Objective To analyze the effects of the histone deacetylase inhibitor suberoylanilide hydroxamic acid(SAHA)on the secondary metabolites of the entomopathogenic fungus Samsoniella hepiali CDB9-31 using thin-layer chromatography(TLC)and high-performance liquid chromatography(HPLC).Methods The fermentation products of Samsoniella hepiali CDB9-31 treated with epigenetic modifiers were separated and purified using methods such as silica gel column chromatography,Sephadex column chromatography and reversed-phase column chromatography.The structures of the compounds were elucidated using modern spectroscopic analysis methods.The antimicrobial activity of the obtained monomeric compounds was determined using the filter paper disc diffusion method.Results The TLC and HPLC analyses of its fermentation extracts revealed that SAHA could induce the strain to produce more diverse array of secondary metabolites,and 11 monomeric compounds were isolated and identified as follows:N'-phenyloctanediamide(1),5-Phenylcarbamoyl-pentanoic(2),ergosterol(3),5,8-Epidioxy-5α,8α-ergosta-6,22E-diene-3β-ol(4),1-monolinolein(5),(4E,8E)-2-N-(2-Hydro-xypalmitoyl)-1-O-(β-D-glucopyranosyl)-9-methyl-4,8-sphingadienine(6),Ergosterol peroxide 3-O-β-D-glucopyranoside(7),(22E,24R)-7,22-diene-3β,5α,6β-ergostatriol(8),(2S,2'R,3R,4E,8E)-N-2'-Hydroxyhexadecanoyl-2-amion-9-methyl-4,8-octadecadiene-1,3-diol(9),Adenosine(10),D-Glulopyranose(11).Compounds 1 and 2 were derivatives of SAHA,and it was speculated that the special metabolic environment of CDB9-31 caused the biotransformation of SAHA.Except for compound 3,all other compounds were isolated from this genus for the first time.The antibacterial activity results showed that six of these compounds exhibited varying degrees of inhibitory effects against at least one pathogenic bacterium.Conclusion This study has enriched the chemical diversity of secondary metabolites from the entomopathogenic fungus Samsoniella hepiali.

Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.

Objective To identify the biomarkers for early rheumatoid arthritis(RA)diagnosis and explore the possible immune regulatory mechanisms.Methods The differentially expressed genesin RA were screened and functionally annotated using the limma,RRA,batch correction,and clusterProfiler.The protein-protein interaction network was retrieved from the STRING database,and Cytoscape 3.8.0 and GeneMANIA were used to select the key genes and predicting their interaction mechanisms.ROC curves was used to validate the accuracy of diagnostic models based on the key genes.The disease-specific immune cells were selected via machine learning,and their correlation with the key genes were analyzed using Corrplot package.Biological functions of the key genes were explored using GSEA method.The expression of STAT1 was investigated in the synovial tissue of rats with collagen-induced arthritis(CIA).Results We identified 9 core key genes in RA(CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL),which regulate synovial inflammation primarily through cytokines-related pathways.ROC curve analysis showed a high predictive accuracy of the 9 core genes,among which STAT1 had the highest AUC(0.909).Correlation analysis revealed strong correlations of CD3G,ITGAL,LCK,CD8A,and STAT1 with disease-specific immune cells,and STAT1 showed the strongest correlation with M1-type macrophages(R=0.68,P=2.9e-08).The synovial tissues of the ankle joints of CIA rats showed high expressions of STAT1 and p-STAT1 with significant differential expression of STAT1 between the nucleus and the cytoplasm of the synovial fibroblasts.The protein expressions of p-STAT1 and STAT1 in the cell nuclei were significantly reduced after treatment.Conclusion CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL may serve as biomarkers for early diagnosis of RA.Gene-immune cell pathways such as CD3G/CD8A/LCK-γδ T cells,ITGAL-Tfh cells,and STAT1-M1-type macrophages may be closely related with the development of RA.

Objective To identify the biomarkers for early rheumatoid arthritis(RA)diagnosis and explore the possible immune regulatory mechanisms.Methods The differentially expressed genesin RA were screened and functionally annotated using the limma,RRA,batch correction,and clusterProfiler.The protein-protein interaction network was retrieved from the STRING database,and Cytoscape 3.8.0 and GeneMANIA were used to select the key genes and predicting their interaction mechanisms.ROC curves was used to validate the accuracy of diagnostic models based on the key genes.The disease-specific immune cells were selected via machine learning,and their correlation with the key genes were analyzed using Corrplot package.Biological functions of the key genes were explored using GSEA method.The expression of STAT1 was investigated in the synovial tissue of rats with collagen-induced arthritis(CIA).Results We identified 9 core key genes in RA(CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL),which regulate synovial inflammation primarily through cytokines-related pathways.ROC curve analysis showed a high predictive accuracy of the 9 core genes,among which STAT1 had the highest AUC(0.909).Correlation analysis revealed strong correlations of CD3G,ITGAL,LCK,CD8A,and STAT1 with disease-specific immune cells,and STAT1 showed the strongest correlation with M1-type macrophages(R=0.68,P=2.9e-08).The synovial tissues of the ankle joints of CIA rats showed high expressions of STAT1 and p-STAT1 with significant differential expression of STAT1 between the nucleus and the cytoplasm of the synovial fibroblasts.The protein expressions of p-STAT1 and STAT1 in the cell nuclei were significantly reduced after treatment.Conclusion CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL may serve as biomarkers for early diagnosis of RA.Gene-immune cell pathways such as CD3G/CD8A/LCK-γδ T cells,ITGAL-Tfh cells,and STAT1-M1-type macrophages may be closely related with the development of RA.

Objective:To conduct a scoping review on the application of family resilience intervention in adults with chronic disease.Methods:Related studies published from database establishment to October 30, 2023 were systematically searched on PubMed, Web of Science, Cochrane Library, PsycINFO, CINAHL, Scopus, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biomedical Database. The included literature was summarized and analyzed.Results:A total of 9 articles were included. The intervention elements for family resilience included increasing awareness of diseases and family characteristics, solving and responding to family problems, engaging in family interaction and communication, integrating internal and external resources, and providing psychological and technical support. The outcome indicators were the level of family resilience and effectiveness.Conclusions:The intervention of family resilience in adults with chronic disease has certain effectiveness and clinical significance, but research is still in the exploratory stage. Further high-quality research is needed to verify the long-term intervention effect and feasibility, and to construct a diversified family resilience intervention program suitable for China.

Objective:To understand the current state of financial toxicity and suicide risk in head and neck cancer patients, to investigate the correlation between the level of financial toxicity and suicide risk in head and neck cancer patients, and to provide a basis for reducing the level of financial toxicity and the risk of suicide in head and neck cancer patients.Methods:A cross-sectional survey was conducted, from March 1 to July 31, 2022, 150 head and neck cancer patients were selected from Oncology Department of East Hospital Affiliated to Tongji Universityby by convenient sampling method. The survey was carried out by means of the general questionnaire, Comprehensive Score for Financial Toxicity based on the Patient-Reported Outcome Measures (COST-PROM), Cancer Suicide Risk Scale (CSRS), and then analysis the datum.Results:The score of COST-PROM of 150 head and neck cancer patients was (18.00 ± 6.12) points, and the score of CSRS of head and neck cancer patients was (36.31 ± 8.51) points. The total score of economic toxicity was significantly negatively correlated with the total score of suicide risk and its dimensions ( r values were -0.446 to 0.235, all P<0.05). The total score of suicide risk was negatively correlated with the total score of economic toxicity and the scores of each dimension ( r values were -0.446 to -0.251, all P<0.05). Conclusions:Patients with head and neck cancer were at higher risk of suicide, and financial toxicity was a significant contributing factor to suicide risk, with higher levels of financial toxicity associated with a higher risk of suicide. Reducing the level of financial toxicity in patients with head and neck cancer has important implications for reducing their risk of suicide.

Objective:To explore the effects of Nie Ji tuina combined with acupoint massage on cellular immune function in children with recurrent respiratory tract infection (RRTI).Methods:Randomized controlled trial. A total of 96 children in the hospital were enrolled as the observation objects between June 2020 and October 2021. According to random number table method, they were divided into control group (acupoint massage) and observation group (Nie Ji tuina combined with acupoint massage), 48 in each group. All were treated for 8 weeks and followed up for 8 months. TCM syndromes were scored before and after treatment. The levels of CD4 +, CD8 + and CD4 +/CD8 + ratio in peripheral blood were detected by flow cytometry. The frequency of RRTI attacks during follow-up was observed, and the clinical curative effect was evaluated. Results:There was no significant difference in total response rate between observation group and control group [93.75% (45/48) vs. 81.25% (39/48); χ2=3.43, P=0.064]. After treatment, scores of TCM syndromes (cough, fatigue, shortness of breath and laziness to speak, spontaneous sweating) were significantly lower in observation group than control group ( t=3.95, 9.64, 7.68, 8.34, P<0.01). After treatment, levels of CD4 + and CD4 +/CD8 + were increased ( P<0.01), while CD8 + level was decreased in both groups ( P<0.01), but there was no significant difference between the two groups ( P>0.05). During follow-up, observation group times of recurrence attacks were fewer than those in the control group ( t=10.60, P<0.01). Conclusion:Nie Ji tuina combined with acupoint massage can improve disease resistance ability and reduce RRTI frequency in children.

Objective:To explore the effect of pediatric massage combined with nerve growth factor treatment on the neurological function of children with acute ischemic hypoxic encephalopathy (HIS).Methods:A total of 96 children with HIS who were treated in Hubei Maternal and Child Health Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from February 2017 to October 2019 were selected for the study. The children were divided into 2 groups using a random number table method, with 48 cases in each group. The control group was treated with nerve growth factor on the basis of conventional treatment, and the observation group was treated with pediatric massage on the basis of the control group. The clinical efficacy, neurobehavior, intelligence index, EEG index, cerebral blood flow and hematology index were compared between the two groups.Results:The total effective rate of the observation group was 95.84%, which was higher than 81.25% of the control group, and the difference between the two groups was statistically significant ( χ2=5.03, P=0.025). The 28-day NBNA score ( t=-2.55, P=0.012) and three-month MDI and PDI of the observation group were significantly higher than those of the control group ( t values were -3.43, -2.65, all Ps<0.01). After treatment, the EEG spike wave amplitude of the two groups of children decreased significantly, and the decrease was greater in the observation group[(35.02 ± 4.16) mV vs. (46.92±5.81)mV, t=11.54]. After treatment, the cerebral blood flow of the two groups of children increased significantly, and the increase was more significant in the observation group [(179.36 ± 22.25) ml/(100 g?min) vs. (158.30±14.92) ml/(100 g?min), t=-5.45]. After treatment, the levels of MBP, NSE and VEGF in the two groups of children decreased significantly, but the decrease in the observation group was greater ( t values were 3.29, 4.07, 8.17, all Ps<0.01). Conclusion:Pediatric massage combined with nerve growth factor alone can improve the curative effect of children with HIS, improve neurobehavioral and intelligent indicators, increase cerebral blood flow, and reduce EEG spike wave amplitude and MBP, NSE and VEGF levels.

Objective:To investigate the effect of peer support-based narrative therapy on postoperative self-image and stigma of patients with head and neck cancer, to provide reference for clinical nursing.Methods:A total of 78 head and neck cancer patients from August 2018 to August 2020 in Fudan University Shanghai Cancer Center were divided into experimental group and control group by random digits table method, each group were 39 cases. The control group was given conventional nursing, while the experimental group implemented support-based narrative therapy on the basis of routine nursing. The intervention time was 4 weeks. The self-image and stigma of the two groups before and after intervention were assessed by Body Image Scale (BIS) and Social Impact Scale (SIS), respectively.Results:Finally, 37 cases were included in the experimental group and 38 cases in the control group. There was no significant difference in BIS, SIS dimension scores and total scores between the two groups before intervention ( P>0.05). After intervention, the emotional demension scores, behavior dimension scores, cognitive dimension scores and total scores in BIS were 4.41 ± 1.04, 1.95 ± 0.51, 3.81 ± 0.63 and 10.16 ± 2.05 in the experimental group, significantly lower than in the control group 5.08 ± 1.08, 2.82 ± 0.60, 5.42 ± 0.76 and 13.32 ± 1.93, the differences were statistically significant ( t values were 2.76-6.86, all P<0.01); the social exclusion scores, internal shame scores, social isolation scores and total stigma scores in SIS were 17.57 ± 2.67, 9.08 ± 1.55, 12.14 ± 3.73 and 46.14 ± 4.95 in the experimental group, significantly lower than in the control group 19.18 ± 3.70, 10.68 ± 1.61, 14.18 ± 3.83 and 51.68 ± 6.09, the differences were statistically significant ( t values were 2.16-4.38, all P<0.05). Conclusions:Peer support-based narrative therapy can effectively alleviate the postoperative self-image problems and stigma of patients with head and neck cancer, which is worthy of clinical application.

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*