A high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the determination of mizoribine in human serum using thiamphenicol as internal standard (IS). The serum samples of mizoribine were precipitated with acetonitrile and separated by HPLC on a reversed phase C18 column with a mobile phase of 0.1% ammonium acetate water solution-methanol (47:53, v/v). Mizoribine and IS were detected in the multiple reaction monitoring mode with precursor/product ion transitions of m/z 258.2/126.0 and 354.1/185.2, respectively. The calibration curves were linear over the range of 0.02-2 microg mL(-1) for mizoribine. The limit of quantification (LOQ) was 0.02 microg mL(-1) with acceptable precision and accuracy. The validated method was successfully applied for the evaluation of a bioequivalence study on Chinese healthy volunteers. The main pharmacokinetics parameters after oral administration of 100 mg mizoribine test or reference formulation were as follows: Cmax (1.00 +/- 0.21), (1.00 +/- 0.22) microg mL(-1); AUC(0-infinity) (6.72 +/- 1.39), (6.48 +/- 1.44) microg h mL(-1); t1/2 (2.77 +/- 0.26), (2.66 +/- 0.29) h; tmax (2.95 +/- 0.78), (2.84 +/- 0.50) h.

Objective To establish a rapid, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of acyclovir (the metabolite of valacyclovir hydrochloride) in human plasma. Methods After addition of ganciclovir as internal standard (IS), plasma samples were prepared by one-step protein precipitation using acetonitrile as precipitant, followed by an isocratic elution with 0.1% formic acid 3.5μm) column. Detection was performed on a triple-quadrupole mass spectrometer utilizing electrospray ionization (ESI) interface operating in positive ion and selected reaction monitoring (SRM) mode with the precursor to product ion transitions m/z 226.2→152.1 for acyclovir and m/z 256.2→152.1 for the IS. Results The analytical results demonstrated a good linearity over the ranges from 0.005 to 4μg/mL (r=0.9999) for valacyclovir hydrochloride. The relative standard deviations (RSD) of intra-batch and inter-batch were less than 4.06% and 9.23%, respectively. The limit of detection and lower limit of quantification in human plasma were 2ng/mL and 5ng/mL, respectively. Conclusion The method was simple, sensitive, accurate and reproducible and has been successfully applied to a bioequivalence study of valacyclovir hydrochloride capsules in Chinese healthy male volunteers.

Objective To evaluate the effects of extremity ischemic preconditioning on liver injury after cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Sixty ASA physical status Ⅱ or Ⅲ patients (NYHA Ⅱ or Ⅲ), weighing 44-72 kg, with ejection fraction≥40％, schedule for elective cardiac valve replacement with CPB, were randomly divided into 2 groups (n =30 each) using a random number table: control group (group C) and extremity ischemic preconditioning group (group E).Immediately after anesthesia induction, an auto-inflatable cuff was placed under the right lower extremity, and was inflated to 300 mmHg to induce ischemia (oxygen saturation at the finger tip undetected or foot pulse untouched on the operated side) which was preceded by 3 cycles of 5 min ischemia-5 min reperfusion in group E.Before anesthesia induction (T0) , and at 2, 12, 24, and 72 h, and 7 days after operation (T1-5) , blood samples were taken from the right internal jugular vein for determination of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities.The expression of serum miR-122 was detected at T0-4 by real-time reverse transcriptase polymerase chain reaction.Results Compared with the value at T0, the serum ALT and AST activities were significantly increased at T2-4, and the expression of miR-122 was up-regulated at T1-3 in the two groups (P＜0.05).Compared with group C, the serum ALT and AST activities were significantly decreased at T2-4, and the expression of miR-122 was down-regulated at T1-3in group E (P＜0.05).Conclusion Extremity ischemic preconditioning can mitigate liver injury after cardiac valve replacement with CPB.

Aim To study pharmacokinetics and bioavailablity of domestic penicillin V dispersion tablet in healthy volunteers. Methods According to the crossover design, each volunteer in two groups was orally given a single dose ( 0.75 g ) of domestic penicillin V dispersion tablet or imported penicillinV tablet alternately and the plasma concentrations were determined by RP HPLC. The pharmacokinetic parameters were obtained by using ATPK program and calculated on the basis of open single compartment model. Results After a single oral dose( 0.75 g ), the t 1/2(ke) was ( 0.75 ? 0.10 ) h and ( 0.70 ? 0.14 ) h ,the c max was( 8.44 ? 2.40 ) mg?L -1 and ( 8.75 ? 3.04 ) mg?L -1 at ( 0.56 ? 0.11 ) h and ( 0.63 ? 0.17 ) h and AUC 0～4 was( 8.44 ? 2.40 ) mg?h?L -1 and ( 8.75 ? 3.04 ) mg?h?L -1 for two formulations, respectively. Relative bioavailability of domestic penicillin V dispersion tablet was ( 90.50 ? 8.84 )%. Conclusion The result shows that the two formulations are bioequivalent.

In order to better construct important diseases of traditional Chinese medicine ( TCM ) clinical re-search base , and strengthen the construction of medical and clinical research of TCM information sharing sys-tem, Hubei Provincial Hospital of Traditional Chinese Medicine has constructed research type clinic. The con-struction idea of research type clinic is the mode of real world TCM clinical research . The construction of research type clinic mode was from three aspects, which were the clinical research, health management and distinctive diagnosis and treatment .

Objective To evaluate the clinical efficacy and safety of antofloxacin hydrochloride tablet for the treatment of acute bacterial infections. Methods A multi-center randomized control, double blind and double dummy clinical trial was conducted; levofloxacin tablet was chosed as controlled drug. The duration of treatment was 7-14 days in both groups. Results A total of 719 patients were enrolled in the study, in which 359 patients treated with antofloxacin and 360 patients treated with levofloxacin were included. Three hundred and thirty and 337 patients completed the study and met with all the criteria for perprotocol analysis, respectively. By the end of chemotherapy, the cured rates in per protocol set (PPS)population were 79.7% and 77.4%, the effective rates were 95.2% and 96. 7%, and the bacterial clearance were 96. 7% and 97. 5% for the treating and control group, respectively. The clinical and bacterial efficacy of antofloxacin and levofloxacin was comparable by the analysis of infectious sites. Three hundred and fifty-seven and 356 patients in antofloxacin and levofloxacin groups were evaluated the safety.The drug adverse events occurred both in 10. 1%, and drug adverse reactions accurred in 7. 8% and 7.9%patients in the two groups. The most common drug adverse reactions were mild gastroenteric symptoms. No QTc prologation was detected in all the patients. One patient in each group had mild blood glucose increase at the end of therapy, but the glucose returned to normal level without any intervention. No statistic significant difference between the two groups in clinical efficacy and safety was detected (P＞0.05).Conclusions Antofloxacin hydrochloride tablet was effective and safe for the treatment of acute bacterial infections.

Objective:To study and analyse the results of postoperative hemorrhage after laparoscopic pancreaticoduodenectomy (LPD).Methods:The clinical data of patients who underwent LPD from May 2011 to December 2019 at Hunan Provincial People's Hospital were retrospectively analyzed. The clinical characteristics of patients, onset time of postoperative hemorrhage, location of postoperative hemorrhage, postoperative biliary fistula, pancreatic fistula, infection and other short-term complications, reoperation and mortality rates were analyzed.Results:Of 356 patients who underwent LPD in this study, there were 200 males and 156 females, aged (58.0±10.5) years. The postoperative complication rate was 33.1% (118/356), the reoperation rate was 6.5% (23/356), and the mortality rate was 2.5% (9/356). The most common complications were postoperative hemorrhage [15.2% (54/356)], pancreatic fistula [14.6%(52/356)] and abdominal infection [13.8%(49/356)]. The onset time of postoperative hemorrhage was usually in the 1st - 14th day, and the highest rate of postoperative hemorrhage was 3.9% (14/356) on the first day after surgery. The postoperative hemorrhage rate then showed a downward trend, but increased again on the 7th day. The extraluminal hemorrhage locations were relatively widely distributed, and the incidence of gastrointestinal anastomotic hemorrhage in patients with intraluminal hemorrhage was the highest [67.9%(19/28)]. Of the 9 patients who died, 7 were related to postoperative bleeding.Conclusions:LPD resulted in a high incidence of complications. Postoperative hemorrhage was a complication that had the greatest impact on short-term recovery of patients. It was also an important cause of reoperation and death. In addition to postoperative bleeding caused by pancreatic fistula, gastrointestinal anastomotic bleeding was also clinically important.