Objective To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of tobramycin in human serum,and examine the utility of the method in a clinical pharmacokinetic study of tobramycin inhalation.Methods Serum samples were pretreated by solid phase extraction with tobramycin-D12 as internal standard.Chromatographic separation was performed on a TitankHilic(2.1 mm × 100 mm,3 μm)column.The mobile phase consisted of0.1％formic acid-acetonitrile and 0.1％formic acid aqueous solution at a flow rate of 0.4 mL/min.Electrospray ionization source and multiple reaction monitoring(MRM)scanning were used for monitoring the quantitative ion pairs with m/z 468.3→m/z 163.3(tobramycin)and m/z 480.6→m/z 166.2(tobramycin-D12).The established method was investigated in terms of selectivity,interaction,concomitant medication,standard curve and lower limit of quantitation,precision and accuracy,recovery,matrix effect,and stability of tobramycinin.Results The linear range of tobramycin was 0.050 0-10.0 mg/L(R2=0.999 5).The intra-and inter-batch precision was satisfactory(coefficient of variation[CV]≤3.6％).The accuracy ranged from-0.4％to 6.0％.The matrix effect factor(MF)in human serum samples(including hemolysis and lipemia)ranged from 92.2％to 94.9％(CV≤2.7％).The recovery of tobramycinin was 79.5％-81.9％in serum samples,while the recovery of internal standard was 78.9％.The analyte was stable in serum samples for 72 h at room temperature and for 274 days at-20℃/-70℃.The pharmacokinetic study of tobramycin inhalation in bronchiectasis patients showed that after continuous administration of tobramycin 300 mg twice a day to 3 patients,the mean Cmax of tobramycin was(0.72±0.61)mg/L on Day 1 and(0.76±0.73)mg/L on Day 28,respectively.The corresponding Tmax was(1.83±0.61)h and(1.50±0.50)h,respectively.Conclusions The UPLC-MS/MS method established in this study is sensitive,accurate and rapid.It is successfully applied to the clinical pharmacokinetic study of tobramycin inhalation.The method may be suitable for therapeutic drug monitoring of tobramycin in clinical practice.

Objective:To summarize the best evidence for external auditory canal irrigation in patients with cerumen embolism.Methods:The clinical decisions, guidelines, systematic reviews, expert consensus, group standards, evidence summaries, and randomized controlled trials regarding external auditory canal irrigation in patients with cerumen embolism were retrieved from databases and websites such as BMJ Best Practice, UpToDate, Guidelines International Network, National Institute for Health and Clinical Excellence, Joanna Briggs Institute Evidence-Based Health Care Center Database, PubMed, Embase, China National Knowledge Infrastructure, WanFang data, and China Biology Medicine disc. The search period was from database establishment to February 15, 2023. Six researchers screened the literature, evaluated the methodological quality, and extracted and summarized the best evidence for external auditory canal irrigation in patients with cerumen embolism.Results:A total of nine articles were included, including one clinical decision, two guidelines, two systematic reviews, one group standard, and three randomized controlled trials. Sixteen pieces of evidence were summarized from six aspects of operators: pre-operation evaluation and preparation, operation process, post-operation handling, health education, and adverse reactions during operation.Conclusions:This paper summarizes the best evidence for external auditory canal irrigation in patients with cerumen embolism. Medical and nursing staff should carefully select and apply evidence based on clinical scenarios and patient's wishes.

It is believed that qi and blood disharmony is the key pathogenesis of essential hypertension， for which mildly regulating qi and blood is recommended. According to the different pathological states and related causes of qi and blood disorders， essential hypertension can be divided into five syndrome types for differentiation and treatment. In terms of blood deficiency and liver constraint， it is recommended to nourish the blood and soften the liver， rectify qi to resolve constraint， using Xiao Yao Powder （逍遥散） or self-made Qihua Jieyu Decoction （七花解郁汤）. For qi stagnation and blood stasis， the method of regulating qi and harmonizing blood， dissolving stasis and unblocking collaterals should be used， with self-made Guitao Tongluo Decoction （桂桃通络汤）. For phlegm-dampness internal obstruction， it is recommended to move qi and promote urination， dissolve phlegm and eliminate dampness， using self-made Zhuanqi Sanzhuo Formula （转气散浊方）. For binding of phlegm and stasis， dissolving phlegm and dispelling stasis， dredging the bowels and directing the turbid downward is advised， and self-made Sanren Tiaozhi Formula （三仁调脂方） can be used. In terms of deficiency of both qi and blood， it is recommended to boost qi and nourish blood， supplement deficiency and consolidate the root， using Gui Pi Decoction （归脾汤） or self-made Shenqi Zaizao Decoction （参芪再造汤）.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

Objective:To compare the changes of biliary microbiota after enteral extended biliary stents (EEBS) implantation with that of conventional plastic stents in animal experiment, and to preliminarily investigate its possible mechanism in preventing stents occlusion.Methods:A total of 12 healthy Bama minipigs were randomly assigned to the conventional plastic stent group ( n=6) and the EEBS group ( n=6) using simple random method. The bile samples of all pigs were collected before stents implantation and 4 weeks after stents placement. The biliary microbiota composition and diversity before and after different stents implantation were analyzed by 16S rRNA gene sequencing and compared. Results:No complications including acute cholangitis, perforation, bleeding, or death occurred in 12 pigs. Eight days after stents implantation, stents were out of bile duct in all pigs under endoscopy, while the bile samples were collected again for analysis. The main composition of biliary microbiota at the phylum level were Proteobacteria, Firmicutes and Bacteroidota. Alpha-diversities revealed the Shannon ( P=0.004) and Simpson index ( P=0.008) significantly decreased in the conventional stent group after stents placement, and Bata diversity analysis also showed a significant difference in microbial composition (Anosim: R=0.514 8, P=0.011). There was no significant difference in Observed species index ( P=0.095), Chao1 index ( P=0.136), Shannon index ( P=0.353), Simpson index ( P=0.227) or Bata diversity (Anosim: R=0.059 3, P=0.187) in the EEBS group before and after stents placement. LEfSe algorithm indicated Bacteroides_ fragilis and Proteobacteria- Gammaproteobacteria- Enterobacterales- Enterobacteriaceae- scherichia_ Shigella- Escherichia_ coli significantly increased in the conventional stent group, and Desulfobacterota- Desulfovibrionia- Desulfovibrionales- Desulfovibrionaceae- Bilophila significantly increased in the EEBS group after stents placement. Conclusion:The biliary microbiota change slightly after EEBS implantation in the short-term, and EEBS may prevent duodenobiliary reflux by prolonging the reflux path.

Objective:To study the teaching effect of traditional teaching combined with virtual simulation teaching in pharmaceutical content analysis using high performance liquid chromatography (HPLC).Methods:The students in two parallel classes of grade 2016 were divided into experimental group (44 students) and control group (38 students). Taking the content analysis and its related analytical methodology of Metronidazole by HPLC as an example, the experimental group adopted the traditional offline teaching combines with virtual simulation teaching, and the control group adopted the traditional offline teaching. The teaching effects of the two groups were compared. SPSS 22.0 was used to conduct independent-samples t-test. Results:According to the mid-term test results, the experimental group was superior to the control group in practical operation assessment [(17.98±6.75) vs. (14.03±5.92)], and the difference was statistically significant ( P < 0.05). But there were no differences between the two groups in the scores of theory, discussion report and presentation. There was no significant difference in the final exam scores between the two groups. Conclusion:The ability of practical training and the teaching effect can be improved by the teaching method of traditional offline teaching combined with virtual simulation. Through the training of this project, students have mastered the operation of HPLC, the content determination of pharmaceutical preparations, the verification of analytical methods, data processing, and the writing of analytical reports, and have certain practical analysis ability.

Objective:To carry out the clinical observation and research of OPT intense pulsed light combined parameters in the treatment of lip hairiness.Methods:A total of 94 female patients with lip hairiness who were treated with OPT intense pulsed light depilation were collected, of which 22 were treated with single parameter and 72 were treated with combined parameters, both once a month for 7 months. The treatment effects of the two groups were compared. From October 2013 to October 2019, the patients were collected from the Department of Medical Cosmetology, the Quzhou Affiliated Hospital of Wenzhou Medical University.Results:With the increase of treatment times, the curative effect of patients gradually appeared, and the χ 2 value was 10.87 in the single parameter group and 105.25 in the combined parameter group. The difference was statistically significant ( P<0.05). There was no statistical significance in the single parameter array between the two comparisons of different treatment times; there was statistical significance in the combined parameter group. The χ 2 value of treatment (1 vs. 3) times was 26.05, (1 vs. 7) times was 73.3, (3 vs. 7) times was 23.82 ( P<0.017). There was significant difference in the constituent ratio and total effective rate between the two groups after 3 and 7 times of treatment. The total effective rate of 3 times of treatment was 36.36% in single parameter group and 70.83% in combined parameter group; The total effective rate of 7 times of treatment was 59.09% in the single parameter group and 81.94% in the combined parameter group ( P<0.05). Conclusions:Combined parameters OPT intense pulsed light therapy has better effect on lip hairiness than single parameter, and the treatment is safe and has good clinical application value.

To investigate the effect of ethanolic extract from Artemisia Argyi Folium on blood glucose and blood lipids in diabetic mice, ICR mice were induced by intraperitoneal injection of 35 mg/kg streptozotocin (STZ) and a high-carbohydrate/high-fat diet to construct type 2 diabetes mellitus model. Diabetic mice were randomly divided into three groups: the model group (5 mL/kg 0.5% CMC-Na), the Artemisia Argyi Folium ethanolic extract low-dose group (100 mg/kg ) and high-dose group (400 mg/kg ). During the treatment for 6 weeks, the amount of drinking water and food intake of mice were recorded every day. Blood glucose and body weight were recorded every week. After treatment for 6 weeks, serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C),and oral glucose tolerance (OGTT) were measured. The results showed that the amount of drinking water and food intake of mice significantly decreased (P < 0.01) in the Artemisia Argyi Folium ethanolic extract high-dose group; oral glucose tolerance was significantly improved (P < 0.01) and the contents of TC, TG and LDL-C were significantly decreased in the Artemisia Argyi Folium ethanolic extract low-dose group (P < 0.01). The ethanolic extract from Artemisia Argyi Folium could significantly improve the glucose and lipid metabolic disorder in T2DM mice in a dose-dependent manner.

Objective:To determine the dose-effect relationship of nalbuphine preventing injection pain of medium plus long chain triglyceride propofol in pediatric patients undergoing gastroenteroscopy.Methods:Pediatric patients, aged 3-8 yr, of American Society of Anesthesiologists physical statusⅠ or Ⅱ, scheduled for elective gastroenteroscopy, were enrolled in the study.The doses of nalbuphine were determined by up-down sequential allocation, nalbuphine 0.2 mg/kg was injected intravenously in the first child, and 5 min later medium plus long chain triglyceride propofol 2.5 mg/kg was given intravenously.Ambesh 4-point method was used to evaluate the injection pain of propofol.When the prevention of injection pain was ineffective, the dose of nalbuphine was increased in the next patient, otherwise the dose was reduced, and the difference between the two successive doses was 0.01 mg/kg.This process was repeated until the 7th turning point occurred.The ED 50 and ED 95 of nalbuphine and 95% confidence interval (CI) preventing injection pain of propofol were calculated by Probit regression. Results:The ED 50 and ED 95 (95% CI) of nalbuphine preventing medium plus long chain triglyceride propofol injection pain were 1.57 (1.50-1.62) and 1.71 (1.64-2.05) mg/kg, respectively. Conclusion:The ED 50 and ED 95 of nalbuphine preventing injection pain of medium plus long chain triglyceride propofol are 1.57 and 1.71 mg/kg, respectively, in pediatric patients undergoing gastroenteroscopy.

The adverse health effects of air pollution remains a daunting public health problem globally. The research of the health effects of air pollution provides important evidence for ambient air quality standard establishments and air pollution interventions. In recent years, causal inference has been gradually introduced into the observational study of environmental epidemiology, which provides more statistical method options for the study of causal relationships between air pollution and population health effects. Controlling confounders in observational studies is a major challenge for causal inference. This study introduces the causal inference methods for the identification and control of confounding factors currently used in the study of air pollution and population health effects, in order to provide methodological reference and basis for the causal inference study of air pollution and population health effects in China.