A novel compound alleviates oxidative stress via PKA/CREB1-mediated DJ-1 upregulation.

Oxidative stress is one of the major culprits causing dopaminergic neuron loss in Parkinson's disease (PD). DJ-1 is a protein with multiple actions against oxidative stress, apoptosis, neuroinflammation, etc. DJ-1 expression is decreased in sporadic PD, therefore increasing DJ-1 expression might be beneficial in PD treatment. However, drugs known to upregulate DJ-1 are still lacking. In this study, we identified a novel DJ-1-elevating compound called ChemJ through luciferase assay-based high-throughput compound screening in SH-SY5Y cells and confirmed that ChemJ upregulated DJ-1 in SH-SY5Y cell line and primary cortical neurons. DJ-1 upregulation by ChemJ alleviated MPP+-induced oxidative stress. In exploring the underlying mechanisms, we found that the transcription factor CREB1 bound to DJ-1 promoter and positively regulated its expression under both unstressed and 1-methyl-4-phenylpyridinium-induced oxidative stress conditions and that ChemJ promoted DJ-1 expression via activating PKA/CREB1 pathway in SH-SY5Y cells. Our results demonstrated that ChemJ alleviated the MPP+-induced oxidative stress through a PKA/CREB1-mediated regulation of DJ-1 expression, thus offering a novel and promising avenue for PD treatment.

A graminan type fructan from Achyranthes bidentata prevents the kidney injury in diabetic mice by regulating gut microbiota.

Diabetic kidney disease (DKD) is the main cause of end-stage renal disease, and few therapeutic options are available. The root of Achyranthis bidentatae (AB) is commonly used for DKD treatment in Traditional Chinese medicine. However, its mechanisms are still unclear. Here, a graminan type fructan ABPW1 with molecular weight of 3998 Da was purified from AB. It was composed of ß-1,2-linked Fruf, ß-2,6-linked-Fruf and ß-1,2,6-linked-Fruf backbone, and terminated with T-Glcp and 2-Fruf residues. ABPW1 protected against kidney injuries and intestinal barrier disruption in Streptozotocin (STZ)/High fat diet (HFD) mice. It could modulate gut microbiota composition, evidenced by a rise in the abundance of Bacteroide and decreases of Rikenella, Alistipes, Laedolimicola and Faecalibaculum. ABPW1 intervention promoted short chain fatty acids (SCFAs) production in STZ/HFD mice, especially propionate and isobutyric acid. Antibiotic treatment further demonstrated the key role of gut microbiota in the renal protective action of ABPW1. In addition, in vitro simulated digestion and fermentation together with in vivo fluorescent labeling studies demonstrated ABPW1 was indigestible in upper digestive tract but could reach the colon and be degraded into SCFAs by gut microbiota there. Overall, these data suggested ABPW1 has the potential application on DKD prevention.

Effects of sodium dehydroacetate on broiler chicken bones.

Sodium dehydroacetate (DHA-Na) is a fungicidal preservative widely used in food and animal feed. DHA-Na can induce coagulation disorders in rats and poultry by inhibiting carboxylation of vitamin K-dependent proteins; it can also impair bone development in zebrafish. However, the effects of DHA-Na on broiler chicken bones remain unknown. Here, we assessed whether DHA-Na impairs bone development in broiler chickens. We administered Suji yellow chickens with 200 to 800 mg/kg DHA-Na, 2 mg/kg vitamin K, or both for 2 mo. Bone metabolite-related serum indicators, tissue micromorphology, and relevant protein expression were monitored during the treatment period. We also assessed primary chicken osteoblast activity, differentiation, and bone metabolite-related proteins after treatment with DHA-Na, vitamin K, or both. The results demonstrated that DHA-Na reduced bone index values and serum and bone osteoblast differentiation marker levels but blocked bone vitamin K cycle. DHA-Na also increased serum osteoclast differentiation marker levels, as well as the bone ratio of receptor activator of nuclear factor kappa-Β ligand to osteoprotegerin ratio. Moreover, DHA-Na reduced bone trabecular number, thickness, and area and increased trabecular separation considerably. In general, compared with the control group, the DHA-Na group demonstrated impairments in osteoblast activity and differentiation, as well as in the vitamin K cycle. By contrast, vitamin K supplementation led to considerable attenuation of the DHA-Na-induced decrease in osteogenic marker levels, along with a considerable increase in serum bone absorption marker levels and restoration of DHA-Na-induced bone microstructure damage. Vitamin K also attenuated DHA-Na-induced impairment in osteoclasts. In conclusion, the results indicated that in broiler chickens, DHA-Na supplementation can damage bones by inhibiting osteoblast function and increasing osteoclast activity; this damage can be prevented through vitamin K supplementation.

Human umbilical cord-derived mesenchymal stromal cells improve myocardial fibrosis and restore miRNA-133a expression in diabetic cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious health-threatening complication of diabetes mellitus characterized by myocardial fibrosis and abnormal cardiac function. Human umbilical cord mesenchymal stromal cells (hUC-MSCs) are a potential therapeutic tool for DCM and myocardial fibrosis via mechanisms such as the regulation of microRNA (miRNA) expression and inflammation. It remains unclear, however, whether hUC-MSC therapy has beneficial effects on cardiac function following different durations of diabetes and which mechanistic aspects of DCM are modulated by hUC-MSC administration at different stages of its development. This study aimed to investigate the therapeutic effects of intravenous administration of hUC-MSCs on DCM following different durations of hyperglycemia in an experimental male model of diabetes and to determine the effects on expression of candidate miRNAs, target mRNA and inflammatory mediators. METHODS: A male mouse model of diabetes was induced by multiple low-dose streptozotocin injections. The effects on severity of DCM of intravenous injections of hUC-MSCs and saline two weeks previously were compared at 10 and 18 weeks after diabetes induction. At both time-points, biochemical assays, echocardiography, histopathology, polymerase chain reaction (PCR), immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to analyze blood glucose, body weight, cardiac structure and function, degree of myocardial fibrosis and expression of fibrosis-related mRNA, miRNA and inflammatory mediators. RESULTS: Saline-treated diabetic male mice had impaired cardiac function and increased cardiac fibrosis after 10 and 18 weeks of diabetes. At both time-points, cardiac dysfunction and fibrosis were improved in hUC-MSC-treated mice. Pro-fibrotic indicators (α-SMA, collagen I, collagen III, Smad3, Smad4) were reduced and anti-fibrotic mediators (FGF-1, miRNA-133a) were increased in hearts of diabetic animals receiving hUC-MSCs compared to saline. Increased blood levels of pro-inflammatory cytokines (IL-6, TNF, IL-1ß) and increased cardiac expression of IL-6 were also observed in saline-treated mice and were reduced by hUC-MSCs at both time-points, but to a lesser degree at 18 weeks. CONCLUSION: Intravenous injection of hUC-MSCs ameliorated key functional and structural features of DCM in male mice with diabetes of shorter and longer duration. Mechanistically, these effects were associated with restoration of intra-myocardial expression of miRNA-133a and its target mRNA COL1AI as well as suppression of systemic and localized inflammatory mediators.

Biosafety aspects of RNAi-based pests control.

While the overuse of classical chemical pesticides has had a detrimental impact on the environment and human health, the discovery of RNA interference (RNAi) offered the opportunity to develop new and sustainable approaches for pest management. RNAi is a naturally occurring regulation and defense mechanism that can be exploited to effectively protect crops by silencing key genes affecting the growth, development, behavior or fecundity of pests. However, as with all technologies, there is a range of potential risks and challenges associated with the application of RNAi, such as dsRNA stability, the potential for off-target effects, the safety of non-target organisms, and other application challenges. A better understanding of the molecular mechanisms involved in RNAi and in-depth discussion and analysis of these associated safety risks, is required to limit or mitigate potential adverse effects. © 2024 Society of Chemical Industry.

Summary of best evidence for prevention and management of frailty.

BACKGROUND: Frailty in older people can seriously affect their quality of life and increase the demand for long-term care and health care expenses. Aims of this study are to provide an evidence-based basis for clinical practice of frailty in older people by systematically searching for the best current evidence on interventions for the prevention and management of frailty. METHODS: According to the '6S' evidence resource model, evidence retrieval is searched from the top-down and collected relevant guidelines, best practices, evidence summaries, systematic reviews and expert consensus. The retrieval time limit was from the database establishment to 20 March 2023. Two reviewers independently screened and evaluated the literature, and then extracted and summarised the evidence according to the JBI grading of evidence and recommendation system. RESULTS: A total of 44 publications were finally included, including 12 guidelines, 5 best practices, 4 expert consensus, 5 evidence summaries and 18 systematic reviews. Through the induction and integration of the evidence, the evidence was finally summarised from eight aspects: frailty screening, frailty assessment, exercise intervention, nutrition intervention, multi-domain intervention, drug administration, social support and health education, and 43 best evidences were formed. CONCLUSIONS: This study summarised the best evidence for the prevention and management of frailty from eight aspects, which can provide guidance for clinical or community medical staff to develop and apply frailty intervention and practice programmes for older people and improved the clinical outcome and quality of life of older people.

A dynamic online nomogram for predicting the heterogeneity trajectories of frailty among elderly gastric cancer survivors.

BACKGROUND: Frailty is very common among older people with gastric cancer and seriously affects their prognosis. The development of frailty is continuous and dynamic, increasing the difficulty and burden of care. OBJECTIVES: The aims of this study were to delineate the developmental trajectory of frailty in older people with gastric cancer 1 year after surgery, identify heterogeneous frailty trajectories, and further explore their predictors to construct a nomogram for prediction. DESIGN: We conducted a prospective longitudinal observation study. Clinical evaluation and data collection were performed at discharge, and at 1, 3, 6, and 12 months. SETTING AND PARTICIPANTS: This study was conducted in a tertiary hospital and 381 gastric cancer patients over 60 years who underwent radical gastrectomy completed the 1-year follow-up. METHODS: A growth mixture model (GMM) was used to delineate the frailty trajectories, and identify heterogeneous trajectories. A regression model was performed to determine their predictors and further construct a nomogram based on the predictors. Bootstrap with 1000 resamples was used for internal validation of nomogram, a receiver operating characteristic (ROC) curve to evaluate discrimination, calibration curves to evaluate calibration and decision curve analysis (DCA) to evaluate the clinical value. RESULTS: GMM identified three classes of frailty trajectories: "frailty improving", "frailty persisting" and "frailty deteriorating". The latter two were referred to as heterogeneous frailty trajectories. Regression analysis showed 8 independent predictors of heterogeneous frailty trajectories and a nomogram was constructed based on these predictors. The area under ROC curve (AUC) of the nomogram was 0.731 (95 % CI = 0.679-0.781), the calibration curves demonstrated that probabilities predicted by the nomogram agreed well with the actual observation with a mean absolute error of 0.025, and the DCA of nomogram indicated that the net benefits were higher than that of the other eight single factors. CONCLUSIONS: Older gastric cancer patients have heterogeneous frailty trajectories of poor prognosis during one-year postoperative survival. Therefore, early assessment to predict the occurrence of heterogeneous frailty trajectories is essential to improve the outcomes of elderly gastric cancer patients. Scientific and effective frailty interventions should be further explored in the future to improve the prognosis of older gastric cancer patients. CONTRIBUTION OF THE PAPER STATEMENTS: This study constructed a static and dynamic online nomogram with good discrimination and calibration, which can help to screen high-risk patients, implement preoperative risk stratification easily and promote the rational allocation of medical resources greatly. REGISTRATION: ClinicalTrials.gov (Number: NCT05982899). TWEETABLE ABSTRACT: Our findings identified three frailty trajectories and constructed a nomogram to implement preoperative risk stratification and improve patient outcomes.

METTL3 facilitates renal cell carcinoma progression by PLOD2 m6A-methylation under prolonged hypoxia.

N6-methyladenosine (m6A) is the most prevalent reversible modification in eukaryotic mRNA, and it plays a critical role in tumor progression. The purpose of this study was to investigate the function and regulatory mechanisms of the methyltransferase METTL3 in renal cell carcinoma (RCC). METTL3 expression was upregulated and predicted a poor prognosis in patients with advanced RCC. METTL3 facilitated the proliferation, migration, and invasion of RCC cells, depending on its methylase activity. METTL3 positively regulated the expression of PLOD2, and both genes were triggered under prolonged hypoxia. Mechanistically, hypoxia-induced the binding of HIF-1α to the METTL3 promoter, which enhanced its transcriptional activity. METTL3-mediated m6A modifications of PLOD2 mRNA at 3'UTR region, promoting the translation of PLOD2 protein. Furthermore, silencing METTL3 impaired RCC progression in vitro. In vivo, administration of highly potent and selective METTL3 inhibitor STM2457 showed anti-tumor effects, whereas AAV9-mediated re-transduction of PLOD2 largely abolished the above phenomenon in a subcutaneous mouse model. These findings reveal that hypoxia and HIF-driven METTL3 transcription promote RCC progression by increasing PLOD2 expression in an m6A-dependent manner, suggesting that METTL3 may serve as a novel pharmaceutical intervention for RCC.

The m6A demethylase FTO targets POLQ to promote ccRCC cell proliferation and genome stability maintenance.

BACKGROUND AND AIM: As the first identified m6A demethylase, FTO has been implicated in the progression of various cancers. However, the specific mechanism of FTO in clear cell renal cell carcinoma (ccRCC) remains incompletely understood. In this study, we aimed to explore the potential molecular mechanisms influencing the progression of ccRCC. METHODS: We initially assessed the expression of FTO in tumor and adjacent tissues using TCGA database, RT-qPCR, and Western blot. We then conducted CCK-8, cell cycle analysis, and colony formation assay to investigate the impact of FTO on ccRCC cell proliferation. MeRIP-seq and RNA-seq were employed to identify potential downstream targets of FTO in ccRCC, and these findings were further validated through dual-luciferase reporter assays and MeRIP-qPCR. Then, DNA damage and cell death were assessed separately through gammaH2AX immunofluorescence detection and the LIVE/DEAD Fixable Dead Cell Stain assay, respectively. Subsequently, we identified downstream pathways influenced by FTO's regulation of POLQ through TCGA database analysis and GSEA enrichment analysis. Validation was carried out through Western blot. RESULTS: FTO is highly expressed in ccRCC tissues and cell lines. Furthermore, ROC curve demonstrates that FTO contributes to the diagnosis of ccRCC. FTO modulates m6A modification, consequently influencing the expression of POLQ, thus facilitating cell proliferation and maintaining genome stability in ccRCC. CONCLUSION: FTO could potentially serve as a diagnostic marker for ccRCC. FTO promotes the progression of ccRCC by regulating m6A modification, making the inhibition of FTO a potential novel therapeutic strategy in ccRCC.

Neural Differentiation and spinal cord organoid generation from induced pluripotent stem cells (iPSCs) for ALS modelling and inflammatory screening.

C9orf72 genetic mutation is the most common genetic cause of ALS/FTD accompanied by abnormal protein insufficiency. Induced pluripotent stem cell (iPSC)-derived two-dimensional (2D) and three-dimensional (3D) cultures are providing new approaches. Therefore, this study established neuronal cell types and generated spinal cord organoids (SCOs) derived from C9orf72 knockdown human iPSCs to model ALS disease and screen the unrevealed phenotype. Wild-type (WT) iPSC lines from three healthy donor fibroblasts were established, and pluripotency and differentiation ability were identified by RT-PCR, immunofluorescence and flow cytometry. After infection by the lentivirus with C9orf72-targeting shRNA, stable C9-knockdown iPSC colonies were selected and differentiated into astrocytes, motor neurons and SCOs. Finally, we analyzed the extracted RNA-seq data of human C9 mutant/knockout iPSC-derived motor neurons and astrocytes from the GEO database and the inflammatory regulation-related genes in function and pathways. The expression of inflammatory factors was measured by qRT-PCR. The results showed that both WT-iPSCs and edited C9-iPSCs maintained a similar ability to differentiate into the three germ layers, astrocytes and motor neurons, forming SCOs in a 3D culture system. The constructed C9-SCOs have features of spinal cord development and multiple neuronal cell types, including sensory neurons, motor neurons, and other neurons. Based on the bioinformatics analysis, proinflammatory factors were confirmed to be upregulated in C9-iPSC-derived 2D cells and 3D cultured SCOs. The above differentiated models exhibited low C9orf72 expression and the pathological characteristics of ALS, especially neuroinflammation.

Exploration of frailty trajectories and their associations with health outcomes in older gastric cancer survivors undergoing radical gastrectomy: A prospective longitudinal observation study.

BACKGROUND: Frailty is commom among gastric cancer survivors and increases the burden of care. AIMS: Our aims were to identify the frailty trajectories and investigate their associations with health outcomes in older gastric cancer survivors. METHODS: We finally recruited 381 patients aged ≧60 who underwent radical gastrectomy and recorded frailty at discharge from the hospital, 1, 3, 6, and 12 months after surgery. Growth mixture modeling was used to investigate the frailty trajectories and linear regression models were used to examine their associations with health outcomes. RESULTS: Three classes of frailty trajectories were identified: the "improving frailty", "maintaining frailty" and "deteriorating frailty". Compared with class 1, patients who followed class 2 and class 3 frailty trajectories were more likely to have more severe disability (ß = -14.22, 95 % CI: -17.92, -10.61, P < 0.001; ß = -48.34, 95 % CI: -52.25, -44.42, P < 0.001), worse quality of life (ß = 10.89, 95 % CI: 7.71,14.08, P < 0.001; ß = 34.82, 95 % CI: 31.46, 38.19, P < 0.001), and more frequency readmission within 1 year (ß = 1.02, 95 % CI: 0.98, 1.06, P < 0.001; ß = 2.10, 95 % CI: 2.01, 2.14, P < 0.001) after controlling potential confounders. However, class 2 and class 3 have no significant difference from class 1 in the total hospitalization costs (ß = 1672.12, 95 % CI: -7145.95, 10496.19, P = 0.709; ß = 7651.60, 95 % CI: -1670.28, 16793.47, P = 0.107). CONCLUSIONS: Our study suggested the significant prognostic heterogeneity in frailty trajectories, and what we need to do is to identify patients with heterogeneous trajectory and intervene in them to reduce adverse outcomes, promote rational use of resources, and reduce the burden of care.

A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Immune checkpoint inhibitors (ICIs) have been widely used to treat various tumors and have changed the landscape of tumor management, but the data from real-world studies of ICIs for TNBC treatment remain limited. The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real-world setting and to explore possible correlates. Methods: The clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army (PLA) General Hospital were collected. Treatment responses, outcomes and adverse events (AEs) were assessed. Results: Eighty-one patients were included in the study. The confirmed objective response rate (ORR) was 32.1%, and the disease control rate (DCR) was 64.2%. The median progression-free survival (PFS) was 4.2 months, and the median overall survival (OS) was 11.0 months. PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later-line ICIs and higher levels of inflammation; specifically, patients with higher TILs had longer PFS. Overall AEs were tolerable. Conclusions: ICIs are effective in the treatment of advanced TNBC, and the adverse reactions are tolerable. A panel of biomarkers including LDH, ALP, and bNLR were identified to predict the efficacies of ICIs in TNBC treatment.

A protocol for a single center, randomized, controlled trial comparing the clinical efficacy of 3% diquafosol and 0.1% hyaluronic acid in diabetic patients with dry eye disease.

BACKGROUND: The global prevalence of diabetes mellitus (DM) continues to rise and 70% of diabetic individuals have dry eye disease (DED) that leads to subsequent abnormalities of the corneal epithelium, corneal nerves, tear film, or corneal endothelium. In addition, persons with diabetes produce fewer tear secretions than healthy individuals. While several anti-inflammatory drug-based therapies for dry eye in diabetic individuals are currently being administered, their efficacy has not been studied in detail. Therefore, the aim of this study was to compare the effectiveness of 3% diquafosol (DQS) vs 0.1% hyaluronic acid (HA) eye drops in diabetic dry eye patients. METHODS: This triple-blind randomized, control trial will include 202 diabetic-related DED and will be assigned to DQS (n = 101) and HA (n = 101) one drop, six times per day for 8 weeks. Tear film lipid layer, non-invasive breakup time, conjunctivocorneal staining score, corneal sensitivity, tear MMP-9 levels, meibomian gland expression and quality, tear meniscus height, corneal nerves, immune/inflammatory cell change, conjunctival hyperemia, and ocular surface disease index questionnaire score will be assessed and compared at baseline, week 4, and week 8. DISCUSSION: This study will be a standardized, scientific, clinical trial designed to evaluate the therapeutic effects and safety of DQS and HA for diabetic dry eye treatment. TRIAL REGISTRATION: ClinicalTrials.govNCT05682547. Registered on December 05, 2022.

Effects of Diquafosol Sodium Ophthalmic Solution on Tear Film Matrix Metallopeptidase-9 and Corneal Nerve Density in Patients with Type 2 Diabetic Dry Eye.

Purpose: Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED's pathology. This preliminary short-term study aimed to evaluate the effects of 3% Diquafosol Sodium ophthalmic solution (DQS) on ocular surface inflammation and corneal nerve density in diabetic dry eye (DDE) patients. Methods: In this perspective, participants used 1 drop of 3% DQS (Diquas; Santen Pharmaceutical Co., Ltd., Osaka, Japan) 6 times daily for 8 weeks. Non-invasive tear breakup time (NITBUT), tear film lipid layer (TFLL), conjunctival hyperemia [redness score (RS)], corneoconjunctival staining (CFS), corneal sensitivity (CS), Meibomian gland quality (MGQ) and Meibomian gland expressibility (MGEx), corneal nerve fiber density (CNFD), and Standard Patient Evaluation Eye Dryness (SPEED) questionnaire were assessed at baseline, at weeks 4, and up to 8 weeks. Matrix metalloproteinase-9 (MMP-9) of tear samples was measured at baseline and weeks 8. Results: The mean age was 61.27 ± 11.68 years. At baseline NITBUT = 5.89 ± 2.81 s, tear meniscus height = 0.17 ± 0.05 mm, TFLL = 2.74 ± 0.51, CFS = 4.35 ± 0.68, CS = 53.83 ± 9.63 mm, MMP-9 = 49.10 ± 10.42 ng/mL, RS = 1.65 ± 0.44, MGEx = 1.85 ± 0.72, MGQ = 2.65 ± 0.50, CNFD = 20.36 ± 8.20 no./mm2, and SPEED = 12.62 ± 3.91. At week 4, significant improvements were found in all parameters except RS (1.59 ± 0.46, P = 0.172) and CNFD (21.46 ± 8.41, P = 0.163). Finally, at week 8, all parameters had significant improvements. Conclusion: Preliminary short-term findings suggest that treatment of DDE patients with DQS was found to be safe and efficacious in improving dry eye parameters. In addition, inflammatory marker and corneal nerve density were significantly improved. This study was registered with ClinicalTrials.gov (NCT05193331).

BMI trajectories, associations with outcomes and predictors in elderly gastric cancer patients undergoing radical gastrectomy: a prospective longitudinal observation study.

OBJECTIVES: Elderly gastric cancer patients undergoing radical gastrectomy are prone to experience unexpected weight loss. Preoperative weight risk prediction may be a promising way to prevent weight loss and improve prognosis. The objectives of this study were to explore the BMI trajectory of elderly gastric cancer patients one year after surgery, evaluate theirs the association with outcomes, and explore their related predictors, so as to provide evidence for weight management and prognosis improvement. METHODS: 412 gastric cancer patients were included and recorded BMI at 6 time points. The trajectories of BMI were analyzed by growth mixture modeling, and the associations of BMI trajectories with outcomes as well as their predictors were investigated by regression models. RESULTS: We identified 3 classes of BMI trajectories: the "slow-decreasing BMI", "rapid-decreasing BMI" and "maintaining BMI". Compared with class1, patients in class 2 were more likely to have a higher frequency of readmission within 1-year(ß = 0.59, 95%CI: 0.29, 0.89, P < 0.001) and a higher rate of mortality within 1-year(ß = 24.74, 95%CI: 9.60, 63.74, P < 0.001) ; patients in class 3 were more likely to have a higher quality of life (ß=-10.46, 95%CI: -17.70, -3.22, P = 0.005) and fewer readmission times within one year (ß=-0.43, 95%CI: -0.77, -0.09, P = 0.015). Predictors of decreasing BMI trajectories were TNM stage, comorbidity, anxiety, family cohesion and social support(P < 0.05). CONCLUSIONS: Our findings can provide a basis for screening high-risk elderly gastric cancer patients with poor prognosis, implementing risk stratification, formulating accurate weight management programs and improving prognosis. IMPLICATIONS FOR CANCER SURVIVORS: The results of our study can provide gastric cancer survivors with preoperative risk screening based on predictive factors so that nutritional support and weight management can be implemented in a timely manner to improve prognosis.

Perilipin-1 immunostaining improves semi-automated digital quantitation of bone marrow adipocytes in histological bone sections.

Bone marrow adipocytes (BMAds) are not just passive fillers inside the bone marrow compartment but respond to various metabolic changes. Assessment of those responses requires evaluation of the number of BMAds and their morphology for which laborious and error-prone manual histological analysis remains the most widely used method. Here, we report an alternative image analysis strategy to semi-automatically quantitate and analyse the morphology of BMAds in histological bone sections. Decalcified, formalin-fixed paraffin-embedded histological sections of long bones of Sprague-Dawley rats were stained with either haematoxylin and eosin (HE) or by immunofluorescent staining for adipocyte-specific protein perilipin-1 (PLIN1). ImageJ-based commands were constructed to detect BMAds sized 200 µm2 or larger from standardized 1 mm2 analysis regions by either classifying the background colour (HE) or the positive and circular PLIN1 fluorescent signal. Semi-automated quantitation strongly correlated with independent, single-blinded manual counts regardless of the staining method (HE-based: r=0.85, p<0.001; PLIN1 based: r=0.95, p<0.001). The detection error was higher in HE-stained sections than in PLIN1-stained sections (14% versus 5%, respectively; p<0.001), which was due to false-positive detections of unstained adipocyte-like circular structures. In our dataset, the total adiposity area from standardised ROIs in PLIN-1-stained sections correlated with that in whole-bone sections (r=0.60, p=0.02).

Tear Film Lipid Layer Changes Following Combined Effect of Heated Eye Mask with Intense Pulsed Light Therapy for Evaporative Dry Eye: A Randomized Control Study.

Background: Dry eye disease (DED) is a complex ocular surface inflammatory disorder with a multifactorial etiology. Therapies such as intense pulsed light (IPL) and heated eye mask (HEM) have been reported to improve the tear film lipid layer (TFLL) and signs and symptoms of DED. Methods: This randomized study aimed to compare the effects of IPL combined with HEM (IPL+HEM) group, IPL group, and control group in participants with evaporative DED. All participants were examined at baseline (D0), day 21 (D21), day 42 (D42), and day 84 (D84) for noninvasive tear breakup time (NITBUT), TFLL, corneal conjunctival staining (CS), meibomian gland quality (MGQ), meibomian gland expressibility (MGEx), and Ocular Surface Disease Index (OSDI). Results: The mean age of participants was IPL+HEM: 28.06 ± 3.88 years, IPL: 29.88 ± 4.68 years, and control: 28.52 ± 3.77 years. At D84, significant improvements in TFLL (p < 0.05), noninvasive tear breakup time (NITBUT) (p < 0.05), corneoconjunctival staining (CS) (p < 0.05), MGQ (p < 0.05), MGEx (p < 0.05), and OSDI (p < 0.05) were found in the IPL+HEM and IPL groups, whereas the control group had no significant improvements. Furthermore, ΔTFLL significantly correlated with ΔNITBUT (r = -0.678, p < 0.001), ΔCS (r = 0.321, p < 0.001), ΔMGQ (r = 0.669, p < 0.001), ΔMGEx (r = 0.598, p < 0.001), and ΔOSDI score (r = 0.649, p < 0.001). Conclusions: IPL therapy in combination with HEM and IPL therapy only can significantly improve the quality of TFLL and clinically reduce the sign and symptoms of evaporative DED. However, IPL therapy in combination with HEM was found to be more effective than IPL therapy alone.