OBJECTIVE: To investigate the effects of LncRNA SNHG20 on epithelial mesenchymal transition (EMT) and microtubule formation in human oral squamous cell carcinoma (OSCC) cells through targeted regulation of the miR-520c-3p/RAB22A pathway. METHODS: After real-time fluorescence quantitative detection of LncRNA SNHG20, miR-520c-3p, RAB22A mRNA expression levels in OSCC tissues and cells, dual luciferase reporter assay was used to detect the relationship between the three. OSCC cells were randomly separated into control group, sh-NC group, sh-SNHG20 group, sh-SNHG20+anti NC group, and sh-SNHG20+anti miR-520c-3p group. Western blotting was used to detect the expression of N-cadherin, vimentin, and E-cadherin proteins in the OSCC cells. The morphology of HSC-3 cells was observed under microscope. Changes in the number of microtubules formed were detected. The effect of LncRNA SNHG20 on the growth of OSCC tumors and the expression levels of LncRNA SNHG20, miR-520c-3p and RAB22 A in the transplanted tumors were detected by nude mice tumorigenesis experiment. RESULTS: LncRNA SNHG20 and RAB22A mRNA were upregulated in the OSCC tissues and cells, while miR-520c-3p was downregulated (P < 0.05). There were binding sites between LncRNA SNHG20 and miR-520c-3p, RAB22A and miR-520c-3p, which had targeted regulation relationship. Compared with the sh-NC group, the sh-SNHG20 group had fewer stromal like cells, more epithelial like cells, incomplete microtubule structure, and fewer nodules. LncRNA SNHG20, RAB22A, N-Cadherin, and vimentin were downregulated, while miR-520c-3p and E-cadherin were upregulated (P < 0.05). Compared with the sh-SNHG20+anti-NC group, the sh-SNHG20+anti-miR-520c-3p group had a higher number of stromal like cells, a lower number of epithelioid cells, tighter microtubule arrangement, and more microtubule nodules. miR-520c-3p and E-cadherin were downregulated, while RAB22A, N-cadherin, and vimentin were upregulated (P < 0.05). The transplanted tumor of OSCC in sh-SNHG20 group was smaller and lower than that in sh-NC group. The expression levels of LncRNA SNHG20 and RAB22A in the transplanted tumor tissues were lower than those in sh-NC group, and the expression level of miR-520c-3p was higher than that in sh-NC group (P < 0.05). CONCLUSION LncRNA SNHG20 promotes epithelial-mesenchymal transition and microtubule formation in human oral squamous cell carcinoma cells by targeting the miR-520c-3p/RAB22A pathway. Inhibiting the expression of LncRNA SNHG20 can target and regulate the miR-520c-3p/RAB22A pathway to inhibit EMT and microtubule formation in OSCC cells.
Humans ; RNA, Long Noncoding/genetics* ; MicroRNAs/metabolism* ; rab GTP-Binding Proteins/metabolism* ; Epithelial-Mesenchymal Transition/genetics* ; Cell Line, Tumor ; Carcinoma, Squamous Cell/metabolism* ; Animals ; Microtubules/metabolism* ; Mouth Neoplasms/genetics* ; Mice, Nude ; Mice ; Gene Expression Regulation, Neoplastic ; Mice, Inbred BALB C

Objective To investigate the mechanism of iron death induced by TRPC6/NF-κB in glomerular podiocytes mediated by high homocysteine(Hcy).Methods Mouse glomerulopocytes were cultured in vitro and divided into Control group(0 μmol/L Hcy)and Hcy group(80 μmol/L Hcy).After 48h of intervention,Western blot was used to detect the expression levels of iron death related proteins GPX4 and SLC7A11 and TRPC6 and NF-κ B.Real-time quantitative fluorescence PCR(qRT-PCR)and immunofluorescence were used to detect the expression of TRPC6.The level of podocyte apoptosis was detected by flow cytometry.Malondialdehyde(MDA)assay kit was used to determine intracellular MDA levels.After transfection of TRPC6 interference fragment and TRPC6 negative control(NC),qRT-PCR was divided into Control,si-NC and si-TRPC6(Si-TRPC6-1,Si-TRPC6-2,Si-TRPC6-3).Western Blot was divided into Control,Hcy,si-NC+Hcy,si-TRPC6+Hcy.The expression of TRPC6 mRNA was detected by qRT-PCR.The expression levels of GPX4,SLC7A11,NF-κB and TRPC6 were detected by Western Blot.The level of podocyte apoptosis after interference was detected by flow cytometry.Results(1)Compared with Control group,the expression levels of iron death related proteins GPX4 and SLC7A11 in Hcy group were decreased,and the apoptosis rate was increased(P<0.05).(2)Compared with Control group,TRPC6 protein,mRNA levels and immunofluorescence expression were increased in Hcy group.The level of MDA and the expression of NF-κB signaling pathway protein increased in Hcy group,and the comparison between the two groups had statistical significance(P<0.05).(3)Compared with the si-NC group,the mRNA expression level of TRPC6 in si-TRPC6(Si-TRPC6-1,Si-TRPC6-2,Si-TRPC6-3)group was decreased,and the interference effect of Si-TRPC6-3 was the best(P<0.05).After transfecting TRPC6 NC and TRPC6 interference fragment and administering Hcy,there was no difference in GPX4,SLC7A11,NF-κB and TRPC6 expression in si-NC+Hcy group compared with Hcy group.Compared with the si-NC+Hcy group,the si-TRPC6+Hcy group had higher expression of iron death related proteins,GPX4 and SLC7A11,lower expression of NF-κB and TRPC6,and decreased apoptosis rate(P<0.05).Conclusion This study confirmed that TRPC6/NF-κB can regulate iron death of renal podocytes under the induc-tion of Hcy,which is one of the mechanisms leading to kidney injury.

BACKGROUND:Current studies have confirmed that Ganoderma lucidum polysaccharides can promote nerve regeneration in neurodegeneration-related diseases.The occurrence of neurodegenerative diseases is closely related to mitochondrial dysfunction,but the role of Ganoderma lucidum polysaccharides on the regulation of apoptosis and mitochondrial function in neurodegenerative diseases is not yet clarified. OBJECTIVE:To explore the regulatory effects and mechanisms of Ganoderma lucidum polysaccharides on apoptosis and mitochondrial dysfunction in H2O2-induced SH-SY5Y cells. METHODS:SH-SY5Y cells were divided into three groups:control group,H2O2 group,and Ganoderma lucidum polysaccharides group.Cells in the control group were normally cultured.Cells in the H2O2 group were treated with 300 μmol/L H2O2 for 24 hours.In the Ganoderma lucidum polysaccharides group,the intervention with 300 μg/L Ganoderma lucidum polysaccharides was conducted first for 1-2 hours,followed by the addition of 300 μmol/L H2O2 for 24 hours.The mitochondrial membrane potential was detected by JC-1 kit.Apoptosis was detected by TUNEL staining kit.The activities of malondialdehyde and superoxide dismutase were detected by malondialdehyde test kit and superoxide dismutase test kit,respectively.The apoptosis and expression of mitochondrial dynamics-related proteins were detected by immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION:(1)Compared with the control group,the mitochondrial membrane potential and superoxide dismutase activity were significantly reduced,as well as apoptotic rate and malondialdehyde levels were significantly increased in the H2O2 group(P<0.05).After treatment with Ganoderma lucidum polysaccharides,the membrane potential and superoxide dismutase activities were significantly increased,and apoptotic rate and malondialdehyde levels were significantly reduced compared with the H2O2 group(P<0.05).(2)The expression levels of pro-apoptotic proteins Bax and Caspase-3 were significantly increased,but the expression of anti-apoptotic protein Bcl-2 was significantly decreased in the H2O2 group compared with the control group(P<0.05).Compared with the H2O2 group,the levels of Bax and Caspase-3 were significantly decreased,but the expression of anti-apoptotic protein Bcl-2 was significantly increased in the Ganoderma lucidum polysaccharides group(P<0.05).(3)Compared with the control group,the expression of mitochondrial splitting proteins Fis1 and p-Drp1 was significantly increased,but the expression of mitochondrial fusion proteins OPA1,Mfn1,and Mfn2 was decreased in the H2O2 group(P<0.05).Compared with the H2O2 group,Fis1 and p-Drp1 expression was significantly reduced,but the expression levels of OPA1,Mfn1,and Mfn2 were significantly increased in the Ganoderma lucidum polysaccharides group(P<0.05).(4)The above results confirm that Ganoderma lucidum polysaccharides can attenuate H2O2-induced oxidative stress damage and apoptosis in SH-SY5Y cells by ameliorating mitochondrial dysfunction.

Objective To investigate the effects of probiotics combined with dietary intervention on pe-ripheral blood glucose and lipid metabolism indicators,placental tissue insulin signaling pathway proteins ex-pression and pregnant outcome in the patients with gestational diabetes mellitus(GDM).Methods A total of 83 patients with GDM in this hospital from December 2021 to December 2022 were selected as the study sub-jects and divided into the probiotics group(probiotics combined with diet intervention,43 cases)and control group(simple diet intervention,40 cases)by the random number table method.The levels of peripheral blood glucose,lipid and insulin resistance related indicators before the intervention and in 8 weeks after the interven-tion were compared between the two groups.The histological changes of placenta were observed by HE stai-ning.The pathological indicators were compared between the two groups.The expression levels of insulin re-ceptor substrate-1(IRS-1),glucose transporter 4(GLUT4)and synaptosome-associated protein of 23 kDa(SNAP23)in placental tissue were detected by immunohistochemistry.The pregnant adverse outcomes were compared between the two groups,and the clinical efficacy of probiotics was evaluated.Results Compared with the control group,the levels of fasting blood glucose(FBG),fasting insulin(FINS),serum triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)in 8 weeks after intervention in the probiotics group were significantly decreased(P＜0.05),and the level of serum high density lipoprotein cholesterol(HDL-C)was significantly increased(P＜0.05).There were no significant differences in the incidence rates of poor villi maturation,thickening of dry villi arterioles and capillary filling in villi interstitial between the two groups(P＞0.05).Compared with the control group,the expression levels of IRS-1,GLUT4 and SNAP23 in placen-tal tissue of the probiotics group were significantly increased(P＜0.05).The incidence rates of neonatal hy-poglycemia and neonatal hyperbilirubinemia in the probiotics group were significantly lower than those in the control group(P＜0.05).Conclusion Compared with simple dietary intervention,probiotics combined with dietary intervention has more advantages in improving glucose and lipid metabolism of GDM patients,moreo-ver reduces the adverse events occurrence in newborns.

Objective To compare the diagnostic value of smear acid-fast staining,TB-DNA,X-pert MTB/RIF and culture of Mycobacterium tuberculosis.Methods Four methods were used to detect the perifocal pus of the patients with bone destruction in orthopaedics department within one year,and the results were analyzed statistically,the indexes included sensitivity,specificity,positive predictive value and negative predictive value.Results The sensitivity,specificity,positive predictive value,negative predictive value,and Youden index were 31.75%,100.00%,100.00%,53.74%and 0.32 respectively.TB-DNA had a sensitivity of 88.89%,a specificity of 98.00%,a positive predictive value of 98.25%,a negative predictive value of 87.50%,and a Youden Index of 0.87.Xpert MTB/Rif had a sensitivity of 95.23%,a specificity of 68.00%,and a positive predictive value of 78.95%,the negative predictive value was 91.90%,the Youden index was 0.63.The sensitivity,the specificity,the positive predictive value,the negative predictive value and the Youden index were 41.27%,100.00%,100.00%,57.47%and 0.41 respectively,(χ2 = 77.354,P<0.005).Conclusion Among the four methods,TB-DNA has a good Sensitivity and specificity,Xpert mtbrif has a good sensitivity,TB-DNA and Xpert mtbrif ha a good authenticity,and both positive and negative predictive values are high,it has good value in the diagnosis of bone tuberculosis.

Objective To survey the levels and distributed status of serum vitamin D in children in Hanzhong city of Shaanxi,and provide a basis for the prevention of children with vitamin D deficiency.Methods A total of 6 780 children aged 1 to 6 years from March 2019 to February 2021 in Children's Health Clinic of Hanzhong Center Hospital for physical examination were selected as subjects.The levels of serum 25-hydroxyvitamin D[25(OH)D],serum 25-hydroxyvitamin D2[25(OH)D2]and serum 25-hydroxyvitamin D3[25(OH)D3]were measured by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and the factors of ages and sexes and seasons were analyzed.Results The levels of serum 25(OH)D,25(OH)D2 and 25(OH)D3 in all children were 38.24±9.84 ng/ml,2.31±3.91 ng/ml and 35.93±9.93 ng/ml,respectively.The vitamin D deficiency rate,insufficiency rate and adequacy rate were 2.75％(186/6 780),18.29％(1 240/6 780)and 78.96％(5 354/6 780),respectively.The levels of serum 25(OH)D and 25(OH)D3 in children aged 1～2,2～3 and 3～6 years were gradually decreased with the growth of age,while the rate of vitamin D deficiency was increased,with significant differences(F=1 153.499,1 165.341,1 374.051,all P＜0.05).There were no significant differences in distributed status of serum of vitamin D and the levels of serum 25(OH)D,25(OH)D2 and 25(OH)D3 levels among different genders(t/x2=0.727,1.271,0.222,2.659,all P＞0.05).The levels of serum 25(OH)D and 25(OH)D3 in winter were lower than those in spring,summer and autumn,and the differences were statistically significant(q=6.853,7.281,6.801;5.341,6.225,5.989,all P＜0.01).The vitamin D deficiency rate in winter was higher than that in spring,summer and autumn(6.60％,2.64％,1.91％,1.66％).and the differences were statistically significant(x2=31.733,52.252,57.756,all P＜0.01).Conclusion A high incidence of vitamin D deficiency or insufficiency was found in children aged 3 to 6 in Hanzhong city.It was necessary to strengthen outdoor activities in winter,encourage monitoring of serum vitamin D levels,and supplement vitamin D if necessary.

Objective To screen the influencing factors of hepatitis C cirrhosis patients progressing to hepatocellular carcinoma(HCC)using commonly used laboratory testing indicators,establish a prediction model using these indicators and validate them.Methods A total of 231 patients with hepatitis C cirrhosis and 179 patients with hepatitis C HCC hospitalized at the First Affiliated Hospital of Xi'an Jiaotong University between June 2020 and May 2023 were enrolled as the training set,and 105 patients with hepatitis C cirrhosis and 86 patients with hepatitis C HCC hospitalized between June 2023 and February 2024 were enrolled as the validation set.The routine laboratory test indexes of the study subjects in the two groups within the training set were compared,and logistic regression analysis was applied to screen the independent predictors of hepatocellular carcinoma occurrence.Receiver operating characteristic(ROC)curve was used to construct the curve model and validate the model.Results The age,male ratio,ALT,AST,AFP,WBC,NEU,MO,PLT,MPV,PDW,Fbg,NLR and PLR levels of the HCC group were higher than those of the cirrhosis group in the training set(H=-9.07～-2.19),while the levels of INR and LMR were lower than those of the cirrhosis group(H=-4.49,-2.65),and the differences were significant(all P＜0.05).The differences in TP,eGFR,LY and AST/ALT values between the two groups of patients were not significant(H=-1.46～-0.15,all P＞0.05).Multifactorial Logistic regression analysis showed that age(OR=1.048,95％CI:1.023～1.074),Male(OR=1.467,95％CI:1.413～1.765),AST(OR=1.010,95％CI:1.002～1.019),NEU(OR=1.186,95％CI:1.018～1.382)and Fbg(OR=2.245,95％CI:1.639～3.076)were independent risk factors for hepatocellular carcinoma patients(all P＜0.05),and these five independent risk factors were used to construct the HCC column-line graph prediction model,with the AUC for the training set and the validation set AUC(95％Cl)were 0.813(0.771～0.854)and 0.712(0.639～0.784),respectively,and the Hosmer-Lemeshow test showed a good fit of the model with P=0.650 for the training set and P=0.310 for the validation set.Conclusion The prediction model of HCC based on age,gender,AST,NEU and Fbg can have good predictive efficacy and clinical application value.

Objective To explore the predictive value of serum homo sapiens microRNA(hsa-miR)-30c-5p expression in patients with type 2 diabetes mellitus(T2DM)for microvascular complications.Methods A total of 205 T2DM patients admitted to Bazhong Central Hospital from May 2021 to September 2022 were selected as the diabetes group,and the diabetes group was further divided into diabetes with combined group(n=124)and non combined group(n=81)according to the microvascular complications of the patients.In addition,205 healthy people who underwent physical examination during the same period were selected as the control group.The expression of hsa-miR-30c-5p in serum was detected by reverse transcription-polymerase chain reaction(RT-PCR)and compared.The factors affecting microvascular complications were analyzed using multivariate logistic regression analysis,and receiver operating characteristic(ROC)curves were plotted to predict the value of serum hsa-miR-30c-5p expression in predicting microvascular complications in T2DM patients.Results The expression of serum hsa-miR-30c-5p in the combined group(0.58±0.06)and the non-combined group(0.72±0.08)were lower than that in the control group(0.89±0.21),and the differences were significant(t=16.038,7.079,all P=0.001).The combined group was lower than the non-combined group,and the difference was significant(t=14.289,P=0.001).The course of diabetes[(OR(95％CI):3.873(2.976～4.770)],uric acid[(OR(95％CI):2.125(1.211～3.040)]and glycosylated hemoglobin[(OR(95％CI):2.680(1.745～3.616)]were independent risk factors for microvascular complications in T2DM patients(all P＜0.05),while the time within the target range of glucose[(OR(95％CI):0.491(0.135～0.846)]and serum hsa-miR-30c-5p[(OR(95％CI):0.532(2.976～4.770)]were protective factors for microvascular complications in T2DM patients(all P＜0.05).The sensitivity,specificity and area under the curve(95％CI)of serum hsa-mir-30c-5p expression in predicting microvascular complications in T2DM patients were 81.45％,85.19％and 0.802(0.741～0.854),respectively.Conclusion The expression of serum hsa-miR-30c-5p in patients with T2DM is abnormally reduced,and serum hsa-miR-30c-5p is a protective factor for microvascular complications in patients with T2DM.It may have a certain predictive value for microvascular complications in patients with T2DM.

Background::Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. Methods::Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. Results::NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. Conclusions::Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

Purpose/Significance The processing links and key technologies of health care big data are deeply discussed to provide in-formation support and guarantee for further promoting the application of health care big data.Method/Process According to the scientific research paradigm driven by big data,and based on the process perspective,the paper introduces the sources and characteristics of health care big data,analyzes the processing links and key technologies of big data,and discusses the current challenges and future development directions of health care big data processing.Result/Conclusion Both China and foreign countries have achieved innovative development in technologies for health care big data processing.However,there are still some challenges in multi-dimensional data collection,multi-mo-dal data integration,large model data analysis,and data security.In the future,through building a comprehensive platform of big data pro-cessing,and developing or integrating targeted functional modules,the existing problems can be effectively addressed.