy, and CS tumour size were found to be significantly related to OS. Ultimately, the key factors for predicting OS were determined, involving sex, age, race, tumour location, SEER historic stage, M, N, grade, surgery, radiation, and chemotherapy. For internal validation, the C-index of the nomogram used to estimate OS in the training set was 0.816 (0.804-0.828). For external validation, the concordance index (C-index) of the nomogram used to predict OS was 0.822 (0.812-0.832). In the training and testing sets, our nomogram produced minimum AIC values and C-index of OS compared with AJCC stage. Decision curve analysis (DCA) indicated that the nomogram was better than the AJCC staging system because more clinical net benefits were obtained within a wider threshold probability range. CONCLUSION: A nomogram combined treatment data may be better discrimination in predicting overall survival than AJCC staging system. The authors highly recommend to use their nomogram to evaluate individual risks based on different clinical features of GEP-NETs, which can improve the diagnosis and treatment outcomes of GEP-NETs patients and improve their quality of life.

Antioxidant properties and changes in vitro digestion of the fermented kiwifruit extract prepared by lactic acid bacteria and yeasts.

The health benefits of fermented fruits have attracted consumers' attention. High levels of antioxidant ability in the fermented kiwifruit extract were found at the early stage of fermentation. The co-fermention with Lactobacillus paracasei LG0260 and Kluyveromyces marxianus J2853 showed the highest ABTS radical scavenging ability (ABTS⋅+-SA) and superoxide dismutase (SOD) activity. Also, the typical antioxidant components of SOD activity, vitamin C concentration and total phenol content were highly correlated with ABTS⋅+-SA. Obviously, polyphenols in the fermented kiwifruit extract evolved into monophenols during fermentation. Compared to undigested samples, the activity of ABTS⋅+-SA and reducing power capacity (RP-CA) after the final intestinal digestion decreased and ranged 387.44-531.89 VCµg/mL, 650.95-981.63 VCµg/mL, respectively (P < 0.05). Meanwhile, SOD activity on the 10th day of fermentation were still remained 222.82 U/mL, 206.98 U/mL and 217.23 U/mL, respectively. These results suggested that the fermented kiwifruit extract could exhibit antioxidant activity through tolerance to the digestive environment.

Pulse irradiation synthesis of metal chalcogenides on flexible substrates for enhanced photothermoelectric performance.

High synthesis temperatures and specific growth substrates are typically required to obtain crystalline or oriented inorganic functional thin films, posing a significant challenge for their utilization in large-scale, low-cost (opto-)electronic applications on conventional flexible substrates. Here, we explore a pulse irradiation synthesis (PIS) to prepare thermoelectric metal chalcogenide (e.g., Bi2Se3, SnSe2, and Bi2Te3) films on multiple polymeric substrates. The self-propagating combustion process enables PIS to achieve a synthesis temperature as low as 150 °C, with an ultrafast reaction completed within one second. Beyond the photothermoelectric (PTE) property, the thermal coupling between polymeric substrates and bismuth selenide films is also examined to enhance the PTE performance, resulting in a responsivity of 71.9 V/W and a response time of less than 50 ms at 1550 nm, surpassing most of its counterparts. This PIS platform offers a promising route for realizing flexible PTE or thermoelectric devices in an energy-, time-, and cost-efficient manner.

Mediating Effect of White Blood Cells and Tobacco Exposure on Cervical Neoplasm Risk Among Taiwanese Women.

Background: Both the high-risk human papillomavirus (HR-HPV) infection and tobacco exposure are significantly associated with cervical neoplasm risk. Immune cells play important roles in carcinogenesis. However, it is still unclear whether immune cells have a mediating effect on the HR-HPV infection and tobacco exposure with cervical neoplasm development. Aim: The aim of this study was to determine how the increased white blood cell (WBC) count affects the relationship between HR-HPV DNA load and tobacco exposure in the development of cervical neoplasia. Methods: A hospital-based case-control study design was conducted with a total of 108 cases of Taiwanese women with ≥ cervical intraepithelial neoplasia (CIN) I confirmed by biopsy, and 222 healthy Taiwanese female subjects with negative findings on a Pap smear were assigned to the control group. The study evaluated HR-HPV status and immune cell counts (WBCs, natural killer (NK) cells) and tobacco exposure by a self-construct questionnaire. Results: Both HR-HPV DNA load and tobacco exposure significantly independently increased cervical neoplasm risk (AORs: 1.28 and 1.42, respectively). Similar significant results were found for WBCs and NK cells, with respective AORs of 1.20 and 1.00. Moreover, increased WBCs (ß = 0.04, 95% CI corrected: 0.01-0.07) and tobacco exposure (ß = 0.02, 95% CI corrected: 0.01-0.04) mediated the relationship between the high-risk HPV DNA load and cervical neoplasm risk. Conclusions: Elevated WBC count acts as both predictor and mediator in cervical neoplasm development linked to HR-HPV DNA load. Monitoring and maintaining WBC levels within the normal range could be a preventive strategy for cervical neoplasm development.

The Efficacy and Safety of Diazepam for Intraoperative Blood Pressure Stabilization in Hypertensive Patients Undergoing Vitrectomy Under Nerve Block Anesthesia: A Prospective, Single-Center, Double-Blind, Randomized, Controlled Trial.

Purpose: To evaluate the effectiveness and safety of diazepam in maintaining stable intraoperative blood pressure (BP) in hypertensive patients undergoing vitrectomy under nerve block anesthesia. Methods: A total of 180 hypertensive patients undergoing vitrectomy with nerve block anesthesia were randomized into two groups. The intervention group was given oral diazepam 60 min before operation, while the control group was given oral placebo 60 min before operation. The primary outcome is the effective rate of intraoperative BP control, defined as systolic blood pressure (SBP) during the operation maintained < 160 mmHg at all timepoints. The logistic regression model will be performed to analyze the compare risk factors for ineffective BP control. Results: The effective rate of intraoperative SBP control in the diazepam group was significant higher than that in the placebo group from 15 min to 70 min of the surgery (P < 0.05). The proportion of patients with SBP ≥180 mmHg at any timepoint from operation to 1 h postoperation was higher in the placebo group (12.22%) than in the diazepam group (2.22%) (P = 0.0096). We observed that the change in SBP from baseline consistently remained higher in the placebo group than in the diazepam group. In the logistic regression analysis, age, years of diagnosed hypertension and SBP 1h before surgery were significant risk factors for ineffective BP control. Conclusion: This study provides robust evidence supporting the effectiveness of oral diazepam as a pre-surgery intervention in maintaining stable blood pressure during vitrectomy in hypertensive patients. Trial Registration: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2100041772.

Pars plana vitrectomy for retinal detachment using perfluoro-n-octane as intraoperative tamponade: a multicenter, randomized, non-inferiority trial.

AIM: To evaluate the efficacy and safety of perfluoro-n-octane (PFO) for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy (PPV) in management of retinal detachment. METHODS: This multicenter, prospective, randomized, double-masked, parallel-controlled, non-inferiority trial was conducted in three ophthalmology clinical centers in China. Patients with retinal detachment, who were eligible for PPV were consecutively enrolled. Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, and dilated fundus examination were performed preoperatively and at 1, 7±1, 28±3d postoperatively. The primary outcome was complete retinal reattachment rate at postoperative day one. The non-inferiority margin was set at 9.8%. The secondary outcomes included intraoperative retinal reattachment rate, and mean changes in IOP and BCVA from baseline to 1, 7±1, 28±3d postoperatively, respectively. Safety analyses were presented for all randomly assigned participates in this study. RESULTS: Totally 124 eligible patients completed the study between Mar. 14, 2016 and Jun. 7, 2017. Sixty of them were randomly assigned to the PFO for ophthalmic surgery group, and 64 were assigned to the F-Octane group. Baseline characteristics were comparable between the two groups. Both groups achieved 100% retinal reattachment at postoperative day one (difference 0, 95%CI: -6.21% to 5.75%, P=1). The pre-defined noninferiority criterion was met. No significant difference was observed in intraoperative retinal reattachment rate (difference 1.77%, P=0.61), mean changes in IOP (difference 0.36, -0.09, 2.22 mm Hg at 1, 7±1, 28±3d postoperatively, with all P>0.05) and BCVA (difference 0.04, -0.02, 0.06 logMAR at 1, 7±1, 28±3d postoperatively, all P>0.05) between the two groups. No apparent adverse events related to the utilization of PFO were reported. CONCLUSION: In patients with retinal detachment undergoing PPV, PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade, and both are safe and well-tolerated.

Alterations in mitochondrial structure and function in response to environmental temperature changes in Apostichopus japonicus.

Global temperatures have risen as a result of climate change, and the resulting warmer seawater will exert physiological stresses on many aquatic animals, including Apostichopus japonicus. It has been suggested that the sensitivity of aquatic poikilothermal animals to climate change is closely related to mitochondrial function. Therefore, understanding the interaction between elevated temperature and mitochondrial functioning is key to characterizing organisms' responses to heat stress. However, little is known about the mitochondrial response to heat stress in A. japonicus. In this work, we investigated the morphological and functional changes of A. japonicus mitochondria under three representative temperatures, control temperature (18 °C), aestivation temperature (25 °C) and heat stress temperature (32 °C) temperatures using transmission electron microscopy (TEM) observation of mitochondrial morphology combined with proteomics and metabolomics techniques. The results showed that the mitochondrial morphology of A. japonicus was altered, with decreases in the number of mitochondrial cristae at 25 °C and mitochondrial lysis, fracture, and vacuolization at 32 °C. Proteomic and metabolomic analyses revealed 103 differentially expressed proteins and 161 differential metabolites at 25 °C. At 32 °C, the levels of 214 proteins and 172 metabolites were significantly altered. These proteins and metabolites were involved in the tricarboxylic acid (TCA) cycle, substance transport, membrane potential homeostasis, anti-stress processes, mitochondrial autophagy, and apoptosis. Furthermore, a hypothetical network of proteins and metabolites in A. japonicus mitochondria in response to temperature changes was constructed based on proteomic and metabolomic data. These results suggest that the dynamic regulation of mitochondrial energy metabolism, resistance to oxidative stress, autophagy, apoptosis, and mitochondrial morphology in A. japonicus may play important roles in the response to elevated temperatures. In summary, this study describes the response of A. japonicus mitochondria to temperature changes from the perspectives of morphology, proteins, and metabolites, which provided a better understanding the mechanisms of mitochondrial regulation under environment stress in marine echinoderms.

Adaptive Event-Triggered Consensus of Multi-Agent Systems in Sense of Asymptotic Convergence.

In this paper, the asymptotic consensus control of multi-agent systems with general linear agent dynamics is investigated. A neighbor-based adaptive event-triggering strategy with a dynamic triggering threshold is proposed, which leads to a fully distributed control of the multi-agent system, depending only on the states of the neighboring agents at triggering moments. By using the Lyapunov method, we prove that the states of the agents converge asymptotically. In addition, the proposed event-triggering strategy is proven to exclude Zeno behavior. The numerical simulation results illustrate that the agent states achieve consensus in sense of asymptotic convergence. Furthermore, the proposed strategy is shown to be scalable in case of variable agent numbers.