ObjectiveTo investigate how vitamin B₁₂ eye drops regulate MMP-9 and TNF-α expression levels in the corneas of dry eye disease （DED） mouse model induced by a combination of an artificially simulated dry environment （air humidity 30%） and subcutaneous injection of hyoscine hydrobromide. MethodsFifty C57BL/6 female mice were used in the study. 10 mice formed A group （blank control）， while the remaining 40 mice were subjected to dry eye disease induction through subcutaneous injection of scopolamine hydrobromide in a controlled environment with 30% air humidity. All mice underwent schirmer I test （SIT）， tear break-up time （TBUT）， and corneal fluorescence staining score（CFS）evaluations. Mice meeting modeling criteria were randomly assigned to three groups： B group （model group）， C group （PBS control）， and D group （vitamin B₁₂ group）. 0， 7， 14， and 21 days after treatment， each group received TBUT， SIT， CFS， and corneal inflammation assessments. Macroscopic analysis evaluated the efficacy of vitamin B₁₂ eye drops in treating dry eye. After 21 days of treatment， all mice were euthanized via cervical dislocation and their corneas analyzed using HE staining to examine morphological changes. ELISA and immunohistochemical methods were employed to detect MMP-9 and TNF-α expression levels in corneal tissues across groups. ResultsIn dry environments （air humidity 30%）， subcutaneous injection of scopolamine hydrobromide induced changes in dry eye-related indicators in mice： SIT significantly decreased， TBUT significantly shortened， corneal fluorescein staining increased， and CFS all significantly elevated （P 0.05）， indicating successful establishment of the dry eye model. A total of 30 dry eye mice were enrolled. When the dry eye model was successfully established without drug intervention， no statistically significant differences were observed between B group， C group and D group in terms of TBUT， SIT， corneal fluorescein staining， or CFS. Compared with A group， B group， C group and D group showed statistically significant differences in reduced SIT， shortened TBUT， increased corneal fluorescein staining， and elevated CFS （P 0.05）. After drug intervention， D group （vitamin B₁₂ group） exhibited significantly increased SIT， prolonged TBUT， reduced corneal fluorescein staining， clearer corneas， decreased fluorescein staining， and lower CFS compared with B and C groups（P 0.05）. ELISA and immunohistochemical staining results showed that compared with A group， B and C groups exhibited significantly increased expression of MMP-9 and TNF-α in corneal tissues （P 0.05）. D group showed decreased expression of MMP-9 and TNF-α compared with B and C groups but remained higher than A group （P 0.05）. ConclusionThe expression of MMP-9 and TNF-α in the corneal tissues of mice with dry eye is elevated， suggesting that both inflammatory factors， MMP-9 and TNF-α， are involved in the development of dry eye. Vitamin B₁₂ eye drops may improve the symptoms of ocular surface discomfort by promoting the repair of the corneal epithelium. Vitamin B₁₂ eye drops may increase tear secretion， prolong tear film break up time， reduce corneal fluorescein staining， and alleviate the inflammatory reaction of the cornea by decreasing the expression of MMP-9 and TNF-α in the corneal tissues of the mice， thus playing a therapeutic role in the treatment of dry eye disease.

Objective:To explore the mediating effect of disease uncertainty on cancer-related fatigue and quality of life in postoperative thyroid cancer patients, and to provide assistance for health management of thyroid cancer patients.Methods:From January 2023 to June 2024, thyroid cancer patients who underwent surgical treatment in Xiang′an Hospital of Xiamen University were selected by convenience sampling method. Conduct a survey using The general information questionnaire, Cancer Quality of Life for Thyroid Cancer 34, Cancer Fatigue Scale, and Mishel Uncertainty in Illness Scale were used to conduct cross-sectional investigation. SPSS 22.0 was used to statistically analyze the relationship between the three factors, and AMOS 24.0 software was used to establish a structural equation model to analyze the mediating effect of disease uncertainty on cancer-related fatigue and quality of life in postoperative thyroid cancer patients.Results:Finally, 495 valid questionnaires were ultimately collected. Among 495 postoperative patients with thyroid cancer, there were 135 males and 360 females, with an age of (39.58 ± 12.97) years old. The uncertainty score of postoperative thyroid cancer patients was (60.98 ± 11.61) points, cancer-related fatigue score was (42.85 ± 7.35) points, and quality of life score was (57.51 ± 9.81) points. Pearson correlation analysis showed that cancer-related fatigue was positively correlated with disease uncertainty ( r=0.392, P<0.01) and negatively correlated with quality of life ( r=-0.465, P<0.01). Disease uncertainty was negatively correlated with quality of life ( r=-0.378, P<0.01). Disease uncertainty partially mediated the relationship between cancer-related fatigue and quality of life in postoperative thyroid cancer patients, with a mediation effect value of -0.14, accounting for 32.56% of the total effect. Conclusions:The disease uncertainty score and the quality of life score of postoperative thyroid cancer patients were at a moderate level, the cancer-related fatigue score was at an upper moderate level. Disease uncertainty is an important mediating variable between cancer-related fatigue and quality of life in postoperative thyroid cancer patients. Improving disease uncertainty in postoperative thyroid cancer patients can reduce cancer-related fatigue and improve their quality of life.

Periodontitis is a chronic inflammatory disease primarily triggered by dysregulation of microbial communities and altered host immune response.It is clinically presented by alveolar bone resorption,which is one of the main causes of loosening of teeth and tooth loss.Cathepsin K(CTSK)is a highly expressed collagenase produced by osteo-clasts and can directly degrade matrix collagen proteins and indirectly increase osteoclast activity.The expression level of CTSK fluctuates in response to the progression of periodontal inflammation.The expression of Toll-like receptors is upregu-lated in periodontitis lesions.Pathogen-associated molecular pattern binds to relevant TLRs,initiating downstream im-mune pathways that promote receptor activator of nuclear factor-κB ligand-dependent osteoclastogenesis,along with in-creased expression of CTSK.Intervening in the process of alveolar bone resorption can be achieved through the regulation of CTSK.This paper provides a summary of the pathogenic mechanism of CTSK in periodontitis and highlights the research progress regarding the use of CTSK as a therapeutic target.The aim is to offer insights and references for the treatment of periodontitis.

Objective:To explore the mediating effect of disease uncertainty on cancer-related fatigue and quality of life in postoperative thyroid cancer patients, and to provide assistance for health management of thyroid cancer patients.Methods:From January 2023 to June 2024, thyroid cancer patients who underwent surgical treatment in Xiang′an Hospital of Xiamen University were selected by convenience sampling method. Conduct a survey using The general information questionnaire, Cancer Quality of Life for Thyroid Cancer 34, Cancer Fatigue Scale, and Mishel Uncertainty in Illness Scale were used to conduct cross-sectional investigation. SPSS 22.0 was used to statistically analyze the relationship between the three factors, and AMOS 24.0 software was used to establish a structural equation model to analyze the mediating effect of disease uncertainty on cancer-related fatigue and quality of life in postoperative thyroid cancer patients.Results:Finally, 495 valid questionnaires were ultimately collected. Among 495 postoperative patients with thyroid cancer, there were 135 males and 360 females, with an age of (39.58 ± 12.97) years old. The uncertainty score of postoperative thyroid cancer patients was (60.98 ± 11.61) points, cancer-related fatigue score was (42.85 ± 7.35) points, and quality of life score was (57.51 ± 9.81) points. Pearson correlation analysis showed that cancer-related fatigue was positively correlated with disease uncertainty ( r=0.392, P<0.01) and negatively correlated with quality of life ( r=-0.465, P<0.01). Disease uncertainty was negatively correlated with quality of life ( r=-0.378, P<0.01). Disease uncertainty partially mediated the relationship between cancer-related fatigue and quality of life in postoperative thyroid cancer patients, with a mediation effect value of -0.14, accounting for 32.56% of the total effect. Conclusions:The disease uncertainty score and the quality of life score of postoperative thyroid cancer patients were at a moderate level, the cancer-related fatigue score was at an upper moderate level. Disease uncertainty is an important mediating variable between cancer-related fatigue and quality of life in postoperative thyroid cancer patients. Improving disease uncertainty in postoperative thyroid cancer patients can reduce cancer-related fatigue and improve their quality of life.

Periodontitis is a chronic inflammatory disease primarily triggered by dysregulation of microbial communities and altered host immune response.It is clinically presented by alveolar bone resorption,which is one of the main causes of loosening of teeth and tooth loss.Cathepsin K(CTSK)is a highly expressed collagenase produced by osteo-clasts and can directly degrade matrix collagen proteins and indirectly increase osteoclast activity.The expression level of CTSK fluctuates in response to the progression of periodontal inflammation.The expression of Toll-like receptors is upregu-lated in periodontitis lesions.Pathogen-associated molecular pattern binds to relevant TLRs,initiating downstream im-mune pathways that promote receptor activator of nuclear factor-κB ligand-dependent osteoclastogenesis,along with in-creased expression of CTSK.Intervening in the process of alveolar bone resorption can be achieved through the regulation of CTSK.This paper provides a summary of the pathogenic mechanism of CTSK in periodontitis and highlights the research progress regarding the use of CTSK as a therapeutic target.The aim is to offer insights and references for the treatment of periodontitis.

Objective:To explore the effect of "Internet plus" exercise prescription intervention on upper limb dysfunction and quality of life of breast cancer patients at home after surgery, so as to provide reference for health management of breast cancer patients after surgery.Methods:Adopting a prospective randomized controlled trial research method. From November 2021 to January 2023, 124 breast cancer patients in the breast and thyroid surgery department of Xiang′an Hospital Affiliated to Xiamen University were selected for the study. According to the random number table method, they were randomly divided into an intervention group (62 cases) and a control group (62 cases). The control group patients were given routine training, and the intervention group patients received routine training in the first four weeks after operation, and "Internet plus" exercise prescription intervention in the fifth week after operation. The upper limb dysfunction, quality of life before and after the intervention and motor compliance after the intervention between the two groups were compared.Results:A total of 117 patients were ultimately included, and they were all female, with 58 patients in the intervention group aged (51.01 ± 9.77) years old and 59 patients in the control group aged (51.47 ± 9.85) years old. There was no statistically significant difference in upper limb dysfunction and quality of life between the two groups of patients before intervention ( P>0.05). After the intervention, the degree of upper limb dysfunction in the intervention group was (63.55 ± 7.02) points, which were lower than that in the control group (67.13 ± 7.25) points, and the difference was statistically significant ( t = 2.71, P<0.01). After the intervention, the total score of quality of life and the scores of physiological status, social/family status, emotional status, functional status and additional attention of breast cancer patients in the intervention group were (115.27 ± 17.35), (22.65 ± 4.53), (22.79 ± 4.36), (20.96 ± 3.95), (19.56 ± 4.22), (29.31 ± 5.24) points, which were higher than those in the control group (104.28 ± 17.04), (20.57 ± 4.48), (20.85 ± 4.23), (18.75 ± 4.04), (17.18 ± 4.06), (26.93 ± 5.21) points, the differences were statistically significant ( t values were 2.44-3.46, all P<0.05). In terms of exercise compliance of breast cancer patients in the intervention group, the aerobic exercise completion rate was 91.38% (53/58), muscle strength training completion rate was 77.59% (45/58), stretching exercise completion rate was 86.21% (50/58), exercise frequency was (3.96 ± 1.13) times/week, exercise duration was (29.51 ± 7.64) min/time, which was superior to 77.97% (46/59), 57.63% (34/59), 69.49% (41/59), (3.38 ± 0.94) times/week, (23.96 ± 7.33) min/time in the control group, the differences were statistically significant ( χ2 = 4.04, 5.31, 4.73, t = 3.02, 4.01, all P<0.05). Conclusions:"Internet plus" exercise prescription intervention has the characteristics of convenience, intuition and strong operability, which is conducive to improving the upper limb dysfunction, quality of life and exercise compliance of breast cancer patients at home after surgery. It is recommended to be popularized and applied clinically.

Objective To explore the mechanism by which soybean isoflavone(SI)reduces calcium overload induced by cerebral ischemia-reperfusion(I/R).Methods Forty-eight SD rats were randomized into 4 groups to receive sham operation,cerebral middle artery occlusion for 2 h followed by 24 h of reperfusion(I/R model group),or injection of adeno-associated virus carrying Frizzled-2 siRNA or empty viral vector into the lateral cerebral ventricle after modeling.Western blotting was used to examine Frizzled-2 knockdown efficiency and changes in protein expressions in the Wnt/Ca2+signaling pathway.Calcium levels and pathological changes in the ischemic penumbra(IP)were measured using calcium chromogenic assay and HE staining,respectively.Another 72 SD randomly allocated for sham operation,I/R modeling,or soy isoflavones pretreatment before modeling were examined for regional cerebral blood flow using a Doppler flowmeter,and the cerebral infarct volume was assessed using TTC staining.Pathologies in the IP area were evaluated using HE and Nissl staining,and ROS level,Ca2+level,cell apoptosis,and intracellular calcium concentration were analyzed using immunofluorescence assay or flow cytometry;the protein expressions of Wnt5a,Frizzled-2,and P-CaMK II in the IP were detected with Western blotting and immunohistochemistry.Results In rats with cerebral I/R,Frizzled-2 knockdown significantly lowered calcium concentration(P<0.001)and the expression levels of Wnt5a,Frizzled-2,and P-CaMK II in the IP area.In soy isoflavones-pretreated rats,calcium concentration,ROS and MDA levels,cell apoptosis rate,cerebral infarct volume,and expression levels of Wnt/Ca2+signaling pathway-related proteins were all significantly lower while SOD level was higher than those in rats in I/R model group.Conclusion Soy isoflavones can mitigate calcium overload in rats with cerebral I/R by inhibiting the Wnt/Ca2+signaling pathway.

Objective To explore the mechanism by which soybean isoflavone(SI)reduces calcium overload induced by cerebral ischemia-reperfusion(I/R).Methods Forty-eight SD rats were randomized into 4 groups to receive sham operation,cerebral middle artery occlusion for 2 h followed by 24 h of reperfusion(I/R model group),or injection of adeno-associated virus carrying Frizzled-2 siRNA or empty viral vector into the lateral cerebral ventricle after modeling.Western blotting was used to examine Frizzled-2 knockdown efficiency and changes in protein expressions in the Wnt/Ca2+signaling pathway.Calcium levels and pathological changes in the ischemic penumbra(IP)were measured using calcium chromogenic assay and HE staining,respectively.Another 72 SD randomly allocated for sham operation,I/R modeling,or soy isoflavones pretreatment before modeling were examined for regional cerebral blood flow using a Doppler flowmeter,and the cerebral infarct volume was assessed using TTC staining.Pathologies in the IP area were evaluated using HE and Nissl staining,and ROS level,Ca2+level,cell apoptosis,and intracellular calcium concentration were analyzed using immunofluorescence assay or flow cytometry;the protein expressions of Wnt5a,Frizzled-2,and P-CaMK II in the IP were detected with Western blotting and immunohistochemistry.Results In rats with cerebral I/R,Frizzled-2 knockdown significantly lowered calcium concentration(P<0.001)and the expression levels of Wnt5a,Frizzled-2,and P-CaMK II in the IP area.In soy isoflavones-pretreated rats,calcium concentration,ROS and MDA levels,cell apoptosis rate,cerebral infarct volume,and expression levels of Wnt/Ca2+signaling pathway-related proteins were all significantly lower while SOD level was higher than those in rats in I/R model group.Conclusion Soy isoflavones can mitigate calcium overload in rats with cerebral I/R by inhibiting the Wnt/Ca2+signaling pathway.

Objective:To observe the inhibitory effect of lentivirus (LV)-mediated miR-191 on the proliferation and angiogenesis of human retinal vascular endothelial cells (hREC) cultured in vitro.Methods:The hREC cell lines were cultured in vitro and divided into control group, hypoxia group, LV-empty vector (LV-vector) group, and LV-miR-191 (LV-191) group. The LV-vector group and LV-191 group were transferred to the corresponding lentiviral vector respectively. Flow cytometry was used to detect cell transfection efficiency. Cell Counting Kit-8 (CCK-8) test was used to detect cell proliferation ability. Scarification test and invasion chamber (Transwell) test were used to detect cell migration ability. Matrigel test was used to detect cell lumen formation ability. Real-time quantitative polymerase chain reaction (qPCR) was used to detect the relative expression of miR-191 and relative mRNA expression of its downstream target genes p21, vascular endothelial growth factor (VEGF), cell division protein kinase (CDK) 6, cyclin-D1 (Cyclin D1). Independent sample t test was used for pairwise comparison. Results:The results of flow cytometry showed that the transfection efficiency of cells in the control group and the LV-191 group were 0.615% and 99.400%, respectively. The results of CCK-8, scarification, Transwell and Matrigel test showed that, compared with the control group, the number of cell proliferation ( t=6.130, 4.606), the cell mobility ( t=4.910, 6.702), the number of stained cells on the microporous membrane ( t=7.244, 6.724) and the lumen formation ability cells ( t=8.345, 9.859) were significantly increased in the hypoxia group and the LV-vector group ( P<0.01), while the LV-191 group showed completely opposite performance ( t=14.710, 6.245, 5.333, 5.892; P≤0.01). The qPCR test results showed that, compared with the control group and the LV-vector group, the relative expression of miR-191 mRNA in the cells of the LV-191 group was significantly up-regulated ( t=44.110, 42.680), the relative expression of Cyclin D1 mRNA ( t=29.940, 14.010) and CDK6 mRNA ( t=15.200, 7.645) decreased significantly, and the difference were statistically significant ( P<0.01); the relative expression of p21 mRNA increased, however, the difference was not statistically significant ( t=2.013, 2.755; P>0.05). There was no significant difference in the relative expression of VEGF mRNA in the 4 groups of cells ( F=0.966, P>0.05). Conclusions:LV-191 can inhibit the proliferation, migration and tubing of hREC by up-regulating p21 and down-regulating CDK6 and Cyclin D1.

Objective:To screening differentially expressed genes (DEGs) in proliferative diabetic retinopathy (DR) patients to provide new biological therapeutic targets for proliferative DR (PDR) therapy.Methods:A basic research. A total of 3 PDR patients (group PDR) and 3 non-diabetic patients (control group) were enrolled in the study in Tianjin Medical University Eye Hospital in October 2020. In addition, 40 cases of PDR and non-diabetic patients were selected and divided into PDR validation group and control validation group. Peripheral blood validation test was performed in PDR validation group and control validation group; RNA sequencing was performed in PDR group and control group. Transcriptomics (RNAseq) sequencing technology was used to screen DEG in PDR group and control group. The selected DEGs were analyzed by gene ontology (GO) function enrichment analysis, signal pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction network (PPI). The gene expression database was used to find the high-throughput data related to PDR, and multi queue comparison analysis was carried out. The target genes of differentially expressed miRNAs were predicted through targetscan platform, so as to clearly screen the correlation between DEG and PDR. Reverse transcription polymerase chain reaction and Western blot were used to verify the expression of DEG mRNA and protein related to PDR. The relative expression of PDR related DEG mRNA and protein between PDR validation group and control validation group were compared by paired t-test. Results:A total of 1 337 DEGs were screened by RNAseq sequencing in the peripheral blood of patients with PDR, of which 419 genes were up-regulated and 918 down-regulated. Among them, direct inhibitor of apoptosis protein-binding protein with low isoelectric point ( DIABLO), zinc finger and BTB domain containing 10 ( ZBTB10), polo-like kinases 3 ( PLK3), regulatory subunit 1 ( PIK3R1) and B cell translocation gene 3 (BTG3) were differentially expressed in PDR patients. The function of GO was enriched from the analysis of molecular function, biological process and cellular composition. The results showed that DIABLO, ZBTB10, PLK3, PIK3R1, BTG3 were involved in the pathological process related to PDR. KEGG enrichment analysis showed that glucose metabolic pathways such as extracellular matrix receptors, cytokine regulatory pathway, p53 signal pathway and galactose metabolism may be involved in the process of differential genes. The analysis of PPI protein interaction network showed that the larger the DEG-associated protein node, the greater the number of associated nodes. Among them, DIABLO, ZBTB10, PLK3, PIK3R1 and BTG3 played significant roles in the formation of the action network. By comparing and analyzing the existing high-throughput data related to diabetic retinopathy in Gene Expression Omnibus database and predicting by Targetscan platform, it was found that some significant differences in miRNA reported in aqueous humor, vitreous fluid and plasma of DR patients can be regulated by the differential genes found in this study. Compared with the control verification group, the relative expressions of DIABLO, ZBTB10, PLK3, PIK3R1 mRNA and protein in peripheral blood of the PDR verification group were up-regulated, and the relative expression of BTG3 mRNA and protein was down-regulated. Conclusion:DIABLO, ZBTB10, PLK3, PIK3R1 and BTG3 are DEGs in patients with PDR, and they can participate in the disease process by regulating the biological processes of cell proliferation, fibrosis and oxidative stress.