ObjectiveTo investigate whether anti-programmed death-1 （PD-1） monoclonal antibody can enhance the efficacy and safety of argon-helium cryoablation combined with targeted therapy in patients with unresectable hepatocellular carcinoma （uHCC） aged 60 years or older. MethodsA retrospective analysis was performed for the clinical data of 124 patients with advanced uHCC aged 60 years or older who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2013 to September 2024. After propensity score matching， 57 patients received cryoablation combined with targeted therapy （double combination group）， while 57 received cryoablation combined with targeted therapy and anti-PD-1 monoclonal antibody （triple combination group）. The indicators for efficacy assessment included objective response rate （ORR）， disease control rate （DCR）， progression-free survival （PFS）， overall survival （OS）， and the incidence rate of adverse events. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison between groups. A Cox proportional-hazards regression model analysis was used to investigate the influencing factors for survival prognosis. ResultsThe triple combination group had a significantly higher ORR than the double combination group （59.6% vs 29.8%， χ²=9.083， P=0.003）， while there was no significant difference in DCR between the two groups （87.7% vs 77.2%， χ²=1.516， P=0.218）， and compared with the double combination group， the triple combination group had significantly longer median PFS （9.1 months vs 4.8 months， χ²=7.813， P=0.005） and median OS （26.1 months vs 13.6 months， χ²=14.199， P<0.001）. The multivariate Cox proportional-hazards regression model analysis showed that triple combination treatment was an independent influencing factor for PFS （hazard ratio ［HR］=0.52， 95% confidence interval ［CI］： 0.35 — 0.78， P=0.001） and OS （HR=0.32， 95%CI： 0.20 — 0.51， P<0.001）. There was no significant difference in the incidence rate of adverse events between the two groups （P>0.05）. ConclusionTriple combination treatment with argon-helium cryoablation， targeted therapy， and anti-PD-1 monoclonal antibody can significantly improve survival benefits in uHCC patients aged 60 years or older， with a controllable safety profile.

Objective To investigate the effect of long non-coding RNA,LINC00839,on the malignant biological behavior of endome-trial cancer(EC)cells via regulating miR-625-5p/MSI1 axis.Methods The expression of LINC00839,miR-625-5p,and MSI1 mRNA in EC tissues and cells was detected by real-time quantitative PCR.Ishikawa cells were selected,and bioinformatics,dual-luciferase reporter gene assay,and RNA-binding protein immunoprecipitation assay were performed to verify the targeting relationship between LINC00839,MSI1,and miR-625-5p.CCK-8,colony formation assay,flow cytometry,and Transwell assay were performed to detect cell proliferation,apoptosis,migration,and invasion.Western blotting was used to detect the expression of MSI1,Bcl-2,Bax,MMP-2,and MMP-9 protein.In vivo tumor formation experiments were conducted to verify the effect of LINC00839 on transplanted tumors in nude mice.Results The expression of LINC00839 and MSI1 mRNA in EC tissues was higher,whereas the expression of miR-625-5p was lower(P＜0.05).LINC00839 and MSI1 targeted miR-625-5p.LINC00839 knockdown or miR-625-5p overexpression suppressed malignant behavior of cells(P＜0.05).Inhibition of miR-625-5p expression or overexpression of MSI1 reversed the inhibitory effect of LINC00839 knockdown or miR-625-5p overexpression on the malignant behavior of cells(P＜0.05).LINC00839 knockdown decreased the volume and mass of transplanted tumors,increased the expression of miR-625-5p,and inhibited the expression of MSI1.Conclusion LINC00839 can target the miR-625-5p/MSI1 axis and regulate the proliferation,apoptosis,migration,and invasion of EC cells.

Objective To evaluate the efficacy of Yunpi Runtong Formula(composed of Haematitum,Atractylodis Macrocephalae Rhizoma,Paeoniae Radix Alba,Cinnamomi Ramulus,Ophiopogonis Radix,Angelicae Sinensis Radix,Cannabis Fructus,Aurantii Fructus Immaturus,Cimicifugae Rhizoma,Picrorhizae Rhizoma,etc.)in treating functional constipation(FC)of spleen deficiency type in children and to analyze its effects on gut microbiota,defecation patterns,and the serotonin(5-HT)signaling pathway.Methods A total of 160 children with FC of spleen deficiency type treated at Shanxi Institute of Traditional Chinese Medicine from August 2022 to August 2024 were enrolled and randomly divided into a control group and a study group,with 80 patients in each group.The control group received conventional western medicine(lactulose oral solution)treatment,while the study group received Yunpi Runtong Formula treatment in addition to the control group's treatment.Both groups underwent treatment for one month.Changes in traditional Chinese medicine(TCM)syndrome scores,defecation parameters[mean defecation time,spontaneous complete bowel movements(SCBM),Bristol Stool Form Scale(BSFS)],gastrointestinal function markers[substance P(SP),gastrin(GAS),motilin(MLT)],gut microbiota composition,and 5-HT signaling pathway components(serum 5-HT levels,5-HT3R and 5-HT4R protein expression)were analyzed.Clinical efficacy and safety were evaluated.Results(1)The intergroup comparison(by chi-square test)showed that the study group exhibited significantly higher total efficacy[95.00％(76/80)]than the control group[81.25％(65/80);P＜0.01].(2)Both groups exhibited reduced TCM syndrome scores(defecation duration,stool features,difficulty of defecation,interval of defecation,and secondary symptoms;all P＜0.05),with greater improvements in the study group(P＜0.01).(3)After treatment,both groups had shorter mean defecation time,increased SCBM,and higher BSFS scores(all P＜0.05),and the study group demonstrated superior improvements(P＜0.01).(4)Serum SP,GAS,and MLT levels increased in both groups(P＜0.05),with more pronounced elevations in the study group(P＜0.01).(5)Gut microbiota analysis revealed decreased levels of Enterococcus and Enterobacter(P＜0.05)and increased levels of Bifidobacterium and Lactobacillus(P＜0.05)in both groups,with the study group showing significantly greater modulation(P＜0.01).(6)The 5-HT pathway activation(serum 5-HT,5-HT3R/5-HT4R expression)was enhanced in both groups(P＜0.05),more markedly in the study group(P＜0.01).(7)No adverse events or abnormal liver/renal function were observed.Conclusion Yunpi Runtong Formula combined with lactulose effectively alleviates FC symptoms,improves defecation patterns,gastrointestinal function,and gut microbiota,likely via 5-HT pathway activation,with high safety.

Objective To investigate the effect of long non-coding RNA,LINC00839,on the malignant biological behavior of endome-trial cancer(EC)cells via regulating miR-625-5p/MSI1 axis.Methods The expression of LINC00839,miR-625-5p,and MSI1 mRNA in EC tissues and cells was detected by real-time quantitative PCR.Ishikawa cells were selected,and bioinformatics,dual-luciferase reporter gene assay,and RNA-binding protein immunoprecipitation assay were performed to verify the targeting relationship between LINC00839,MSI1,and miR-625-5p.CCK-8,colony formation assay,flow cytometry,and Transwell assay were performed to detect cell proliferation,apoptosis,migration,and invasion.Western blotting was used to detect the expression of MSI1,Bcl-2,Bax,MMP-2,and MMP-9 protein.In vivo tumor formation experiments were conducted to verify the effect of LINC00839 on transplanted tumors in nude mice.Results The expression of LINC00839 and MSI1 mRNA in EC tissues was higher,whereas the expression of miR-625-5p was lower(P＜0.05).LINC00839 and MSI1 targeted miR-625-5p.LINC00839 knockdown or miR-625-5p overexpression suppressed malignant behavior of cells(P＜0.05).Inhibition of miR-625-5p expression or overexpression of MSI1 reversed the inhibitory effect of LINC00839 knockdown or miR-625-5p overexpression on the malignant behavior of cells(P＜0.05).LINC00839 knockdown decreased the volume and mass of transplanted tumors,increased the expression of miR-625-5p,and inhibited the expression of MSI1.Conclusion LINC00839 can target the miR-625-5p/MSI1 axis and regulate the proliferation,apoptosis,migration,and invasion of EC cells.

AIM: To investigate the prognostic factors of idiopathic choroidal neovascularization treated with anti-vascular endothelial growth factor(VEGF)drugs and construct predictive model.METHODS:A total of 57 patients(57 eyes)with idiopathic choroidal neovascularization who received the treatment of anti-VEGF in our hospital from January 2020 to June 2023 were retrospectively included and grouped according to regression or recurrence of the disease. Univariate and multivariate analysis was performed on the influencing factor of regression or recurrence of idiopathic choroidal neovascularization lesions treated with anti-VEGF drugs. Clinical prediction model was constructed for the regression of idiopathic choroidal neovascularization lesions treated with anti-VEGF drugs.RESULTS:After treatment, the lesions disappeared in 17 eyes and recurred in 13 eyes, with incidence rates of 30% and 23%, respectively. The results of univariate analysis showed that the course of disease, baseline best corrected visual acuity, and baseline macular fovea retinal thickness may all be related to the regression or recurrence of idiopathic choroidal neovascularization lesions treated with anti-VEGF drugs(all P<0.05). Logistic multivariate analysis showed that the course of the disease, baseline best corrected visual acuity level, and baseline macular fovea retinal thickness may all be related to the regression of idiopathic choroidal neovascularization treated with anti-VEGF drugs(all P<0.05), while those factors were not related to the recurrence of idiopathic choroidal neovascularization treated with anti-VEGF drugs(all P>0.05). The influencing factors of the regression model and the P-value prediction probability were used to predict the regression of idiopathic choroidal neovascular lesions treated with anti-VEGF drugs, and the Youden index was 83.00%, 75.74%, 45.47% and 85.00%, respectively.CONCLUSION:The regression of idiopathic choroidal neovascularization treated with anti-VEGF drugs was closely related to the course of disease, baseline best corrected visual acuity level and baseline macular foveal retinal thickness, while the risk of recurrence has not been determined by corresponding influencing factors. The data model constructed by the above three factors has shown good efficiency in predicting the regression of patients with idiopathic choroidal neovascularization lesions treated with anti-VEGF drugs.

Antibodies, Neutralizing/immunology* ; Antibodies, Viral/immunology* ; COVID-19/virology* ; COVID-19 Vaccines/immunology* ; Humans ; SARS-CoV-2/pathogenicity* ; Spike Glycoprotein, Coronavirus/immunology* ; Vaccines, Inactivated/immunology*

Objective:To investigate the expression of eukaryotic translation initiation 2α (p-elF2α) and activated translation factor 4 (ATF4) in liver tissues of patients with chronic hepatitis B and their correlation with liver fibrosis.Methods:From Jan.2016 to Jan.2019, 158 cases of chronic hepatitis B patients were enrolled in our hospital. The expression levels of p-elF2α and ATF4 in different stages of liver fibrosis were evaluated by hematoxy-eosin (HE) and immunohistochemical staining, and the correlation was analyzed by Spearman rank correlation.Results:The pathological results of liver specimens showed that there were 19 normal controls (S0), 29 S1, 42 S2, 35 S3 and 33 S4 in each stage of fibrosis. The levels of p-eIF2α and ATF4 in fibrosis group were significantly higher than those in normal control group ( P< 0.001). Additionally, the levels of p-eIF2α and ATF4 in different stages of fibrosis were significantly different. The grade of hepatic fibrosis was positively correlated with the scores of p-eIF2α and ATF4 staining in liver tissues, and the correlation coefficients were 0.473 and 0.422 respectively ( P< 0.05). Conclusions:Hepatic fibrosis in patients with chronic hepatitis B is positively correlated with p-eIF2α and ATF4. p-eIF2α-ATF4 pathway may involve in the process of chronic hepatitis B-induced hepatic fibrosis.

Objective: To explore the genes that may be regulated by cell division cycle 25A (CDC25A) with gene chip technology, and to elucidate and verify that CDC25A has a regulatory effect on the expression of liver cancer related genes. Methods: CDC25A expression in human liver cancer HepG2 cells was silenced by siRNA interference technology and a nude mouse xenograft model of liver cancer was successfully constructed in our previous research. Affymetrix human gene expression profiling microarray was used to further screen differentially expressed genes (DEGs) after silencing CDC25A in liver cancer xenografts, and GO analysis and KEGG analysis were performed. Some of the DEGs were verified by qPCR. Results: The chip screened 188 DEGs in liver cancer xenograft tissues after CDC25A silence, including 78 up-regulated genes and 110 down-regulated genes. These DEGs mainly involved in cell proliferation, apoptosis, protein complex binding, extracellular space, etc., and associated with the changes in pathways such as focal adhesions and extracellular matrix (ECM) receptor interactions. qPCR showed that the expression of HIPK2 mRNA was up-regulated and the mRNA expressions of (microfibrillar-associated protein 5(MFAP5) and cyclin D1 (CCND1) were down-regulated, which were consistent with the results of microarray detection. Conclusion: Using human gene expression profiling chip, the DEGs in liver cancer xenograft tissues in nude mice after silencing CDC25Awere successfully screened, providing effective clues for exploring the effect of CDC25Aon the growth of liver cancer.

Glaucoma is the leading cause of irreversible blindness, but its early symptoms are not obvious and are easily overlooked, so early screening for glaucoma is particularly important. The cup to disc ratio is an important indicator for clinical glaucoma screening, and accurate segmentation of the optic cup and disc is the key to calculating the cup to disc ratio. In this paper, a full convolutional neural network with residual multi-scale convolution module was proposed for the optic cup and disc segmentation. First, the fundus image was contrast enhanced and polar transformation was introduced. Subsequently, W-Net was used as the backbone network, which replaced the standard convolution unit with the residual multi-scale full convolution module, the input port was added to the image pyramid to construct the multi-scale input, and the side output layer was used as the early classifier to generate the local prediction output. Finally, a new multi-tag loss function was proposed to guide network segmentation. The mean intersection over union of the optic cup and disc segmentation in the REFUGE dataset was 0.904 0 and 0.955 3 respectively, and the overlapping error was 0.178 0 and 0.066 5 respectively. The results show that this method not only realizes the joint segmentation of cup and disc, but also improves the segmentation accuracy effectively, which could be helpful for the promotion of large-scale early glaucoma screening.
Diagnostic Techniques, Ophthalmological ; Fundus Oculi ; Glaucoma/diagnostic imaging* ; Humans ; Neural Networks, Computer ; Optic Disk/diagnostic imaging*

Objective: To explore the effect of working memory intervention training on working memory and literacy of children with developmental dyslexia,so as to provide a preference for practice of the trianing of working memory among children with dyslexia. Methods: A total of 32 children with dyslexia of grade 3-5 in a primary school in Guiyang were randomly divided into two groups: the study group (n=16) and the control group (n=16),and the software of training exercises of working memory was applied to conduct interventional trainings of different durations to 2 gruops of children. Results: Through the intervention training of working memory, the scores of literacy and working memory tasks in the study group (2 217.88±252.32, 105.13±7.68) were significantly higher than those in the control group (1 907.69 ± 545.15, 96.50 ± 11.04) (t=2.06, 2.56, P<0.05). Conclusion The working memory ability of children with dyslexia can be improved by working memory intervention training for a certain period of time. The intervention effect is not only significant in the trained working memory task, but also can be extended to other untrained contents such as literacy.