A fast,reliable,and cost-effective liquid chromatography-tandem mass spectrometry method was established to determine the effects of the traditional Chinese medicine employed to treat coronavirus disease 2019,namely,Lianhua Qingwen granules,Huoxiang Zhengqi capsules,Jinhua Qinggan granules,Shufeng Jiedu capsules,and Angong Niuhuang pills,on the pharmacokinetics of lopinavir/ritonavir in rats.Blood samples were prepared using the protein precipitation method and atazanavir was selected as the internal standard(IS).Separation was performed on an Agilent ZORBAX eclipse plus C18(2.1 mm x 50 mm,1.8 μm)column using acetonitrile and water containing 0.1％formic acid as the mobile phase for gradient elution.The flow rate was 0.4 mL/min and the injection volume was 2 μL Agilent Jet Stream electrospray ionization was used for mass spectrometry detection under positive ion multiple reaction monitoring mode at a transition of m/z 629.3→447.3 for lopinavir,m/z 721.3→296.1 for rito-navir,and m/z 705.4→168.1 for the IS.The method showed good linearity in the concentration range of 25-2500 ng/mL(r=0.9981)for lopinavir and 5-500 ng/mL(r=0.9984)for ritonavir.The intra-day and inter-day precision and accuracy were both within±15％.Items,such as dilution reliability and residual effect,were also within the acceptable limits.The method was used to determine the effects of five types of traditional Chinese medicines on the pharmacokinetics of lopinavir/ritonavir in rats.The pharmaco-kinetic results showed that the half-life of ritonavir in the groups administered Lianhua Qingwen granules and Huoxiang Zhengqi capsules combined with lopinavir/ritonavir was prolonged by approx-imately 1.5-to 2-fold relative to that in the control group.Similarly,the pharmacokinetic parameters of lopinavir were altered.Overall,the results of this study offer important theoretical parameters for the effective clinical use of five types of traditional Chinese medicines combined with lopinavir/ritonavir to reduce the occurrence of clinical adverse reactions.

OBJECTIVETo summarize and analyze the clinical features, diagnosis methods, surgical approaches and treatment outcomes of patients with primary parapharyngeal space tumors.

METHODSA retrospective review of 91 cases with primary parapharyngeal space tumors treated from January 1999 to December 2011 was performed. All patients underwent preoperative enhanced CT scan and postoperative histopathologic examination. Intraoperative frozen section biopsies were performed in 36 of 91 cases. The surgical approaches included trans-cervical approach in 73 cases, trans-parotid approach in 5 cases, trans-oral approach in 5 cases, and mandibulotomy in 8 cases.

RESULTSThe postoperative pathological diagnoses consisted of 29 variants, including 20 for benign tumors and 9 for malignant tumors. Of the 80 cases with benign tumors, 6 cases were lost to follow-up and 74 cases were followed up for 31-84 months with no recurrence. Eleven cases with malignant tumor were followed up for 8-51 months (median 29 months), of them 7 cases died and 1 case was lost to follow-up. The post-operative complications included Horner syndrome in 3 cases, hoarseness in 2 cases, hypoglossal nerve palsy in 1 case, accessory nerve palsy in 1 case, upper airway obstruction in 1 case, and internal carotid artery cavernous sinus fistula in 1 case.

CONCLUSIONSParapharyngeal space tumors are rare, with atypical clinical manifestation, and have pathological types of diversification. CT or MRI is helpful to evaluate the tumor size, location and possible sources, and to make operation scheme. Surgery is the first choice for parapharyngeal space tumors. Trans-cervical approach can be applied to most tumors. Parapharyngeal benign tumors have good prognosis, but malignant tumors have poor prognosis.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Head and Neck Neoplasms ; diagnosis ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Pharyngeal Neoplasms ; diagnosis ; pathology ; surgery ; Retrospective Studies ; Treatment Outcome ; Young Adult