Comparative study of ultrasonic-guided betamethasone local injection and extracorporeal shock wave therapy in post-stroke hemiplegic shoulder pain: a randomized clinical trial.

Objective: This study aimed to compare the efficacy and safety of ultrasound-guided local injection (UGLI) of betamethasone around the shoulder and extracorporeal shock wave therapy (ESWT) in patients with hemiplegic shoulder pain. Method: Forty-two patients with hemiplegic shoulder pain were randomly divided into the UGLI group (N = 21) and the ESWT group (N = 21). In the UGLI group, betamethasone was injected at the pain point around the shoulder under ultrasonic localization. In the ESWT group, an extracorporeal shock wave was performed at the pain points around the shoulder for 20 min of time, once a week, for 4 consecutive weeks. Both groups received rehabilitation training. The visual analog scale (VAS) evaluation was performed at baseline, 1 h, 1 week, and 1 month after treatment. Furthermore, Neer shoulder joint function scores, upper limb Fugl-Meyer assessment (FMA), modified Barthel index (MBI), Hamilton Depression Scale (HAMD), the MOS-item short-form health survey (SF-36) scores, and serum expression level of cytokine were evaluated at baseline and 1 month after treatment. Results: After 1-h treatment, the UGLI group showed a greater effect on the degree of pain than the ESWT group (P = 0.017). After 4 consecutive weeks of intervention, the UGLI group showed a significant improvement in the serum level of cytokine expression compared with the ESWT group (P < 0.05). The range of motion (ROM) of the hemiplegic shoulder (P < 0.05) has no difference between the two groups (P > 0.05). Conclusion: The ultrasonic-guided betamethasone local injection and extracorporeal shock wave both can improve hemiplegic shoulder pain. However, the UGLI can induce a more cytokine expression level.

LINC00938 alleviates hypoxia ischemia encephalopathy induced neonatal brain injury by regulating oxidative stress and inhibiting JNK/p38 MAPK signaling pathway.

Hypoxic-ischemic encephalopathy (HIE) is an important factor leading to permanent damage of central nervous system (CNS) and even neonatal death. Long non-coding RNAs (lncRNAs) has been shown to get involved in the pathogenesis of nervous system diseases. LINC00938 is an intergenic lncRNA which is reported to be involved in neurodegenerative disease. However, the potential role of LINC00938 in nerve injury of neonatal HIE is undetermined. Here, we found that the expression of LINC00938 in the whole blood of neonates with HIE was downregulated compared with the non-HIE group. Functional study revealed that the expression of LINC00938 was significantly decreased in oxygen-glucose deprivation (OGD)-induced SH-SY5Y. Knockdown of LINC00938 induced the neural cell apoptosis by increased the protein level of Bax, Cleaved-Caspase3 and decreased the expression of Bcl-2. In addition, overexpression of LINC00938 prevented the apoptosis of SH-SY5Y from OGD injury. RNA-seq analysis showed that MAPK signaling was involved in the anti-apoptosis function of LINC00938. LINC00938 knockdown induced the activation of c-Jun-N-terminal kinase (JNK), p38 mitogen-activated protein kinase, and inhibited the activation of ERK signaling. However, LINC00938 play neuroprotective role in OGD-induced SH-SY5Y by suppression the phosphorylation of JNK and p38 MAPK rather than regulation of ERK signaling pathway. Further analyses illustrated that the cell apoptosis of neuronal cell was dependent on the elevation of reactive oxygen species (ROS) and result in mitochondria dysfunction in LINC00938 knockdown SH-SY5Y. Pretreated with ROS inhibitor N-acetylcysteine amide (NACA) dramatically suppressed LINC00938 knockdown induced oxidative stress and mitochondria dysfunction which induced cell apoptosis. In addition, NACA treatment significantly reduced the expression of p-JNK and p-p38 in OGD-induced SH-SY5Y. Furthermore, overexpression of LINC00938 displayed a notably neuroprotective effect by suppress central nervous system cell apoptosis via alleviating oxidative stress in CoCl2-induced hypoxic HIE model of zebrafish. Taken together, these results suggested that LINC00938 can act as a neuroprotective factor to inhibit oxidative stress and apoptosis of CNS under HIE conditions.

Effect of Different Ameliorants on the Infiltration and Decontamination Capacities of Soil.

The expansion of urban construction areas can reduce the infiltration rate of rainwater in permeable land, and a large amount of runoff rainwater cannot penetrate the soil. In extreme rainstorm weather, it is easy to cause serious urban waterlogging problems. To improve the infiltration and decontamination ability of green space soil, two types of inorganic ameliorants (i.e., sand and grain shell) and structural ameliorants (i.e., desulfurization gypsum and polyacrylamide) were utilized as amendments in the soil. The influence of the selected ameliorants on the infiltration and decontamination ability was analyzed through a soil infiltration test, soil pore distribution determination and a soil decontamination test. Three parameters including the soil infiltration rate, pore distribution characteristics and pollutant removal rate were proposed. The results showed that sand, grain shells and desulfurization gypsum (FGD gypsum) all enhanced the infiltration capacity of soil, while PAM decreased the infiltration capacity. Meanwhile, mixed sand and grain shell with the FGD gypsum and polyacrylamide can effectively improve the decontamination capacity of the soil. Comprehensive analysis showed that the better improvement combination is 10% sand + 20% grain hull + 0.5 g/kg FGD gypsum + 0.1 g/kg PAM.

Clinical study on swallowing function of brainstem stroke by tDCS.

OBJECTIVE: To investigate the effect of transcranial direct current stimulation (tDCS) combined with conventional comprehensive rehabilitation on dysphagia after brainstem stroke. MATERIALS AND METHODS: Forty brainstem stroke patients were randomly divided into tDCS group and conventional comprehensive treatment group, including 20 patients in each group. Both groups were given routine swallowing function training, and tDCS group added transcranial direct current stimulation (tDCS). The Dysphagia Outcome and Severity Scale (DOSS) and Functional Dysphagia Scale (FDS) were evaluated respectively before and after 8 weeks of continuous treatment with VFSS. The white blood cell (WBC), c-reactive protein, prealbumin (PAB), albumin (Alb), and hemoglobin (Hb) were also compared between the two groups before and after 8 weeks of continuous treatment. RESULTS: After 8 consecutive weeks of treatment, the score of DOSS scale and FDS scale in both groups was improved (P < 0.05), WBC and CRP were decreased (P < 0.05), and Alb and Hb were improved (P < 0.05), and PAB had no differences (P=0.474). The tDCS group was superior to conventional comprehensive group in improving the swallowing function and nutritional indexes (P < 0.05). CONCLUSIONS: tDCS therapy combined with routine training can improve the swallowing function and nutritional status of patients, and reduce infection.

Effects of mirror neuron system-based training on rehabilitation of stroke patients.

OBJECTIVE: To investigate the clinical effects of the mirror neuron system (MNS)-based training on upper extremity motor function and cognitive function in stroke patients. METHODS: Sixty stroke patients (time from stroke onset 3-9 months) with upper extremity paresis (Brunnstrom stage II-IV) and cognitive impairment (MoCA score ≥ 15) were enrolled in this study. Patients were randomly allocated into MNS treatment group (N = 30) and control group (N = 30). Both groups underwent regular training for upper extremity motor function and cognitive function, and the MNS group was trained with a therapeutic apparatus named mirror neuron system training (MNST) including different levels of action observation training (AOT). Training lasted 20 min/day, 5 days/week for 8 weeks. MoCA, reaction time, and Wisconsin Card Sorting Test (WCST) were assessed at baseline and 8 weeks after training. Furthermore, Fugl-Meyer assessment (FMA) and Modified Barthel index (MBI) were adopted to evaluated upper extremity motor function and daily life ability. RESULTS: After 8 consecutive weeks' training, both groups showed significant improvements on the upper extremity motor function, cognitive function, and daily life ability score after training (p < .05). The MNS group showed significantly improved upper extremity motor function and cognitive function (p < .05) compared with control group. CONCLUSIONS: Combining MNS-based and conventional training can improve upper extremity motor function and cognitive function in stroke patients.

Wnt pathway is involved in 5-FU drug resistance of colorectal cancer cells.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. 5-Fluorouracil (5-FU) is widely used in the treatment of cancers, but its antineoplastic activity is limited in drug-resistant cancer cells. To investigate the detailed mechanism of 5-FU resistance, we developed a model of 5-FU-resistant cells from HCT-8 cells, a well-established colorectal cancer cell line. We found that the drug-resistant cells demonstrated high expression of TCF4 and ß-catenin, indicating an upregulated Wnt pathway. A microarray analysis revealed that the suppression of the checkpoint kinase 1 (CHK1) pathway explained the resistance to 5-FU, especially in p53 wild-type cancer cells such as HCT-8. Our data also demonstrated that the CHK1 pathway is suppressed by the Wnt pathway in 5-FU-resistant cells. In summary, we have discovered a novel mechanism for 5-FU resistance mediated by histone deacetylation, which also revealed the crosstalk between the Wnt pathway and CHK1 pathway.

Synergistic antitumor effect of combined paclitaxel with FEN1 inhibitor in cervical cancer cells.

Studies on cervical cancer are urgently required to improve clinical outcomes. As a major anticancer drug for cervical cancer, paclitaxel has been used for many years in clinical therapy but its therapeutic efficacy is limited by common obstacle from cancer cells. The enhanced DNA repair pathways of cancer cells have been proved to survive DNA damage induced by chemotherapeutic drug. Inhibitors of specific DNA repair pathway can sensitize cancer cells to the treatment of chemotherapeutic drugs. In this paper we found that the effect of paclitaxel can be significantly improved when used in combination with FEN1 inhibitor SC13, suggesting a synergistic mechanism between the two compounds. Our studies suggest that FEN1 inhibition could be a novel strategy of tumor-targeting therapy for cervical cancer. Our work also revealed that paclitaxel demonstrates stronger synergistic effect with SC13 than other common used chemical drugs such as doxorubicin, carboplatin or camptothecin on cervical cancer cells.

Selection and characterization of human PCSK9 antibody from phage displayed antibody library.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), which involves in low-density lipoprotein cholesterol (LDL-C) metabolism by interacting with the LDL receptor, is considered as a potent therapeutic target for treating hypercholesterolemia. Here, a fab antibody phage display library was constructed and employed for bio-panning against recombinant PCSK9. A Fab fragment (designated PA4) bound with high affinity to PCSK9 was isolated after four rounds of panning. The fully human antibody IgG1-PA4 bound specifically to PCSK9 with nanomolar affinity. In vitro, IgG1-PA4 inhibited PCSK9 binding to LDLR and attenuated PCSK9-mediated degradation of LDLR on the HepG2 cell surface. In C57BL/6 mice, administration of IgG1-PA4 at 30 mg/kg increased hepatic LDLR protein levels by as much as 3 fold when compared with control. Taken together, these results suggested that the IgG1-PA4 can be served as a potential candidate for the treatment of hypercholesterolemia by inhibiting PCSK9-mediated degradation of cell surface LDLRs.