Safety and immunogenicity of inactivated COVID-19 vaccine CoronaVac and the RBD-dimer-based COVID-19 vaccine ZF2001 in chronic hepatitis B patients.

Background and aims: Although COVID-19 vaccination is recommended for the patients with chronic liver disease, the clinical outcomes of COVID-19 vaccinated in patients with chronic hepatitis B (CHB) has not been well characterized. The study aimed to explore the safety and specific antibody responses following COVID-19 vaccination among CHB patients. Methods: Patients with CHB were included. All patients were vaccinated with two doses of inactivated vaccine (CoronaVac) or three doses of adjuvanted protein subunit vaccine (ZF2001). The adverse events were recorded and neutralizing antibody (NAb) were determined 14 days following the whole-course vaccination. Results: A total of 200 patients with CHB were included. Specific NAb against SARS-CoV-2 were positive in 170 (84.6%) patients. The median (IQR) concentrations of NAb were 16.32 (8.44-34.10) AU/ml. Comparison of immune responses between CoronaVac and ZF2001 vaccines showed no significant differences in neither the concentrations of NAb nor the seropositive rates (84.4 vs. 85.7%). Moreover, we observed lower immunogenicity in older patients and in patients with cirrhosis or underlying comorbidities. The incidences of adverse events were 37 (18.5%) with the most common adverse event as injection side pain [25 (12.5%)], followed by fatigue [15 (7.5%)]. There were no differences in the frequencies of adverse between CoronaVac and ZF2001 (19.3% vs. 17.6%). Almost all of the adverse reactions were mild and self-resolved within a few days after vaccination. Severe adverse events were not observed. Conclusions: COVID-19 vaccines, CoronaVac and ZF2001 had a favorable safety profile and induced efficient immune response in patients with CHB.

WZ4003 sensitizes non-small cell lung cancer cells to gefitinib via inhibition of ARK5 and epithelial-to-mesenchymal transition.

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, is used as a first-line treatment for advanced non-small cell lung cancer (NSCLC); however, its utility is hampered by the development of chemoresistance. This study aimed to investigate the synergistic role of WZ4003, a novel (nua) kinase (NUAK) inhibitor, in enhancing gefitinib sensitivity in NSCLC cells. Our data indicated WZ4003 enhances the sensitivity of NSCLC cells to gefitinib. We also found ARK5 knockdown in NSCLC cell lines increased their sensitivity to gefitinib. However, WZ4003 did not affect gefitinib sensitivity when ARK5 was knocked down in NSCLC cell lines (using siRNA). Both WZ4003 and ARK5 inhibition suppressed epithelial-to-mesenchymal transition by reducing the expression of vimentin and increasing E-cadherin expression. Together, our results demonstrate WZ4003 plays a vital role in releasing acquired resistance to gefitinib by inhibiting ARK5 and epithelial-to-mesenchymal transition. Therefore, synergistic use of WZ4003 and gefitinib may prevent the development of gefitinib resistance in NSCLC.

Chinese guidelines for the diagnosis and treatment of hand, foot and mouth disease (2018 edition).

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treatments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed. METHODS: National Health Commission of China assembled an expert committee for a revision of the guidelines. The committee included 33 members who are specialized in diagnosis and treatment of HFMD. RESULTS: Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia; (2) involvement of nervous system; (3) worsening respiratory rate and rhythm; (4) circulatory dysfunction; (5) elevated peripheral WBC count; (6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases. CONCLUSION: The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

High CHD9 expression is associated with poor prognosis in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma. The chromo-helicase-DNA binding proteins (CHDs), containing nine members named CHD1-9, act as regulators of the chromatin remodeling process and gene expression. To determine the correlation between CHD9 expression and ccRCC, we performed an immunohistochemical staining in a tissue microarray (TMAs) containing tissue samples from 88 ccRCC patients. The results showed that cytoplasm CHD9 expression was statistically decreased in tumor tissues compared to adjacent tissues (8.54±2.90 vs 12.61±2.05, P=0.000), while nuclear CHD9 expression was upregulated in the tumor tissues (1.47±2.93 vs 0.29±1.24, P=0.000). A univariate analysis found that cytoplasm CHD9 expression in cancer tissues was correlated with the patients' pathological grading (P=0.002, r=0.330), the clinical stages (P=0.02, r=0.250) and the T grading (P=0.024, r=0.241) significantly. In addition, cytoplasm CHD9 expression in non-tumor tissues was correlated with the ccRCC patients' pathological grading (P=0.031, r=-0.231) significantly. Patients with high cytoplasm CHD9 expression had a significantly worse prognosis than those with low cytoplasm CHD9 expression levels (59.7% vs 85.7%, P=0. 042). In conclusion, our study indicated the important role of CHD9 in ccRCC and suggested CHD9 may be a potential biomarker for prognostic prediction and a new target for therapy.