BACKGROUND:Studies have confirmed that up-regulation of microRNA-140 expression can partially inhibit osteoarthritis-like changes in knee cartilage tissues and cells and delay the progression of osteoarthritis,suggesting that microRNA-140 is involved in the pathogenesis of osteoarthritis.OBJECTIVE:To further analyze the mechanism of microRNA-140 involvement in osteoarthritis by loading exosomes overexpressing microRNA-140 with sodium alginate/collagen hydrogel.METHODS:Lentivirus was used to infect rat bone marrow mesenchymal stem cells to overexpress microRNA-140,then exosomes were isolated and exosomes overexpressing microRNA-140 were obtained.Sodium alginate/collagen hydrogels loaded with exosomes were prepared.Thirty-two SD rats were randomly divided into four groups,with 8 rats in each group.Normal control group did not receive any treatment.The osteoarthritis model was established by injecting sodium iodoacetate into the knee cavity in the osteoarthritis group,the non-transfected exosome group and the transfected exosome group.Two weeks later,PBS was injected into the knee cavity in the osteoarthritis group.Sodium alginate/collagen hydrogel carrying non-overexpressing microRNA-140 and overexpressing microRNA-140 exosomes were injected into the knee cavity of the non-transfected exosome group and transfected exosome group.At 6 weeks after modeling,the threshold of mechanical foot withdrawal response,the concentration of inflammatory factors in synovial fluid,the expression of chondrogen-related genes,the histological changes of knee cartilage and the expression of pyroptosis related proteins were detected in rats.RESULTS AND CONCLUSION:(1)Compared with normal control group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and Type Ⅱ collagen immunofluorescence intensity were decreased in the osteoarthritis group(P<0.05),and proinflammatory cytokine levels were increased in synovial fluid(P<0.05).The mRNA expressions of matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS-5)were increased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were increased(P<0.05).Immunofluorescence intensity of GSDMD and cleaved caspase-1 was increased(P<0.05),and cartilage tissue was severely damaged.(2)Compared with osteoarthritis group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and type Ⅱ collagen immunofluorescence intensity in the non-transfected and transfected exosome groups were increased(P<0.05);proinflammatory cytokine levels were decreased in synovial fluid(P<0.05).The mRNA expression of matrix metalloproteinase 13 was decreased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were decreased(P<0.05).The immunofluorescence intensity of GSDMD and cleaved caspase-1 decreased(P<0.05),and the cartilage tissue damage was reduced(P<0.05),and the effect was stronger in the transfected exosome group.(3)These results conclude that microRNA-140 can reduce the pain response of rats with osteoarthritis by inhibiting inflammation,maintaining cartilage homeostasis,and inhibiting cartilaginous pyroptosis,thereby reducing cartilage damage and playing a therapeutic role in osteoarthritis.

Objective:To investigate the expression and clinical significance of non coding RNA GATA binding protein 6 antisense RNA1 (lncRNA GATA6-AS1) and GATA binding protein 6 messenger RNA (GATA6 mRNA) in ovarian cancer.Methods:A prospective study was conducted on 98 patients with ovarian cancer treated at the Second Hospital of Tianjin Medical University, from January 2022 to January 2025, and 98 patients with benign ovarian lesions during the same period were selected as the control group. Real-time quantitative polymerase chain reaction (qPCR) was used to detect the serum and tissue expression levels of lncRNA GATA6-AS1 and GATA6 mRNA in patients with ovarian cancer and benign ovarian lesions. Pearson analysis was performed to assess the correlation between serum lncRNA GATA6-AS1 and GATA6 mRNA levels in patients with ovarian cancer. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic value of serum lncRNA GATA6-AS1 and GATA6 mRNA levels in patients with ovarian cancer.Results:Compared with the control group, the serum levels of lncRNA GATA6-AS1 and GATA6 mRNA in the study group were decreased: 0.76 ± 0.18 vs. 1.00 ± 0.22, 0.75 ± 0.19 vs. 1.01 ± 0.21, with statistically significant differences ( P<0.05). Pearson analysis revealed a positive correlation between serum lncRNA GATA6-AS1 and GATA6 mRNA levels in the study group ( r = 0.61, P<0.05). Compared with benign ovarian lesion tissues, the expression levels of lncRNA GATA6-AS1 and GATA6 mRNA in ovarian cancer tissues were reduced: 0.65 ± 0.15 vs. 1.01 ± 0.20, 0.59 ± 0.12 vs. 1.01 ± 0.24, with statistically significant differences ( P<0.05). In serous ovarian cancer tissues, the expression levels of lncRNA GATA6-AS1 and GATA6 mRNA were lower than those in mucinous ovarian cancer tissues: 0.61 ± 0.10 vs. 0.77 ± 0.16, 0.54 ± 0.11 vs. 0.74 ± 0.14, with statistically significant differences ( P<0.05). The expression of lncRNA GATA6-AS1 and GATA6 mRNA in ovarian cancer tissues was associated with tumor size, International Federation of Gynecology and Obstetrics stage, differentiation degree, lymph node metastasis, peritoneal metastasis, and ascites ( P<0.05). The ROC curve indicated that the combined diagnosis of serum lncRNA GATA6-AS1 and GATA6 mRNA for ovarian cancer had an area under the curve (AUC) of 0.905, which was significantly higher than that of lncRNA GATA6-AS1 alone ( Z = 2.45, P = 0.014) and GATA6 mRNA alone ( Z = 2.16, P = 0.031). Conclusions:The lncRNA GATA6-AS1 and GATA6 mRNA in serum and tissue of ovarian cancer patients decrease, showing a positive correlation. The joint of the two has high diagnostic value for ovarian cancer.

Objective:To investigate the expression and clinical significance of non coding RNA GATA binding protein 6 antisense RNA1 (lncRNA GATA6-AS1) and GATA binding protein 6 messenger RNA (GATA6 mRNA) in ovarian cancer.Methods:A prospective study was conducted on 98 patients with ovarian cancer treated at the Second Hospital of Tianjin Medical University, from January 2022 to January 2025, and 98 patients with benign ovarian lesions during the same period were selected as the control group. Real-time quantitative polymerase chain reaction (qPCR) was used to detect the serum and tissue expression levels of lncRNA GATA6-AS1 and GATA6 mRNA in patients with ovarian cancer and benign ovarian lesions. Pearson analysis was performed to assess the correlation between serum lncRNA GATA6-AS1 and GATA6 mRNA levels in patients with ovarian cancer. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic value of serum lncRNA GATA6-AS1 and GATA6 mRNA levels in patients with ovarian cancer.Results:Compared with the control group, the serum levels of lncRNA GATA6-AS1 and GATA6 mRNA in the study group were decreased: 0.76 ± 0.18 vs. 1.00 ± 0.22, 0.75 ± 0.19 vs. 1.01 ± 0.21, with statistically significant differences ( P<0.05). Pearson analysis revealed a positive correlation between serum lncRNA GATA6-AS1 and GATA6 mRNA levels in the study group ( r = 0.61, P<0.05). Compared with benign ovarian lesion tissues, the expression levels of lncRNA GATA6-AS1 and GATA6 mRNA in ovarian cancer tissues were reduced: 0.65 ± 0.15 vs. 1.01 ± 0.20, 0.59 ± 0.12 vs. 1.01 ± 0.24, with statistically significant differences ( P<0.05). In serous ovarian cancer tissues, the expression levels of lncRNA GATA6-AS1 and GATA6 mRNA were lower than those in mucinous ovarian cancer tissues: 0.61 ± 0.10 vs. 0.77 ± 0.16, 0.54 ± 0.11 vs. 0.74 ± 0.14, with statistically significant differences ( P<0.05). The expression of lncRNA GATA6-AS1 and GATA6 mRNA in ovarian cancer tissues was associated with tumor size, International Federation of Gynecology and Obstetrics stage, differentiation degree, lymph node metastasis, peritoneal metastasis, and ascites ( P<0.05). The ROC curve indicated that the combined diagnosis of serum lncRNA GATA6-AS1 and GATA6 mRNA for ovarian cancer had an area under the curve (AUC) of 0.905, which was significantly higher than that of lncRNA GATA6-AS1 alone ( Z = 2.45, P = 0.014) and GATA6 mRNA alone ( Z = 2.16, P = 0.031). Conclusions:The lncRNA GATA6-AS1 and GATA6 mRNA in serum and tissue of ovarian cancer patients decrease, showing a positive correlation. The joint of the two has high diagnostic value for ovarian cancer.

BACKGROUND:Studies have confirmed that up-regulation of microRNA-140 expression can partially inhibit osteoarthritis-like changes in knee cartilage tissues and cells and delay the progression of osteoarthritis,suggesting that microRNA-140 is involved in the pathogenesis of osteoarthritis.OBJECTIVE:To further analyze the mechanism of microRNA-140 involvement in osteoarthritis by loading exosomes overexpressing microRNA-140 with sodium alginate/collagen hydrogel.METHODS:Lentivirus was used to infect rat bone marrow mesenchymal stem cells to overexpress microRNA-140,then exosomes were isolated and exosomes overexpressing microRNA-140 were obtained.Sodium alginate/collagen hydrogels loaded with exosomes were prepared.Thirty-two SD rats were randomly divided into four groups,with 8 rats in each group.Normal control group did not receive any treatment.The osteoarthritis model was established by injecting sodium iodoacetate into the knee cavity in the osteoarthritis group,the non-transfected exosome group and the transfected exosome group.Two weeks later,PBS was injected into the knee cavity in the osteoarthritis group.Sodium alginate/collagen hydrogel carrying non-overexpressing microRNA-140 and overexpressing microRNA-140 exosomes were injected into the knee cavity of the non-transfected exosome group and transfected exosome group.At 6 weeks after modeling,the threshold of mechanical foot withdrawal response,the concentration of inflammatory factors in synovial fluid,the expression of chondrogen-related genes,the histological changes of knee cartilage and the expression of pyroptosis related proteins were detected in rats.RESULTS AND CONCLUSION:(1)Compared with normal control group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and Type Ⅱ collagen immunofluorescence intensity were decreased in the osteoarthritis group(P<0.05),and proinflammatory cytokine levels were increased in synovial fluid(P<0.05).The mRNA expressions of matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS-5)were increased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were increased(P<0.05).Immunofluorescence intensity of GSDMD and cleaved caspase-1 was increased(P<0.05),and cartilage tissue was severely damaged.(2)Compared with osteoarthritis group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and type Ⅱ collagen immunofluorescence intensity in the non-transfected and transfected exosome groups were increased(P<0.05);proinflammatory cytokine levels were decreased in synovial fluid(P<0.05).The mRNA expression of matrix metalloproteinase 13 was decreased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were decreased(P<0.05).The immunofluorescence intensity of GSDMD and cleaved caspase-1 decreased(P<0.05),and the cartilage tissue damage was reduced(P<0.05),and the effect was stronger in the transfected exosome group.(3)These results conclude that microRNA-140 can reduce the pain response of rats with osteoarthritis by inhibiting inflammation,maintaining cartilage homeostasis,and inhibiting cartilaginous pyroptosis,thereby reducing cartilage damage and playing a therapeutic role in osteoarthritis.

Objective:To identify the trajectory of fatigue-related symptom clusters(fatigue-decreased appetite-pain)in patients with lung cancer receiving immunotherapy and their influencing factors.Methods:From March 2022 to March 2023,114 patients with lung cancer receiving immunotherapy for the first time in Fudan University Shanghai Cancer Center were selected as research subjects.A 6-month longitudinal follow-up was performed using the PRO-CTCAE-based subset for lung cancer immunotherapy,and the demographic,disease physiological,psychological,social and healthy lifestyle data of patients were collected before the first dose.Growth mixed model and logistic regression analysis were used to identify the trajectory categories and influencing factors of fatigue-related symptom clusters.Results:Two fatigue trajectories of patients with lung cancer receiving immunotherapy were identified,named"mild to moderate fatigue persistent group"and"mild fatigue production-relief group".Three trajectories of decreased appetite were identified and named"decreased appetite aggravation group","mild decreased appetite maintenance group"and"decreased appetite exacerbation-relief group".Three trajectories of pain were identified,named"mild pain relief group","mild pain maintenance group"and"mild to moderate pain aggravation group".Logistic regression analysis showed that the age(OR=1.076,P=0.015)and targeted therapy(OR=10.743,P=0.009)were influential factors for fatigue.Duration of disease(OR=0.112,P=0.015),pemetrexed(OR=3.210,P=0.027)and targeted therapy(OR=7.077,P=0.032)were influential factors for pain.No influencing factors for decreased appetite have been identified.Conclusion:There is variability in the trajectory of symptom change in the fatigue-related symptom cluster in patients receiving immunotherapy for lung cancer.A small number of patients showed a trend of persistent worsening of appetite loss and pain.Future studies may continue to analyze intervention nodes based on symptom profile categories and help healthcare professionals identify key populations through influencing factors to provide personalized and holistic symptom management for patients with lung cancer receiving immunotherapy.

Objective:To identify the trajectory of fatigue-related symptom clusters(fatigue-decreased appetite-pain)in patients with lung cancer receiving immunotherapy and their influencing factors.Methods:From March 2022 to March 2023,114 patients with lung cancer receiving immunotherapy for the first time in Fudan University Shanghai Cancer Center were selected as research subjects.A 6-month longitudinal follow-up was performed using the PRO-CTCAE-based subset for lung cancer immunotherapy,and the demographic,disease physiological,psychological,social and healthy lifestyle data of patients were collected before the first dose.Growth mixed model and logistic regression analysis were used to identify the trajectory categories and influencing factors of fatigue-related symptom clusters.Results:Two fatigue trajectories of patients with lung cancer receiving immunotherapy were identified,named"mild to moderate fatigue persistent group"and"mild fatigue production-relief group".Three trajectories of decreased appetite were identified and named"decreased appetite aggravation group","mild decreased appetite maintenance group"and"decreased appetite exacerbation-relief group".Three trajectories of pain were identified,named"mild pain relief group","mild pain maintenance group"and"mild to moderate pain aggravation group".Logistic regression analysis showed that the age(OR=1.076,P=0.015)and targeted therapy(OR=10.743,P=0.009)were influential factors for fatigue.Duration of disease(OR=0.112,P=0.015),pemetrexed(OR=3.210,P=0.027)and targeted therapy(OR=7.077,P=0.032)were influential factors for pain.No influencing factors for decreased appetite have been identified.Conclusion:There is variability in the trajectory of symptom change in the fatigue-related symptom cluster in patients receiving immunotherapy for lung cancer.A small number of patients showed a trend of persistent worsening of appetite loss and pain.Future studies may continue to analyze intervention nodes based on symptom profile categories and help healthcare professionals identify key populations through influencing factors to provide personalized and holistic symptom management for patients with lung cancer receiving immunotherapy.

Infant, Newborn ; Humans ; Retrospective Studies ; Case-Control Studies ; Tracheotomy ; Respiration, Artificial

Objective:To promote evidence-based practice in the pre-chemotherapy nursing assessment among adult cancer patients.Methods:The Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice audit tools were used. The project was conducted in Shanghai Cancer Center of Fudan University from May to October 2018, 12 audit criteria were developed in the program including nursing training, patient medical and allergic history, medical diagnosis, lab data and so on.Results:A baseline audit of pre-chemotherapy nursing assessment among adult cancer patients was conducted, with a sample size of 68 patients and 36 nursing staff, during this stage, the compliance of audit 11 and 12 were 100%. After the implementation of systematic strategies, a follow-up audit involving similar sample as first audit was conducted using the same audit criteria. In the follow-up audit, except criterion 4 and 10, the compliance of the remaining 8 criteria had significantly improved, and χ2 value was 10.29-132.06, P<0.01. The result of history adverse reaction in the follow-up audit showed that among 68 patients, 3 had experienced chemotherapy infusion reactions in the past (The drugs were oxaliplatin, gemcitabine and paclitaxel), 39 had chemotherapy-related symptoms before admission (most of them were relieved at admission), of which the top five were loss of appetite, fatigue, nausea, neurotoxicity and vomiting. Conclusions:The aims of the project were fulfilled. We achieved increased compliance with evidence-based best practice recommended by JBI in most of audit criteria. Further audit will need to be carried out to improve the validity and quality of nursing assessment.

[摘 要] 目的：探讨敲减中心体相关激酶2（never in mitosis A-related kinase 2，NEK2）对结直肠癌细胞5-FU化疗敏感性的影响及其可能的机制。方法：采用qPCR和Western blotting检测结直肠癌细胞中NEK2 mRNA及蛋白的表达水平。构建针对NEK2基因的小干扰RNA（siRNA）并转染至结直肠癌细胞HCT116及SW620，实验分为阳性干扰组1（转染NEK2 siRNA1）、阳性干扰组2（转染NEK2 siRNA2）和阴性对照组（转染si-NC），均用5-FU处理。采用CCK-8实验、V-FICT/PI Annexin双染色流式细胞术实验观察敲减NEK2基因对5-FU作用下结肠癌细胞的增殖、周期分布及凋亡的影响，采用Western blotting检测敲减NEK2基因对5-FU作用下结直肠癌细胞内Wnt/β-catenin信号通路相关蛋白表达的影响。结果：NEK2蛋白及mRNA在结直肠癌细胞HCT116、SW620中均呈高表达（P<0.05或P<0.01），转染NEK2 siRNA可高效抑制HCT116、SW620细胞中NEK2蛋白及mRNA表达（均P<0.01）。经不同浓度5-FU作用后，阳性干扰组1和阳性干扰组2的细胞存活率和IC50均显著低于阴性对照组（均P<0.01），细胞发生G0/G1期阻滞且凋亡率显著升高（均P<0.01），胞核β-catenin、c-myc和cyclin D1表达水平显著下降而胞质β-catenin表达水平升高（均P<0.01）。结论：敲减NEK2基因可有效提高人结直肠癌细胞对5-FU的化疗敏感性，该作用可能是通过调控Wnt/β-catenin信号通路相关蛋白表达来实现的。

To explore the role of progesterone in the pathogenesis and development of hemangioma in nude mice.
 Methods: The hemangioma model was established. Progesterone was injected intramuscularly at different doses (0.2, 0.4, and 0.8 mg/d) for one week. Camellia oil (0.4 mL/d) was injected intramuscularly as control. The size of hemangioma was observed dynamically. The subcutaneous implants were harvested on the 14th and 28th days. The expression of vascular endothelial growth factor in the tumor tissues were evaluated using immunohistochemistry and microvessel density (MVD) was counted under the microscope.
 Results: On the 14th day, the expression of vascular endothelial growth factor (P<0.01 and P<0.05, respectively) was higher, the volume of tumors (All P<0.01) and MVD (All P<0.01) were greater in the high-dose progesterone group than those in the control and low-dose progesterone group. On the 28th day, there was no significant difference in the volume of tumors among 4 groups (P>0.05). The expression of vascular endothelial growth factor (P<0.01) was lower, and MVD (All P<0.05) were less in the middle-dose and high-dose progesterone group than those in the control and low-dose progesterone group.
 Conclusion: Progesterone promotes angiogenesis via upregulation of vascular endothelial growth factor expression, promotion of hemangiomas proliferation, suggesting that excessive progesterone supplementation may be one of the initial factors for early hemangioma formation.
Animals ; Cell Line, Tumor ; Hemangioma ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neovascularization, Pathologic ; Progesterone ; Vascular Endothelial Growth Factor A