Objective To prepare the sinomenine hydrochloride multivesicular liposomes with high entrapment efficiency and sustained release character.Methods Multiple emulsion method was used to prepare the sinomenine hydrochloride multivesicular liposomes.Uniform design was applied to optimize the formulation and pharmaceutical process.The shape,the particle size,and the release charcter of the liposome were evaluated.Results The sinomenine hydrochloride multivesicular liposomes prepared were spherical and the size of majority particles was in the range of 20—30 ?m and well distributed.The encapsulation efficiency was more than 80% and its in-vitro release profile accorded well with the Higuchi model with t1/2 up to 52.7 h.Conclusion The formulation and pharmaceutical process of the sinomenine hydrochloride multivesicular liposomes are stable and feasible with the high encapsulation efficiency and good sustained-release character.

Objective To study the epidemiology and genotypes of extended-spectrum beta-lactamases (ESBL)-producing Escherichia coli (EC) and Klebsiella pneumoniae (KP) that caused community-onset bloodstream infections (COBSI) in 9 county hospitals of Zhejiang Province.Methods This is a multi-center, prospective, observational study.The cases and isolates with COBSI caused by EC and KP were consecutively collected from 9 county hospitals in Zhejiang Province between 1st March 2014 and 30th April 2015.The double disk diffusion method was used to confirm the production of ESBL.The ESBL genotypes were determined by polymerase chain reaction(PCR) amplification and sequence analysis.Multi-locus Sequence Typing (MLST) was used to analyze the homology of ESBL-producing isolates.Minimal inhibitory concentration (MIC) of frequently used drugs for ESBL-producing isolates was determined by in-vitro antimicrobial susceptibility tests.Results During the study period, a total of 172 cases with COBSI were collected and 171 cases were eligible, among which 126 were caused by EC and 45 were caused by KP.The overall prevalence of ESBL was 34.5% (59/171),and the prevalence of ESBL-EC and-KP was 41.3% (52/126) and 15.6% (7/45), respectively.CTX-M-type ESBL accounted for 96.6% (57/59) of all the ESBLs-producing isolates, and the most common type was CTX-M-14 (27.1%, 16/59), followed by CTX-M-55 (22%, 13/59).MLST analyses revealed significant genetic diversity among ESBL-EC and-KP.The most prevalent ST of ESBL-EC was ST131 (23.1%).In addition to carbapenems, cefoperazone/sulbactam, piperacillin/tazobactam, moxalactam, amikacin and fosfomycin also showed good in-vitro activity against ESBL-EC and-KP.Conclusions The prevalence of ESBL in EC and KP is high in 9 county hospitals of Zhejiang Province, and the most common genotypes are CTX-M-14 and CTX-M-55.The detection rate of ESBL in EC is higher than in KP.It could be considered adequate empirical therapy according to the results of antimicrobial susceptibility tests.Carbapenems, cefoperazone/sulbactam, piperacillin/tazobactam, moxalactam, amikacin and fosfomycin have good in-vitro activity against ESBL-EC and-KP.

Objective To prepare sinomenine hydrochloride transfersomes and evaluate their qualities. MethodsThree different preparation methods including film dispersion, reverse phase evaporation, and ethanol injection methods were compared according to the encapsulation efficiency of transfersomes. Uniform design was applied to optimize the formulation and pharmaceutical process of reverse phase evaporation. The particle size, the appearance, the Z-potential, and the stability were also evaluated. ResultsThe transfersomes prepared by reverse-phase evaporation method possessed the highest encapsulation efficiency. The ideal combinations of preparation and formulation were: soya lecithin/sodium cholate was 200/30 mg/mg, chloroform/PBS was 5 mL/mL, pH of PBS was 6.5, added sinomenine hydrochloride was 10 mg. The transfersomes obtained were milky white translucent suspension, with a mean encapsulation efficiency of 62.2%. The shape of their particles was spherical or similar to spherical under microscope, which was smooth and disconglutinated with an average diameter of 96.4 nm, and a Z-potential of-35.93 mV. Aggregation or deposition was not observed after exposure under the temperature of 4 ℃ for 30 d. ConclusionThe preparation process of sinomenine hydrochloride transfersomes is feasible, the quality of obtained transfersomes is stable.It is expected to provide a new preparation for clinical use of sinomenine hydrochloride.

Medical ethics is an important constitutes of medicine project. The medical ethics of military has its particularity and realism meaning. Combined with the spirit of anti-SARS and the actuality of military medicine ethnics,we must adopt some availability measure to promote the education of military medicine ethnics.

Objectives To analyze the incidence of cranial nerve injury in patients after receiving carotid endarterectomy ( CEA) in a single-center and to investigate its correlation with surgical experiences. Methods The clinical data of patients underwent CEA at Beijing Xuanwu Hospital, Capital Medical University from January. 2001 to December 2013 were analyzed retrospectively. Cranial nerve injury was assessed at day 7 after procedure according to the clinical symptoms,and they were followed up at 1,3,6, and 12 months. The incidence of permanent cranial nerve injury was evaluated. The incidences of permanent cranial nerve injury were further analyzed at two time periods ( from January 2001 to September 2011 and from October 2011 to December 2013 ) . Results ( 1 ) A total of 598 consecutive patients treated with CEA were enrolled,and 15 (2. 5%) of them had cranial nerve injury,including 2 (0. 3%) facial nerve injury,7 (1. 2%) hypoglossal nerve injury,and 6 (1. 0%) vagus nerve injury. Only 1 case (0. 2%) did not recover completely at 6 months after procedure. ( 2 ) The patients with cranial nerve injury were 10 (3. 2%,10/308) and 5 (1. 7%,5/290) respectively from January 2001 to September 2011 and from October 2011 to December 2013). There was no significant difference (P < 0. 05). Conclusion The incidence of cranial nerve injury was low after CEA,and most patients could recover completely. The increased surgical experiences did not show the reduction of cranial nerve injury rate evidently after CEA.

Objective To evaluate Parecoxi on postoperative analgesia for the elderly patients undering colorectomy.Methods 82 patients were randomly divided into group of 44 patients undergoing open surgery and 38 patients receiving laparoscopic colorectomy.22 patients in open surgery using Parecoxib sodium combined with PCA analgesic way were named as observation group,while the other 22 patients using placebo combined with PCA analgesic way named as control group.19 laparoscopic surgery patients using Parecoxib sodium analgesia were named as observation group,while the other 19 patients using Tramadol analgesia named as control group.Results In the absence of any differences of VAS pain score,in the open surgery group,the average dosage of Fentanyl in observation group was (0.45 ± 0.23) mg vs.(0.78 ± 0.16) mg in observation group (P ＜ 0.05).Parecoxib reduced the dosage of Fentanyl of PCA in the open surgery group.In laparoscopic group,at the time of postoperative 6,12,24,48,72 h,in the observation group patients resting pain scores were 5.01 ±0.36,4.44 ±0.37,4.02 ±0.46,3.35 ±0.52,2.54 ±0.23 respectively,while in the control group patients resting pain scores were 5.86 ± 0.45,5.03 ± 0.64,4.89 ± 0.75,3.94 ± 0.73,2.56 ± 0.41 respectively,(P ＜ 0.01).The postoperative gastrointestinal function recovery time was (3.1 ±0.7) d in observation group vs.(5.9 ±0.4) d in the control group (P ＜0.01).The incidence of postoperative nausea and vomiting,were lower in observation group,(P ＜ 0.01).Conclusion Parecoxib can be used for postoperative analgesia in elderly patients with colorectal cancer,reducing the dosage of opioids,and protecting the patient's immune function.

Objective To analyze the characteristics of alcohol-related brain damage according to 18F-fluorodeoxy-glucose (18F-FDG) position emission tomography-computer tomography (PET-CT).Methods Excessive alcohol consumption patients accepted 18F-FDG PET-CT in our hospital from August 2016 to November 2018 were chosen as excessive alcohol consumption group and non-drinking patients accepted 18F-FDG PET-CT in our hospital at the same time were chosen as non-drinking group according to 1:4 ratio.The 18F-FDG PET-CT imaging data were analyzed;the characteristics of abnormal changed rate of CT sequences after stratification by age and the relations of alcohol consumption with abnormal CT sequences and PET sequences were compared between the two groups.Results A total of 52 patients with excessive alcohol consumption and 200 non-drinking patients were chosen.Among patients aged 45-59 years,the abnormal changed rate of CT sequences in the excessive alcohol consumption group was significantly higher than that in the non-drinking group (P＜0.05).In the CT sequences,33 patients in the 2 groups presented abnormalities,mainly including cerebral atrophy and lacunar infarction.In the PET sequences,62 patients in the two groups presented abnormalities,mainly manifesting as reduced metabolism level of bilateral frontal and parietal lobes.Among the 52 patients from excessive alcohol consumption group,those with abnormal CT sequences were older,had longer drinking history and had higher total drinking amount than those with normal CT sequences,and the differences were statistically significant (P＜0.05).As compared with those in patients with normal PET sequences,those with abnormal PET sequences had higher weekly and total alcohol consumption,and longer drinking history,and the differences were statistically significant (P＜0.05).Conclusion Excessive alcohol consumption is an important risk factor for structural damages in middle-aged men,which can cause a decrease of glucose metabolism level in the frontal and parietal lobes.

Misuse and abuse of veterinary antimicrobial agents have led to an alarming increase in bacterial resistance, clinical treatment failure, and drug residues. To address these problems, consistent and appropriate dosage regimens for veterinary antimicrobial agents are needed. Pharmacokinetics/Pharmacodynamics (PK/PD) models have been widely used to establish rational dosage regimens for veterinary antimicrobial agents that can achieve effective prevention and treatment of bacterial diseases and avoid the development of bacterial resistance. This review introduces building methods for PK/PD models and describes current PK/PD research progress toward rational dosage regimens for veterinary antimicrobial agents. Finally, the challenges and prospects of PK/PD models in the design of dosage regimens for veterinary antimicrobial agents are reviewed. This review will help to increase awareness of PK/PD modeling among veterinarians and hopefully promote its development and future use.
Anti-Infective Agents ; Bacterial Infections ; Drug Residues ; Humans ; Treatment Failure ; Veterinarians

Objective: To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance time in patients with COVID-19. Methods: A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, School of Medicine, Zhejiang University were recruited. All patients received oral abidol and/or combined lopinavir/ritonavir, darunavir antiviral, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg^-1·d^-1) (glucocorticoid treatment group), and 21 patients who did not use glucocorticoid were the control group. The time of stable virologic conversion insputumand the time of radiologic recovery in lungsince onset were compared between the two groups and among the normal patients.The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results: The median ages of the glucocorticoid group and the control group were 52 [interquartile range (IQR):45, 62] years and 46 (IQR: 32, 56)years, and the differences were significant (P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). There were 52.0% critical ill patients in the glucocorticoid treatment group, compared to that of 71.4% normal patients in the control group. The median times from the onset tostable virologic conversion to negative in the two groups were 15 (IQR:13,20) days and 14 (IQR:12,20) days (P>0.05), and the difference was no statistically significant. The median times from onset to radiologic recovery were 13 (IQR: 11,15) days and 13 (IQR:12,17) days in the two groups, and there was no difference (P>0.05). In ordinary patients, the median timesfrom the onset tostable virologic conversion insputum were no difference (P>0.05), with 13 (IQR:11,18) days in the glucocorticoid group and 13 (IQR:12,15) days in the control group; The median times from onset to radiologic recovery in lungwere also no difference (P>0.05), with 12 (IQR: 10,15)days in the glucocorticoid group and 13 (IQR: 12,17) days inthe control group. Conclusions Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19. The glucocorticoid is not recommended since no effectiveness on accelerating the improvement of radiologic recovery in lung has been observed.

Objective:To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19.Methods:A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg -1·d -1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results:The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years ( χ2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups ( P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days ( P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups ( P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group ( P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively ( P>0.05). Conclusions:Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.