A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity.

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

Effects of 12 weeks of Tai Chi Chuan intervention on the postural stability and self-reported instability in subjects with functional ankle instability: Study protocol for a randomized controlled trial.

Background: Tai Chi Chuan (TCC) is a physical activity modality that originated in China and is now widely popular around the world. Although there are a series of articles reporting that TCC can improve balance and other functional symptoms in a variety of populations, including the elderly, patients with stroke, and patients with Parkinson's disease, its efficiency has not been scientifically and methodically evaluated in subjects with functional ankle instability (FAI). Moreover, there is no literature directly comparing TCC and conventional balance training (CBT) interventions for FAI. The objective of this study is to investigate the comparative effects of TCC intervention and CBT protocols in improving postural balance and subjective instability feelings in patients with FAI. Methods: This study will be a single-center, parallel group, randomized controlled trial. Sixty-eight patients with FAI will be included and randomly assigned in a 1:1 ratio to either an intervention group (n =34) or a control group (n = 34). The participants in the intervention group will complete 12 weeks of TCC intervention (40 min/time, 3 times/week for 12 weeks) on the basis of health education treatment. The control group will receive health education and 36 CBT sessions during a 12-week period. Outcome measures include postural stability and self-reported feelings of instability at baseline, after the end of the intervention, and 3-month follow-up. The postural stability assessment of patients with FAI will be detected by performing static and dynamic postural tests, which will be carried out through a specific balance platform (TecnoBody ProKin). Self-reported feelings of instability will be assessed by Cumberland Ankle Instability Tool (CAIT), American Orthopedics Foot and Ankle Society's Ankle-Hindfoot Evaluation Scale (AOFAS-AHES), and the MOS item Short Form Health Survey (SF-36). Discussion: This trial will demonstrate whether a 12-week TCC intervention positively affects postural stability and self-reported outcomes in patients with FAI. At the same time, the superiority of its clinical efficacy will also be compared with that of CBT. This study may also help to redefine the value of traditional Chinese exercises in the treatment of chronic ankle instability. Clinical trial registration: Chinese Clinical Trial Registry: ChiCTR2100041790. Registration date: 22 March 2021. http://www.chictr.org.cn/edit.aspx?pid=119501&htm=4.

Correlation between BRCA1 and TopBP1 protein expression and clinical outcome of non-small cell lung cancer treated with platinum-based chemotherapy.

PURPOSE: To investigate the correlation between protein expression of breast cancer susceptibility gene 1 (BRCA1) and topoisomerase IIß-binding protein 1 (TopBP1) and clinical outcome of non-small cell lung cancer treated with platinum-based chemotherapy. METHODS: Immunohistochemical staining was conducted to detect the protein expression of BRCA1 and TopBP1 in 101 cases of NSCLC and to correlate these with clinical features, disease progression, and patient survival. Chi-square test (χ (2)-test) was used to evaluate categorical variables. Spearman's rank order correlation was used to analyze continuous variables. Overall survival rate of NSCLC patients was analyzed by Kaplan-Meier survival curve and log-rank test. Relevant factors affecting the survival of patients with advanced NSCLC were analyzed by COX proportional hazards regression model. RESULTS: A total of 101 NSCLC patients were included in the present study. In tumor tissue specimens, positive expression rates of BRCA1 and TopBP1 proteins were 51.5 and 57.4 %, respectively. A significant correlation between the positive expression of BRCA1 and the positive expression of TopBP1 was observed (P < 0.001, r = 0.326). No significant correlation between BRCA1/TopBP1 and age, gender, smoking status, performance status score, pathohistological type, or clinical stage was detected (P > 0.05). During the follow-up period, 65 patients died, and 86 patients showed progression at the end of the study. The survival rate of patients with negative BRCA1 protein expression was higher than that in patients with positive BRCA1 protein expression [median overall survival (OS) 34 vs. 21 months, HR 1.913, 95 % CI 1.161-3.150, P = 0.011]. Similarly, the survival rate of patients with negative TopBP1 expression was higher than that in patients with positive TopBP1 (median OS 36 vs. 23 months, HR 1.931, 95 % CI 1.157-3.224, P = 0.012). No significant correlation between protein expression of BRCA1 or TopBP1 with NSCLC disease progression was observed (P > 0.05). CONCLUSIONS: The present study indicates NSCLC patients with negative BRCA1 and TopBP1 expression showed better prognosis than those with positive protein expression.

Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway.

Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromises its efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620) long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX). Compared with parental cell lines, IC50s for various chemotherapeutic agents (oxaliplatin, cisplatin and doxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclear factor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1). Furthermore, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and GSTα1/2] expression and decreased reduced glutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/- mice. Luteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to the development of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell lines to chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeutic response.

Integration of the Image-Guided Surgery Toolkit (IGSTK) into the Medical Imaging Interaction Toolkit (MITK).

The development cycle of an image-guided surgery navigation system is too long to meet current clinical needs. This paper presents an integrated system developed by the integration of two open-source software (IGSTK and MITK) to shorten the development cycle of the image-guided surgery navigation system and save human resources simultaneously. An image-guided surgery navigation system was established by connecting the two aforementioned open-source software libraries. It used the Medical Imaging Interaction Toolkit (MITK) as a framework providing image processing tools for the image-guided surgery navigation system of medical imaging software with a high degree of interaction and used the Image-Guided Surgery Toolkit (IGSTK) as a library that provided the basic components of the system for location, tracking, and registration. The electromagnetic tracking device was used to measure the real-time position of surgical tools and fiducials attached to the patient's anatomy. IGSTK was integrated into MITK; at the same time, the compatibility and the stability of this system were emphasized. Experiments showed that an integrated system of the image-guided surgery navigation system could be developed in 2 months. The integration of IGSTK into MITK is feasible. Several techniques for 3D reconstruction, geometric analysis, mesh generation, and surface data analysis for medical image analysis of MITK can connect with the techniques for location, tracking, and registration of IGSTK. This integration of advanced modalities can decrease software development time and emphasize the precision, safety, and robustness of the image-guided surgery navigation system.

Ultrasonic elastography in clinical quantitative assessment of fatty liver.

AIM: To investigate the clinical application of ultrasonic elastography in quantitative assessment of fatty liver grading. METHODS: A total of 105 patients with fatty liver were divided into mild group (n = 46), moderate group (n = 39), and severe group (n = 20). Forty-five healthy individuals served as a normal control group. All patients who underwent routine ultrasound scan and further ultrasonic elastography were evaluated accordingly to the evaluation standards for ultrasonic elastography. The ratio of surface areas of blue region/total surface area in the desired region was measured. RESULTS: Ultrasonic elastography technique, in comparison to traditional ultrasound, had a rather high consistence in grading of fatty liver [κ value = (95.3%-63.6%)/(1%-63.6%) = 0.87, P = 0.001]. The score of ultrasonic elastography increased with the severity of fatty liver with a sensitivity of 97.14% and a specificity of 91.11%. A significant difference was found in the ratio of surface areas of blue regions between different groups (P < 0.05). CONCLUSION: Ultrasonic elastography can be used in quantitative assessment of the severity of fatty liver.

Effects of transferred NK4 gene on proliferation, migration, invasion and apoptosis of human prostate cancer DU145 cells.

We investigated the ability of NK4, an antagonist of human hepatocyte growth factor (HGF), to inhibit the influence of HGF on proliferation, migration, invasion and apoptosis of human prostate cancer cells. Expression vector pBudCE4.1-EGFP-NK4 containing NK4 cDNA was used to transfect human prostate cancer DU145 cells, and the effects of the autocrine NK4 on tumor cell proliferation, migration, invasion and apoptosis were assessed in vitro. In vivo, we subcutaneously implanted DU145 cells, mock-transfected clone (DU145/empty vector) cells and NK4-transfected clone (DU145/NK4) cells into nude mice, and then evaluated tumor growth, cell proliferation and cell apoptosis in vivo. We found that DU145/NK4 cells expressed NK4 protein. In the in vitro study, autocrine NK4 attenuated the HGF-induced tumor cell proliferation, migration and invasion, and stimulated apoptosis. Furthermore, autocrine NK4 effectively inhibited the HGF-induced phosphorylation of c-Met, extracellular signal-regulated kinase-1 (ERK1). and protein kinase B 1/2 (Akt1/2). Histological examination revealed that autocrine NK4 inhibited proliferation and accelerated apoptosis of prostate cancer cells. These results show that genetic modification of DU145 cells with NK4 cDNA yields a significant effect on their proliferation, migration, invasion and apoptosis. Molecular targeting of HGF/c-Met by NK4 could be applied as a novel therapeutic approach to prostate cancer.

Epidemiological investigation on Wenchuan earthquake-struck trauma patients admitted to two hospitals of Chongqing.

OBJECTIVE: To study epidemiological characteristics and influential factors of in-hospital patients struck by the Wenchuan earthquake disaster. METHODS: The clinical data of 196 cases were collected from 2 hospitals of Chongqing city, including age, sex, occupation, injury site, dwelling and injury severity score. RESULTS: In this series, 31.63% victims'age was over 60 years, and 54.08% were farmers. Multiple trauma accounted for 35.71%, and lower limb injury for 33.67%. There was no significant difference on injury severity score between city dwellers and rural ones (P>0.05). CONCLUSION: The earthquake injury is influenced by many factors. More attention should be paid to the treatment at first 5 days after injury and high risk population.

Constructing channel structures based on the assembly of p-sulfonatocalix[4]arene nanocapsules and [M(bpdo)3]2+ (M=Cu, Zn).

Novel channel structures based on [M(bpdo)(3)](2+) and p-sulfonatocalix[4]arene nanocapsules have been established; these are sustained exclusively by charge-assisted pi...pi interactions and sorption experiments show the porous materials have selective guest sorption properties.

A new system in organooxotin cluster chemistry incorporating inorganic and organic spacers between two ladders each containing five tin atoms.

Hydrolysis of dibenzyltin dichloride in ethanol has been found to give an unprecedented carbonate anion (CO(3) (2-))-bridged double-ladder organooxotin cluster, [(R(2)SnO)(3)(R(2)SnOH)(2)(CO(3))](2) (1, R = C(6)H(5)CH(2)), with five tin atoms in each ladder. With the aim of obtaining organooxotin clusters with large cavities suitable for host-guest chemistry, we used 1,1'-ferrocenedicarboxylic acid (H(2)L(a)) and hexanedioic acid (H(2)L(b)) to replace the carbonate anions (CO(3) (2-)), and thereby clusters [(R(2)SnO)(3)(R(2)SnOH)(2)L(a)](2) (2) and [(R(2)SnO)(3)(R(2)SnOH)(2)L(b)](2) (3) were obtained. When 1 was treated with benzoic acid (HL(c)) in different stoichiometric ratios (1:4, 1:10), ladder cluster (R(2)SnO)(3)(R(2)SnOH)(2)(L(c))(2) (4) and drum cluster [RSn(O)L(c)](6) (5) were obtained. Through the hydrolysis of Cy(2)SnCl(2) (Cy = C(6)H(11)) and (C(6)H(5)CH(2))(2)SnCl(2), two interesting ethanolate-modified clusters [Cy(2)(C(2)H(5)O)SnOSn(C(2)H(5)O)Cy(2)](2) (6) and [(R(2)SnO)(3)(R(2)SnOH)(R(2)SnOC(2)H(5))(CO(3))](2) (7) were obtained. All the tin atoms in these ladder clusters are five-coordinate surrounded by two alkyl groups and three O atoms, and have distorted trigonal-bipyramidal coordination environments with two carbon atoms and one O atom in the equatorial positions and two O atoms in the axial positions. The structures of all these compounds have been established by single-crystal X-ray diffraction analyses.