Clinical characteristics of 41 patients with pneumonia due to 2019 novel coronavirus disease (COVID-19) in Jilin, China.

BACKGROUND: The clinical characteristics of patients with confirmed 2019 novel coronavirus disease (COVID-19) in Jilin Province, China were investigated. METHODS: Clinical, laboratory, radiology, and treatment data of 41 hospitalized patients with confirmed COVID-19 were retrospectively collected. The population was stratified by disease severity as mild, moderate, or severe, based on guidelines of the National Health and Medical Commission of China. RESULTS: The 41 hospitalized patients with COVID-19 were studied, and the median age was 45 years (interquartile range [IQR], 31-53; range, 10-87 years) and 18 patients (43.9%) were female. All of the patients had recently visited Wuhan or other places (ie, Beijing, Thailand) or had Wuhan-related exposure. Common symptoms included fever (32[78%]) and cough (29[70.7%]). All patients were without hepatitis B/C virus hepatitis. CRP (C-reactive protein, 11.3 mg/L [interquartile range {IQR}, 2.45-35.2]) was elevated in 22 patients (53.7%), and cardiac troponin I (1.5 ng/mL [IQR, 0.8-5.0]) was elevated in 41 patients (100%). Chest computed tomographic scans showed bilateral ground glass opacity (GGO) or GGO with consolidation in the lungs of 27(65.9%) patients. 31(75.6%) patients had an abnormal electrocardiograph (ECG). Comparing the three groups, the levels of CRP and cardiac troponin I, GGO distribution in bilateral lungs, and electrocardiogram changes were statistically significant (p < 0.05). Cardiac troponin I had a strong positive correlation with CRP (r = 0.704, p = 0.042) and LDH (r = 0.738, p = 0.037). CONCLUSION: Significant differences among the groups suggest that several clinical parameters may serve as biomarkers of COVID-19 severity at hospital admission. Elevated cTnI could be considered as a predictor of severe COVID-19, reflecting the prognosis of patients with severe COVID-19. The results warrant further inspection and confirmation.

Monitoring the course of Brucella infection with qPCR-based detection.

OBJECTIVES: To determine blood Brucella DNA loads between brucellosis patients and those without brucellosis. METHODS: The patient group included 350 brucellosis patients. The control was composed of 200 subjects without brucellosis. The extracted DNA from blood was tested by quantitative polymerase chain reaction (qPCR). The cutoff value was determined by receiver operating characteristic curve analysis. A portion of the brucellosis patients were monitored by qPCR during therapy. RESULTS: The detection limit of qPCR was between 1E+01cfu/µL and 1E+08cfu/µL. The standard curve R2 reached 0.998. The cutoff value was 4E+01cfu/µL, which was determined by comparison of the patient group and the control. The qPCR assay had a specificity of 100% and a sensitivity of 93.14%. The monitoring results showed that the Brucella DNA load decreased in most patients during the first 4 weeks of treatment. One patient with bad treatment compliance showed a rebound. CONCLUSIONS: The qPCR results were in accordance with the course of brucellosis in the clinic. The DNA load often reflects the situation of the Brucella-infected patient. The cutoff value provides an important reference of infection. This qPCR-based method can be used to assist in the diagnosis of brucellosis and to adjust the therapy.

Resveratrol­loaded nanoparticles inhibit enterovirus 71 replication through the oxidative stress­mediated ERS/autophagy pathway.

A number of studies have demonstrated that resveratrol (RES) has a variety of biological functions, including cardiovascular protective effects, treatment of mutations, and anti­inflammatory, anti­tumor and antiviral effects. In the present study, RES­loaded nanoparticles (RES­NPs) were used to protect rhabdosarcoma (RD) cells from enterovirus 71 (EV71) infection, and the relevant mechanisms were also explored. An amphiphilic copolymer, monomethoxy poly (ethylene glycol)­b­poly (D,L­lactide), was used as vehicle material, and RES­NPs with necessitated drug­loading content and suitable sizes were prepared under optimized conditions. RES­NPs exhibited the ability to inhibit the increase of intracellular oxidative stress. The prospective mechanism for the function of RES­NPs suggested was that RES­NPs may inhibit the oxidative stress­mediated PERK/eIF2α/ATF4 signaling pathway, downregulate the autophagy pathway and resist EV71­induced RD cells injury. Furthermore, RES­NPs treatment markedly inhibited the secretion of inflammatory factors, including interleukin (IL)­6, IL­8 and tumor necrosis factor­α elicited by EV71 infection. Concomitantly, inhibitors of oxidative stress, endoplasmic reticulum stress (ERS) or autophagy were demonstrated to negate the anti­inflammatory and antiviral effects of RES­NPs on EV71­infected RD cells. These results demonstrated that RES­NPs attenuated EV71­induced viral replication and inflammatory effects by inhibiting the oxidative stress­mediated ERS/autophagy signaling pathway. In view of their safety and efficiency, these RES­NPs have potential applications in protecting RD cells from EV71 injury.

Antitumor potential of a novel camptothecin derivative, ZBH-ZM-06.

Camptothecin (CPT) is a cytotoxic quinoline alkaloid that is used clinically as an anticancer drug. However, the clinical application of CPT is limited due to its low solubility as well as serious and unfathomable side-effects. In the present study, we created a novel 10-hydroxy CPT prodrug, ZBH-ZM­06. Its cellular cytotoxic activity was analyzed in terms of cellular viability, acetylcholinesterase (AchE) inhibition, DNA relaxation, cellular cycling and apoptosis properties. Our results showed that the AchE inhibition rate of 10 µmol/l ZBH-ZM-06 was 12.5%, compared to 96.5% for carbonyl-oxycamptothecin (CPT-11). In a chemical stability assay, only 4.9% of ZBH-ZM-06 remained after 4 h at pH 7.4. In addition, 10 µmol/l ZBH-ZM-06 significantly inhibited the tumor cell viability of nine tumor cell lines, compared to CPT-11 and the CPT active ingredient, 7-ethyl-10-hydroxy-camptothecin (SN38) (p<0.01-0.05). In the apoptosis assay, ZBH-ZM-06 increased the ratio of annexin V+/propidium iodide (PI)-/+ cells by flow cytometric analysis (p<0.05). Moreover, ZBH-ZM-06 activated caspase-3 and poly(ADP-ribose)polymerase (PARP) expression by immunoblotting. Furthermore, ZBH-ZM-06 induced a greater G2/M phase arrest ratio, compared to CPT-11 and SN38. These results indicated that ZBH-ZM-06 had higher antitumor activity than CPT-11 and SN38, which was shown by its: i) release of the effective ingredient; ii) growth inhibition of a broad spectrum of tumor cells; iii) inhibition of DNA topoisomerase (Topo-1); and iv) promotion of apoptosis through an intrinsic signaling pathway. Thus, ZBH-ZM-06 may be applied in the preclinic study for cancer treatment.

[Cleavage of HCV by HCV specific deoxyribozyme in vitro].

OBJECTIVE: To study the cleavage activity of specific deoxyribozyme to hepatitis C virus in vitro. METHODS: Three deoxyribozymes were designed to cleave at sites 157, 168, 173 in HCV 5'-noncoding region with the active region of 5'-GGCTAGCTACAACGA-3' respectively. Plasmid pCMV/T7-NCRC -Delta Luc was completely linearized with restriction endonuclease Xba I. HCV RNA5'-NCRC was transcribed in vitro from the linearized products and radiolabelled with [alpha-32P] UTP. Under the conditions of 37 degrees C, pH7.5, Mg2+ 10 mmol/L, the three deoxyribozymes were mixed with substrate RNA individually for 120 minutes and then the reactions were terminated. The cleavaged products were separated with 8% denaturated polyacrylamide gel electrophoresis and displayed by autoradiography. DRz3 was mixed with the substrate RNA at different Mg2+ concentrations. The cleavage efficiency was analyzed with a gel document action analyzing systems. RESULTS: Under the adopted conditions the three deoxyribozymes efficiently cleaved to the target RNA in vitro and the cleavage activity of DRz3 was increased with the increase of Mg2+ concentration. CONCLUSION: The designed deoxyribozymes can cleave 5'-NCR mRNA of HCV efficiently in vitro and it is dose-respondent to Mg2+ concentration.

[Clinical and experimental study of xiaoshui decoction in the treatment of primary liver cancer caused ascites].

OBJECTIVE: To observe the clinical efficacy of Xiaoshui Decoction (XSD) in treating ascites in patients suffered from primary liver cancer of Pi-deficiency with damp harassment syndrome (PDDHS) as well as to study the effect through the experiment in mice. METHODS: Sixty-one patients confirmed to be primary liver cancer of PDDHS and accompanied with ascites were randomly divided into the treated group (n=33) and the control group (n=28). The treated group was treated by XSD combined with chemotherapy by locally applying of DDP via abdominal infusion, while the control group treated by DDP infusion alone. The treatment lasted for two months. The conditions of ascites, quality of life (QOL), survival period, and TCM syndrome after treatment were observed. In the experimental study, the mice models of ascites were grouped and treated to observe the conditions of ascites and their survival period. RESULTS: The short-term total effective rate of the treated group and the control group was 42.4% and 21.4%, the interval of aspirating ascites after treatment was 17.95 +/- 9.63 days and 10.87 +/- 7.76 days, and the 1-year survival rate 33.3% and 14.3%, respectively, significant difference was shown between the two groups in the three parameters (all P < 0.05 ). QOL was improved in both groups with insignificant difference (P > 0.05). Besides, the main symptoms were improved in patients of both groups, especially in the ameliorating of fatigue, abdominal distension, nausea and vomiting. Evaluation on safety of treatment showed that XSD had no obvious toxic and adverse reaction, and so it was safe in use. Experimental study showed that on the two mice models of ascites induced by inoculating two kinds of tumor cell, the effect of XSD was superior to that of the control group in aspects of reducing ascites and prolonging survival period, showing significant difference (P < 0.05). CONCLUSION: Satisfactory short-term efficacy in treating primary liver cancer with ascites of the Pi-deficiency with damp harassment syndrome could be obtained by XSD. Its effect in prolonging survival period was confirmed by experimental study. XSD can also improve the symptoms and QOL of patients, therefore, it is an effective and reliable remedy for treatment of primary liver cancer with ascites.