OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

Objective To investigate the clinical diagnostic value of serum sTREM2 level in patients with cerebral small vessel disease(CSVD)and its correlation with depression and its severity.Methods A total of 208 CSVD inpatients admitted in Department of Neurology of the First Affiliated Hospital of Shihezi University from December 2023 to November 2024 were en-rolled,and according to their score of HAMD,they were divided into a depression group(CSVD+D group,112 cases)and a non-depression group(CSVD—D group,96 cases).According to the 17-item HAMD,the depression group(CSVD+D group)was further divided into mild(8-17,n=80),moderate(18-24,n=27)and severe depression(≥25,n=5)subgroups.Another 208 healthy individuals who taking health checkups in the same period were selected and served as the control group.The general clinical data were compared among the groups and subgroups,and mul-tivariate logistic regression analysis was applied to identify the risk factors for the occurrence of depression and the relationship between sTREM2 and depression severity in the CSVD patients.ROC curve was plotted to evaluate the predicative performance of serum sTREM2 level for the occurrence of depression in the CSVD patients.Results The serum sTREM2 level was remark-ably higher in the CSVD patients than the control group(5.95±3.82 μg/L vs 1.40±1.21 μg/L,P＜0.01).ROC curve analysis indicated that the AUC value of serum sTREM2 level in predicting CSVD was 0.917,with a sensitivity of 87.52％and a specificity of 85.64％,and an optimal cut-ff value of 2.272 μg/L.The CSVD+D group also had significantly higher serum sTREM2 level than the CSVD—D group(6.40±3.93 μg/L vs 5.01±2.87 μg/L,P＜0.01).Multivariate logistic regression analysis showed that serum sTREM2 level was an independent influencing factor for occurrence of depression in the CSVD patients(OR=1.115,95％CI:1.019-1.220,P=0.018).Statistical difference was also observed in the patients without and with mild,moderate and severe depression(P＜0.05).Multivariate ordinal logistic regression analysis revealed that serum sTREM2 level was an independent influencing factor for mild,moderate and severe depression(OR=1.113,95％CI:1.013-1.223,P=0.026;OR=1.135,95％CI:1.004-1.284,P=0.043).The AUC value of serum sTREM2 level in predicting depressive symptoms in CSVD patients was 0.603.Conclusion Serum sTREM2 is closely associated with CSVD patients.Its level may provide certain reference value for clinical diagnosis of CSVD,and has potentially predictive value for the occurrence of depression in the CSVD patients.

Objective To explore the relationship between overactive bladder(OAB)and neuropsychological characteristics in patients with cerebral small-vessel disease(CSVD).Methods A total of 208 patients with CSVD admitted to the First Affiliated Hospital of Shihezi University from December 2023 to November 2024 were selected as research subjects.They were divided into OAB group(44 cases)and non-OAB group(164 cases)according to overactive bladder symptom score.The general information and imaging data of two groups of patients were compared.The cognitive function,anxiety and depression of patients were evaluated by using Montreal cognitive assessment(MoCA),digit span test(DST),auditory verbal learning test(AVLT),verbal fluency test(VFT),clock drawing test(CDT),Hamilton anxiety scale(HAMA)and Hamilton depression scale(HAMD).Logistic regression analysis was used to analyze the influencing factors of OAB in patients with CSVD.Pearson correlation analysis was used to analyze the correlation between imaging indicators and anxiety symptoms of patients in OAB group.Results The HAMA and HAMD scores of patients in OAB group were higher than those in non-OAB group(P＜0.05),but there were no statistically significant differences in MoCA,DST,AVLT,VFT,and CDT scores between two groups(P＞0.05).There was a statistically significant difference in the incidence of anxiety among patients with different degrees of OAB(P＜0.05).Multivariate Logistic regression analysis after adjusting for confounding factors showed that anxiety was an independent influencing factor for OAB in patients with CSVD(P＜0.05).The periventricular white matter hyperintensity of patients in OAB group was negatively correlated with the HAMA score(P＜0.05),while basal ganglia lacunar infarction,centrum semiovale lacunar infarction,basal ganglia enlarged perivascular space and centrum semiovale enlarged perivascular space were all positively correlated with the HAMA score(P＜0.05).Conclusion The anxiety and depression symptoms of patients with CSVD accompanied by OAB were more severe than those of non-OAB patients.Anxiety may be an independent influencing factor for the occurrence of OAB in patients with CSVD.

Objective To explore the relationship between overactive bladder(OAB)and neuropsychological characteristics in patients with cerebral small-vessel disease(CSVD).Methods A total of 208 patients with CSVD admitted to the First Affiliated Hospital of Shihezi University from December 2023 to November 2024 were selected as research subjects.They were divided into OAB group(44 cases)and non-OAB group(164 cases)according to overactive bladder symptom score.The general information and imaging data of two groups of patients were compared.The cognitive function,anxiety and depression of patients were evaluated by using Montreal cognitive assessment(MoCA),digit span test(DST),auditory verbal learning test(AVLT),verbal fluency test(VFT),clock drawing test(CDT),Hamilton anxiety scale(HAMA)and Hamilton depression scale(HAMD).Logistic regression analysis was used to analyze the influencing factors of OAB in patients with CSVD.Pearson correlation analysis was used to analyze the correlation between imaging indicators and anxiety symptoms of patients in OAB group.Results The HAMA and HAMD scores of patients in OAB group were higher than those in non-OAB group(P＜0.05),but there were no statistically significant differences in MoCA,DST,AVLT,VFT,and CDT scores between two groups(P＞0.05).There was a statistically significant difference in the incidence of anxiety among patients with different degrees of OAB(P＜0.05).Multivariate Logistic regression analysis after adjusting for confounding factors showed that anxiety was an independent influencing factor for OAB in patients with CSVD(P＜0.05).The periventricular white matter hyperintensity of patients in OAB group was negatively correlated with the HAMA score(P＜0.05),while basal ganglia lacunar infarction,centrum semiovale lacunar infarction,basal ganglia enlarged perivascular space and centrum semiovale enlarged perivascular space were all positively correlated with the HAMA score(P＜0.05).Conclusion The anxiety and depression symptoms of patients with CSVD accompanied by OAB were more severe than those of non-OAB patients.Anxiety may be an independent influencing factor for the occurrence of OAB in patients with CSVD.

Objective To investigate the clinical diagnostic value of serum sTREM2 level in patients with cerebral small vessel disease(CSVD)and its correlation with depression and its severity.Methods A total of 208 CSVD inpatients admitted in Department of Neurology of the First Affiliated Hospital of Shihezi University from December 2023 to November 2024 were en-rolled,and according to their score of HAMD,they were divided into a depression group(CSVD+D group,112 cases)and a non-depression group(CSVD—D group,96 cases).According to the 17-item HAMD,the depression group(CSVD+D group)was further divided into mild(8-17,n=80),moderate(18-24,n=27)and severe depression(≥25,n=5)subgroups.Another 208 healthy individuals who taking health checkups in the same period were selected and served as the control group.The general clinical data were compared among the groups and subgroups,and mul-tivariate logistic regression analysis was applied to identify the risk factors for the occurrence of depression and the relationship between sTREM2 and depression severity in the CSVD patients.ROC curve was plotted to evaluate the predicative performance of serum sTREM2 level for the occurrence of depression in the CSVD patients.Results The serum sTREM2 level was remark-ably higher in the CSVD patients than the control group(5.95±3.82 μg/L vs 1.40±1.21 μg/L,P＜0.01).ROC curve analysis indicated that the AUC value of serum sTREM2 level in predicting CSVD was 0.917,with a sensitivity of 87.52％and a specificity of 85.64％,and an optimal cut-ff value of 2.272 μg/L.The CSVD+D group also had significantly higher serum sTREM2 level than the CSVD—D group(6.40±3.93 μg/L vs 5.01±2.87 μg/L,P＜0.01).Multivariate logistic regression analysis showed that serum sTREM2 level was an independent influencing factor for occurrence of depression in the CSVD patients(OR=1.115,95％CI:1.019-1.220,P=0.018).Statistical difference was also observed in the patients without and with mild,moderate and severe depression(P＜0.05).Multivariate ordinal logistic regression analysis revealed that serum sTREM2 level was an independent influencing factor for mild,moderate and severe depression(OR=1.113,95％CI:1.013-1.223,P=0.026;OR=1.135,95％CI:1.004-1.284,P=0.043).The AUC value of serum sTREM2 level in predicting depressive symptoms in CSVD patients was 0.603.Conclusion Serum sTREM2 is closely associated with CSVD patients.Its level may provide certain reference value for clinical diagnosis of CSVD,and has potentially predictive value for the occurrence of depression in the CSVD patients.

Objective:To analyze the effect of montelukast combined with budesonide in the treatment of children with intermittent asthma, and the impact on airway remodeling and T helper type 1 (Th1)/T helper type 2 (Th1/Th2) related cytokines.Methods:A prospective study was conducted among 120 children with intermittent asthma admitted to Huanghua Municipal People′s Hospital from December 2021 to February 2023. The children were randomly divided into the control group (60 children treated with budesonide atomizationinhalation) and the observation group (60 children treated with montelukast on the basis of the treatment of control group). Clinical efficacy, airway remodeling indicators [total area of airway (Ao), outer diameter of airway (D) and wall area to total airway cross-sectional area (WA%)], pulmonary function [peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV 1)/forced vital capacity (FVC) and the maximum expiratory flow at 25% of vital capacity (MEF25%)], Th1/Th2 related cytokines, inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6) and interferon-gamma (IFN-γ)], recurrence, and the incidence of adverse reactions were compared between the two groups. Results:The total effective rate in the observation group was higher than that in the control group: 90.00% (54/60) vs. 75.00% (45/60) ( P<0.05). After treatment, Ao, D and WA% in the observation group were lower than those in the control group: (17.58 ± 1.89) mm 2 vs. (19.22 ± 1.94) mm 2, (4.25 ± 0.48) mm vs. (4.48 ± 0.49) mm, (63.75 ± 6.49)% vs. (69.22 ± 7.14)% ( P<0.05). PEF, FEV 1/FVC and MEF25% in the observation group were higher than those in the control group: (3.13 ± 0.34) L/s vs. (2.86 ± 0.35) L/s, (87.45 ± 8.86) % vs. (83.59 ± 8.42) %, (87.63 ± 8.86)% vs. (82.15 ± 8.43)% ( P<0.05). The levels of Th1 and Th1/Th2 in the observation group were higher than those in the control group: (14.13 ± 1.46) % vs. (10.27 ± 1.25) %, 3.46 ± 0.39 vs. 1.88 ± 0.25, and the level of Th2 was lower than that in the control group: (3.96 ± 0.45)% vs. (5.48 ± 0.56)% ( P<0.05). After treatment, the levels of TNF-α and IFN-γ in the observation group were higher than those in the control group: (76.15 ± 7.78) ng/L vs. (66.38 ± 6.47) ng/L, (7.15 ± 0.74) ng/L vs. (6.14 ± 0.66) ng/L. The levels of IL-4 and IL-6 were lower than those in the control group: (77.85 ± 7.96) ng/L vs. (86.42 ± 8.74) ng/L, (37.25 ± 3.89) mg/L vs. (44.23 ± 4.57) mg/L ( P<0.05). The recurrence rate in the observation group was lower than that in the control group: 3.33% (2/60) vs. 15.00% (9/60) ( P<0.05). The incidence rates of adverse reactions in the two groups were without statistically significant difference between the groups ( P>0.05). Conclusions:Montelukast combined with budesonide can reduce airway remodeling in children with intermittent asthma, improve their pulmonary function, Th1/Th2 related cytokines and inflammatory response indicators, and reduce recurrence rate, with good safety.

Objective To explore the relationship between serum high mobility group protein B1(HMGB1)level and anxiety symptoms in patients with cerebral small vessel disease(CSVD).Methods A total of 165 CSVD patients admitted in our department from December 2022 to July 2023 were enrolled as the research subjects.All of them were evaluated by neurologists with Hamilton Anxiety Rating Scale(HAMA),and then those with HAMA score ≥7 were assigned into an anxiety group(70 cases),and the other into a non-anxiety group(95 cases).Non paramet-ric rank sum test was used to compare the serum level of HMGB1 between the two groups of pa-tients.Logistic regression analysis was employed to analyze the risk factors affecting anxiety symptoms in CSVD patients.ROC curve was plotted to evaluate the predictive value of HMGB1 for anxiety symptoms in the patients.Results The serum HMGB1 level was significantly higher in the anxiety group than the non-anxiety group[287.01(188.19,355.54)ng/L vs 260.87(146.48,328.16)ng/L,P＜0.05].Multivariate logistic regression analysis showed that after adjusting for confounding factors,serum HMGB1 level was still a risk factor for anxiety symptoms in CSVD patients(OR=1.004,95％CI:1.000-1.007,P=0.046).Spearman correlation analysis indicated that HMGB1 level was positively correlated with total score of HAMA,insomnia score,and psy-chogenic score(P＜0.05,P＜0.01).The AUC value of HMGB1 in predicting anxiety symptoms in CSVD patients was 0.609(P=0.020).Conclusion Serum HMGB1 level is associated with the oc-currence of anxiety symptoms in CSVD patients,and it has predictive value for the anxiety symp-toms in CSVD patients.

Objective:Aldo-keto reductase family 1 member B10 (AKR1B10) pathogenesis, early diagnosis and prognosis are closely related with hepatoma. Therefore, this study explores the effect and mechanism of AKR1B10 on cell cycle in hepatoma cells.Methods:HepG2 cells were infected with lentivirus LV-AKR1B10-shRNA or treated with epalrestat, an AKR1B10 inhibitor. The expression level of AKR1B10 was detected by Western blot assay and real-time fluorescence quantitative PCR (RT-qPCR). Decreased AKR1B10 activity was detected by reduced coenzyme II (NADPH) absorbance at 340 nm. The low expression of AKR1B10 and the effect of different concentrations of epalrestat on cell proliferation and cell cycle were detected by CCK-8 method and flow cytometry. The protein expression levels of p-rb, cyclin D1, E1, p27 in HepG2 cells were detected by Western blot. The mean of the two samples was tested using independent sample t-test.Results:AKR1B10 expression level in hepatoma cells was significantly increased compared to normal liver cells, and the relative expression level of AKR1B10 protein in HepG2 cells was 6.71 ± 1.11 ( P = 0.012). Epalrestat was significantly inhibited with the enzymatic activity of AKR1B10 in a dose-dependent manner. AKR1B10 gene in HepG2 cells was effectively silenced. HepG2 cells treated with different concentrations of epalrestat (AKR1B10 inhibitor) for 24, 48 and 72 h had inhibited cell proliferation, promoted G0/G1 cell cycle arrest, reduced the expression of p-Rb, cyclin D1, and cyclin E1 and increased the expression of cyclin dependent kinase inhibitor p27 expression. Conclusion:AKR1B10 inhibitory expression and activity can promote G0/G1 cell cycle arrest in HepG2 cells through the p27 / p-Rb pathway.

Muscle strength training plays an important role in improving limb movement function, preventing muscle atrophy and promoting muscle function recovery in patients with various bone and joint diseases. The sports function of elbow joint is closely related to people's daily life activity ability. At present, Chinese muscle strength training devices are depended on import. Therefore, it is of great significance to develop muscle strength training devices. Based on the concepts and characteristics of isometric training, isotonic training, passive training and isokinetic training, in the upper computer, the servo driver and servo motor are controlled through the LabView interface, and the real-time torque is detected by the torque sensor, realizing four training modes. The main parameters of the multi-mode elbow joint muscle strength training device meet the requirements, and the trainers have a good experience.
Elbow Joint ; physiology ; Humans ; Muscle Strength ; Muscle, Skeletal ; Resistance Training ; Torque

Objective: To investigate the inhibitory effect of AKR1B10 inhibitor combined with sorafenib on hepatocellular carcinoma (HCC) xenograft growth. Methods: HepG2 xenograft model was established in nude mice. The mice were then randomly divided into four groups: control group, epalrestat monotherapy group, sorafenib monotherapy group and combination treatment group. Tumor volume, tumor weight, T/C ratio and the change in body weight of nude mice in each group were compared to evaluate the curative effect. Immunohistochemistry staining was used to detect the expression of Ki-67 in tumor tissues to evaluate the proliferation status of tumor cells. One-way analysis of variance was used to compare the differences between the groups. Student’s t-test was used to test means of two groups and chi-square test was used for multiple samples. Results: The differences of the grafted tumor volume before and after treatment between the control group, epalrestat group, sorafenib group and combined therapy group was 238.940 ± 39.813, 124.991 ± 84.670, -26.111 ± 11.518, and -54.072 ± 17.673(mm³), respectively, (F = 37.048, P < 0.001). The tumor mass were 0.273 ± 0.140, 0.158 ± 0.078, 0.079 ± 0.054, 0.045 ± 0.024 (g), (F = 16.594, P < 0.001); T/C ratio were 100%, 57.9%, 28.9%, 16.5%, and Ki-67 positive rate were 23.295 ± 6.218, 13.503 ± 3.392, 7.325 ± 2.257, 4.664 ± 1.189 (%), (χ² = 822.203, P < 0.001) . The tumor volume (t = -3.579, P = 0.002) and Ki-67 positive rate (t = -10.003, P < 0.001) in epalrestat monotherapy group were significantly lower than control group. The tumor volume (t = 2.056, P = 0.025), tumor mass (t = 2.101, P = 0.043), and Ki-67 positive rate (t = -2.850, P = 0.005) in combination treatment group were significantly lower than sorafenib monotherapy group. Compared with the control group, the body weight of nude mice in the treatment group decreased to a certain extent, but there was no statistically significant difference between epalrestat monotherapy group and control group (t = -1.599, P = 0.262), and combined therapy and sorafenib monotherapy group (t = -0.051, P = 0.96). Conclusion AKR1B10 inhibitor enhanced the inhibitory effect of sorafenib on hepatocellular carcinoma xenograft.