Chromosomal integration and plasmid fusion occurring in ST20 carbapenem-resistant Klebsiella pneumoniae isolates coharboring blaNDM-1 and blaIMP-4 induce resistance transmission and fitness variation.

To investigate the epidemiology of ST20 carbapenem-resistant Klebsiella pneumoniae (CRKP) in China, and further explore the genomic characteristics of blaIMP-4 and blaNDM-1 coharboring isolates and plasmid contributions to resistance and fitness. Seven ST20 CRKP isolates were collected nationwide, and antimicrobial susceptibility testing was performed. Antimicrobial resistance genes, virulence genes, and plasmid replicons were identified via whole-genome sequencing, and clonality assessed via core-genome multilocus sequence typing. Furthermore, we found four dual-metallo-ß-lactamases (MBL)-harbouring isolates, the gene location was detected by Southern blotting, and plasmid location analysis showed that blaIMP-4 was located on a separate plasmid, a self-conjugative fusion plasmid, or the bacterial chromosome. These isolates were subjected to long-read sequencing, the presence of blaIMP-4 in different locations was identified by genomic comparison, and transposon units were detected via inverse PCR. We subsequently found that blaIMP-4 on the fusion plasmid and bacterial chromosome was formed via intact plasmid recombination by the IS26 and ltrA, respectively, and the circular transposon unit was related to cointegration, however, blaIMP-4 in different locations did not affect the gene stability. The blaNDM-1-harbouring plasmid contributed to the increased resistance to ß-lactams and shortened survival lag time which was revealed in plasmid cured isolates. In summary, the K. pneumoniae ST20 clone is a high-risk resistant clone. With the use of ceftazidime/avibactam, MBL-positive isolates, especially dual-MBL-harbouring isolates, should be given additional attention.

Excessive processing and acetylation of OPA1 aggravate age-related hearing loss via the dysregulation of mitochondrial dynamics.

The pathogenesis of age-related hearing loss (ARHL) remains unclear. OPA1 is the sole fusion protein currently known to be situated in the inner mitochondrial membrane, which is pivotal for maintaining normal mitochondrial function. While it has already been demonstrated that mutations in OPA1 may lead to hereditary deafness, its involvement in the occurrence and development of ARHL has not been previously explored. In our study, we constructed D-gal-induced senescent HEI-OC1 cells and the cochlea of C57BL/6J mice with a mutated SUMOylation site of SIRT3 using CRISPR/Cas9 technology. We found enhanced L-OPA1 processing mediated by activated OMA1, and increased OPA1 acetylation resulting from reductions in SIRT3 levels in senescent HEI-OC1 cells. Consequently, the fusion function of OPA1 was inhibited, leading to mitochondrial fission and pyroptosis in hair cells, ultimately exacerbating the aging process of hair cells. Our results suggest that the dysregulation of mitochondrial dynamics in cochlear hair cells in aged mice can be ameliorated by activating the SIRT3/OPA1 signaling. This has the potential to alleviate the senescence of cochlear hair cells and reduce hearing loss in mice. Our study highlights the significant roles played by the quantities of long and short chains and the acetylation activity of OPA1 in the occurrence and development of ARHL. This finding offers new perspectives and potential targets for the prevention and treatment of ARHL.

The association between ambient air pollution exposure and connective tissue sarcoma risk: a nested case-control study using a nationwide population-based database.

A nationwide population-based database was utilized in a nested case-control study to explore the association between ambient air pollution exposure and the likelihood of developing connective tissue sarcoma. The study examined 280 cases of connective tissue sarcoma diagnosed between 2000 and 2012. A random sample of 1120 control subjects was selected from a subpopulation of claim records without a connective tissue sarcoma diagnosis in a 1:4 ratio. The control subjects were selected based on similar characteristics as the connective tissue sarcoma patients, including gender, birth year, and the year of diagnosis of the case group with medical records. Risk factors for connective tissue sarcoma were collected for analysis. Our data on exposure to air pollutants was collected from Taiwan's Air Quality Monitoring Network, which has been gathering air quality data from a growing network of sampling stations (now 76) throughout the country since 1997. It was discovered that the risk of connective tissue sarcoma was significantly increased by the Charlson comorbidity index (CCI), elevated levels of specific air pollution indices (e.g., total hydrocarbons (THC), fine particulate matter (PM2.5), and O3_8 (the annual mean of the daily maximum 8-h average concentration of O3), the High Pollutant Standards Index (hPSI) (the percentage of days in a given year in Taiwan where the PSI exceeds 100), and an insurable monthly wage over US$1100. Further investigation is needed to explore the involvement of these air pollutants in the formation of connective tissue sarcoma.

Prevalence and characteristics of coronary artery fistulas among 20 259 patients undergoing invasive coronary angiography.

BACKGROUND: Coronary artery fistula (CAF) is a rare coronary anomaly. This study aimed to investigate the prevalence, clinical features, and imaging characteristics of CAF among patients undergoing coronary angiography (CAG). METHOD: This was a retrospective study including 20 259 consecutive patients (12 458 were male) who underwent CAG at our institution from September 2018 to March 2023. Electronic angiography records were reviewed, and a total of 86 (0.42%) CAF patients were enrolled and analyzed. RESULT: Of the 86 CAF patients, 42 (49%) were male. Thus, the prevalence of CAF for males and females was 0.34% and 0.56%, respectively. Arrhythmia, left ventricular (LV) hypertrophy, LV dilation, and LV systolic dysfunction were observed in 38, 25, 10 and 5 cases, respectively. Among the 86 CAF patients, a total of 117 CAFs were detected. 61 (71%) patients had a single CAF, and the remaining 25 (29%) patients had multiple CAFs. Of the 117 CAFs, the most common origins and terminations were the left anterior descending artery (n = 50) and the pulmonary artery (n = 73), respectively. The CAF diameters were greatly varied, ranging from unmeasurable to 7.8 mm, and 22 (18%) CAFs were larger than 3 mm. CONCLUSION: In the present study, the prevalence of CAF was 0.42% with a female predilection. Arrhythmia, LV remodeling and dysfunction were common. Seventy-one percent of patients had a single CAF. The left anterior descending artery and the pulmonary artery were the most common origin and termination of CAFs, respectively. Most CAFs were small, and 18% of CAFs were larger than 3 mm.

Maternal exposure to SSRIs or SNRIs and the risk of congenital abnormalities in offspring: A systematic review and meta-analysis.

BACKGROUND: The association of maternal exposure to selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with the risk of system-specific congenital malformations in offspring remains unclear. We conducted a meta-analysis to examine this association and the risk difference between these two types of inhibitors. METHODS: A literature search was performed from January 2000 to May 2023 using PubMed and Web of Science databases. Cohort and case-control studies that assess the association of maternal exposure to SSRIs or SNRIs with the risk of congenital abnormalities were eligible for the study. RESULTS: Twenty-one cohort studies and seven case-control studies were included in the meta-analysis. Compared to non-exposure, maternal exposure to SNRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.64 with 95% CI: 1.36, 1.97), anomalies of the kidney and urinary tract (pooled OR: 1.63 with 95% CI: 1.21, 2.20), malformations of nervous system (pooled OR: 2.28 with 95% CI: 1.50, 3.45), anomalies of digestive system (pooled OR: 2.05 with 95% CI: 1.60, 2.64) and abdominal birth defects (pooled OR: 2.91 with 95%CI: 1.98, 4.28), while maternal exposure to SSRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.25 with 95%CI: 1.20, 1.30), anomalies of the kidney and urinary tract (pooled OR: 1.14 with 95%CI: 1.02, 1.27), anomalies of digestive system (pooled OR: 1.11 with 95%CI: 1.01, 1.21), abdominal birth defects (pooled OR: 1.33 with 95%CI: 1.16, 1.53) and musculoskeletal malformations (pooled OR: 1.44 with 95%CI: 1.32, 1.56). CONCLUSIONS: SSRIs and SNRIs have various teratogenic risks. Clinicians must consider risk-benefit ratios and patient history when prescribing medicines.

Highly accurate OAM mode detection network for ring Airy Gaussian vortex beams disturbed by atmospheric turbulence based on interferometry.

Atmospheric turbulence reduces the detection accuracy of orbital angular momentum (OAM) modes, which affects the performance of OAM optical communication. In this paper, we propose a method based on interferometry and a residual network (ResNet) to detect the OAM modes of ring Airy Gaussian vortex beams (RAGVBs) disturbed by atmospheric turbulence. The RAGVBs first interfere with spherical waves to obtain the sign features of the OAM modes, and then ResNet is employed to recognize OAM modes from the interferograms. The results demonstrate that the detection accuracy is higher than that of the OAM spectrum method under different turbulence strengths. The detection accuracy can even reach over 99% under strong fluctuations. Our research provides a reference for improving the performance of OAM optical communication through atmospheric turbulence.

Melatonin attenuates cellular senescence and apoptosis in diabetic nephropathy by regulating STAT3 phosphorylation.

AIMS: Melatonin is an endogenous hormone related to the regulation of biorhythm. Previous researchers have found that melatonin can ameliorate diabetic nephropathy (DN), but the mechanism remains to be elucidated. To discover the possible mechanism by which melatonin prevents DN, we investigated the potential effects of melatonin on signal transducer and activator of transcription 3 (STAT3) on the progression of cellular senescence and apoptosis. MAIN METHODS: Cellular senescence, apoptosis and the underlying mechanism of melatonin were investigated both in vivo and in vitro. C57BL/6 mice were intraperitoneally injected with streptozotocin (STZ) to establish DN. For an in vitro model of DN, human renal cortex proximal epithelial tubule (HK-2) cells were exposed to high glucose conditions. KEY FINDINGS: Melatonin inhibited the phosphorylation of STAT3, decreased the expression of senescence proteins p53, p21 and p16INK4A. Melatonin also downregulated the expression of apoptotic proteins, including cleaved PARP1, cleaved caspase-9 and -3. Melatonin treatment decreased the positive area of senescence-associated galactosidase (SA-ß-gal) staining and the number of TUNEL-positive cells in kidneys of DN mice. In vitro, melatonin inhibited STAT3 phosphorylation and lowered cellular senescence and apoptosis markers, in a manner similar to the STAT3 inhibitor S3I-201. In addition, the inhibition effect of melatonin on cellular senescence and apoptosis in HK-2 cells was reversed by the usage of recombinant IL-6 (rIL-6), which can induce STAT3 phosphorylation. SIGNIFICANCE: We, for the first time, demonstrate that melatonin inhibits STAT3 phosphorylation, which is involved in alleviating the cellular senescence and apoptosis in DN.

Development of a POCT detection platform based on a locked nucleic acid-enhanced ARMS-RPA-GoldMag lateral flow assay.

In this study, a novel genotyping point-of-care testing (POCT) rapid detection device, the locked nucleic acid (LNA)-amplification refractory mutation system (ARMS)-recombinase polymerase amplification (RPA)-GoldMag lateral flow assay (LFA) platform, was provided by mining and synthesis based on prior technology. Research methods based on system-integrated innovation and knowledge-integrated generation have become a new trend in technology development. Here, we exploit the combination of LNA-coupled ARMS-RPA and gold nanoparticle probe technology for detection signal amplification, thus pioneering a new tool for accurate, rapid, and cost-effective genotyping. We also performed SNP typing detection and clinical validation of this new assay platform using common glucose-6-phosphate dehydrogenase (G6PD) gene single nucleotide polymorphism (SNP) loci, and the results demonstrated the high sensitivity, specificity, stability, accuracy and feasibility of the LNA-ARMS-RPA-GoldMag lateral flow assay platform. It is hoped that this new technology will make a significant contribution to the field of POCT rapid diagnosis and aim to expand the application space, reflecting its clinical application value and development prospects.

Influence of Pilocarpine Eyedrops on the Ocular Biometric Parameters and Intraocular Lens Power Calculation.

Objective: To evaluate the influence of pilocarpine eyedrops on the ocular biometric parameters and whether these parameter changes affect the intraocular lens (IOL) power calculation in patients with primary angle-closure glaucoma (PACG). Methods: Twenty-two PACG patients and fifteen normal subjects were enrolled. Ocular biometric parameters including the axial length (AL), anterior chamber depth (ACD), lens thickness (LT), mean keratometry (Km), and white-to-white distance (WTW) were measured by using a Lenstar LS 900 device before and at least 30 minutes after instillation of 2% pilocarpine eyedrops. Lens position (LP) was calculated, and the IOL power prediction based on the ocular biometric parameters was performed using the Barrett Universal II, Haigis, Hoffer Q, Holladay I, or SRK/T formulas before and after pilocarpine application. Results: In both PACG and normal groups, pilocarpine eyedrops induced a slight but statistically significant increase in the mean AL (0.01 mm for both groups) and mean LT (0.02 mm and 0.03 mm, respectively) but a significant decrease in the mean ACD (0.03 mm and 0.05 mm, respectively) and mean LP (0.02 mm and 0.04 mm, respectively). No significant changes in the mean Km and WTW were noticed in both groups. In addition, the IOL power calculation revealed insignificant changes before and after the pilocarpine instillation in both groups, regardless of the formula used. Conclusions: Pilocarpine eyedrops can induce slight changes in the ocular biometric parameters including the AL, ACD, LT, and LP. However, these parameter changes will not result in a significant difference in IOL power estimation.

Rapid and Ultrasensitive Detection of Plasmodium spp. Parasites via the RPA-CRISPR/Cas12a Platform.

Microscopic examination of thick and thin blood smears stained with Giemsa dye is considered the primary diagnostic tool for the confirmation and management of suspected clinical malaria. However, detecting gametocytes is relatively insensitive, particularly in asymptomatic individuals with low-density Plasmodium infections. To complement existing diagnostic methods, a rapid and ultrasensitive point-of-care testing (POCT) platform for malaria detection is urgently needed and necessary. A platform based on recombinase polymerase amplification (RPA) followed by CRISPR/Cas12a (referred to as RPA-CRISPR/Cas12a) was developed and optimized for the determination of Plasmodium spp. parasites, particularly Plasmodium falciparum, using a fluorescence-based assay (FBDA), lateral flow test strips (LFTS), or naked eye observation (NEO). Then, the established platform was assessed with clinical malaria isolates. Under optimal conditions, the detection threshold was 1 copy/µL for the plasmid, and the limit of detection was 3.11-7.27 parasites/µL for dried blood spots. There was no cross-reactivity against blood-borne pathogens. For the accuracies of RPA-CRISPR/Cas12a, Plasmodium spp. and P. falciparum testing were 98.68 and 94.74%, respectively. The method was consistent with nested PCR results and superior to the qPCR results. RPA-CRISPR/Cas12a is a rapid, ultrasensitive, and reliable platform for malaria diagnosis. The platform requires no or minimal instrumentation for nucleic acid amplification reactions and can be read with the naked eye. Compared with similar diagnostic methods, this platform improves the reaction speed while reducing detection requirements. Therefore, this platform has the potential to become a true POCT for malaria parasites.

C-Terminal Truncated HBx Facilitates Oncogenesis by Modulating Cell Cycle and Glucose Metabolism in FXR-Deficient Hepatocellular Carcinoma.

Farnesoid X receptor (FXR) is a nuclear receptor known to play protective roles in anti-hepatocarcinogenesis and regulation of the basal metabolism of glucose, lipids, and bile acids. FXR expression is low or absent in HBV-associated hepatocarcinogenesis. Full-length HBx and HBx C-terminal truncation are frequently found in clinical HCC samples and play distinct roles in hepatocarcinogenesis by interacting with FXR or FXR signaling. However, the impact of C-terminal truncated HBx on the progression of hepatocarcinogenesis in the absence of FXR is unclear. In this study, we found that one known FXR binding protein, a C-terminal truncated X protein (HBx C40) enhanced obviously and promoted tumor cell proliferation and migration by altering cell cycle distribution and inducing apoptosis in the absence of FXR. HBx C40 enhanced the growth of FXR-deficient tumors in vivo. In addition, RNA-sequencing analysis showed that HBx C40 overexpression could affect energy metabolism. Overexpressed HSPB8 aggravated the metabolic reprogramming induced by down-regulating glucose metabolism-associated hexokinase 2 genes in HBx C40-induced hepatocarcinogenesis. Overall, our study suggests that C-terminal truncated HBx C40 synergizes with FXR deficiency by altering cell cycle distribution as well as disturbing glucose metabolism to promote HCC development.

Tailoring and application of a multi-responsive cellulose nanofibre-based 3D nanonetwork wound dressing.

The rapid loss of drugs and the weak curative effects due to cyclical urination are the main reasons why wound heal with difficulty after bladder tumour resection. Here, a bioinspired cellulose nanofibre (CNF)-based magnetic 3D nanonetwork wound dressing with excellent tissue adhesion and biocompatibility is designed by the assembly of pH- and near infrared-responsive CNF nanoskeletons, magnetic switching Fe3O4 nanoparticles, and temperature switching Pluronic®F-127. The dressing with high loading capacity for mitomycin and indocyanine green can form a sticky 3D nanonetwork at the wound site and remain for a long time to release drugs through an external magnetic field. Interestingly, the dressing possessed excellent antibacterial activity, bacterial biofilm elimination, T24 tumour cell killing, and wound healing promotion through photothermal, photodynamic, and chemotherapy. Therefore, it has promising application for bladder postoperative infected wound healing to avoid rapid loss of drugs due to cyclical urination.

Genome-wide identification and characterization of polycomb repressive complex 2 core components in upland cotton (Gossypium hirsutum L.).

BACKGROUND: The evolutionarily conserved Polycomb Repressive Complex 2 (PRC2) plays a vital role in epigenetic gene repression by depositing tri-methylation on lysine residue K27 of histone H3 (H3K27me3) at the target loci, thus participating in diverse biological processes. However, few reports about PRC2 are available in plant species with large and complicated genomes, like cotton. RESULTS: Here, we performed a genome-wide identification and comprehensive analysis of cotton PRC2 core components, especially in upland cotton (Gossypium hirsutum). Firstly, a total of 8 and 16 PRC2 core components were identified in diploid and tetraploid cotton species, respectively. These components were classified into four groups, E(z), Su(z)12, ESC and p55, and the members in the same group displayed good collinearity, similar gene structure and domain organization. Next, we cloned G. hirsutum PRC2 (GhPRC2) core components, and found that most of GhPRC2 proteins were localized in the nucleus, and interacted with each other to form multi-subunit complexes. Moreover, we analyzed the expression profile of GhPRC2 genes. The transcriptome data and quantitative real-time PCR (qRT-PCR) assays indicated that GhPRC2 genes were ubiquitously but differentially expressed in various tissues, with high expression levels in reproductive organs like petals, stamens and pistils. And the expressions of several GhPRC2 genes, especially E(z) group genes, were responsive to various abiotic and biotic stresses, including drought, salinity, extreme temperature, and Verticillium dahliae (Vd) infection. CONCLUSION: We identified PRC2 core components in upland cotton, and systematically investigated their classifications, phylogenetic and synteny relationships, gene structures, domain organizations, subcellular localizations, protein interactions, tissue-specific and stresses-responsive expression patterns. Our results will provide insights into the evolution and composition of cotton PRC2, and lay the foundation for further investigation of their biological functions and regulatory mechanisms.

Effectiveness and safety of electroacupuncture combined with conventional drugs in the treatment of stable angina pectoris in coronary artery disease: A systematic evaluation and meta-analysis.

BACKGROUND: The objective of this study is to systematically evaluate the clinical effectiveness and safety of electroacupuncture combined with conventional drugs in the treatment of stable angina pectoris. METHODS: Computer searches of 3 Chinese literature databases (CNKI, VIP, WangFang) and 4 English literature databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science), all searched from the time of database construction to October 2022. Two researchers were selected to independently perform literature screening, data extraction, and risk of bias evaluation, and meta-analysis of the included studies was performed using RevMan 5.3 software. RESULTS: A total of 7 publications with a total of 1042 patients were included, and electroacupuncture combined with conventional drug therapy compared with drug therapy alone was effective in improving clinical symptoms of angina pectoris (relative risk [RR] = 1.19, 95% CI = [1.09, 1.31], P = .0002), clinical treatment efficiency of electrocardiography (RR = 1.34, 95% CI = [1.19, 1.50], P = .00001), visual analog score (VAS) (mean deviation = 0.07, 95% CI = [-0.11, 0.25], P = .44), and Seattle Angina Scale (mean deviation = 4.91, 95% CI = [2.91, 6.91], P < .00001) were better than conventional drug therapy, while the number of adverse events in the intervention group was lower than that in the control group. One of the outcome indicators with greater heterogeneity was tested by sensitivity analysis, and each outcome indicator was found to be more robust. The risk of bias evaluation of each outcome indicator using funnel plots suggested the possibility of publication bias. CONCLUSION: The current study results found that electroacupuncture combined with conventional drugs can significantly improve the clinical symptoms of patients with stable angina pectoris compared with conventional drug therapy, with a low incidence of adverse reactions, but the number of high-quality literature with rigorous study design protocols is currently low, which may cause bias in the results of this study, so the above conclusions need to be further verified through clinical trials.

Proteomic analysis of exosome-like vesicles from Fasciola gigantica adult worm provides support for new vaccine targets against fascioliasis.

BACKGROUND: Extracellular vesicles (EVs) released by helminths play an important role in parasite-host communication. However, little is known about the characteristics and contents of the EVs of Fasciola gigantica, a parasitic flatworm that causes tropical fascioliasis. A better understanding of EVs released by F. gigantica will help elucidate the mechanism of F. gigantica-host interaction and facilitate the search for new vaccine candidates for the control and treatment of fascioliasis. METHODS: Two different populations of EVs (15k EVs and 100k EVs) were purified from adult F. gigantica culture media by ultracentrifugation. The morphology and size of the purified EVs were determined by transmission electron microscopy (TEM) and by the Zetasizer Nano ZSP high performance particle characterization system. With the aim of identifying diagnostic markers or potential vaccine candidates, proteins within the isolated 100k EVs were analyzed using mass spectrometry-based proteomics (LC-MS/MS). Mice were then vaccinated with excretory/secretory products (ESPs; depleted of EVs), 15k EVs, 100k EVs and recombinant F. gigantica heat shock protein 70 (rFg-HSP70) combined with alum adjuvant followed by challenge infection with F. gigantica metacercariae. Fluke recovery and antibody levels were used as measures of vaccine protection. RESULTS: TEM analysis and nanoparticle tracking analysis indicated the successful isolation of two subpopulations of EVs (15k EVs and 100k EVs) from adult F. gigantica culture supernatants using differential centrifugation. A total of 755 proteins were identified in the 100k EVs. Exosome biogenesis or vesicle trafficking proteins, ESCRT (endosomal sorting complex required for transport) pathway proteins and exosome markers, heat shock proteins and 14-3-3 proteins were identified in the 100k EVs. These results indicate that the isolated 100k EVs were exosome-like vesicles. The functions of the identified proteins may be associated with immune regulation, immune evasion and virulence. Mice immunized with F. gigantica ESPs, 15k EVs, 100k EVs and rFg-HSP70 exhibited a reduction in fluke burden of 67.90%, 60.38%, 37.73% and 56.6%, respectively, compared with the adjuvant control group. The vaccination of mice with F. gigantica 100k EVs, 15k EVs, ESP and rFg-HSP70 induced significant production of specific immunoglobulins in sera, namely IgG, IgG1 and IgG2a. CONCLUSION: The results of this study suggest that proteins within the exosome-like vesicles of F. gigantica have immunomodulatory, immune evasion and virulence functions. This knowledge may lead to new strategies for immunotherapy, vaccination and the diagnosis of fascioliasis.

The impact of Teach-back method on preoperative anxiety and surgical cooperation in elderly patients undergoing outpatient ophthalmology surgery: A randomized clinical trial.

BACKGROUND: The literatures have demonstrated that Teach-back method is an effective communication tool to understand health education, especially in the elderly patients. However, there is limited research of Teach-back method in preoperative education for outpatient surgical patients. This study was conducted to investigate the effects of the Teach-back method on preoperative anxiety and surgical cooperation in elderly patients undergoing outpatient ophthalmology surgery. METHODS: One hundred sixteen elderly patients who underwent outpatient ophthalmology surgery were selected as the research objects. They were divided into the observation group (58 cases) and the control group (58 cases). The Teach-back preoperative education was adopted in the observation group and the standard preoperative education method was adopted in the control group. The degree of anxiety, surgical cooperation, and awareness of health knowledge were compared between the 2 groups, and the variations of blood pressure and heart rate, as well as the highest values of intraoperative blood pressure and heart rate before and after method, were recorded and compared. RESULTS: The preoperative systolic blood pressure in the observation group was significantly lower than that in the control group. The intraoperative (the highest value) heart rate, systolic blood pressure, and diastolic blood pressure in the observation group were lower than those in the control group, and the differences were statistically significant (P < .05). After intervention, the anxiety score and information demand score of the observation group were lower than those of the control group, and the differences were statistically significant (P < .05). The degree of surgery cooperation and awareness of perioperative health knowledge in the observation group were all higher than those in the control group; the differences were statistically significant (P < .05). CONCLUSION: The Teach-back method could relieve the preoperative anxiety of the patients, improve the quality of patients surgery cooperation, and facilitate the awareness of health knowledge. Moreover, it could effectively improve the intraoperative stress response of the elderly patients and reduce the large fluctuations of blood pressure and heart rate.

Investigation of the clinical effects of acipimox in patients with vulnerable carotid atherosclerosis.

OBJECTIVE: To investigate the clinical effects of acipimox in patients with vulnerable carotid atherosclerosis. METHODS: 80 patients with vulnerable carotid atherosclerosis who were admitted to the Department of Cardiology in Wuxi Second People's Hospital between February 2020 and October 2021 were enrolled in this study. All of these patients were randomly divided into an observation group (n = 40), who were given acipimox and conventional treatment, and a control group (n = 40), who were given conventional treatment. The levels of blood lipids and adiponectin (APN), the carotid intima-media thickness (IMT), the area, thickness and number of CAS, peak systolic velocities (PSV) and end-diastolic blood velocity (EDV) of common carotid artery (CCA), and the level of inflammatory markers were measured and compared between the two groups pretherapy and posttreatment. Then, the adverse events were collected and compared between the two groups posttreatment. RESULTS: The demographics and basic clinical characteristics were not significantly different between the two groups. At posttreatment, the levels of TC, LDL-C, ANP, IL-6, TNF-α and hs-CRP in the observation group were significantly lower than those in the control group at posttreatment. Moreover, the IMT and the area and thickness of CAS in the observation group were significantly lower than those in the control group. After treatment, PSV was lower and EDV was higher in two groups than before treatment; after treatment, compared with control group, PSV in observation group was lower, while EDV was higher. Most importantly, the rate of adverse events was similar in the two groups. CONCLUSIONS: Acipimox reduced the blood lipid levels in patients with vulnerable carotid atherosclerosis. It also stabilized vulnerable plaques and reduced CAS.

Framework Nucleic Acids as Blood-Retinal-Barrier-Penetrable Nanocarrier for Periocular Administration.

Designing an ocular drugs delivery system that can permeate the outer blood-retinal barrier (oBRB) is crucial for the microinvasive or noninvasive treatment of ocular fundus diseases. However, due to the lack of a nanocarrier that can maintain structure and composition at the oBRB, only intravitreal injection at the eyeball can deliver therapeutics directly to the ocular fundus via paracellular and intercellular routes, despite the intraocular operations risks. Here, we demonstrated tetrahedral framework nucleic acids (tFNAs) can penetrate the oBRB and deliver therapeutic nucleic acids to the retina of the rat eye in vivo following subconjunctival injection. We also discovered that tFNAs were transported via a paracellular route across the intercellular tight junctions at the oBRB. The histology analysis for ocular layers indicated that individual and aptamer/doxorubicin-loaded tFNAs penetrated all layers of the posterior segment of the eyeball to reach the innermost retina and persisted for over 3 days with minimal systemic biodistribution. We expect that the programmability and penetrability of tFNAs will provide a promising method for drug delivery across oBRB and long-term sustenance at the target site via periocular administration to various tissues.

Impact of cholesterol homeostasis within cochlear cells on auditory development and hearing loss.

Cholesterol is the most abundant sterol molecule in mammalian cells, which not only constitutes the cell membrane but also plays essential roles in the synthesis of important hormones, synapse formation, and cell signal transduction. The effect of hypercholesterolemia on hearing has been studied extensively, and multiple studies have demonstrated that hypercholesterolemia is a risk factor for hearing loss. However, the impact of cholesterol homeostasis within auditory cells on peripheral auditory development and maintenance has not been evaluated in detail. Mutations in certain cholesterol metabolism-related genes, such as NPC1, SERAC1, DHCR7, and OSBPL2, as well as derivatives of cholesterol metabolism-related ototoxic drugs, such as ß-cyclodextrin, can lead to disruptions of cholesterol homeostasis within auditory cells, resulting in hearing loss. This article aims to review the impact of cholesterol homeostasis within auditory cells on the peripheral auditory function from the following two perspectives: (1) changes in cholesterol homeostasis regulatory genes in various hearing loss models; (2) mechanisms underlying the effects of some drugs that have a therapeutic effect on hearing loss via regulating cholesterol homeostasis. This article aims to summarize and analyze the impact of disruption of cellular cholesterol homeostasis within auditory cells on hearing, in order to provide evidence regarding the underlying mechanisms.

Marrow Mesenchymal Stem Cell-Derived Exosomes Upregulate Astrocytic Glutamate Transporter-1 Expression via miR-124/mTOR Pathway against Oxygen-Glucose Deprivation/Reperfusion Injury.

BACKGROUND: Experimental investigations have reported the efficacy of marrow mesenchymal stem cell-derived exosomes (MSC-Exos) for the treatment of ischemic stroke. The therapeutic mechanism, however, is still unknown. The purpose of the study is to show whether MSC-Exos increases astrocytic glutamate transporter-1 (GLT-1) expression in response to ischemic stroke and to investigate further mechanisms. METHODS AND RESULTS: An in vitro ischemia model (oxygen-glucose deprivation/reperfusion, OGD/R) was used. MSC-Exos was identified by Western blot (WB) and transmission electron microscopy (TEM). To further investigate the mechanism, MSC-Exos, miR-124 inhibitor, and mimics, and a mTOR pathway inhibitor (rapamycin, Rap) were used. The interaction between GLT-1 and miR-124 was analyzed by luciferase reporter assay. The GLT-1 RNA expression and miR-124 was assessed by quantitative real-time polymerase chain reaction (qRTPCR). The protein expressions of GLT-1, S6, and pS6 were detected by WB. Results demonstrated that MSC-Exos successfully inhibited the decrease of GLT-1 and miR-124 expression and the increase of pS6 expression in astrocytes after OGD/R. miR-124 inhibitor suppressed the effect of MSC-Exos on GLT-1 upregulation after OGD/R. Rapamycin notably decreased pS6 expression with significantly higher GLT-1 expression in astrocytes injured by OGD/R. Luciferase activity of the reporter harboring the wild-type or mutant GLT-1 3'UTR was not inhibited by miR-124 mimics. Further results showed that the inhibiting effect of MSC-Exos on pS6 expression and promoting effect of MSC-Exos on GLT-1 expression could be reversed by miR-124 inhibitor after OGD/R; meanwhile, the above conditions could be reversed again by rapamycin. CONCLUSIONS: Results show that miR-124 and the mTOR pathway are involved in regulation of MSC-Exos on GLT-1 expression in astrocytes injured by OGD/R. miR-124 does not directly target GLT-1. MSC-Exos upregulates GLT-1 expression via the miR-124/mTOR pathway in astrocytes injured by OGD/R.