Effects of computerized cognitive training on functional brain networks in patients with vascular cognitive impairment and no dementia.

AIMS: Previous neuroimaging studies of vascular cognitive impairment, no dementia (VCIND), have reported functional alterations, but far less is known about the effects of cognitive training on functional connectivity (FC) of intrinsic connectivity networks (ICNs) and how they relate to intervention-related cognitive improvement. This study provides comprehensive research on the changes in intra- and inter-brain functional networks in patients with VCIND who received computerized cognitive training, with a focus on the underlying mechanisms and potential therapeutic strategies. METHODS: We prospectively collected 60 patients with VCIND who were randomly divided into the training group (N = 30) receiving computerized cognitive training and the control group (N = 30) receiving fixed cognitive training. Functional MRI scans and cognitive assessments were performed at baseline, at the 7-week training, and at the 6-month follow-up. Utilizing templates for ICNs, the study employed a linear mixed model to compare intra- and inter-network FC changes between the two groups. Pearson correlation was applied to calculate the relationship between FC and cognitive function. RESULTS: We found significantly decreased intra-network FC within the default mode network (DMN) following computerized cognitive training at Month 6 (p = 0.034), suggesting a potential loss of functional specialization. Computerized training led to increased functional coupling between the DMN and sensorimotor network (SMN) (p = 0.01) and between the language network (LN) and executive control network (ECN) at Month 6 (p < 0.001), indicating compensatory network adaptations in patients with VCIND. Notably, the intra-LN exhibited enhanced functional specialization after computerized cognitive training (p = 0.049), with significant FC increases among LN regions, which correlated with improvements in neuropsychological measures (p < 0.05), emphasizing the targeted impact of computerized cognitive training on language abilities. CONCLUSIONS: This study provides insights into neuroplasticity and adaptive changes resulting from cognitive training in patients with VCIND, with implications for potential therapeutic strategies.

A Comprehensive Prognostic Model for Colon Adenocarcinoma Depending on Nuclear-Mitochondrial-Related Genes.

Background: Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. Methods: COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. Results: A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including LARS2, PARS2, ETHE1, LRPPRC, TMEM70, AARS2, ACAD9, VARS2, and ATP8A2. The high-RS group had more inflamed immune features, including T and CD4+ memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. Conclusion: This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.

Clinical outcomes and biomarker exploration of first-line PD-1 inhibitors plus chemotherapy in patients with low PD-L1-expressing of gastric or gastroesophageal junction adenocarcinoma.

BACKGROUND: The beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial. METHODS: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis. RESULTS: Of 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09-4.90; P = 0.029). CONCLUSIONS: PD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy.

Profiling the interplay and coevolution of Microcystis aeruginosa and cyanosiphophage Mic1.

The cyanosiphophage Mic1 specifically infects the bloom-forming Microcystis aeruginosa FACHB 1339 from Lake Chaohu, China. Previous genomic analysis showed that its 92,627 bp double-stranded DNA genome consists of 98 putative open reading frames, 63% of which are of unknown function. Here, we investigated the transcriptome dynamics of Mic1 and its host using RNA sequencing. In the early, middle, and late phases of the 10 h lytic cycle, the Mic1 genes are sequentially expressed and could be further temporally grouped into two distinct clusters in each phase. Notably, six early genes, including gp49 that encodes a TnpB-like transposase, immediately reach the highest transcriptional level in half an hour, representing a pioneer cluster that rapidly regulates and redirects host metabolism toward the phage. An in-depth analysis of the host transcriptomic profile in response to Mic1 infection revealed significant upregulation of a polyketide synthase pathway and a type III-B CRISPR system, accompanied by moderate downregulation of the photosynthesis and key metabolism pathways. The constant increase of phage transcripts and relatively low replacement rate over the host transcripts indicated that Mic1 utilizes a unique strategy to gradually take over a small portion of host metabolism pathways after infection. In addition, genomic analysis of a less-infective Mic1 and a Mic1-resistant host strain further confirmed their dynamic interplay and coevolution via the frequent horizontal gene transfer. These findings provide insights into the mutual benefit and symbiosis of the highly polymorphic cyanobacteria M. aeruginosa and cyanophages. IMPORTANCE: The highly polymorphic Microcystis aeruginosa is one of the predominant bloom-forming cyanobacteria in eutrophic freshwater bodies and is infected by diverse and abundant cyanophages. The presence of a large number of defense systems in M. aeruginosa genome suggests a dynamic interplay and coevolution with the cyanophages. In this study, we investigated the temporal gene expression pattern of Mic1 after infection and the corresponding transcriptional responses of its host. Moreover, the identification of a less-infective Mic1 and a Mic1-resistant host strain provided the evolved genes in the phage-host coevolution during the multiple-generation cultivation in the laboratory. Our findings enrich the knowledge on the interplay and coevolution of M. aeruginosa and its cyanophages and lay the foundation for the future application of cyanophage as a potential eco-friendly and bio-safe agent in controlling the succession of harmful cyanobacterial blooms.

Application of convolutional neural network for differentiating ovarian thecoma-fibroma and solid ovarian cancer based on MRI.

BACKGROUND: Ovarian thecoma-fibroma and solid ovarian cancer have similar clinical and imaging features, and it is difficult for radiologists to differentiate them. Since the treatment and prognosis of them are different, accurate characterization is crucial. PURPOSE: To non-invasively differentiate ovarian thecoma-fibroma and solid ovarian cancer by convolutional neural network based on magnetic resonance imaging (MRI), and to provide the interpretability of the model. MATERIAL AND METHODS: A total of 156 tumors, including 86 ovarian thecoma-fibroma and 70 solid ovarian cancer, were split into the training set, the validation set, and the test set according to the ratio of 8:1:1 by stratified random sampling. In this study, we used four different networks, two different weight modes, two different optimizers, and four different sizes of regions of interest (ROI) to test the model performance. This process was repeated 10 times to calculate the average performance of the test set. The gradient weighted class activation mapping (Grad-CAM) was used to explain how the model makes classification decisions by visual location map. RESULTS: ResNet18, which had pre-trained weight, using Adam and one multiple ROI circumscribed rectangle, achieved best performance. The average accuracy, precision, recall, and AUC were 0.852, 0.828, 0.848, and 0.919 (P < 0.01), respectively. Grad-CAM showed areas associated with classification appeared on the edge or interior of ovarian thecoma-fibroma and the interior of solid ovarian cancer. CONCLUSION: This study shows that convolution neural network based on MRI can be helpful for radiologists in differentiating ovarian thecoma-fibroma and solid ovarian cancer.

Toxicity and fate of cadmium in hydroponically cultivated lettuce (Lactuca sativa L.) influenced by microplastics.

Although more attention has been paid to microplastics (MPs) pollution in environment, research on the synthetic influence of microplastic and heavy metals remains limited. To help fill this information gap, we investigated the adsorption behavior of virgin polyvinyl chloride microplastics (PVCMPs) (≤450 µm white spherical powder) on cadmium (II). The effects on seed germination, seedling growth, photosynthetic system, oxidative stress indicators of lettuce, and changes in Cd bioavailability were evaluated under Cd2+ (25 µmol/L), PVCMPs (200 mg/L), and PVCMP-Cd combined (200 mg/L + 25 µmol/L) exposures in hydroponic system. The results demonstrated that the PVCMPs effectively adsorbed Cd ions, which validated by the pseudo-second-order kinetic and the Langmuir isotherm models, indicating the sorption of Cd2+ on the PVCMPs was primary chemisorption and approximates monomolecular layer sorption. Compared to MPs, Cd significantly inhibits plant seed germination and seedling growth and development. However, Surprising improvement in seed germination under PVCMPs-Cd exposure was observed. Moreover, Cd2+ and MPs alone or combined stress caused oxidative stress with reactive oxygen species (ROS) including H2O2, O2- and Malondialdehyde (MDA) accumulation in plants, and substantially damaged to photosynthesis. With the addition of PVCMPs, the content of Cd in the leaves significantly (P<0.01) decreased by 1.76-fold, and the translocation factor and Cd2+removal rate in the water substantially (P<0.01) decreased by 6.73-fold and 1.67-fold, respectively in contrast to Cd2+ stress alone. Therefore, it is concluded the PVCMP was capable of reducing Cd contents in leaves, alleviating Cd toxicity in lettuce. Notably, this study provides a scientific foundation and reference for comprehending the toxicological interactions between microplastics and heavy metals in the environment.

Seven oral traditional Chinese medicine combined with chemotherapy for the treatment of non-small cell lung cancer: a network meta-analysis.

CONTEXT: Traditional Chinese medicines (TCMs) have emerged as potential adjuvant therapies to treat non-small cell lung cancer. More direct comparative studies must be conducted among various oral TCMs. OBJECTIVE: This network meta-analysis evaluates the efficacy and safety of seven oral TCMs combined with chemotherapy in treating NSCLC. METHODS: The analysis included Zilongjin, Banmao, Hongdoushan, Huachansu, Kanglaite, Xihuang, and Pingxiao TCMs. Randomized-controlled trials (RCTs) were identified from the following databases: China National Infrastructure, Wanfang, PubMed, Embase, and the Cochrane Library up to April 2023. Two researchers independently extracted data. RESULTS: Sixty-eight RCTs (5,099 patients) were included. Compared to chemotherapy, Banmao capsules [odds ratio (OR) = 2.69, 95% confidence interval (CI) 1.96-3.69)] and Huachansu tablets [OR = 2.35, 95%CI (1.81, 3.05)] ranked in the top two in terms of increasing disease control rate. The two main TCMs to improve the objective response rate were Banmao capsules [OR = 3.49, 95%CI (2.17, 5.60)] and Zilongjin tablets [OR = 2.62, 95%CI (1.92, 3.57)]. Zilongjin tablets [OR = 3.47, 95%CI (2.14, 5.63)] and Huachansu tablets [OR = 3.30, 95%CI (1.65, 6.60)] were ranked as the top two in improving Karnofsky performance status. Hongdoushan capsules (SUCRA = 18.8%) and Banmao capsules (SUCRA = 19.8%) were the top two in reducing gastrointestinal toxicity. Zilongjin tablets (SUCRA = 18.9%) and Banmao capsules (SUCRA = 26.6%) were the top two to reduce liver and kidney toxicity. Hongdoushan capsules (SUCRA = 15.7%) and Huachansu tablets (SUCRA = 16.8%) ranked the top two in reducing thrombocytopenia. Banmao capsules (SUCRA = 14.3%) and Zilongjin tablets (SUCRA = 26.3%) were the top two decreasing leukopenia. CONCLUSIONS: Combining oral TCMs with platinum-based chemotherapy has shown superior efficacy compared to platinum-based chemotherapy alone in treating NSCLC.

Organellophagy regulates cell death:A potential therapeutic target for inflammatory diseases.

BACKGROUND: Dysregulated alterations in organelle structure and function have a significant connection with cell death, as well as the occurrence and development of inflammatory diseases. Maintaining cell viability and inhibiting the release of inflammatory cytokines are essential measures to treat inflammatory diseases. Recently, many studies have showed that autophagy selectively targets dysfunctional organelles, thereby sustaining the functional stability of organelles, alleviating the release of multiple cytokines, and maintaining organismal homeostasis. Organellophagy dysfunction is critically engaged in different kinds of cell death and inflammatory diseases. AIM OF REVIEW: We summarized the current knowledge of organellophagy (e.g., mitophagy, reticulophagy, golgiphagy, lysophagy, pexophagy, nucleophagy, and ribophagy) and the underlying mechanisms by which organellophagy regulates cell death. KEY SCIENTIFIC CONCEPTS OF REVIEW: We outlined the potential role of organellophagy in the modulation of cell fate during the inflammatory response to develop an intervention strategy for the organelle quality control in inflammatory diseases.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience.

OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. METHODS: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. RESULTS: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. CONCLUSIONS: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

Dual-energy CT quantitative parameters to evaluate occult peritoneal metastasis in advanced gastric cancer preoperatively.

PURPOSE: To explore whether dual-energy CT (DECT) quantitative parameters could provide analytic value for the diagnosis of patients with occult peritoneal metastasis (OPM) in advanced gastric cancer preoperatively. MATERIALS AND METHODS: This retrospective study included 219 patients with advanced gastric cancer and DECT scans. The patient's clinical data and DECT related iodine concentration (IC) parameters and effective atomic number (Zeff) were collated and analyzed among noun-peritoneal metastasis (NPM), OPM and radiologically peritoneal metastasis (RPM) groups. The predictive performance of the DECT parameters was compared with that of the conventional CT features and clinical characteristics through evaluating area under curve of the precision-recall (AUC-PR), F1 score, balanced accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Borrmann IV type diagnosed on CT and serum tumor indicator CA125 index were statistically different between the NPM and OPM groups. DECT parameters included IC, normalized IC (NIC), and Zeff of PM group were lower than the NPM group. The DECT predictive nomogram combined three independent DECT parameters produced a better diagnostic performance than the conventional CT feature Borrmann IV type and serum CA125 index in AUC-PR with 0.884 vs 0.368 vs 0.189, but similar to the combined indicator which was based on the DECT parameters, the conventional CT feature, and serum CA125 index in AUC-PR with 0.884 vs 0.918. CONCLUSION: The lower quantitative NIC, IC ratio, and Zeff on DECT was associated with peritoneal metastasis in advanced gastric cancer and was promising to identify patients with OPM noninvasively.

ERH Impacts Patient Prognosis and Tumor Immune Microenvironment: A Pan-Cancer Analysis.

BACKGROUND: The enhancer of rudimentary homolog (ERH) has been shown to play significant roles in tumorigenesis and progression. However, few systematic pan-cancer analyses about ERH have been described. METHODS: From the tumor immune estimation resource web server2.0 (TIMER2.0), the Genotype-Tissue Expression database (GTEx) and the Gene Expression Profile Interactive Analysis version 2 (GEPIA2) databases, we explored the expression profiles and prognostic significance of ERH in 33 cancers. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (HPA) databases were further used to examine the differential expression of ERH at the protein level. The genetic alteration profile was obtained from the cBioPortal. The correlation between ERH expression and the quantities of immune infiltrating cells was examined by the TIMER tool. Spearman's correlation test was conducted to analyze the association between ERH expression status and a number of prognostic indicators, including immune checkpoints, TMB, MSI, immune neoantigen, MMR genes, and DNA methyltransferases. ProteinProtein Interaction analyses were performed in the String and GeneMANIA databases, and enrichment analysis and predicted signaling pathways were identified through GO and KEGG. To make our results convincing, we validated them in six datasets in the Gene Expression Omnibus (GEO) database. In addition, we verified the expression of ERH between gastric cancer tissues and adjacent normal tissues by RT-qPCR. RESULTS: ERH expression was elevated in numerous tumors, and it was not associated with the patient's prognosis. Furthermore, the quantities of immune infiltrating cells and immune checkpoint genes were remarkably associated with ERH. TMB and MSI were related to ERH expression in 14 and 15 cancer types, respectively. Moreover, the expression of ERH was strongly associated with MMR defects in multiple cancer types, and almost all tumors showed coexpression of ERH and four DNA methyltransferases. The results of GO and KEGG analysis confirmed that ERH potentially impacts several important signaling pathways. Both the GEO datasets and the RT-qPCR experiment validated our previous analysis. CONCLUSION: Our pan-cancer analysis demonstrated the characterization of ERH in multiple tumors. ERH may be a valuable novel biological indicator for assessing immunotherapy efficacy and prognosis in various malignancies.

Trends and risk factors for drug-resistant tuberculosis among children in Sichuan, China: A 10-year retrospective analysis, 2013-2022.

To investigate the status of the drug-resistant tuberculosis (DR-TB) among children in Sichuan, and to find out the risk factors and high-risk population related to drug resistance among children. The clinical data of tuberculosis patients ≤14 years old with culture-confirmed tuberculosis hospitalized in Chengdu Public Health Clinical Center from January 2013 through December 2022 were collected. Clinical data such as gender, age, ethnicity, history of anti-TB treatment, history of exposure to tuberculosis, nutritional status, and specific drug resistance of the children were collected and recorded. The drug resistance of children in different age groups (0-4 years old, 5-9 years old, 10-14 years old) and different periods (2013-2017 and 2018-2022) were grouped and compared. Logistic regression analysis was to analyze analysis of risk factors of drug resistance in children. A total of 438 children with culture-confirmed tuberculosis were screened. Among them, 26.19% (11/42) were 0 to 4 years old, 33.33% (22/66) were 5 to 9 years old, and 36.67% (121/330) were 10 to 14 years old among the resistant children. There was no statistically significant difference in the resistance rate among the 3 groups (P = .385). The proportions of DR-TB, monoresistant tuberculosis, polydrug-resistant tuberculosis were decreased during 2019 to 2022 compared with 2013 to 2017 (P < .0001). The resistance rates of drug resistant, monoresistant, polydrug-resistant, isoniazid-resistant, and rifampicin resistant during 2018 to 2022 were decreased compared with those from 2013 to 2017 (P < .05), but the multi-drug resistance rate was not decreased (P = .131, without statistical difference). The results of logistic regression analysis showed that male gender OR = 1.566 (95% CI 1.035-2.369), a history of antituberculosis therapy OR = 4.049 (95% CI 1.442-11.367), and pulmonary and extrapulmonary tuberculosis OR = 7.335 (95% CI 1.401-38.392) were risk factors for the development of drug resistance; but fever OR = 0.581 (95% CI 0.355-0.950) was Protective factor. The total drug resistance rate of children in Sichuan showed a downward trend, but the rate of multi-drug-resistant tuberculosis was still at a high level, and the form of drug resistance was still severe. Absence of fever, male, retreatment, and pulmonary concurrent with extrapulmonary tuberculosis are risk factors for DR-TB in children.

Deep learning-accelerated T2WI: image quality, efficiency, and staging performance against BLADE T2WI for gastric cancer.

PURPOSE: The purpose of our study is to investigate image quality, efficiency, and diagnostic performance of a deep learning-accelerated single-shot breath-hold (DLSB) against BLADE for T2-weighted MR imaging (T2WI) for gastric cancer (GC). METHODS: 112 patients with GCs undergoing gastric MRI were prospectively enrolled between Aug 2022 and Dec 2022. Axial DLSB-T2WI and BLADE-T2WI of stomach were scanned with same spatial resolution. Three radiologists independently evaluated the image qualities using a 5-scale Likert scales (IQS) in terms of lesion delineation, gastric wall boundary conspicuity, and overall image quality. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated in measurable lesions. T staging was conducted based on the results of both sequences for GC patients with gastrectomy. Pairwise comparisons between DLSB-T2WI and BLADE-T2WI were performed using the Wilcoxon signed-rank test, paired t-test, and chi-squared test. Kendall's W, Fleiss' Kappa, and intraclass correlation coefficient values were used to determine inter-reader reliability. RESULTS: Against BLADE, DLSB reduced total acquisition time of T2WI from 495 min (mean 4:42 per patient) to 33.6 min (18 s per patient), with better overall image quality that produced 9.43-fold, 8.00-fold, and 18.31-fold IQS upgrading against BALDE, respectively, in three readers. In 69 measurable lesions, DLSB-T2WI had higher mean SNR and higher CNR than BLADE-T2WI. Among 71 patients with gastrectomy, DLSB-T2WI resulted in comparable accuracy to BLADE-T2WI in staging GCs (P > 0.05). CONCLUSIONS: DLSB-T2WI demonstrated shorter acquisition time, better image quality, and comparable staging accuracy, which could be an alternative to BLADE-T2WI for gastric cancer imaging.

Impact of circadian clock protein Bmal1 on experimentally-induced periodontitis-associated renal injury.

OBJECTIVES: To investigate the mechanism of circadian clock protein Bmal1 (Bmal1) on renal injury with chronic periodontitis, we established an experimental rat periodontitis model. METHODS: Twelve male Wistar rats were randomly divided into control and periodontitis groups (n=6, each group). The first maxillary molars on both sides of the upper jaw of rats with periodontitis were ligated by using orthodontic ligature wires, whereas the control group received no intervention measures. After 8 weeks, clinical periodontal parameters, including probing depth, bleeding index, and tooth mobility, were evaluated in both groups. Micro-CT scanning and three-dimensional image reconstruction were performed on the maxillary bones of the rats for the assessment of alveolar bone resorption. Histopatholo-gical observations of periodontal and renal tissues were conducted using hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining. Renal function indicators, such as creatinine, albumin, and blood urea nitrogen levels, and oxidative stress markers, including superoxide dismutase, glutathione, and malondialdehyde levels, were measured using biochemical assay kits. MitoSOX red staining was used to detect reactive oxygen species (ROS) content in the kidneys. The gene and protein expression levels of Bmal1, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in rat renal tissues were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical staining. RESULTS: Micro-CT and HE staining results showed significant bone resorption and attachment loss in the maxillary first molar region of the periodontitis group. Histological examination through HE and PAS staining revealed substantial histopathological damage to the renal tissues of the rats in the periodontitis group. The findings of the assessment of renal function and oxidative stress markers indicated that the periodontitis group exhibited abnormal levels of oxidative stress, whereas the renal function levels showed abnormalities without statistical significance. MitoSOX Red staining results showed that the content of ROS in the renal tissue of the periodontitis group was significantly higher than that of the control group, and RT-qPCR and immunohistochemistry results showed that the expression levels of Bmal1, Nrf2, and HO-1 in the renal tissues of the rats in the periodontitis group showed a decreasing trend. CONCLUSIONS: Circadian clock protein Bmal1 plays an important role in the oxidative damage process involved in the renal of rats with periodontitis.

Inflammation-Responsive Hydrogel Accelerates Diabetic Wound Healing through Immunoregulation and Enhanced Angiogenesis.

Angiogenesis is a prominent component during the highly regulated process of wound healing. The application of exogenous vascular endothelial growth factor (VEGF) has shown considerable potential in facilitating angiogenesis. However, its effectiveness is often curtailed due to chronic inflammation and severe oxidative stress in diabetic wounds. Herein, an inflammation-responsive hydrogel incorporating Prussian blue nanoparticles (PBNPs) is designed to augment the angiogenic efficacy of VEGF. Specifically, the rapid release of PBNPs from the hydrogel under inflammatory conditions effectively alleviates the oxidative stress of the wound, therefore reprogramming the immune microenvironment to preserve the bioactivity of VEGF for enhanced angiogenesis. In vitro and in vivo studies reveal that the PBNPs and VEGF co-loaded hydrogel is biocompatible and possesses effective anti-inflammatory properties, thereby facilitating angiogenesis to accelerate the wound healing process in a type 2 diabetic mouse model.

Utility of Combined Use of Imaging Features From Abdominopelvic CT and CA 125 to Identify Presence of CT Occult Peritoneal Metastases in Advanced Gastric Cancer.

OBJECTIVE: The purpose of this study is to identify the presence of occult peritoneal metastasis (OPM) in patients with advanced gastric cancer (AGC) by using clinical characteristics and abdominopelvic computed tomography (CT) features. METHODS: This retrospective study included 66 patients with OPM and 111 patients without peritoneal metastasis (non-PM [NPM]) who underwent preoperative contrast-enhanced CT between January 2020 and December 2021. Occult PMs means PMs that are missed by CT but later diagnosed by laparoscopy or laparotomy. Patients with NPM means patients have neither PM nor other distant metastases, indicating there is no evidence of distant metastases in patients with AGC. Patients' clinical characteristics and CT features such as tumor marker, Borrmann IV, enhancement patterns, and pelvic ascites were observed by 2 experienced radiologists. Computed tomography features and clinical characteristics were combined to construct an indicator for identifying the presence of OPM in patients with AGC based on a logistic regression model. Receiver operating characteristic curves and the area under the receiver operating characteristic curve (AUC) were generated to assess the diagnostic performance of the combined indicator. RESULTS: Four independent predictors (Borrmann IV, pelvic ascites, carbohydrate antigen 125, and normalized arterial CT value) differed significantly between OPM and NPM and performed outstandingly in distinguishing patients with OPM from those without PM (AUC = 0.643-0.696). The combined indicator showed a higher AUC value than the independent risk factors (0.820 vs 0.643-0.696). CONCLUSIONS: The combined indicator based on abdominopelvic CT features and carbohydrate antigen 125 may assist clinicians in identifying the presence of CT OPMs in patients with AGC.

Causal Relationship between Sex Hormones and Risk of Developing Common Neurodegenerative Diseases: A Mendelian Randomization Study.

BACKGROUND: Neurodegenerative diseases are a group of unexplained disorders of the central nervous system, and studies have shown that a large number of genetic and environmental factors are associated with these diseases. Since these diseases show significant gender differences in epidemiology, sex hormones are thought to be strongly associated with these diseases. In this study, we used Mendelian randomization to explore the causal relationship between sex hormones and the risk of developing neurodegenerative diseases. METHODS: We obtained genetic instrumental variables for sex hormones (sex hormone-binding globulin [SHBG], estradiol levels [EL], and bioavailable testosterone [BT]) separately through the Integrative Epidemiology Unit (IEU) database (https://gwas.mrcieu.ac.uk/). We analyzed the causal relationship of each with the risk of developing neurodegenerative diseases (Amyotrophic Lateral Sclerosis [ALS], Parkinson's disease [PD], and Alzheimer's disease [AD]) using inverse variance weighted (IVW) in Mendelian randomization. Data were then analyzed for sensitivity. RESULTS: BT was negatively associated with the risk of developing ALS (odds ratio [OR] = 0.794; 95% confidence interval [95% CI] = 0.672-0.938; p = 0.006). EL and SHBG were not associated with a risk for developing neurodegenerative diseases (ALS, PD, AD). CONCLUSIONS: Elevated BT is associated with a reduced risk of developing ALS. Further research is needed to investigate the underlying mechanisms of action for this correlation and how it can be used as a potential target of action to reduce the risk of developing ALS.

[Clinical study of electroacupuncture therapy on postoperative rehabilitation of patients with knee fractures].

OBJECTIVE: To investigate the effect of electroacupuncture therapy on postoperative rehabilitation training of patients with knee fractures. METHODS: Patients with knee fractures from July 2020 to July 2021 were randomly assigned to either the experimental group or a control group according to the double-blind principle. Both groups were given surgical treatment and postoperative conventional rehabilitation training. There were 40 cases in the control group, including 27 males and 13 females;the age ranged from 20 to 66 years old with an average of (36.46±6.29) years old, continuous passive motion (CPM) training was performed after operation. There were 40 patients in the experimental group, including 24 males and 16 females. The age ranged from 21 to 68 years old with an average of (37.62±7.08) years old, on the basis of the control group, electroacupuncture was given. After 4 weeks of intervention, the excellent rate of knee function score, visual analogue scale (VAS) before and after intervention, serum pain mediators, prostaglandin E (PGE), substance P (SP), bradykinin (BK), joint range of motion and quality of life were compared between the two groups. RESULTS: After 4 weeks of intervention, the Rasmussen score for knee function in the experimental group (24.15±1.36) scores was higher than that in the control group (21.25±2.20) scores (P<0.001). The VAS in the experimental group (2.04±0.51) scores was lower than that in the control group (2.78±0.60) after 4 weeks of intervention (P<0.05). Serum PGE (2.25±0.37) mg·L-1, SP (4.43±1.05) ng·ml-1, BK (2.67±0.68) ng·ml-1 in the experimental group were lower than those in the control group (3.91±0.44) mg·L-1, (6.12±1.37) ng·ml-1, (4.55±1.03) ng·ml-1 after 4 weeks of intervention(P<0.05);in the experimental group, the active knee flexion angle of the knee joint was (108.63±9.76)°, the active knee extension angle (-2.46±0.70)°, passive knee flexion angle (116.83±6.57)°, passive knee extension angle (1.44±0.38)° were better than control group (100.24±8.15)°, (-3.51±0.86)°, (111.04±8.22)°, (0.78±0.24)° (P<0.05);the experimental group's psychological score (73.12±5.08), physiological score (72.26±5.89), social function score (72.57±4.23), overall health score (75.12±5.16) were higher than that of the control group (68.49±4.13), (68.13±5.27), (69.04±3.42), and(70.88±3.97) respectvely(P<0.05). CONCLUSION: Electroacupuncture combined with CPM training after knee fracture surgery can significantly improve knee function and range of motion, reduce pain levels, and also improve quality of life and reduce the incidence of adverse events.