OBJECTIVE To investigate and compare the enzyme kinetic characters of psoralen (PRN)and isopsoralen(IPRN)in rat and human liver microsomes. METHODS PRN and IPRN in liver microsomes incubates were determined using LC-MS/MS. The enzyme kinetic and metabolic stability of PRN and IPRN were investigated by employing the optimized rat and human liver microsomes incubations. The Vmax and Km values were calculated using the nonlinear regression method. RESULTS The quanti?tative method showed good linearity within the range of 0.1-50.0 μmol · L-1 and was suitable for the assay in biological samples. The in vitro elimination was linear with the substrate concentrations lower than 1 μmol,the protein concentration within 0.5 g · L-1,and the incubation time within 40 min. The t1/2 values of PRN and IPRN in rat and human liver microsomes were 74.5,95.0,74.5 and 173.3 min, respectively. The Vmax values of PRN in rat and human liver microsomes were(1.140±0.080)μmol·min-1·g-1 protein,(0.620±0.060)μmol·min-1·g-1 protein,while Km values of PRN in rat and human liver microsomes were (12.9 ± 0.3)μmol · L- 1,(7.4 ± 1.3)μmol · L- 1,respectively. The Vmax values of IPRN in rat and human liver microsomes were(0.251±0.012)and(0.103±0.014)μmol·min-1·g-1 protein,while Km values of IPRN in rat and human liver microsomes were (3.0 ± 0.4)μmol · L-1,(3.4 ± 0.7)μmol · L-1,respectively. CONCLUSION The enzyme kinetic characters and metabolic stability of PRN and IPRN show species and chemical structures related differences. Interestingly,the metabolic eliminations of PRN and IPRN are similar in rats. However,the metabolic elimination of IPRN in humans involved in CYP enzymes may be much slower than that of PRN.

OBJECTIVE: To study brainstem auditory evoked potential (BAEP) in neonates with hyperbilirubinemia using short auditory stimuli (60 dBnHL), and to investigate the differences in the inter-aural latency difference (ILD) of wave V between neonates with different total serum bilirubin (TSB) levels. METHODS: A prospective study was conducted in neonates with hyperbilirubinemia who were admitted to the Department of Neonatology, Yuhuan People's Hospital of Zhejiang Province, from May 2019 to October 2020. The neonates were divided into a severe group ( RESULTS: Compared with the mild group, the severe group had significantly higher proportions of neonates with abnormal hearing threshold and abnormal ILD ( CONCLUSIONS Serum bilirubin in neonates affects the ILD of BAEP wave V, especially in those with severe hyperbilirubinemia. ILD at the optimal cut-off value of ≥0.4 ms shows potential value in the diagnosis of hearing impairment caused by neonatal hyperbilirubinemia.
Bilirubin ; Evoked Potentials, Auditory, Brain Stem ; Hearing Loss ; Humans ; Hyperbilirubinemia ; Hyperbilirubinemia, Neonatal ; Infant, Newborn ; Prospective Studies

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.

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.