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Objective:To determine the current status of multiple antibiotic residues in meat and meat products in Shanghai based on a 5-year surveillance， and perform the health risk assessment. Methods:We performed the examination in accordance with the Manual for National Food Contamination and Harmful Factor Risk Monitoring， and conduct health risk assessment according to the national limit standards on the monitoring data of 2016‒2020. Results:The total detection rate of multiple antibiotics in meat and meat products in Shanghai was determined to be 16.03%， in which the total unqualified rate was 1.97%. Moreover， the detection rate of quinolones was 2.78% and its unqualified rate was 0.83%. The unqualified rate of loxacin in cooked meat products was 2.12%. The detection rate of tetracyclines was 17.06% and its unqualified rate was 0.34%， in which the highest detection rate was identified in doxycycline （11.64%）. The detection rate of sulfonamides was 3.16%， in which the highest detection rate was in sulfamethazine （1.05%）. The detection rate of florfenicol was 5.15% and its unqualified rate was 0.12%. The difference of ofloxacin residues between diverse food categories （χ2=17.44， P<0.05） and processing links （χ2 =14.10， P<0.05） was statistically significant. In addition， the sum amount of ofloxacin， enrofloxacin and ciprofloxacin in cooked meat products was higher than other food categories； the unqualified rate and residual amount of ofloxacin available in online stores and catering links were both higher. The residual amount of doxycycline and the unqualified rate in the online store link were significantly higher than those in other links. Based on preliminary assessment， the high exposure values in the 97.5 percentile of meat and meat products accounted for a very low proportion of the corresponding acceptable daily intake （ADI） and posed a low health risk to the population. Conclusion:The total detection rate of tetracyclines in meat and meat products is relatively high， which obviously accumulates in the offals of livestock and poultry. In addition， some antibiotics， such as ofloxacin and doxycycline， are relatively high in catering and online stores. It is recommended to strengthen the supervision of quinolones in cooked meat products， especially ofloxacin， enrofloxacin， and ciprofloxacin， and improve the supervision of doxycycline in meat and meat products in online stores.
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The human coronavirus HCoV-19 infection can cause acute respiratory distress syndrome (ARDS), hypercoagulability, hypertension, extrapulmonary multiorgan dysfunction. Effective antiviral and anti-coagulation agents with safe clinical profiles are urgently needed to improve the overall prognosis. We screened an FDA approved drug library and found that an anticoagulant agent dipyridamole (DIP) suppressed HCoV-19 replication at an EC50 of 100 nM in vitro. It also elicited potent type I interferon responses and ameliorated lung pathology in a viral pneumonia model. In analysis of twelve HCoV-19 infected patients with prophylactic anti-coagulation therapy, we found that DIP supplementation was associated with significantly increased platelet and lymphocyte counts and decreased D-dimer levels in comparison to control patients. Two weeks after initiation of DIP treatment, 3 of the 6 severe cases (60%) and all 4 of the mild cases (100%) were discharged from the hospital. One critically ill patient with extremely high levels of D-dimer and lymphopenia at the time of receiving DIP passed away. All other patients were in clinical remission. In summary, HCoV-19 infected patients could potentially benefit from DIP adjunctive therapy by reducing viral replication, suppressing hypercoagulability and enhancing immune recovery. Larger scale clinical trials of DIP are needed to validate these therapeutic effects.
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Objective:To investigate the clinical characteristics of patients with lymphoplasmacytic lymphoma/Waldenstr?m macroglobulinemia (LPL/WM), and the diagnosis and optimal treatment of LPL/WM.Methods:The clinical data of 13 LPL/WM patients treated in Zhongnan Hospital of Wuhan University from January 2013 to June 2018 were retrospectively analyzed, and the literature was reviewed.Results:The median age of 13 patients was 60 years old (35-79 years old). There were 12 males and 1 female. Initial symptom was fatigue or edema of both lower limbs for majority of patients. All patients had immunoglobulin M (IgM) monoclonal, 3 of them had elevated immunoglobulin G (IgG) level, including 1 patient with monoclonal IgG. LDH was increased in 2 patients. Coombs test was positive in 5 patients. MyD88 gene mutation status was detected in 8 patients, of which gene mutation in 5 patients was positive. Among 13 patients, 1 patient lost follow-up, 3 patients died, 9 patients were alive with the median survival of 36 months (19-81 months).Conclusions:Incidence of LPL/WM is relatively low with a generally indolent evolution, but heterogeneity is not negligible. Few patients have poor treatment response with a quick disease progress. The high-risk patients undergoing hematopoietic stem cell transplantation after remission-induction chemotherapy may improve the prognosis.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.
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The phase I metabolizing enzyme and phase II metabolizing enzyme play vital roles in carcinogenesis, but little is known about the changes of their activities in patients with hepatocellular carcinoma (HCC) secondary to chronic hepatitis B virus (HBV) infection. In this study phenacetin, a probe drug (1 g for men and 0.85 g for women orally), was applied for the detection of sulfotransferase 1A1 (SULT1A1) and cytochrome P4501A2 (CYP1A2) activities in 82 healthy participants and 148 HCC, 106 cirrhosis, and 41 chronic hepatitis B patients. In addition, a prospective cohort study for susceptibility to HCC was performed in 205 patients with cirrhosis secondary to chronic HBV infection. Compared with the healthy participants, SLUT1A1 activity increased by 9.7-fold in the HCC patients (P < 0.01). CYP1A2 activity did not significantly differ between the healthy participants and HCC patients. CYP1A2 activity decreased by 91.2% (P < 0.01) and 67.7% (P < 0.05) in the patients with cirrhosis and chronic hepatitis B, respectively; SULT1A1 activity did not increase significantly. During an approximate 2-year follow up, three of the 46 cirrhosis patients with elevated SULT1A1 activity and normal CYP1A2 activity developed HCC, but none of the 159 cirrhosis patients used as parallel controls did (P = 0.012). These results indicate that SLUT1A1 activity is dramatically upregulated in patients with HCC secondary to chronic HBV infection. The upregulation of SULT1A1 activity is not caused by the tumor itself. The interaction between SULT1A1 and CYP1A2 can play an important role in hepatocarcinogenesis in the Chinese population.
