BACKGROUND: Meningeal metastasis (MM) is a form of malignant metastasis where tumor cells spread from the primary site to the pia mater, dura mater, arachnoid, subarachnoid space, and other cerebrospinal fluid compartments. Lung cancer is one of the most common malignant tumor types with MM. MM not only signifies that the lung cancer has progressed to an advanced stage but also leads to a range of severe clinical symptoms due to meningeal involvement. Currently, the risk factors associated with the development of MM are not fully elucidated. The aim of this study was to investigate the risk factors for MM in patients with lung adenocarcinoma (LUAD) who underwent non-surgical interventions, in order to identify LUAD patients at high risk for MM. METHODS: This retrospective study analyzed the clinical data of patients diagnosed with LUAD at the First Affiliated Hospital of Zhengzhou University from January 2020 to July 2024. Missing data were imputed using multiple imputation methods, and risk factors were identified through LASSO, univariate, and multivariate Logistic regression analyses. RESULTS: A total of 170 patients with LUAD were included in this study and divided into two groups: 87 patients with MM and 83 patients without MM. Univariate and multivariate Logistic regression analyses revealed that younger age at diagnosis (P=0.004), presence of the epidermal growth factor receptor (EGFR) L858R gene mutation (P=0.008), and concurrent liver metastasis at baseline (P=0.004) were independent risk factors for developing MM in LUAD patients who did not undergo surgical intervention. Conversely, higher baseline globulin levels (P=0.039) and the presence of the anaplastic lymphoma kinase (ALK) gene mutation (P=0.040) were associated with a reduced risk of MM development. CONCLUSIONS Age at diagnosis, EGFR L858R mutation status, ALK gene mutation status, concurrent liver metastasis, globulin levels at baseline were significantly associated with the risk of developing MM in patients with LUAD patients who did not undergo surgical intervention. For patients diagnosed at a younger age, carrying the EGFR L858R mutation, or presenting with baseline liver metastasis, early implementation of tertiary prevention strategies for MM is crucial. Regular monitoring of MM status should be conducted in these high-risk groups.
Humans ; Male ; Adenocarcinoma of Lung/therapy* ; Female ; Middle Aged ; Risk Factors ; Lung Neoplasms/therapy* ; Retrospective Studies ; Aged ; Meningeal Neoplasms/genetics* ; Adult

Objective To investigate the role of miR-147a targeting inhibin subunit beta A(INHBA)in transforming growth factor-β1(TGF-β1)/Smads signaling pathway in the invasion and metastasis of cervical cancer HeLa cells.Methods The miR-147a mimics,miR-147a inhibitors and their negative controls(mimicsNC and inhibitor NC)were transfected into HeLa cells and divid-ed into five groups:control group(blank control),mimics NC group,miR-147a mimics group,inhibitor NC group,and miR-147a in-hibitor group.The proliferation activity of HeLa cells after miR-147a intervention was detected by the MTT method,the invasion and me-tastasis abilities of HeLa cells after the intervention of miR-147a were detected by Transwell and cell scratch assay,the mRNA expres-sion changes of miR-147a and INHBA in different groups were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR),the relationship between miR-147a and the target gene INHBA was detected by dual-luciferase reporter gene assay,the protein expressions of TGF-β1,TGFBR1,Smad3,Smad2 and INHBA in different groups were detected by Western blot,and the ex-pression changes of TGF-β1 were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with blank control and negative control,miR-147a mimics inhibited cell proliferation,decreased cell invasion and migration ability,and decreased cell healing ability.miR-147a inhibitor promoted cell proliferation,increased invasion and migration ability,and improved cell healing abili-ty.In the miR-147a mimics group,miR-147a was significantly increased,and the target gene INHBA was significantly decreased(P＜0.05).In the miR-147a inhibitor group,miR-147a was significantly decreased,and the target gene INHBA was significantly in-creased(P＜0.05).The fluorescence intensity ratio of miR-147a mimics+WT group was significantly lower than that of mimics NC+WT group(P＜0.05).The expression levels of TGFBR1,TGF-β1,Smad3,Smad2 and INHBA in miR-147a mimics group were sig-nificantly decreased(P＜0.05).The expression levels of TGFBR1,TGF-β1,Smad3,Smad2,and INHBA in miR-147a inhibitor group were significantly increased(P＜0.05).Conclusion miR-147a targets the TGF-β1/Smads signaling pathway mediated by IN-HBA,which plays an important role in inhibiting the proliferation,invasion and migration of cervical cancer HeLa cells,and provides a potential molecular target and theoretical basis for the treatment of cervical cancer.

BACKGROUND:Due to the aging population and the increase in elderly diseases,research and utilization of epidermal stem cells in the elderly have become increasingly important.However,due to the weak proliferation and drying ability of epidermal stem cells in the elderly,their application in biomedical and clinical research is limited.OBJECTIVE:To investigate the ability of rotating cell culture system to promote the proliferation and maintenance of epidermal stem cells in elderly individuals.METHODS:Epidermal stem cells were obtained from children (7-12 years old) and the elderly (over 60 years old) using traditional planar culture methods.After identification by cell morphology and cell immunofluorescence,the differences in proliferation ability of epidermal stem cells between the children and the elderly were analyzed by flow cytometry,CCK-8 assay,and cell clone formation assay.Elderly epidermal stem cells were cultured using a rotating cell culture system and 3D TableTrix? microcarriers.The cell proliferation and expression of stemness markers were detected by Live/Dead staining,cell doubling efficiency,cell doubling time,and real-time quantitative polymerase chain reaction.RESULTS AND CONCLUSION:(1) Under planar culture conditions,the children group had stronger proliferative ability than the elderly group.(2) Compared with planar culture,the dynamic cultivation of elderly epidermal stem cells using a rotating cell culture system had a higher population doubling (P<0.01) and a shorter population doubling time (P<0.01).(3) The dynamic cultivation of rotating cell culture system promoted the self-assembly of elderly epidermal stem cells to form 3D human epidermal stem cell spheres based on microcarrier scaffolds,which had similar epidermal stem cell proliferation as the children group.(4) After dynamic culture,the expression of stemness marker genes (ITGA6 and ITGB1),basal cell marker genes (K5) and differentiation marker genes (K10 and K1) of elderly epidermal stem cells reached the same level as that of children.The results showed that the dynamic cultivation of rotating cell culture system can not only improve the efficiency of elderly epidermal stem cell culture,promote cell proliferation and self-assembly into 3D cell spheres,but also maintain a certain stemness of elderly epidermal stem cells without complete terminal differentiation.

Objective:To investigate the effect of phosphorus-containing replacement solution for the prevention and treatment of hypophosphatemia during continuous renal replacement therapy (CRRT) in critically ill patients with blood phosphorus level ≤1.45 mmol/L, and to provide clinical reference.Methods:It was a historical prospective cohort study. The critically ill patients receiving CRRT with blood phosphorus ≤ 1.45 mmol/L in the intensive care unit of Henan Provincial People's Hospital from October 2021 to January 2023 and from April 2023 to January 2024 was selected as the study subjects. The patients were divided into test group (from April 2023 to January 2024) and control group (from October 2021 to January 2023) according to whether phosphate (1.0 mmol/L) was added to the replacement solution during CRRT, and the differences of clinical data before and after CRRT between the two groups were compared. The patients were divided into hypophosphatemia group and non-hypophosphatemia group according to whether blood phosphorus < 0.81 mmol/L within 24 h after the end of CRRT, and the differences of clinical data between the two groups were compared. Logistic regression analysis was used to analyze the related factors of hypophosphatemia.Results:A total of 149 critically ill patients with blood phosphorus level ≤1.45 mmol/L undergoing CRRT were enrolled in the study, with age of 64(47, 75) years and 87 males (58.4%). Among 149 patients, 84(56.4%) had hypophosphatemia after CRRT, and no hyperphosphatemia occurred. The incidence of hypophosphatemia in test group and control group was 40.0% (30/75) and 73.0% (54/74), respectively. There was no statistically significant difference in baseline clinical data before CRRT between test group and control group (all P>0.05). C-reactive protein ( Z=-3.356, P=0.001), blood calcium ( Z=-3.835, P<0.001) and proportion of hypophosphatemia ( χ2=16.467, P<0.001) in the test group were lower than those in the control group, and blood phosphorus ( Z=3.886, P<0.001) in the test group was higher than that in the control group within 24 h after CRRT. Compared with non-hypophosphatemia group, the proportion of parenteral nutrition ( χ2=6.802, P=0.009) and blood calcium within 24 h after CRRT ( Z=-2.515, P=0.012) in the hypophosphatemia group were higher, and blood phosphorus within 24 h after CRRT ( Z=-10.451, P<0.001), blood phosphorus after 24 h after CRRT treatment ( Z=-5.331, P<0.001) and the proportion of applied replacement solution containing phosphorus ( χ2=16.467, P<0.001) in the hypophosphatemia group were lower. The results of multivariate logistic regression analysis showed that parenteral nutrition ( OR=2.521, 95% CI 1.228-5.175, P=0.012) and application of phosphorus- containing replacement solution ( OR=0.241, 95% CI 0.119-0.491, P<0.001) were independent relevant factors of hypophosphatemia after CRRT in the whole cohort of patients. Conclusions:The application of phosphorus-containing replacement solution in critically ill patients with blood phosphorus level ≤1.45 mmol/L undergoing CRRT is safe and effective, and the incidence of hypophosphatemia is low. Application of phosphorus-containing replacement solution in critically ill patients with blood phosphorus level ≤1.45 mmol/L undergoing CRRT can reduce the incidence risk of hypophosphatemia after CRRT.

Objective To investigate the effects of imatinib mesylate and sunitinib malate on the migration and invasion of gastroin-testinal stromal tumor(GIST)cells.Methods After identifying primary-cultured GIST cells,their morphology was characterized using atomic force microscopy(AFM).Changes in the expression of genes related to the PI3K/AKT signaling pathway were analyzed using quan-titative real-time PCR following drug treatments.Changes in the binding of related molecules were detected using AFM,and alterations in cell migration,invasive ability,and apoptosis were determined using scratch assay,Transwell assay,and flow cytometry,respectively.Results AFM imaging showed that pseudopods were flatly spread around the GIST cells,indicating characteristics consistent with easy metastasis.Administration of either imatinib or sunitinib significantly reduced the expression of genes related to the PI3K/AKT signaling pathway,the density of epidermal growth factor receptor(EGFR)on the surface of GIST cells,and molecular binding force with EGF.These changes were more pronounced with the combination treatment.Correspondingly,the invasive and migratory abilities of GIST cells were significantly reduced when either drug was administered alone and the inhibitory effect was more significant when the drugs were combined.Conclusion Both imatinib and sunitinib can significantly inhibit the expression of genes related to the PI3K/AKT signaling pathway,reduce the density of EGFR on the surface of GIST cells,and attenuate their molecular binding to EGF,thereby reducing the migration and invasion of GIST cells.However,the combination of these two drugs has a more significant effect.

Objective To compare the effect of different intensity of neuromuscular training(NMT)on muscle strength and knee joint function of patients after anterior cruciate ligament reconstruction(ACLR).Methods From January,2023 to January,2024,60 ACLR patients in Changhai Hospital were selected,and they received the same intensity of NMT from one to eight weeks after surgery.Eight weeks after surgery,they were randomly divided into low intensity group(n=30)and high intensity group(n=30),and then they received different inten-sities of NMT from nine to 16 weeks after surgery,each training session lasted one hour,with three sessions per week,totaly 48 sessions.The Lysholm score,knee flexor and extensor muscle strength and muscle endurance-were compared at eight weeks and 16 weeks after surgery.Results After group training,the Lysholm score significantly increased in both groups(|t|>13.739,P<0.001),and was higher in the high intensity group than in the low intensity group(t=-2.574,P<0.05);in the high intensity group,the relative peak torque and endurance of the extensor and flexor muscles improved at angular velocities of 60°/s,120°/s and 180 °/s(|t|>2.320,P<0.05);in the low intensity group,the flexor peak torque improved at all the three angular velocities(t>2.177,P<0.05),the extensor peak torque improved at angular velocities of 60°/s and 180°/s(|t|>1.715,P<0.05),and the extensor endurance improved at angular velocity of 60°/s(t=-2.293,P<0.05).However,there was no significant difference in the relative peak torque and endurance of the extensor and flexor muscles at all the three angular velocities(P>0.05).Conclusion Both high and low intensity NMT could improve the muscle strength,muscle endurance and knee joint func-tion.Maybe,high intensity is superior to low intensity.Further verification is still needed.

Objective To investigate the role of miR-147a targeting inhibin subunit beta A(INHBA)in transforming growth factor-β1(TGF-β1)/Smads signaling pathway in the invasion and metastasis of cervical cancer HeLa cells.Methods The miR-147a mimics,miR-147a inhibitors and their negative controls(mimicsNC and inhibitor NC)were transfected into HeLa cells and divid-ed into five groups:control group(blank control),mimics NC group,miR-147a mimics group,inhibitor NC group,and miR-147a in-hibitor group.The proliferation activity of HeLa cells after miR-147a intervention was detected by the MTT method,the invasion and me-tastasis abilities of HeLa cells after the intervention of miR-147a were detected by Transwell and cell scratch assay,the mRNA expres-sion changes of miR-147a and INHBA in different groups were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR),the relationship between miR-147a and the target gene INHBA was detected by dual-luciferase reporter gene assay,the protein expressions of TGF-β1,TGFBR1,Smad3,Smad2 and INHBA in different groups were detected by Western blot,and the ex-pression changes of TGF-β1 were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with blank control and negative control,miR-147a mimics inhibited cell proliferation,decreased cell invasion and migration ability,and decreased cell healing ability.miR-147a inhibitor promoted cell proliferation,increased invasion and migration ability,and improved cell healing abili-ty.In the miR-147a mimics group,miR-147a was significantly increased,and the target gene INHBA was significantly decreased(P＜0.05).In the miR-147a inhibitor group,miR-147a was significantly decreased,and the target gene INHBA was significantly in-creased(P＜0.05).The fluorescence intensity ratio of miR-147a mimics+WT group was significantly lower than that of mimics NC+WT group(P＜0.05).The expression levels of TGFBR1,TGF-β1,Smad3,Smad2 and INHBA in miR-147a mimics group were sig-nificantly decreased(P＜0.05).The expression levels of TGFBR1,TGF-β1,Smad3,Smad2,and INHBA in miR-147a inhibitor group were significantly increased(P＜0.05).Conclusion miR-147a targets the TGF-β1/Smads signaling pathway mediated by IN-HBA,which plays an important role in inhibiting the proliferation,invasion and migration of cervical cancer HeLa cells,and provides a potential molecular target and theoretical basis for the treatment of cervical cancer.

BACKGROUND:Due to the aging population and the increase in elderly diseases,research and utilization of epidermal stem cells in the elderly have become increasingly important.However,due to the weak proliferation and drying ability of epidermal stem cells in the elderly,their application in biomedical and clinical research is limited.OBJECTIVE:To investigate the ability of rotating cell culture system to promote the proliferation and maintenance of epidermal stem cells in elderly individuals.METHODS:Epidermal stem cells were obtained from children (7-12 years old) and the elderly (over 60 years old) using traditional planar culture methods.After identification by cell morphology and cell immunofluorescence,the differences in proliferation ability of epidermal stem cells between the children and the elderly were analyzed by flow cytometry,CCK-8 assay,and cell clone formation assay.Elderly epidermal stem cells were cultured using a rotating cell culture system and 3D TableTrix? microcarriers.The cell proliferation and expression of stemness markers were detected by Live/Dead staining,cell doubling efficiency,cell doubling time,and real-time quantitative polymerase chain reaction.RESULTS AND CONCLUSION:(1) Under planar culture conditions,the children group had stronger proliferative ability than the elderly group.(2) Compared with planar culture,the dynamic cultivation of elderly epidermal stem cells using a rotating cell culture system had a higher population doubling (P<0.01) and a shorter population doubling time (P<0.01).(3) The dynamic cultivation of rotating cell culture system promoted the self-assembly of elderly epidermal stem cells to form 3D human epidermal stem cell spheres based on microcarrier scaffolds,which had similar epidermal stem cell proliferation as the children group.(4) After dynamic culture,the expression of stemness marker genes (ITGA6 and ITGB1),basal cell marker genes (K5) and differentiation marker genes (K10 and K1) of elderly epidermal stem cells reached the same level as that of children.The results showed that the dynamic cultivation of rotating cell culture system can not only improve the efficiency of elderly epidermal stem cell culture,promote cell proliferation and self-assembly into 3D cell spheres,but also maintain a certain stemness of elderly epidermal stem cells without complete terminal differentiation.

Objective To compare the effect of different intensity of neuromuscular training(NMT)on muscle strength and knee joint function of patients after anterior cruciate ligament reconstruction(ACLR).Methods From January,2023 to January,2024,60 ACLR patients in Changhai Hospital were selected,and they received the same intensity of NMT from one to eight weeks after surgery.Eight weeks after surgery,they were randomly divided into low intensity group(n=30)and high intensity group(n=30),and then they received different inten-sities of NMT from nine to 16 weeks after surgery,each training session lasted one hour,with three sessions per week,totaly 48 sessions.The Lysholm score,knee flexor and extensor muscle strength and muscle endurance-were compared at eight weeks and 16 weeks after surgery.Results After group training,the Lysholm score significantly increased in both groups(|t|>13.739,P<0.001),and was higher in the high intensity group than in the low intensity group(t=-2.574,P<0.05);in the high intensity group,the relative peak torque and endurance of the extensor and flexor muscles improved at angular velocities of 60°/s,120°/s and 180 °/s(|t|>2.320,P<0.05);in the low intensity group,the flexor peak torque improved at all the three angular velocities(t>2.177,P<0.05),the extensor peak torque improved at angular velocities of 60°/s and 180°/s(|t|>1.715,P<0.05),and the extensor endurance improved at angular velocity of 60°/s(t=-2.293,P<0.05).However,there was no significant difference in the relative peak torque and endurance of the extensor and flexor muscles at all the three angular velocities(P>0.05).Conclusion Both high and low intensity NMT could improve the muscle strength,muscle endurance and knee joint func-tion.Maybe,high intensity is superior to low intensity.Further verification is still needed.

Objective To investigate the effects of imatinib mesylate and sunitinib malate on the migration and invasion of gastroin-testinal stromal tumor(GIST)cells.Methods After identifying primary-cultured GIST cells,their morphology was characterized using atomic force microscopy(AFM).Changes in the expression of genes related to the PI3K/AKT signaling pathway were analyzed using quan-titative real-time PCR following drug treatments.Changes in the binding of related molecules were detected using AFM,and alterations in cell migration,invasive ability,and apoptosis were determined using scratch assay,Transwell assay,and flow cytometry,respectively.Results AFM imaging showed that pseudopods were flatly spread around the GIST cells,indicating characteristics consistent with easy metastasis.Administration of either imatinib or sunitinib significantly reduced the expression of genes related to the PI3K/AKT signaling pathway,the density of epidermal growth factor receptor(EGFR)on the surface of GIST cells,and molecular binding force with EGF.These changes were more pronounced with the combination treatment.Correspondingly,the invasive and migratory abilities of GIST cells were significantly reduced when either drug was administered alone and the inhibitory effect was more significant when the drugs were combined.Conclusion Both imatinib and sunitinib can significantly inhibit the expression of genes related to the PI3K/AKT signaling pathway,reduce the density of EGFR on the surface of GIST cells,and attenuate their molecular binding to EGF,thereby reducing the migration and invasion of GIST cells.However,the combination of these two drugs has a more significant effect.