AIM: To investigate the effects of insulin-like growth factor 1(IGF-1)on the secretion of transforming growth factor β2(TGF-β2), matrix metalloproteinase 2(MMP-2)and hypoxia-inducible factor 1α(HIF-1α)in human scleral fibroblasts(HSF)and their mechanism.METHODS: The cells were cultured with IGF-1 and PI3K/AKT pathway inhibitor LY294002, respectively. CCK-8 method was used to detect cell viability and determine the optimal concentration and time of drug action. Cell migration activity was observed by cell scratch method. To determine the effects of IGF-1 on HSF cells and the regulatory role of PI3K/AKT pathway, HSF cells were divided into control group(without drugs), IGF-1(80 μg/L)group, IGF-1+LY294002(80 μg/L+5 mmol/L)group, and LY294002(5 mmol/L)group, and were cultured for 24 h; the protein expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT were detected by Western blot; the fluorescence expression of TGF-β2, MMP-2 and HIF-1α was detected by cellular immunofluorescence.RESULTS: The results of CCK-8 showed that the cell viability of the 80 μg/L IGF-1 group cultured with different concentrations of IGF-1 was the highest(all P<0.05), and the cell viability of the 80 μg/L IGF-1 group at 24 h was the highest under different culture times. Therefore, the concentration of IGF-1 was selected as 80 μg/L for 24 h. The viability of cells cultured with different concentrations of LY294002 gradually decreased from 6 h(all P<0.05). According to the IC50 value, therefore, the concentration of LY294002 was selected as 5 mmol/L for 24 h. The cell scratch results showed that compared with the control group, the cell mobility of 40 μg/L and 80 μg/L IGF-1 groups was increased(all P<0.05). Compared with the control group, cell mobility in the 2.5 and 5 mmol/L LY294002 groups was decreased(all P<0.05). Western blot results showed that compared with the control group, the protein expressions of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1+LY294002 group were decreased(all P<0.05). The results of cell immunofluorescence showed that compared with the control group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1+LY294002 group were significantly decreased(all P<0.05).CONCLUSION: IGF-1 promoted the proliferation and migration of human HSF. IGF-1 may up-regulate the expression of TGF-β2, MMP-2 and HIF-1α in HSF through the PI3K/AKT signaling pathway, and participate in the occurrence and development of myopia.

BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

ObjectiveTo evaluate the clinical efficacy of Xu's Shenqiyizhu （SQYZ） decoction combined with chemotherapy in the treatment of cancer-related fatigue （CRF） of stagnated-toxin spleen deficiency type after gastric cancer surgery and explore its possible mechanism. MethodsFifty postoperative gastric cancer patients with CRF of stagnated-toxin spleen deficiency type were selected and randomly divided into an experimental group and a control group by using a random number table，with 25 cases in each group. The control group was treated with FLOT chemotherapy （50 mg·m^-2 docetaxel （iv drip on day 1） + 85 mg·m^-2 oxaliplatin （iv drip on day 1） + 200 mg·m^-2 calcium folinate （iv drip on day 1） + 2 600 mg·m^-2 fluorouracil （iv drip for 24 h on day 1），once every three weeks） and basic and symptomatic supportive treatment. The experimental group was treated with Xu's SQYZ decoction （decocted twice，200 mL taken orally twice a day） in addition to the treatment of the control group. One course of treatment lasted for three weeks，with a total of four courses conducted. Observation was performed on the piper fatigue scale （PFS） scores，karnofsky performance status （KPS） scores，European Organization for Research and Treatment of cancer quality of life questionnaire （EORTC QLQ-C30） scores，traditional Chinese medicine syndrome scores，and serum levels of tumor necrosis factor-α （TNF-α），interferon-γ （IFN-γ），and interleukin-6 （IL-6）detected via enzyme linked immunosorbent assay （ELISA） before and after treatment in the two groups. The safety test results before and after treatment for the two groups of patients，as well as the occurrence of adverse events during treatment， were recorded. Transcriptome sequencing data of peripheral blood samples from gastric adenocarcinoma patients and normal individuals were downloaded from the gene expression omnibus （GEO） database，and differentially expressed genes between the tumor and normal groups were identified. Differential gene enrichment analysis was made based on the Kyoto Encyclopedia of Genes and Genomes （KEGG） and Gene Ontology （GO）. The CRF relevance scores of genes were retrieved from the GeneCards database. Results① Compared with that before treatment，the total PFS score in the experimental group was significantly reduced （P<0.05）. Compared with the control group after treatment，the experimental group showed significantly reduced total PFS score （P<0.05）. ② Compared with that before treatment，the KPS score in the experimental group decreased significantly （P<0.05）. Compared with the control group after treatment，the experimental group exhibited a significantly decreased KPS score （P<0.05）. The experimental group demonstrated significantly increased functional scores （physical function，role function，emotional function，social function，and overall health） （P<0.05） and significantly reduced symptom scores （fatigue，shortness of breath，loss of appetite，constipation，and diarrhea） of the EORTC QLQ-C30 scale after treatment compared with before treatment. Compared with the control group after treatment，the experimental group presented significantly increased functional scores （physical function，emotional function，social function，and overall health） （P<0.05） and significantly reduced symptom scores （fatigue，nausea and vomiting，shortness of breath，loss of appetite，and diarrhea） of the EORTC QLQ-C30 scale （P<0.05）. Compared with those before treatment，the traditional Chinese medicine syndrome scores （eating too little and poor digestion，fatigue and weakness，postprandial bloating，abnormal bowel movements，lassitude and weakness，and total score） in the experimental group were significantly reduced （P<0.05）. Compared with the control group after treatment，the experimental group had significantly reduced traditional Chinese medicine syndrome scores （eating too little and poor digestion，fatigue and weakness，nausea and vomiting，and sallow complexion） （P<0.05）， which indicated better efficacy in the experimental group than in the control group （χ²=7.996，P<0.05）. The serum levels of TNF-α，IL-6，and IFN-γ were significantly correlated with each other （P<0.01）. Compared with those before treatment，the levels of serum cytokines TNF-α，IL-6，and IFN-γ in the experimental group were significantly reduced （P<0.05）. Compared with the control group after treatment，the experimental group showed significantly reduced serum levels of cytokines TNF-α，IL-6，and IFN-γ （P<0.05）. ③ There were no significant intra-group and inter-group differences in the safety test results of the two groups before and after treatment. During the treatment period，there was no significant difference in the incidence of adverse reactions between the two groups of patients. ④ Compared with the normal group，the tumor group exhibited a total of 328 significantly up-regulated genes in the peripheral blood （P<0.05），and KEGG and GO analyses showed that they were significantly enriched in signaling pathways such as TNF （P<0.05）. ⑤ TNF，IL6，IFNG， and other cytokine encoding genes may be key pathogenic genes for CRF. ConclusionXu's SQYZ decoction can alleviate symptoms such as fatigue in postoperative chemotherapy patients with gastric cancer and improve their functional status and quality of life. Its mechanism may be related to improving cytokine imbalance.

Objective:To analyze the prognosis of hepatocellular carcinoma (HCC) patients with thrombocytosis (platelet count ≥350×10 9) after transcatheter arterial chemoembolization (TACE), and the effect of thrombocytosis on the prognosis of patients with HCC after TACE. Methods:Clinical data of 867 patients with HCC admitted to the Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University from January 2013 to May 2018 were retrospectively analyzed. After propensity score matching, 99 patients were enrolled, including 70 males and 29 females, aged (60.1±12.1) years. Patients were divided into the groups with thrombocytosis ( n=33) and without thrombocytosis ( n=66). The gender, maximum tumor diameter, Barcelona clinical liver cancer (BCLC) stage, and total bilirubin were compared between the two groups. The association of thrombocytosis with the prognosis of HCC after TACE treatment were analyzed using univariate and multivariate Cox regression. Results:After propensity score matching, the male proportion, maximum tumor diameter, BCLC stage, and serum level of total bilirubin were comparable between the groups (all P>0.05). Before TACE treatment, the platelet count of patients with thrombocytosis was (394.4±54.5)×10 9/L, which was higher than that after TACE [(278.2±86.4)×10 9/L, t=7.63, P<0.001]. The progression-free survival rates after TACE in without thrombocytosis group were 83.3%, 24.2%, and 7.6% at 3, 6 and 9 months, respectively, better than those in thrombocytosis group (51.5%, 3.0%, and 3.0%, respectively; χ2=31.24, P<0.001). The overall survival rates after TACE in without thrombocytosis group were 81.8%, 30.3%, and 4.5% at 1, 2 and 3 years, respectively, better than those in thrombocytosis group (15.2%, 9.1%, and 3.0%, respectively; χ2=27.89, P<0.001). Multivariate Cox regression analysis showed that patients of HCC with thrombocytosis had an increased risk of tumor progression ( HR=5.785, 95% CI: 3.291-10.168, P<0.001) and increased risk of death ( HR=4.090, 95% CI: 2.482-6.740, P<0.001) after TACE. Conclusion:The prognosis of TACE for HCC might be worse in patients with thrombocytosis. Thrombocytosis is a risk factor for cumulative survival and progression-free survival of HCC patients after TACE.

Objective:To evaluate the relationship between red blood cell distribution width (RDW) and prognosis of patients with hepatocellular carcinoma (HCC) andergoing transcatheter arterial chemoembolization (TACE).Methods:Clinical data of 212 patients with HCC andergoing TACE for the first time in Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University from January 2011 to May 2018 were retrospectively analyzed, including 184 males and 28 females, aged (56.8±11.2) years. Follow-up for survival. X-tile software was used to determine 13.1% as the optimal threshold for preoperative RDW prediction of prognosis, and enrolled patients were divided into a low level group (RDW<13.1%, n=70) and a high level group (RDW≥13.1%, n=142). Aspartate aminotransferase, total bilirubin, albumin, hemoglobin and lipoprotein a, Barcelona clinical liver cancer (BCLC) stage and other indexes were compared between the two groups. Survival analysis was performed by Kaplan-Meier method, survival rate was compared by log-rank test, and the effect of RDW on prognosis was analyzed by Cox regression. Results:The 1-year, 2-year and 3-year cumulative survival rates in RDW high level group were 34.5%, 14.1% and 6.3%, respectively, while those in RDW low level group were 64.3%, 38.6% and 21.4%, respectively, with significant difference ( χ2=23.09, P<0.001). Compared with the low level group, the levels of aspartate aminotransferase and total bilirubin were higher, the levels of albumin, hemoglobin and lipoprotein a were lower, the proportion of portal vein cancer thrombin was higher, and the stage of BCLC was later, with statistical significance (all P<0.05). Cox regression analysis showed that HCC patients with RDW≥13.1%( HR=1.732, 95% CI: 1.223-2.452, P=0.002) had poor survival prognosis after TACE. Conclusion:Preoperative RDW≥13.1% is an independent risk factor for survival after TACE in patients with HCC. RDW has potential predictive value for prognosis of patients with HCC.

Generative artificial intelligence (GAI) refers to AI technology capable of generating new content such as text, images, or audio from training data. GAI tools not only demonstrate rapid and efficient potential in literature screening, data extraction, and literature appraisal in systematic reviews, but can also be used for guideline evaluation and dissemination, enhancing the readability and promotion efficiency of guidelines. However, the accuracy of content generated by GAI tools, the rationality of cited evidence, the level of evidence, and the reliability of data still need verification. Additionally, data privacy protection and ethical issues are challenges that need to be addressed. This article aims to overview the current status of GAI tools in the formulation, evaluation, dissemination, and implementation of guidelines, explore the feasibility and new models of GAI tools in the field of guidelines, and improve the efficiency and quality of guideline formulation to better serve guideline developers and users.

Objective:To systematically evaluate the qualitative research on the practical experience of hospice care among medical staff in nursing homes, and to provide a reference basis for the implementation of hospice care services in nursing homes.Methods:The qualitative research on the practical experience of hospice care among medical staff in nursing homes was searched from databases including the Web of Science, PubMed, Cochrane Library, Embase, CINAHL, China National Knowledge Infrastructure, China Biology Medicine disc, Wanfang Data and VIP Database. The retrieval period was from the establishment of the database to March 21, 2024. The quality evaluation standards for qualitative research of the Australian Joanna Briggs Institute Evidence-Based Health Care Center were used to evaluate the quality of the literature. The results were integrated by the method of aggregative integration.Results:A total of 15 studies were included, and 47 clear research results were extracted, summarized into 11 categories, and 4 integrated results were obtained: the palliative care work responsibilities of medical staff; the emotional experience of medical staff in practice; coping with negative experience and gaining personal growth;the practical dilemmas faced by nursing homes when implementing hospice care.Conclusions:Nursing homes face multiple obstacles and challenges in the process of providing hospice care services. It is recommended that future research should focus on improving the policy system of hospice care in nursing homes, building a support system for hospice care services, and promoting the development and practice of death literacy among the public, so as to promote the healthy and long-term development of hospice care services in nursing homes.

Objective To explore the short-term and long-term efficacy of arthroscopic surgery,different non-surgical ther-apy and sham operation intervention in the treatment of meniscus related injuries,and to compare their advantages and disadvan-tages,so as to provide guidance for clinical practice.Methods Randomized controlled trials on arthroscopic surgery,meniscecto-my and other surgical and non-surgical treatments for knee meniscus injury were searched in PubMed,Embase,Cochrane Librar-y and Web of Science,and the search time was from its inception to July 2023.Two researchers independently screened the liter-ature according to the established literature ranking criteria,and the Cochrane Risk of Bias Assessment Tool was used to evalu-ate the risk of bias of the included literature,while the PEDro Scale Evaluation Tool was used to evaluate the quality of the liter-ature of the randomized controlled trials,and the collected data were quantitatively analyzed using RevMan 5.3 software.Results From the qualitative analysis,it was clear that surgical therapies might be more appropriately applied to patients without osteo-arthritis and without mechanical symptoms,and that meniscal suture repair surgery had a more favorable long-term outcome compared with traditional partial meniscectomy.Quantitative analysis showed that there was no statistical significance between arthroscopic surgery and other non-surgical therapies in several short and long term efficacy(all P＞0.05).For example,MD=0.15,95％CI:-4.05～4.35,I2=0％in the short-term comparison of Lysholm knee score;MD=-1.30,95％CI:-3.16～0.57,I2=0％;Short-term VAS score MD=-0.18,95％CI:-0.59～0.23,I2=45％;MD=-0.01,95％CI:-0.20～0.19,I2=36％.In addition,in the subgroup analysis of degenerative meniscus injury alone,the difference in clinical efficacy between the two therapies was also not statistically significant(all P＞0.05).Conclusion There is no practical difference between surgi-cal therapy and non-surgical therapy in the short-term and long-term outcomes.For single type injury,such as degenerative me-niscus injury,there is no practical difference between the two therapies.

Objective:Studying the effect of PRDX4 on esophageal squamous cell carcinoma cells(esophageal carcinoma,ESCC)proliferation and apoptosis as well as its potential mechanism.Methods:The University of Alabama at Birmingham cancer data analysis portal(UALCAN),gene expression profiling interactive analysis(GEPIA)and the Cancer Genome Atlas(TCGA)databases were used to predict PRDX4 expres-sion in ESCC and its relationship with pathological features and prognosis.The cancer and adjacent tissues of 60 patients with ESCC who un-derwent radical resection in the Affiliated Hospital of Weifang Medical College from August 2010 to August 2023 were selected as research samples.The expression level of PRDX4 in the patients was detected by immunohistochemistry(IHC).The extracted cancer and adjacent tis-sues were homogenized to analyze its mRNA expression.The expression levels of PRDX4 mRNA and related signaling proteins in ESCC cells were analyzed by real-time quantitative PCR and Western blot.Cell Counting Kit-8(CCK-8)assay and flow cytometry were used to analyze the effect of PRDX4 on cell proliferation and apoptosis.Finally,a subcutaneous tumor model in nude mice was constructed to validate the in vitro experimental results.Results:The data from the GEPIA and UALCAN showed that PRDX4 expression was abnormally increased and re-lated to the pathology stage,grade,and survival rate of patients.After knockdown and overexpression of PRDX4 in an ESCC cell line,the ex-pression of PRDX4,phos-phosphatidylinositol 3-kinase(p-PI3K),phos-protein kinase B(p-AKT),cyclinD1,and survivin protein decreased and increased,respectively;cell proliferation and apoptosis were positively regulated.Compared with the sh-NC group,tumor volume and weight in the sh-PRDX4 group were decreased.Conclusions:PRDX4 regulates the proliferation and apoptosis of ESCC cells by activating the PI3K/AKT signaling pathway.

Objective To investigate the role of macrophages in the process of fine particulate matter (PM2.5)exposure induced damage to pulmonary blood-air barrier.Methods Eighteen male BALB/C mice (aged of 10 weeks,weighing 24～27 g)were randomly divided into control group and low-and high-dose PM2.5 exposure groups (receiving 1 .8 and 16.2 mg/kg,respectively),with 6 mice in each group.The control group received tracheal instillations of normal saline on days 1,4,and 7,whereas the exposure groups were administered corresponding dose of PM2.5 exposure at the same time points.In 24 h after last exposure,pathological changes in the lung tissues were observed,and the contents of total protein (TP ),lactate dehydrogenase (LDH ),and alkaline phosphatase (AKP ) in bronchoalveolar lavage fluid (BALF ),and F4/80 protein level in lung tissue were measured to evaluate the blood-air barrier damage and macrophage infiltration within the lung tissues.Additionally,an in vitro model of the blood-air barrier was established using A549 alveolar epithelial cells and EA.hy926 vascular endothelial cells.In combination with a THP-1 macrophage model,the supernatant PM2.5 supernatant,macrophage supernatant,and PM2.5-macrophage supernatant were incubated with the barrier model for 24 h,respectively.Transmembrane electrical resistance (TEER),sodium fluorescein permeability of the barrier model,and LDH release from the barrier cells were measured to ascertain the extent of macrophage-mediated enhancement in barrier damage induced by PM2.5 exposure.Furthermore,the expression of inflammatory cytokines,such as TNF-α,IL-1β,IL-6,and IL-8 in the macrophages after PM2.5 exposure was analyzed with quantitative real-time PCR (qPCR)and enzyme-linked immunosorbent assay (ELISA).Results PM2.5 exposure induced lung tissue damage in mice in a dose-dependent manner,significantly elevated the contents of TP,LDH and AKP in the BALF and caused marked infiltration of macrophages into the lung tissue,especially the high-dose exposure when compared with the mice from the control group (P<0.01 ).In vitro barrier model exposure experiments showed that in comparison with the treatment of 150 and 300 μg/mL PM2.5 and macrophage supernatant,the same doses of PM2.5-macrophage supernatant resulted in notably decreased TEER and significantly enhanced permeability in the barrier model (P<0.01 ),and markedly increased LDH release from epithelial and endothelial barrier cells (P<0.01 ).Additionally,the exposure of 150 and 300μg/mL PM2.5 led to a significant up-regulation of TNF-α,IL-1β,IL-6,and IL-8 in the macrophages (P<0.01 ).Conclusion Macrophages deteriorate PM2.5-induced functional impairment of the pulmonary blood-air barrier.