Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

Objective:To study the prevalence of occupational pneumoconiosis in Qinhuangdao from 1961 to 2020 and offer a foundation for developing occupational pneumoconiosis prevention and control methods.Methods:In December 2020, the data of occupational pneumoconiosis cases diagnosed by medical institutions with occupational disease diagnosis qualifications in Qinhuangdao City from 1961 to 2020 were collected Anova or kruskal-Walls tests and chi-square tests were used for inter-group comparisons of continuous and categorical variables, and LSD tests or Tamhane T2 tests were used for multiple comparisons. Results:Between 1961 and 2020, 384 cases of pneumoconiosis were documented in Qinhuangdao, of which 382 (99.5%) patients were men and 2 (0.5%) were women. The average dust service duration is 15 (9, 25) years, with a minimum duration of 0.5 years and a maximum duration of 49 years; Cases were primarily distributed in Qinglong Manchu Autonomous County (187 cases, 48.7%) and the Haigang district (160 cases, 41.7%) ; Type of pneumoconiosis was silicosis (340 cases, 88.5%), mainly 273 cases (71.1%) of stage I, 88 cases (22.9%) of stage II, and 23 cases (6.0% of stage III) ; Cases of Phase II and III and with short lengths of service are mainly concentrated in medium-sized, small, private limited liability companies and collective enterprises. Rrock work (166 cases, 43.2%), and loading kiln workers (42 cases, 10.9%) were the main types.Conclusion:Because the distribution of pneumoconiosis cases in Qinhuangdao city is concentrated and the length of service is decreasing, it is important to enhance the oversight of important area, businesses, industries, and job categories in line with the growth of the region's mineral resources.

Objective:To study the prevalence of occupational pneumoconiosis in Qinhuangdao from 1961 to 2020 and offer a foundation for developing occupational pneumoconiosis prevention and control methods.Methods:In December 2020, the data of occupational pneumoconiosis cases diagnosed by medical institutions with occupational disease diagnosis qualifications in Qinhuangdao City from 1961 to 2020 were collected Anova or kruskal-Walls tests and chi-square tests were used for inter-group comparisons of continuous and categorical variables, and LSD tests or Tamhane T2 tests were used for multiple comparisons. Results:Between 1961 and 2020, 384 cases of pneumoconiosis were documented in Qinhuangdao, of which 382 (99.5%) patients were men and 2 (0.5%) were women. The average dust service duration is 15 (9, 25) years, with a minimum duration of 0.5 years and a maximum duration of 49 years; Cases were primarily distributed in Qinglong Manchu Autonomous County (187 cases, 48.7%) and the Haigang district (160 cases, 41.7%) ; Type of pneumoconiosis was silicosis (340 cases, 88.5%), mainly 273 cases (71.1%) of stage I, 88 cases (22.9%) of stage II, and 23 cases (6.0% of stage III) ; Cases of Phase II and III and with short lengths of service are mainly concentrated in medium-sized, small, private limited liability companies and collective enterprises. Rrock work (166 cases, 43.2%), and loading kiln workers (42 cases, 10.9%) were the main types.Conclusion:Because the distribution of pneumoconiosis cases in Qinhuangdao city is concentrated and the length of service is decreasing, it is important to enhance the oversight of important area, businesses, industries, and job categories in line with the growth of the region's mineral resources.

Objective To retrieve,analyse and integrate the best evidences in perioperative fluid management for elderly patients with hip fracture,therefore to provide references for patient care.Methods Following the 6S evidence model,databases and websites were searched to collect the evidences on perioperative fluid management of elderly patients with hip fracture.The searched databases including BMJ Best Practice,UpToDate,AAOS Clinical Practice Guidelines,ASBMR,ANZHFR,ESTES,NICE,SIGN,JBI,Cochrane Library,CINAHL,Embase,PubMed,Web of Science,CNKI,Wanfang Data,VIP database,CEBM Database,Medive,China Science and Technology Journal Database,SinoMed,and other websites about orthopaedics.The searched literatures included guidelines,clinical decision-making,best practices,expert consensus and systematic reviews.The time span for the published literatures was from the inception of the databases and websites to August 2022.Two researchers independently completed quality evaluations of the retrieved literatures,as well as extraction,assessment and integration of the abstracted evidences.Results A total of 15 articles were included,they were 2 guidelines,3 clinical decision-makings,1 best practice,7 expert consensus,and 2 systematic reviews.Thirty pieces of evidence were summarised from 7 aspects,covering multidisciplinary team collaboration,dynamic assessment and monitoring of fluid status,fluid resuscitation,fluid management before and after the surgery and health education.Conclusions This study summarised the best evidences in perioperative fluid management for elderly patients with hip fracture.The evidences provide an evidence-based solution which will enable the healthcare workers to fully combine the clinical scenarios,evaluate changes in fluid volume status dynamically,develope personalised fluid management strategies and improve patient outcomes.

Objective:To explore the correlation between defecation disorders and diet in patients undergoing sphincter-preserving surgery for rectal cancer.Methods:This study was a cross-sectional survey. From 2021 to 2023, convenience sampling was used to select 159 patients with rectal cancer who underwent sphincter-preserving surgery at Peking University Third Hospital as participants. The General Information Questionnaire, Food Frequency Questionnaire, and Defecation Questionnaire were used for the survey.Results:The incidence of defecation disorders in 159 patients with rectal cancer after sphincter-preserving surgery was 74.2% (118/159), and the types of defecation disorders with high to low incidence were "frequent defecation (96/159, 60.4%) " "constipation (37/159, 23.3%) " "diarrhea (33/159, 20.8%) " and "fecal incontinence" (24/159, 15.1%). Diets were clustered into 9 categories (vegetables and fruits, carbohydrate staple foods, red meat foods, gas producing foods, dairy products, white meat foods, dessert foods, high-fat foods, and spicy and stimulating foods). Binomial Logistic regression analysis showed that red meat foods and gas producing foods were the influencing factors of frequent defecation ( P<0.05), red meat foods was the influencing factor of diarrhea ( P<0.05), and carbohydrate staple foods was the influencing factor of fecal incontinence ( P<0.05) . Conclusions:The incidence of defecation disorders in patients with rectal cancer after sphincter-preserving surgery is relatively high, and the intake of red meat foods, gas producing foods, and carbohydrate staple foods should be appropriately controlled. Clinical medical and nursing staff should pay close attention to the diet of elderly patients.

Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H₂S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H₂S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H₂S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.
Humans ; Mice ; Animals ; Gastrointestinal Microbiome ; Intestinal Barrier Function ; Mice, Inbred C57BL ; Colitis/metabolism* ; Inflammatory Bowel Diseases/drug therapy* ; Inflammation ; Anti-Inflammatory Agents/pharmacology* ; Disease Models, Animal

Bulimia nervosa (BN) is a kind of mental disorder characterized by repeated episodes of uncontrollable overeating, accompanied by compensatory behavior to prevent weight gain and excessive attention to one's own weight and body shape. Cognitive control, reward processing, and emotional processing are three interrelated neuropsychological processes.Cognitive control regulates reward processing while also being regulated by emotional effects. This article reviews functional magnetic resonance imaging(fMRI) researches on cognitive control, reward processing, emotional processing and intervention in BN, aiming to summarize substantive progress and provide inspiration for future interventions targeting BN. It can be seen from the review that the abnormal cognitive control of BN patients is related to the decreased functional activity of the frontal lobe striatum circuit.Abnormal activation of brain regions related to reward processing such as anterior and posterior cingulate cortex, ventral striatum and insula.The reaction of the right amygdala, the left anterior cingulate cortex and the left insular lobe of BN patients under negative emotion was weaker than that of healthy people. After medication and psychotherapy, the abnormalities of the prefrontal lobe and limbic system were improved to some extent.

Objective:To identify the risk factors of heart failure in elderly patients with hip fracture by Meta-analysis.Methods:The clinical studies on perioperative heart failure in elderly patients with hip fracture were searched by computer in Pubmed, EMbase, Cochrane Library, Medline, Web of Science, CNKI, CBM, Wanfang and VIP database. The retrieval period was from the establishment of the databases to October 2021. The literature screening, data extraction and quality evaluation were completed by two researchers, and the selected literature were statistically analyzed by RevMan5.3 software.Results:A total of 17 articles were included in this study, involving 1 76 611 patients and 24 related risk factors. Cardiac history ( OR= 4.47, 95% CI 3.56-5.62), positive balance of perioperative inflow and outflow ( OR=5.99, 95% CI 3.30-10.87), anemia ( OR= 3.78, 95% CI 2.50-5.69), and the number of complications >4 ( OR=6.21, 95% CI 3.71-10.38), electrolyte disorder ( OR=7.40, 95% CI 3.77-14.54), preoperative cognitive impairment ( OR=3.60, 95% CI 1.39-9.31) and American Society of Anesthesiologists (ASA) grade ≥ 3 ( OR= 4.73, 95% CI 2.73-8.12) were statistically significant risk factors ( P<0.05). Conclusions:Cardiac history, positive balance of perioperative inflow and outflow, anemia, number of complications >4, electrolyte disorder, preoperative cognitive impairment and ASA grade ≥3 were the risk factors of perioperative heart failure in elderly patients with hip fracture.