[Evaluation of the feasibility of endoscopic tympanoplasty in two-person three-hand operation].

Objective:To study the difference of postoperative efficacy between two-person three-hand ear endoscopy and microscopic tympanoplasty in patients with chronic suppurative otitis media, and to explore the advantages and disadvantages of two-person three-hand ear endoscopy. Methods:A retrospective study was conducted on 100 patients who underwent tympanoplasty in the Department of Otolaryngology and Head and Neck Surgery of Hunan People's Hospital from April 2019 to March 2023, and they were divided into 2 groups with 50 cases each according to random number table method. Among them, 50 cases underwent endoscopic tympanoplasty in two-person three-hand（group A） and 50 cases underwent routine microscopic tympanoplasty（group B）. The operation and postoperative conditions of the two groups were followed up. Results:In group A, the mean operation time was（65.78±18.21） min, the mean intraoperative blood loss was（12.94±4.46） mL, the postoperative pain score was（1.82±0.60） points, and the mean postoperative hospital stay was（2.76±0.72） d. The mean operation time of group B was（89.45±20.38） min, the mean intraoperative blood loss was（22.78±5.74） mL, the postoperative pain score was（2.98±0.85） points, and the mean postoperative hospital stay was（3.82±0.75） d, which with statistical significance between the two groups（P<0.05）. Hearing in both groups was significantly improved 6 months after surgery, and the difference was statistically significant before and after surgery（P<0.05）, but there was no significant difference between the two groups before surgery and 6 months after surgery（P>0.05）. There were 2 cases in group A（4%） and 1 case in group B（2%） complicated with tympanic cord injury during operation, and the difference was not statistically significant（P>0.05）. There were 47 cases of A group（94%） of one-time healing of tympanic membrane after operation, 48 cases（96%） of group B, and the difference was not statistically significant（P>0.05）. Conclusion:There is no significant difference in cure rate and hearing improvement between two-person three-hand ear endoscopic tympanoplasty and conventional microscope surgery, and the operation time is significantly shortened, the amount of blood loss is less, and the postoperative recovery is faster. It has the advantages of clear operating field, two-person three-hand operation, minimally invasive, and can reach the range of middle ear tympanic sinus and mastoid apex, and the surgical complications are seldom, which is worth promoting.

Robust speed estimation for a moving harmonic acoustic source with a single stationary sensor.

A noise-insensitive cost function was developed for estimating the speed of harmonic acoustic sources in uniform linear motion. This function weighs and integrates the energy distribution of received tones in the time-frequency plane to enhance the robustness of parameter estimation under low signal-to-noise ratio conditions, where weight values are intentionally combined with the law of observed instantaneous frequency. As the cost function is differentiable, the procedure of parameter estimations also has high computing efficiency. Processing data of SWellEx-96 experiments with real ocean noise confirmed the anti-noise capabilities of this cost function to conventional processing methods.

Diabetic Retinopathy and Brain Structure, Cognition Function, and Dementia: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Accumulating evidence has demonstrated that hyperglycemia is a possible risk factor for mild cognitive impairment or Alzheimer's disease. Diabetic retinopathy (DR) has been identified as a risk factor for dementia in patients with diabetes. OBJECTIVE: This study aimed to investigate the causal relationships between DR and brain structure, cognitive function, and dementia. METHODS: We performed bidirectional two-sample Mendelian randomization for DR, brain structure, cognitive function, and dementia using the inverse-variance weighted method. RESULTS: Inverse-variance weighted analysis showed the association of DR with vascular dementia (OR = 1.68, 95% CI: 1.01-2.82), and dementia was significantly associated with the increased risk of non-proliferative DR (NPDR) (OR = 1.76, 95% CI: 1.04-2.98). Furthermore, better cognitive performance was significantly associated with a reduced risk of NPDR (OR = 0.85, 95% CI: 0.74-0.98). No association was observed between DR and brain structure. CONCLUSIONS: These findings suggest that the association of DR with vascular dementia. The reciprocal effect of cognitive performance and dementia on NPDR risk highlights the potential benefits of dementia prevention for reducing the burden of DR.

STAT4 facilitates PD-L1 level via IL-12R/JAK2/STAT3 axis and predicts immunotherapy response in breast cancer.

Signal transducer and activator of transcription 4 (STAT4) is a critical transcription factor for T helper cell differentiation and tumor cells. Although its prognostic role and gene function have been reported in several carcinomas, the role of STAT4 in vitro and in vivo in breast cancer remains poorly understood. The effect of STAT4 in immunotherapy is also unclear. Therefore, we integrated bulk transcriptomics, experiments, and single-cell transcriptomics to systematically analyze its function in prognosis and signaling pathway. Several clinical breast cancer cohorts confirmed STAT4 as a T-cell relevant prognostic biomarker. Overexpressed STAT4 increased programmed cell death ligand 1 (PD-L1) and major histocompatibility complex class II levels in breast cancer cells. In molecular mechanism, transcriptional synergy between STAT4 and STAT3 transactivated interleukin (IL)-12R and involved a positive feedback loop: STAT4/IL-12R/JAK2-STAT3-STAT4, which contributed to the upregulation of PD-L1 expression. The above signaling axis was defined as the STAT4-related pathway and its score was used to predict T-cell expansion and anti-PD1 treatment response. These findings highlight a novel molecular mechanism indirectly regulating PD-L1 through the STAT4-related pathway: IL-12R/JAK2-STAT3-STAT4/PD-L1, and it has potential application in predicting anti-PD-1 immunotherapy response, which may pave the way for stratified immunotherapy in breast cancer.

Deep unsupervised adversarial domain adaptation for underwater source range estimation.

In this study, an underwater source range estimation method based on unsupervised domain adaptation (UDA) is proposed. In contrast to traditional deep-learning frameworks using real-world data, UDA does not require labeling of the measured data, making it more practical. First, a classifier based on a deep neural network is trained with labeled simulated data generated using acoustic propagation models and, then, the adaptive procedure is applied, wherein unlabeled measured data are employed to adjust an adaptation module using the adversarial learning algorithm. Adversarial learning is employed to alleviate the marginal distribution divergence, which reflects the difference between the measured and theoretically computed sound field, in the latent space. This divergence, caused by environmental parameter mismatch or other unknown corruption, can be detrimental to accurate source localization. After the completion of the adaptive procedure, the measured and simulated data are projected to the same space, eliminating distribution discrepancy, which is beneficial for source localization tasks. Experimental results show that range estimation based on UDA outperforms the match-field-processing method under four scenarios of few snapshots, few array elements, low signal-to-noise ratio, and environmental parameter mismatch, verifying the robustness of the method.

MiR-30a-5p Enhances Cisplatin Sensitivity by Downregulating RIF1 in Ovarian Cancer.

OBJECTIVE: Ovarian cancer (OC) is a common malignant tumor in females with high recurrence and poor prognosis. Cisplatin is commonly used for OC clinical treatment, but its efficacy is usually challenged by the chemotherapy resistance of cancer cells. MicroRNAs (miRNAs), including miR-30a-5p, were identified to modulate drug resistance in numerous tumors. However, molecular mechanisms of miR-30a-5p in OC chemoresistance need more illumination. METHODS: MiR-30a-5p and Rap1 interacting factor 1 (RIF1) expression in OC tissues and cells were measured by qRT-PCR. The IC50 of cisplatin-resistant and cisplatin-sensitive OC cells was assessed by MTT assays. OC cell proliferation, apoptosis and migration were measured by EdU assays, TUNEL staining, and wound healing assays, respectively. The protein levels of EMT markers and RIF1 in OC cells were examined by western blotting. The binding capacity between miR-30a-5p and RIF1 was validated by luciferase reporter assays. RESULTS: Our study disclosed miR-30a-5p as a remarkably lowly-expressed miRNA in OC tissues in comparison to matched noncancerous tissues. Compared to parental cell lines, miR-30a-5p was also greatly downregulated in cisplatin-resistant OC cell lines. Additionally, functional assays indicated that miR-30a-5p suppressed malignant behaviors and cisplatin resistance of OC cells. Further, miR-30a-5p was revealed to target and negatively regulate RIF1 expression in OC. Moreover, it was validated that overexpressing RIF1 reverses the inhibitory influence of miR-30a-5p overexpression on malignant behaviors and cisplatin resistance of OC cells. CONCLUSION: MiR-30a-5p reduced cisplatin resistance in OC through downregulation of RIF1, which may be meaningful for targeting drug-resistant tumors.

Predicted lean body mass in relation to cognitive function in the older adults.

Background: Previous findings about lean body mass (LBM) and cognitive function remain unclear. We aimed to examine this association by using data from the National Health and Nutrition Examination Survey (NHANES). Methods: Using data from the NHANES 2011-2014, we conducted logistic regression models to investigate the relation between the predicted LBM and domain-specific cognitive function assessed by Digit Symbol Substitution Test (DSST), Consortium to Establish a Registry for Alzheimer's Disease Word Learning test (CERAD-WL) and Delayed Recall test (CERAD-DR), and Animal Fluency (AF) for information processing speed, memory, and executive function, respectively. Cognitive impairment was defined as the lowest quartile of each cognitive test in the total population. Sex-stratified analysis was further made. Results: A total of 2955 participants aged 60 and above (mean [SD] age, 69.17[0.20] years; 1511 female [51.13%]) were included in the study. After being adjusted for social economic factors, anthropometric parameters, and diseases, we found a positive association between predicted LBM and information processing speed (Odds ratio of DSST impairment= 0.95, 95%CI= 0.91 to 0.99) regardless of body mass index and sex. Compared with patients in the first quartile of predicted LBM, those in the fourth quartile had an odds ratio of 0.355 (95% confidence interval 0.153-0.822) for DSST impairment. No significant relation in other cognitive tests and predicted LBM was found whether stratified by sex or not. Conclusion: Our findings point to the association between predicted lean body mass and cognitive dysfunction in information processing speed, which could be used for early detection and prevention of deterioration of cognitive function among older adults.

Impact of ectopic fat on brain structure and cognitive function: A systematic review and meta-analysis from observational studies.

Ectopic fat, defined as a specific organ or compartment with the accumulation of fat tissue surrounding organs, is highly associated with obesity which has been identified as a risk factor for cognitive impairment and dementia. However, the relationship between ectopic fat and changes in brain structure or cognition is yet to be elucidated. Here, we investigated the effects of ectopic fat on brain structure and cognitive function via systemic review and meta-analysis. A total of 21 studies were included from electronic databases up to July 9, 2022. We found ectopic fat was associated with decreased total brain volumeand increased lateral ventricle volume. In addition, ectopic was associated with decreased cognitive scores and negatively correlated with cognitive function. More specifically, dementia development were correlated with increased levels of visceral fat. Overall, our data suggested that increased ectopic fat was associated with prominent structural changes in the brain and cognitive decline, an effect driven mainly by increases in visceral fat, while subcutaneous fat may be protective. Our results suggest that patients with increased visceral fat are at risk of developing cognitive impairment and, therefore, represent a subset of population in whom appropriate and timely preventive measures could be implemented.

New advances in the research of clinical treatment and novel anticancer agents in tumor angiogenesis.

In 1971, Folkman proposed that tumors could be limited to very small sizes by blocking angiogenesis. Angiogenesis is the generation of new blood vessels from pre-existing vessels, considered to be one of the important processes in tumor growth and metastasis. Angiogenesis is a complex process regulated by various factors and involves many secreted factors and signaling pathways. Angiogenesis is important in the transport of oxygen and nutrients to the tumor during tumor development. Therefore, inhibition of angiogenesis has become an important strategy in the clinical management of many solid tumors. Combination therapies of angiogenesis inhibitors with radiotherapy and chemotherapy are often used in clinical practice. In this article, we will review common targets against angiogenesis, the most common and up-to-date anti-angiogenic drugs and clinical treatments in recent years, including active ingredients from chemical and herbal medicines.

Pancreatic cancer and fibrosis: Targeting metabolic reprogramming and crosstalk of cancer-associated fibroblasts in the tumor microenvironment.

Pancreatic cancer is one of the most dangerous types of cancer today, notable for its low survival rate and fibrosis. Deciphering the cellular composition and intercellular interactions in the tumor microenvironment (TME) is a necessary prerequisite to combat pancreatic cancer with precision. Cancer-associated fibroblasts (CAFs), as major producers of extracellular matrix (ECM), play a key role in tumor progression. CAFs display significant heterogeneity and perform different roles in tumor progression. Tumor cells turn CAFs into their slaves by inducing their metabolic dysregulation, exacerbating fibrosis to acquire drug resistance and immune evasion. This article reviews the impact of metabolic reprogramming, effect of obesity and cellular crosstalk of CAFs and tumor cells on fibrosis and describes relevant therapies targeting the metabolic reprogramming.

A study on endovascular treatment alone and bridging treatment for acute ischemic stroke.

OBJECTIVES: To investigate whether intravenous thrombolysis (IVT) with alteplase (a recombinant tissue plasminogen activator, rt-PA) before endovascular treatment (EVT) is beneficial for acute ischemic stroke (AIS) patients in different periods. METHODS: This study enrolled a total of 140 patients hospitalized between 2019 and 2022 with AIS from large vessel occlusion (LVO) in the anterior circulation. Those patients were divided into the EVT alone group and IVT + EVT group, in which EVT was preceded by intravenous rt-PA. According to the time from onset to femoral artery puncture, the above two groups were divided into the following subgroups: < 4.5 h, between 4.5 and 6 h, between 6 and 8 h, and between 8 and 10 h. There were 78 patients in the EVT alone group and 62 patients in the IVT + EVT group. RESULTS: There was no statistically significant difference in functional independence, recanalization rate, favorable outcome rate, or mortality between the EVT and IVT + EVT groups (P > 0.05). After adjusting for confounding factors, a lower incidence of intracerebral hemorrhage was observed in the EVT group (P < 0.05). A comparison of time-dependent efficacy between the two groups showed that within 6-8 h, there were statistically significant differences between admission and postoperation in the National Institutes of Health Stroke Scale scores at 24 h (P = 0.01) or 7 days (P = 0.02). CONCLUSIONS: Although there was no difference in clinical efficacy and safety between the abovementioned two groups, treatment with IVT + EVT could increase the risk of bleeding compared to EVT. Moreover, in the 6-8 h subgroup, the efficacy of EVT alone was better than that of IVT + EVT.

The Association Between Diabetes Duration and Domain-Specific Cognitive Impairment: A Population-Based Study.

BACKGROUND: Diabetes is a risk factor for cognitive impairment, and disease duration is associated with geriatric decline and functional disabilities. OBJECTIVE: This study aimed to examine the association of diabetes duration with domain-specific cognitive impairment in elderly. METHODS: A total of 3,142 participants from the National Health and Nutrition Examination Survey (NHANES) from the period between 2011 and 2014 were included. We assessed cognitive function using the Digit Symbol Substitution Test (DSST), the CERAD Word Learning (CERAD-WL) test, the CERAD Delayed Recall (CERAD-DR) test and animal fluency (AF) test. RESULTS: After adjusting for age, sex, race/ethnicity, education level, and annual household income, we found that diabetes with a duration longer than 20 years were at 3.32-fold increased risk of DSST impairment (OR = 3.32, 95% CI: 1.95 to 5.67), 1.72-fold increased risk of CERAD-WL impairment (OR = 1.72, 95% CI: 1.13 to 2.62), and 1.76-fold increased risk of AF impairment (OR = 1.76, 95% CI: 1.23 to 2.53), compared with those with no diabetes. Associations were generally stronger in women than in men. Participants with diabetes, who were diagnosed at 50-59 years old were at increased risk of DSST impairment, CERAD-WL impairment, CERAD-DR impairment, and AF impairment per 5 years longer duration of diabetes. CONCLUSION: Longer diabetes duration was associated with the increased risk of cognitive impairment, especially in processing speed and attention. The presence of chronic kidney disease was associated with the increased risk of DSST impairment.

Relationship Between Weight-Change Patterns and Cognitive Function: A Retrospective Study.

BACKGROUND: Obesity has been linked to cognitive impairment. However, how changes in body mass index (BMI) over the life course influence cognitive function remains unclear. OBJECTIVE: The influence of distinct weight-change patterns from young adulthood to midlife and late adulthood on cognitive function in older adults was explored. METHODS: A total of 5,809 individuals aged≥60 years were included and categorized into four groups on the basis of BMI change patterns. Cognitive function was assessed using four cognition tests in the baseline survey. The relationship between the weight-change patterns and cognition was evaluated using regression models. RESULTS: In comparison with participants who remained at non-obese, those moving from the non-obese to obese weight-change pattern from young (25 years of age) to middle adulthood showed lower Digit Symbol Substitution Test (DSST) scores (ß= -1.28; 95% confidence interval [CI]: -2.24 to -0.32). A non-obese to obese change pattern from age 25 years of age to 10 years before baseline was associated with a higher risk of DSST impairment (odds ratio = 1.40; 95% CI: 1.09 to 1.79). In comparison with participants whose heaviest weight was recorded after 60 years of age, those with the heaviest weight between 18 and 40 years of age had lower DSST scores (ß= -1.46; 95% CI: -2.77 to -1.52). CONCLUSION: Our results suggest that the transition from the non-obese to obese category in early adulthood and appearance of the heaviest weight between 18 and 40 years of age are associated with lower cognitive function in later life.

Genomic Analysis of Pseudomonas asiatica JP233: An Efficient Phosphate-Solubilizing Bacterium.

The bacterium Pseudomonas sp. strain JP233 has been reported to efficiently solubilize sparingly soluble inorganic phosphate, promote plant growth and significantly reduce phosphorus (P) leaching loss from soil. The production of 2-keto gluconic acid (2KGA) by strain JP233 was identified as the main active metabolite responsible for phosphate solubilization. However, the genetic basis of phosphate solubilization and plant-growth promotion remained unclear. As a result, the genome of JP233 was sequenced and analyzed in this study. The JP233 genome consists of a circular chromosome with a size of 5,617,746 bp and a GC content of 62.86%. No plasmids were detected in the genome. There were 5097 protein-coding sequences (CDSs) predicted in the genome. Phylogenetic analyses based on genomes of related Pseudomonas spp. identified strain JP233 as Pseudomonas asiatica. Comparative pangenomic analysis among 9 P. asiatica strains identified 4080 core gene clusters and 111 singleton genes present only in JP233. Genes associated with 2KGA production detected in strain JP233, included those encoding glucose dehydrogenase, pyrroloquinoline quinone and gluoconate dehydrogenase. Genes associated with mechanisms of plant-growth promotion and nutrient acquisition detected in JP233 included those involved in IAA biosynthesis, ethylene catabolism and siderophore production. Numerous genes associated with other properties beneficial to plant growth were also detected in JP233, included those involved in production of acetoin, 2,3-butanediol, trehalose, and resistance to heavy metals. This study provides the genetic basis to elucidate the plant-growth promoting and bio-remediation properties of strain JP233 and its potential applications in agriculture and industry.

Pregnancy Outcomes after Frozen Embryo Transfer and Fresh Embryo Transfer in Women of Advanced Maternal Age: Single-Center Experience.

Delayed childbearing leads to increased assisted reproductive technology use by women of advanced maternal age (AMA). It is unclear whether fresh or frozen embryo transfer (FET) is the better option. We aimed to assess maternal and neonatal outcomes in patients having their first FET after a freeze-all cycle versus those having their first fresh embryo transfer (ET). We reviewed 720 women of AMA undergoing a first fresh ET (n = 375) or FET (n = 345) between January 2016 and April 2021. No significant difference in the live birth rate was found between FET and fresh ET (19.7% vs. 24.3%, p = 0.141). The clinical pregnancy rate was significantly lower in the FET group than in the fresh ET group (26.4 % (91/345) vs. 33.6% (126/375), p = 0.035), but FET resulted in higher birthweights (3217.16 ± 734.44 vs. 3003.37 ± 635.00, p = 0.037) and was associated with a lower incidence of preterm births (2.6% vs. 5.6%, p = 0.046). The risks of other maternal and neonatal outcomes did not differ significantly between the groups. Among women of AMA, the transfer of frozen embryos did not result in significantly higher rates of live birth than fresh embryos did; however, a freeze-all strategy may not be beneficial for the women of AMA.

Daphnoretin relieves IL-1ß-mediated chondrocytes apoptosis via repressing endoplasmic reticulum stress and NLRP3 inflammasome.

BACKGROUND: Osteoarthritis (OA), mainly caused by severe joint degeneration, is often accompanied by joint pain and dysfunction syndrome. Inflammatory mediators and apoptosis play key roles in the evolution of OA. It is reported that daphnoretin has significant antiviral and anti-tumor values. The present study aims at investigating the role of daphnoretin in OA. METHODS: The OA mouse model was constructed by performing the destabilization of the medial meniscus through surgery, and the OA cell model was induced in ATDC5 chondrocytes with IL-1ß (10 ng/mL) in vitro. Chondrocyte viability and apoptosis were measured by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), Caspase-3 activity, and flow cytometry. The levels of COX-2, iNOS, TNF-α, IL-6, Bax, Bcl2, cleaved-Caspase3, endoplasmic reticulum stress (ERS) proteins (GRP78, CHOP, ATF6, and Caspase-12), and NLRP3-ASC-Caspase1 inflammasome were determined by quantitative real-time PCR or western blot. The concentrations of TNF-α, IL-6, and PGE2 were tested by enzyme-linked immunosorbent assay. The content of nitrates was detected by the Griess method. In vivo, morphologic differences in knee joint sections and the thickness of the subchondral bone density plate in mice were observed by hematoxylin-eosin (H&E) staining and safranin O-fast green staining. RESULTS: Daphnoretin effectively choked IL-1ß-induced chondrocyte apoptosis and facilitated cell viability. Daphnoretin dose-dependently abated ERS, inflammatory mediators, and the activation of NLRP3 inflammasomes in IL-1ß-induced chondrocytes. What's more, in vivo experiments confirmed that daphnoretin alleviated OA progression in a murine OA model by mitigating inflammation and ERS. CONCLUSION: Daphnoretin alleviated IL-1ß-induced chondrocyte apoptosis by hindering ERS and NLRP3 inflammasome.

Impact of glucagon-like peptide 1 analogs on cognitive function among patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

Background: Diabetes is an independent risk factor for cognitive impairment. However, little is known about the neuroprotective effects of glucagon-like peptide 1 (GLP-1) analogs on type 2 diabetes mellitus (T2DM). Herein, we assessed the impact of GLP-1 analogs on the general cognitive functioning among patients with T2DM. Methods: Relevant studies were retrieved from PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases from their inception till June 30, 2022, without any language restrictions. For continuous variables, the mean and standard deviation (SD) were extracted. Considering the heterogeneity in general cognitive functioning assessments among the pooled studies, the standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs), were calculated. Results: Five studies including 7,732 individuals with T2DM were selected for the meta-analysis. The use of GLP-1 analogs exerted no significant effects on the general cognitive functioning in self-controlled studies (SMD 0.33, 95% CI -0.03 to 0.69). Subgroup analyses among the self-controlled studies based on age and history of cardio-cerebrovascular disease showed that GLP-1 analogs significantly improved the general cognitive functioning in T2DM patients younger than 65 years (SMD 0.69, 95% CI 0.31 to 1.08) or those without cardio-cerebrovascular diseases (SMD 0.69, 95% CI 0.31 to 1.08). Similarly, differences in the general cognitive functioning for GLP-1 analogs between treated and non-treated patients with T2DM were significant in subgroups with patients younger than 65 years (SMD 1.04, 95% CI 0.61 to 1.47) or those with no history of cardio-cerebrovascular diseases (SMD 1.04, 95% CI 0.61 to 1.47). Conclusion: Limited evidence suggests that the use of GLP-1 analogs exerts no significant effects on general cognitive functioning but may be beneficial for patients with T2DM younger than 65 years or those without a history of cardio-cerebrovascular diseases. Further prospective clinical studies with large sample sizes are needed to validate these findings. Systematic Review Registration: www.inplasy.com, identifier 202260015.