Enhancing Hospital Efficiency and Patient Care: Real-Time Tracking and Data-Driven Dispatch in Patient Transport.

Inefficient patient transport in hospitals often leads to delays, overworked staff, and suboptimal resource utilization, ultimately impacting patient care. Existing dispatch management algorithms are often evaluated in simulation environments, raising concerns about their real-world applicability. This study presents a real-world experiment that bridges the gap between theoretical dispatch algorithms and real-world implementation. It applies process capability analysis at Taichung Veterans General Hospital in Taichung, Taiwan, and utilizes IoT for real-time tracking of staff and medical devices to address challenges associated with manual dispatch processes. Experimental data collected from the hospital underwent statistical evaluation between January 2021 and December 2021. The results of our experiment, which compared the use of traditional dispatch methods with the Beacon dispatch method, found that traditional dispatch had an overtime delay of 41.0%; in comparison, the Beacon dispatch method had an overtime delay of 26.5%. These findings demonstrate the transformative potential of this solution for not only hospital operations but also for improving service quality across the healthcare industry in the context of smart hospitals.

Activation of aryl hydrocarbon receptor (AhR) alleviates depressive-like behaviors in LPS-induced mice.

The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.

APHS-YOLO: A Lightweight Model for Real-Time Detection and Classification of Stropharia Rugoso-Annulata.

The classification of Stropharia rugoso-annulata is currently reliant on manual sorting, which may be subject to bias. To improve the sorting efficiency, automated sorting equipment could be used instead. However, sorting naked mushrooms in real time remains a challenging task due to the difficulty of accurately identifying, locating and sorting large quantities of them simultaneously. Models must be deployable on resource-limited devices, making it challenging to achieve both a high accuracy and speed. This paper proposes the APHS-YOLO (YOLOv8n integrated with AKConv, CSPPC and HSFPN modules) model, which is lightweight and efficient, for identifying Stropharia rugoso-annulata of different grades and seasons. This study includes a complete dataset of runners of different grades in spring and autumn. To enhance feature extraction and maintain the recognition accuracy, the new multi-module APHS-YOLO uses HSFPNs (High-Level Screening Feature Pyramid Networks) as a thin-neck structure. It combines an improved lightweight PConv (Partial Convolution)-based convolutional module, CSPPC (Integration of Cross-Stage Partial Networks and Partial Convolution), with the Arbitrary Kernel Convolution (AKConv) module. Additionally, to compensate for the accuracy loss due to lightweighting, APHS-YOLO employs a knowledge refinement technique during training. Compared to the original model, the optimized APHS-YOLO model uses 57.8% less memory and 62.5% fewer computational resources. It has an FPS (frames per second) of over 100 and even achieves 0.1% better accuracy metrics than the original model. These research results provide a valuable reference for the development of automatic sorting equipment for forest farmers.

Effectiveness of fentanyl buccal soluble film in cancer patients with inadequate breakthrough pain control.

BACKGROUND: Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. METHODS: The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. RESULTS: A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. CONCLUSION: FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. TRIAL REGISTRATION: This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

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To accurately estimate the age of individual tree and to achieve full-cycle sustainable management of natural Larix gmelinii forest in Great Xing'an Mountains of northeastern China, we constructed individual tree age prediction model using stepwise regression and random forest algorithms based on 44 fixed plots data and 280 stan-dard tree cores obtained from the Pangu Forest Farm. We analyzed the influence of stand structure, site conditions, and competition index on the accuracy of model prediction. The model was evaluated by the coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE). The results showed that the random forest model had the highest prediction accuracy when number of decision trees was 1500 and number of node con-tention variables was 8. The random forest model had better accuracy and prediction ability than the stepwise regression model, with R2, RMSE and MAE of 0.5882, 9.9259 a, 8.1155 a. Diameter at breast height was the most important factor affecting age prediction (83.8%), followed by tree height (34.4%), elevation (17.9%), and basal area per hectare (17.5%). The random forest algorithm exhibited better adaptability and modeling effect on constructing a predictive model for individual tree age. This research contributed to improving the accuracy of growth and harvest estimation for L. gmelinii, and could provide a reference for other scientific studies related to tree age estimation in forests.

Glycyrrhizic acid conjugates with amino acid methyl esters target the main protease, exhibiting antiviral activity against wild-type and nirmatrelvir-resistant SARS-CoV-2 variants.

COVID-19 pandemic is predominantly caused by SARS-CoV-2, with its main protease, Mpro, playing a pivotal role in viral replication and serving as a potential target for inhibiting different variants. In this study, potent Mpro inhibitors were identified from glycyrrhizic acid (GL) derivatives with amino acid methyl/ethyl esters. Out of the 17 derivatives semisynthesized, Compounds 2, 6, 9, and 15, with methionine methyl esters, D-tyrosine methyl esters, glutamic acid methyl esters, and methionines in the carbohydrate moiety, respectively, significantly inhibited wild-type SARS-CoV-2 Mpro-mediated proteolysis, with IC50 values ranging from 0.06 µM to 0.84 µM. They also demonstrated efficacy in inhibiting trans-cleavage by mutant Mpro variants (Mpro_P132H, Mpro_E166V, Mpro_P168A, Mpro_Q189I), with IC50 values ranging from 0.05 to 0.92 µM, surpassing nirmatrelvir (IC50: 1.17-152.9 µM). Molecular modeling revealed stronger interactions with Valine166 in the structural complex of Mpro_E166V with the compounds compared to nirmatrelvir. Moreover, these compounds efficiently inhibited the post-entry viral processes of wild-type SARS-CoV-2 single-round infectious particles (SRIPs), mitigating viral cytopathic effects and reducing replicon-driven GFP reporter signals, as well as in vitro infectivity of wild-type, Mpro_E166V, and Mpro_Q189I SRIPs, with EC50 values ranging from 0.02 to 0.53 µM. However, nirmatrelvir showed a significant decrease in inhibiting the replication of mutant SARS-CoV-2 SRIPs carrying Mpro_E166V (EC50: >20 µM) and Mpro_Q189I (EC50: 13.2 µM) compared to wild-type SRIPs (EC50: 0.06 µM). Overall, this study identifies four GL derivatives as promising lead compounds for developing treatments against various SARS-CoV-2 strains, including Omicron, and nirmatrelvir-resistant variants.

Fucoidan-hybrid hydroxyapatite nanoparticles promote the osteogenic differentiation of human periodontal ligament stem cells under inflammatory condition.

Inflammation-related bone defects often lead to poor osteogenesis. Therefore, it is crucial to reduce the inflammation response and promote the osteogenic differentiation of stem/progenitor cells to revitalize bone physiology. Here, a kind of hybrid nano-hydroxyapatite was prepared using the confined phosphate ion release method with the participation of fucoidan, a marine-sourced polysaccharide with anti-inflammation property. The physicochemical analyses confirmed that the fucoidan hybrid nano-hydroxyapatite (FC/n-HA) showed fine needle-like architectures. With a higher amount of fucoidan, the crystal size and crystallinity of the FC/n-HA reduced while the liquid dispersibility was improved. Cell experiences showed that FC/n-HA had an optimal cytocompatibility at concentration of 50 µg/mL. Moreover, the lipopolysaccharide-induced cellular inflammatory model with PDLSCs was established and used to evaluate the anti-inflammatory and osteogenic properties. For the 1%FC/n-HA group, the expression levels of TNF-α and IL-1ß were significantly reduced at 24 h, while the expression of alkaline phosphatase of PDLSCs was significantly promoted at days 3 and 7, and calcium precipitates was enhanced at 21 days. In this study, the FC/n-HA particles showed effective anti-inflammatory properties and facilitated osteogenic differentiation of PDLSCs, indicating which has potential application in treating bone defects associated with inflammation, such as periodontitis.

Expression and localization of HSD17B13 along mouse urinary tract.

17ß-hydroxysteroid dehydrogenase-13 (HSD17B13), a newly identified lipid droplet-associated protein, plays an important role in the development of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Emerging evidence demonstrates that NASH is an independent risk factor for chronic kidney disease (CKD), which is frequently accompanied by renal lipid accumulation. In addition, the HSD17B13 rs72613567 variant is associated with lower levels of albuminuria in patients with biopsy-proven NAFLD. At present, the role of HSD17B13 in lipid accumulation in the kidney is unclear. ​This study utilized bioinformatic and immunostaining approaches to examine the expression and localization of HSD17B13 along mouse urinary tract. We found that HSD17B13 is constitutively expressed in the kidney, ureter and urinary bladder. Our findings reveal for the first time the precise localization of HSD17B13 in mouse urinary system, providing a basis for further studying the pathogenesis of HSD17B13 in various renal and urological diseases.

Effect of metabolic dysfunction on the risk of liver-related events in patients cured of hepatitis C virus.

The impact of metabolic dysfunction or metabolic dysfunction-associated fatty liver disease (MAFLD) on liver-related events (LREs) in patients with chronic hepatitis C (CHC) who had achieved a sustained virologic response (SVR) to direct-acting antiviral agents (DAAs) is unknown. A total of 924 patients with cured CHC and documented body mass index (BMI) were included in the analysis, and the data period was from September 2012 to April 2022. Hepatic steatosis was identified either through ultrasonography or blood biomarkers. Metabolic dysfunction was defined as the presence of overweight or obesity (BMI ≥ 23 kg/m2), type 2 diabetes mellitus (DM), and metabolic dysregulation. Patients may have more than one metabolic dysfunction. Variables at 12 or 24 weeks after DAA therapy (PW12) were used to identify predictors of LREs. The median age of the 924 patients was 58 (49-65) years. Of the participants, 418 (45.2%) were male. The median BMI was 24.01 (21.78-26.73) kg/m2, and 174 (18.8%) patients had DM. A multivariable Cox regression analysis revealed that age, male, albumin, total bilirubin, alpha-fetoprotein (AFP), metabolic dysfunction (hazard ratio: 1.709, 95% confidence interval: 1.128-2.591, P = .011), and FIB-4 > 3.25 were independent predictors of LREs. Type 2 DM and metabolic dysregulation exhibited a larger time-dependent area under the receiver operating characteristic curve for LREs than did overweight or obesity. Moreover, metabolic dysfunction was identified to be an independent predictor of hepatocellular carcinoma. Metabolic dysfunction increased the risk of LREs and HCC in patients with CHC who had achieved an SVR to DAA therapy.

Clinical implications of dextrocardia based on four visceroatrial situs studies.

BACKGROUND: Previous studies on congenital heart diseases (CHD) associated with dextrocardia were based on selective patient databases and did not reflect the full spectrum of dextrocardia in the general population. Additionally, these studies had complex classification and presentation. Nor did these studies elaborate on the distribution of the associated CHD's complexity, the various segmental connections, and associated CHD among the four visceroatrial situs. METHODS: We retrospectively reviewed the medical records of 211 children with primary dextrocardia. We used a segmental approach to diagnose CHD. We then analyzed and compared the distribution of the above-mentioned issues among the four visceroatrial situs. RESULTS: Dextrocardia occurred most commonly with situs inversus (52.6%), followed by situs solitus (28.4%), asplenia (17.1%), and polysplenia (1.9%). Although some patients had a structurally normal heart (22.7%) or they were associated with simple CHD (17.5%), most patients had complex CHD (59.7%) consisting of a single ventricle (34.6%) or conotruncal anomaly (25.1%) (double-outlet right ventricle [7.6%], corrected transposition of the great arteries [6.2%], complete transposition of the great arteries [5.7%], tetralogy of Fallot [4.7%], etc.). Situs inversus or polysplenia had a higher prevalence of a structurally normal heart or associated with simple CHD, two patent atrioventricular (AV) valves connections, and biventricular AV connections. Situs solitus or asplenia had a higher prevalence of associated complex CHD, common AV valve connection, univentricular AV connection, pulmonary outflow tract obstruction, and anomalous pulmonary venous drainage. CONCLUSION: Our study finds that situs inversus is the most common visceroatrial situs in dextrocardia. Although some patients had a structurally normal heart or were associated with simple CHD, most patients have associated complex CHD consisting of a single ventricle or conotruncal anomaly. Dextrocardia is associated with a higher incidence of complex CHD in situs solitus and asplenia groups than in situs inversus and polysplenia groups.

Exosomes regulate doxorubicin resistance in breast cancer via miR-34a-5p/NOTCH1.

Breast cancer (BRCA) is the most common cancer among women. Adriamycin (ADR), also known as doxorubicin (Dox), is a commonly used chemotherapeutic agent for BRCA patients, however, the susceptibility of tumor cells to develop resistance to Dox has severely limited its clinical use. One new promising therapeutic target for breast cancer patients is exosomes. The objective of this study was to investigate the role of exosomes in regulating Dox resistance in BRCA. In this study, the exosomes from both types of cells were extracted by differential centrifugation. The effect of exosomes on drug resistance was assessed by laser confocal microscopy, MTT assay, and qRT-PCR. The miRNA was transfected into cells using Lipofectamine 2000, which was then evaluated for downstream genes and changes in drug resistance. Exosomes from MCF-7 cells (MCF-7/exo) and MCF-7/ADR cells (ADR/exo) were effectively extracted in this study. The ADR/exo was able to endocytose MCF-7 cells and make them considerably more resistant to Dox. Moreover, we observed a significant difference in miR-34a-5p expression in MCF-7/ADR and ADR/exo compared to MCF-7 and MCF-7/exo. Among the miR-34a-5p target genes, NOTCH1 displayed a clear change with a negative correlation. In addition, when miR-34a-5p expression was elevated in MCF-7/ADR cells, the expression of miR-34a-5p in ADR/exo was also enhanced alongside NOTCH1, implying that exosomes may carry miRNA into and out of cells and perform their function. In conclusion, exosomes can influence Dox resistance in breast cancer cells by regulating miR-34a-5p/NOTCH1. These findings provide novel insights for research into the causes of tumor resistance and the enhancement of chemotherapy efficacy in breast cancer.

Automatic Localization of Soybean Seedlings Based on Crop Signaling and Multi-View Imaging.

Soybean is grown worldwide for its high protein and oil content. Weeds compete fiercely for resources, which affects soybean yields. Because of the progressive enhancement of weed resistance to herbicides and the quickly increasing cost of manual weeding, mechanical weed control is becoming the preferred method of weed control. Mechanical weed control finds it difficult to remove intra-row weeds due to the lack of rapid and precise weed/soybean detection and location technology. Rhodamine B (Rh-B) is a systemic crop compound that can be absorbed by soybeans which fluoresces under a specific excitation light. The purpose of this study is to combine systemic crop compounds and computer vision technology for the identification and localization of soybeans in the field. The fluorescence distribution properties of systemic crop compounds in soybeans and their effects on plant growth were explored. The fluorescence was mainly concentrated in soybean cotyledons treated with Rh-B. After a comparison of soybean seedlings treated with nine groups of rhodamine B solutions at different concentrations ranging from 0 to 1440 ppm, the soybeans treated with 180 ppm Rh-B for 24 h received the recommended dosage, resulting in significant fluorescence that did not affect crop growth. Increasing the Rh-B solutions reduced crop biomass, while prolonged treatment times reduced seed germination. The fluorescence produced lasted for 20 days, ensuring a stable signal in the early stages of growth. Additionally, a precise inter-row soybean plant location system based on a fluorescence imaging system with a 96.7% identification accuracy, determined on 300 datasets, was proposed. This article further confirms the potential of crop signaling technology to assist machines in achieving crop identification and localization in the field.

Restricted responses of AcMYB68 and AcERF74/75 enhanced waterlogging tolerance in kiwifruit.

Most of kiwifruit cultivars (e.g. Actinidia chinensis cv. Donghong, "DH") were sensitive to waterlogging, thus, waterlogging resistant rootstocks (e.g. Actinidia valvata Dunn, "Dunn") were widely used for kiwifruit industry. Those different species provided ideal materials to understand the waterlogging responses in kiwifruit. Compared to the weaken growth and root activities in "DH", "Dunn" maintained the relative high root activities under the prolonged waterlogging. Based on comparative analysis, transcript levels of pyruvate decarboxylase (PDCs) and alcohol dehydrogenase (ADHs) showed significantly difference between these two species. Both PDCs and ADHs had been significantly increased by waterlogging in "DH", while they were only limitedly triggered by 2 days stress and subsided during the prolonged waterlogging in "Dunn". Thus, 19 differentially expressed transcript factors (DETFs) had been isolated using weighted gene co-expression network analysis combined with transcriptomics and transcript levels of PDCs and ADHs in waterlogged "DH". Among these DETFs, dual luciferase and electrophoretic mobility shift assays indicated AcMYB68 could bind to and trigger the activity of AcPDC2 promoter. The stable over-expression of AcMYB68 significantly up-regulated the transcript levels of PDCs but inhibited the plant growth, especially the roots. Moreover, the enzyme activities of PDC in 35S::AcMYB68 were significantly enhanced during the waterlogging response than that in wild type plants. Most interestingly, comparative analysis indicated that the expression patterns of AcMYB68 and the previously characterized AcERF74/75 (the direct regulator on ADHs) either showed no responses (AcMYB68 and AcERF74) or very limited response (AcERF75) in "Dunn". Taken together, the restricted responses of AcMYB68 and AcERF74/75 in "Dunn" endow its waterlogging tolerance.

Comparison between the Clancy Behavior Scale and the Modified Checklist for Autism in Toddlers in Taiwan.

(1) Background: Precise diagnosis and early intervention are crucial for toddlers with autism spectrum disorder (ASD) to achieve a better prognosis. This study investigated the efficacy of the Clancy Behavior Scale (CBS) and Modified Checklist for Autism in Toddlers (M-CHAT) in detecting ASD among toddlers under 30 months of age. (2) Methods: A total of 215 toddlers (117 with ASD and 98 with development delays) aged between 18 and 29 months participated in this study. All the primary caregivers of these toddlers were recruited to complete the CBS and M-CHAT. (3) Results: The findings indicated that the accuracy of the CBS and M-CHAT was promising, and the short forms of these two instruments performed better than their full versions. The CBS:9 critical items presented a sensitivity of 0.75 and a specificity of 0.74, while the M-CHAT:14 brief items showed a sensitivity of 0.72 and a specificity of 0.85. (4) Conclusions: The diagnostic accuracy of high-risk ASD toddlers improved via the combination of CBS and M-CHAT, particularly when the information gathered from these two instruments were consistent. The findings may provide implications for enhancing the early detection of ASD.

Genetic or pharmacologic blockade of mPGES-2 attenuates renal lipotoxicity and diabetic kidney disease by targeting Rev-Erbα/FABP5 signaling.

Diabetic kidney disease (DKD) is one of the most common complications of diabetes, and no specific drugs are clinically available. We have previously demonstrated that inhibiting microsomal prostaglandin E synthase-2 (mPGES-2) alleviated type 2 diabetes by enhancing ß cell function and promoting insulin production. However, the involvement of mPGES-2 in DKD remains unclear. Here, we aimed to analyze the association of enhanced mPGES-2 expression with impaired metabolic homeostasis of renal lipids and subsequent renal damage. Notably, global knockout or pharmacological blockage of mPGES-2 attenuated diabetic podocyte injury and tubulointerstitial fibrosis, thereby ameliorating lipid accumulation and lipotoxicity. These findings were further confirmed in podocyte- or tubule-specific mPGES-2-deficient mice. Mechanistically, mPGES-2 and Rev-Erbα competed for heme binding to regulate fatty acid binding protein 5 expression and lipid metabolism in the diabetic kidney. Our findings suggest a potential strategy for treating DKD via mPGES-2 inhibition.

Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing.

Objective: Viral encephalitis is an infectious disease severely affecting human health. It is caused by a wide variety of viral pathogens, including herpes viruses, flaviviruses, enteroviruses, and other viruses. The laboratory diagnosis of viral encephalitis is a worldwide challenge. Recently, high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections. Thus, In this study, we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods: We designed nine pairs of specific polymerase chain reaction (PCR) primers for the 12 viruses by reviewing the relevant literature. The detection ability of the primers was verified by software simulation and the detection of known positive samples. Amplicon sequencing was used to validate the samples, and consistency was compared with Sanger sequencing. Results: The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×, and the sequence lengths were consistent with the sizes of the predicted amplicons. The sequences were verified using the National Center for Biotechnology Information BLAST, and all results were consistent with the results of Sanger sequencing. Conclusion: Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis. It is also a useful tool for the high-volume screening of clinical samples.

APLF facilitates interstrand DNA crosslink repair and replication fork protection to confer cisplatin resistance.

Replication stress converts the stalled forks into reversed forks, which is an important protection mechanism to prevent fork degradation and collapse into poisonous DNA double-strand breaks (DSBs). Paradoxically, the mechanism also acts in cancer cells to contribute to chemoresistance against various DNA-damaging agents. PARP1 binds to and is activated by stalled forks to facilitate fork reversal. Aprataxin and polynucleotide kinase/phosphatase-like factor (APLF) binds to PARP1 through the poly(ADP-ribose) zinc finger (PBZ) domain and is known to be involved in non-homologous end joining (NHEJ). Here, we identify a novel function of APLF involved in interstrand DNA crosslink (ICL) repair and fork protection. We demonstrate that PARP1 activity facilitates the APLF recruitment to stalled forks, enabling the FANCD2 recruitment to stalled forks. The depletion of APLF sensitizes cells to cisplatin, impairs ICL repair, reduces the FANCD2 recruitment to stalled forks, and results in nascent DNA degradation by MRE11 nucleases. Additionally, cisplatin-resistant cancer cells show high levels of APLF and homologous recombination-related gene expression. The depletion of APLF sensitizes cells to cisplatin and results in fork instability. Our results reveal the novel function of APLF to facilitate ICL repair and fork protection, thereby contributing to cisplatin-resistant phenotypes of cancer cells.

Comparison of laparoscopic common bile duct exploration plus cholecystectomy and endoscopic retrograde cholangiopancreatography followed by laparoscopic cholecystectomy for elderly patients with common bile duct stones and gallbladder stones.

BACKGROUND: Common bile duct (CBD) stones commonly occur in cholecystectomy cases. The management options include laparoscopic CBD exploration (LCBDE) or endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC). Although ERCP is fully developed, it has complications, and LCBDE is a proven alternative. This study aimed to evaluate the safety and efficacy of these treatments in elderly individuals aged ≥70 years. METHODS: A retrospective study between January 2015 and July 2022 included 160 elderly patients (aged ≥70 years) diagnosed with cholelithiasis and choledocholithiasis. The patients were divided into 1-stage (LCBDE [n = 80]) or 2-stage (ERCP followed by LC [n = 80]) treatment groups. Data collected encompassed comorbidities, symptoms, bile duct clearance, postoperative complications, and long-term outcomes for systematic analysis. RESULTS: This study analyzed 160 patients treated for CBD stones, comparing 1-stage and 2-stage groups. The 1-stage group had more female patients than the 2-stage group (57.5% vs 37.5%, respectively). The 1-stage group had a mean age of 80.55 ± 7.00 years, which was higher than the mean age in the 2-stage group. American Society of Anesthesiologists classification, Charlson Comorbidity Index, and laboratory findings were similar. Pancreatitis and cholangitis occurred after ERCP in the 2-stage group. Stone clearance rates (92.35% [1-stage group] vs 95.00% [2-stage group]) and biliary leakage incidence (7.5% [1-stage group] vs 3.0% [2-stage group]) were similar, as were postoperative complications and long-term recurrence rates (13.0% [1-stage group] vs 12.5% [2-stage group]). CONCLUSION: Our research indicates that both the combination of LCBDE and LC and the sequence of ERCP followed by LC are equally efficient and secure when treating CBD stones in elderly patients. Consequently, the 1-stage procedure may be considered the preferred treatment approach for this demographic.

CDKN2A promoter methylation enhances self-renewal of glioblastoma stem cells and confers resistance to carmustine.

BACKGROUND: Glioblastoma, a highly aggressive form of brain cancer, poses significant challenges due to its resistance to therapy and high recurrence rates. This study aimed to investigate the expression and functional implications of CDKN2A, a key tumor suppressor gene, in glioblastoma cells, building upon the existing background of knowledge in this field. METHOD: Quantitative reverse transcription PCR (qRT-PCR) analysis was performed to evaluate CDKN2A expression in U87 glioblastoma cells compared to normal human astrocytes (NHA). CDKN2A expression levels were manipulated using small interfering RNA (siRNA) and CDKN2A overexpression vector. Cell viability assays and carmustine sensitivity tests were conducted to assess the impact of CDKN2A modulation on glioblastoma cell viability and drug response. Sphere formation assays and western blot analysis were performed to investigate the role of CDKN2A in glioblastoma stem cell (GSC) self-renewal and pluripotency marker expression. Additionally, methylation-specific PCR (MSP) assays and demethylation treatment were employed to elucidate the mechanism of CDKN2A downregulation in U87 cells. RESULT: CDKN2A expression was significantly reduced in glioblastoma cells compared to NHA. CDKN2A overexpression resulted in decreased cell viability and enhanced sensitivity to carmustine treatment. CDKN2A inhibition promoted self-renewal capacity and increased pluripotency marker expression in U87 cells. CDKN2A upregulation led to elevated protein levels of p16INK4a, p14ARF, P53, and P21, which are involved in cell cycle regulation. CDKN2A downregulation in U87 cells was associated with high promoter methylation, which was reversed by treatment with a demethylating agent. CONCLUSION: Our findings demonstrate that CDKN2A downregulation in glioblastoma cells is associated with decreased cell viability, enhanced drug resistance, increased self-renewal capacity, and altered expression of pluripotency markers. The observed CDKN2A expression changes are mediated by promoter methylation. These results highlight the potential role of CDKN2A as a therapeutic target and prognostic marker in glioblastoma.