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COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.
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Objective To evaluate the effect on nexible ureteroscope one-step treat and step-by-step treat for impacted upper ureteral calculi. Methods The clinical data of 98 cases of impacted upper ureteral calculi were retrospectivelv analvzed between January 2016 and January 2018. The one-step nexible ureteroscopic lithotripsy was used in 48 cases (observation group), and the step-by-step nexible ureteroscopic lithotripsy was used in 50 cases (control group). During the one-step nexible ureteroscopic lithotripsy, only flexible ureteroscope was used to crush the stone, no matter whether the stone located in the ureter or returned to the renal pelvis. During step-by-step nexible ureteroscopic lithotripsy, the rigid ureteroscopy was firstly used for crushing the stone in the ureter. When the stone returned to the renal pelvis, the rigid ureteroscopy was changed into nexible uretemscope for continuous crushing the stone. Operating time, 2 weeks stone clearance rate and the cases of fever after operation were compared between two groups. Results Compared with that of the control group, the operation time of the observation group was significantly shortened [(38.3 ± 10.5) min vs. (55.1 ± 12.7) min, t=-6.415], and the proportion of postoperative body temperature ≥ 38.5 ℃ was also reduced [(4.2％ (2/48) vs. 22.0％(11/50), χ2=5.276]. The differences between the two groups were statistically significant (P<0.05). Two weeks stone clearance rate was 89.6％(43/48) in observation group and 82.0％(41/50)in control group, and there was no significant difference between two groups (χ2=0.493, P > 0.05). Conclusions Flexible ureteroscope one-step method is a safe and effective alternation for incarcerated upper ureteral calculi.
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Objective@#To investigate the safety and efficacy of needle-tract assisted standard percutaneous nephrolithotomy (PCNL) for the treatment of complicated upper urinary tract calculi.@*Methods@#The clinical data of 1 562 patients with complicated upper urinary calculi who received standard PCNL from December 2013 to December 2017 at Department of Urology, the First Affiliated Hospital of Xiamen University were retrospectively analyzed. There were large residual stones in 256 patients through B-ultrasound exploration after standard PCNL, could′t be detected with nephoscope in standard PCNL tracts. 16 F mini PCNL tract were established in 120 cases for treatment of residual stones, while needle-tract were established in order to guide nephroscope to find residual stones in 126 cases. Needle-tract were transferred to 16 F mini PCNL tract for treatment of residual stones in 10 patients if these residual stones could′t be detected through needle-tract. Operation time, change of hemoglobin level after operation, incidence of postoperative complications, time of hospitalization and rate of stone clearance were measured in two groups. The statistical methods used included t test, Wilcoxon rank sum test, and χ2 test.@*Results@#There were 1 to 3 mini tracts (M(QR): 1(1)) established in the mini tracts group and 1 to 7 needle-tracts (M(QR): 3(2)) established in the needle-tract group (Z=-10.57, P=0.000). Compared with mini tract group, the operation time ((62.0±18.0) minutes vs. (84.0±15.5) minutes, t=10.242, P=0.000), hospitalization time ((4.40±0.86) days vs. (5.20±0.81) days, t=7.570, P=0.049), hemoglobin dropped ((1.31±0.47) g/L vs. (2.74±0.63) g/L, t=20.12, P=0.000), and incidence of postoperative complications (7.9% (10/126) vs. 19.2% (23/120), χ2=6.674, P=0.01) of needle-tract group were lower, while postoperative stone clearance rate was higher (89.7% vs. 76.7%, χ2=7.497, P=0.006). No perioperative severe complications such as pleural injury, pneumatothorax, perforation of renal, trauma of abdominal organ occurred in two groups.@*Conclusion@#Needle-tract assisted standard PCNL for the treatment of complicated upper urinary calculi can significantly improve stone clearance rate, reduce operation time, decrease risk of kidney and surrounding organs damage.
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As a leading cause of respiratory disease, influenza A virus (IAV) presents a pandemic threat in annual seasonal outbreaks. Given the limitation of existing anti-influenza therapies, there remains to be a requirement for new drugs. Compound Yi-Zhi-Hao pellet (CYZH) is a famous traditional Chinese medicine (TCM) used in the clinic, whose formula has been recorded into treat common cold. In this study, we found that CYZH exhibited a broad-spectrum anti-influenza activity and inhibited the expression of viral RNA and proteins. Mechanistically, CYZH had no inhibitory activities against viral protein hemagglutinin and IAV RNA-dependent RNA polymerase. Instead, it induced activation of erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-B), which subsequently upregulated heme oxygenase-1 (HO-1) expression. Also, CYZH protected cells from oxidative damage induced by reactive oxygen series. In conclusions, CYZH inhibits IAV replication, at least partly by activating expression of the Nrf2/HO-1 pathway.
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Objective To investigate the proportion, risk factors and tendency of the change of stones composition in recurrent urolithiasis. Methods One hundred and fifty-six recurrent urolithiasis patients from January 2011 to January 2016 were enrolled. Compositions of initial and recurrent stones were measured by infrared spectrophotometry. Stones types, recurrence interval and recurrence frequency were studied as potential risk factors for composition change. Chi square test and Logistic regression analysis was employed in the statistical analysis. Results Stones composition changed during recurrence in 48 patients (30.8%). 22.8%(18/79) of calcium oxalate stones change to infection stones, and 25.8%(8/31) of infection stones changed to calcium oxalate. Univariate analysis showed the risk ratio of composition change in the patients with recurrence interval of 1- 5 years was 0.529(P = 0.039) , compared with those of less than 1 year or more than 5 years. Logistic regression analysis showed the odds ratio of recurrence interval of 1- 5 years was 0.242 (95%CI: 0.086- 0.718, P = 0.012). Conclusions Stones composition changes in about 30.8% of recurrent urolithiasis. The mutual conversion between calcium oxalate and infection stones is the most common. Recurrence interval is an independent risk factor to predict composition change.
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Objective To investigate the clinical value of different double-J tube indwelling time in the treatment of ureteral stone-street complications after flexible ureteroscope lithotripsy. Methods Clinical data of 64 kidney calculi patients with ureteral stone-street complications after flexible ureteroscope holmium laser lithotripsy were retrospectively analyzed. The patients were divided into observation group (extubating the double-J tube 2 weeks after the surgery) and control group (retaining the double-J tube) with 32 cases in each group. The calculi clearance results and complication were compared between 2 groups. Results The success rate of stone removal in observation group was significantly higher than that in control group: 100.0% (32/32) vs. 65.6%(21/32), the calculi elimination time was significantly shorter than that in control group:(26.4 ± 6.6) d vs. (45.3 ± 10.9) d, the treatment cost was significantly lower than that in control group:(768.4 ± 152.6) yuan vs. (1 262.3 ± 156.8) yuan, the incidences of irritation symptoms of bladder and macroscopic hematuria were significantly lower than those in control group: 15.6% (5/32) vs. 90.6%(29/32) and 15.6% (5/32) vs. 100.0% (32/32), and there were statistical differences (P0.05). Conclusions Removing the double-J tube 2 weeks after flexible ureteroscope lithotripsy results in higher stone clearance rate and less complications compared with retaining the double-J tube. It can reduce the occurrence of irritation symptoms of bladder, macroscopic hematuria and treatment cost.
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A series of novel N-phenylbenzamide and N-phenylacetophenone compounds were synthesized and evaluated for their antiviral activity against HCV and EV71 (strain SZ-98). The biological results showed that three compounds (23, 25 and 41) exhibited considerable anti-HCV activity (IC50=0.57-7.12 μmol/L) and several compounds (23, 28, 29, 30, 31 and 42) displayed potent activity against EV71 with the IC50 values lower than 5.00 μmol/L. The potency of compound 23 (IC50=0.57 μmol/L) was superior to that of reported compounds IMB-1f (IC50=1.90 μmol/L) and IMB-1g (IC50=1.00 μmol/L) as anti-HCV agents, and compound 29 possessed the highest anti-EV71 activity, comparable to the comparator drug pirodavir. The efficacy in vivo and antiviral mechanism of these compounds warrant further investigations.
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This study is to investigate the effect of recombinant human interferon alpha 2b against broad-spectrum respiratory viruses in vitro. At the cellular level, the effect of the recombinant human interferon alpha 2b on influenza A virus was detected using real-time fluorescence quantitative RT-PCR. The effects of the recombinant human interferon alpha 2b on influenza B virus, parainfluenza virus, respiratory syncytial virus (RSV) and coronavirus were detected using cytopathic effect (CPE) method. In this study, the therapeutic index of recombinant human interferon alpha 2b anti-HPIV was 1476.63, the therapeutic index of recombinant human interferon alpha 2b anti-RSV was 141.37, the therapeutic index of recombinant human interferon alpha 2b anti-coronavirus was more than 2820.76, and the antiviral effect of recombinant human interferon alpha 2b was better than ribavirin (RBV). Recombinant human interferon alpha 2b has a stronger inhibitory effect on different influenza A virus RNA than drug control. The therapeutic index of recombinant human interferon alpha 2b anti-influenza B virus was 2.74, with modest effect. Recombinant human interferon alpha 2b in vitro has broad spectrum antiviral activities, low toxicity and high therapeutic index. Recombinant human interferon alpha 2b is expected to become the efficient medicine in clinical against respiratory viruses, as well as provide better services for prevention and treatment of respiratory viruses' infections.
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Coxsackievirus B type 3 (CVB3) is one of the major causative pathogens associated with viral meningitis and myocarditis, which are widespread in the human population and especially prevalent in neonates and children. These infections can result in dilated cardiomyopathy (DCM) and other severe clinical complications. There are no vaccines or drugs approved for the prevention or therapy of CVB3-induced diseases. During screening for anti-CVB3 candidates in our previous studies, we found that jiadifenoic acids C exhibited strong antiviral activities against CVB3 as well as other strains of Coxsackie B viruses (CVBs). The present studies were carried out to evaluate the antiviral activities of jiadifenoic acids C. Results showed that jiadifenoic acids C could reduce CVB3 RNA and proteins synthesis in a dose-dependent manner. Jiadifenoic acids C also had a similar antiviral effect on the pleconaril-resistant variant of CVB3. We further examined the impact of jiadifenoic acids C on the synthesis of viral structural and non-structural proteins, finding that jiadifenoic acids C could reduce VP1 and 3D protein production. A time-course study with Vero cells showed that jiadifenoic acids C displayed significant antiviral activities at 0-6 h after CVB3 inoculation, indicating that jiadifenoic acids C functioned at an early step of CVB3 replication. However, jiadifenoic acids C had no prophylactic effect against CVB3. Taken together, we show that jiadifenoic acids C exhibit strong antiviral activities against all strains of CVB, including the pleconaril-resistant variant. Our study could provide a significant lead for anti-CVB3 drug development.
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Animal model is very important for anti-EV71 (enterovirus 71) drug and vaccine development. 1-day-old suckling EV71 mouse model is the main in vivo model used in China. 1-day-old suckling EV71 mouse is too small to perform antiviral experiment. And the route of administration and dosage capacity are also restricted. A strong virulence EV71 virus strain was selected after screening from five EV71 strains with 1-day-old suckling mice. A mouse-adapted EV71 strain with increased virulence in 12-day-old suckling mice, EV71-M5, was generated after five serial passages of the parental EV71 strain in mice. Virus titers of EV71 infected mice heart, liver, spleen, lung, kidney, small intestine, brain and muscle tissue were determined by cytopathic effect (CPE) assay. The virus used in this model is the first isolated EV71 strain in China. And 2-week-old suckling mice were used in this model. This is a supplement for the EV71 animal model in China. Establishment of this EV71 model will provide an attractive platform for anti-EV71 vaccine and drug development.