Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Objective To retrieve,evaluate and summarize the best evidence on the management of ocular complications in intensive care patients ventilated in prone position,and to provide references for clinical practice.Methods Evidence on management of ocular complications in intensive care patients ventilated in prone position was systemically retrieved in the guideline websites,professional association websites and databases,such as the BMJ Best Practice,UpToDate,Cochrane Library,Joanna Briggs Institute,PubMed,Web of Science,Science Direct,Embase,CNKI,Wanfang and other databases,including guidelines,clinical decisions,evidence summaries,expert consensuses,group standards,systematic reviews and scoping reviews,published from January 2013 to June 2023.The guidelines were individually evaluated by 4 researchers,and the remaining literature was individually evaluated by 2 researchers.The literature that met the criteria was extracted and graded.Results A total of 15 articles were involved,including 6 guidelines,2 clinical decisions,2 evidence summaries,3 systematic reviews,1 scoping review and 1 group standard.Finally,6 evidence topics and 16 pieces of best evidence were formed,including organization and training,risk identification,eye assessment,eye protection,position management and regular observation.Conclusion This study summarized the best evidence on the management of ocular complications in intensive care patients ventilated in prone position.In the application,the best evidence should be selected according to the clinical situation,so as to reduce the incidence of ocular complications and improve the quality of life of patients.

OBJECTIVE To investigate the efficacy and safety of aerosol inhalation of polycolistin B in the treatment of severe pneumonia combined with mechanical ventilation， and to provide a reference of real-world data for clinical drug therapy. METHODS A retrospective cohort study was conducted to analyze the clinical data of 87 patients with severe pneumonia combined with mechanical ventilation at the First Affiliated Hospital of Shandong First Medical University from January 2021 to February 2023. According to route of administration， all patients were divided into combined group （24 cases， receiving aerosol YXH2021ZX013） inhibition of polycolistin B combined with intravenous dripping） and routine group （63 cases， intravenous dripping of polycolistin B alone）. The differences in efficacy （mortality，clinical response rate and bacterial clearance rate）and safety （elevated serum creatinine， bronchospasm and skin pigmentation） were compared between two groups； the influential factors of primary outcome index as mortality were analyzed through univariate analysis and multivariate Logistic regression analysis. RESULTS In terms of efficacy， there were no statistical differences in mortality（37.50% vs. 41.27%， P＝0.749）， clinical response rate （54.17% vs. 55.56%， P＝0.907） and bacterial clearance rate （45.83% vs. 44.44%， P＝0.907） between the two groups. In terms of safety， the incidence of bronchospasm in the combined group was significantly higher than that of the routine group （12.50% vs. 0， P＝0.028）， but the differences in incidence of elevated serum creatinine and skin pigmentation between two groups were not statistically significant （P＞0.05）. Univariate analysis showed that the moralities were higher in the case of infected with Acinetobacter baumannii， Klebsiella pneumoniae and combined use of quinolones （P＜0.05）； multivariate Logistic regression analysis showed that infection with A. baumannii （OR＝3.36， P＝0.014） and combined use of quinolones （OR＝3.54， P＝0.013） were independently associated with mortality （P＜0.05）. CONCLUSIONS For severe pneumonia patients with mechanical ventilation， intravenous dripping of polycolistin B combined with aerosol inhalation does not show superior efficacy compared with intravenous dipping of polycolistin B alone， but significantly increases the incidence of bronchospasm. Infection with A. baumannii and combined use of quinolones are independent risk factors for the increase of mortality.

OBJECTIVE To improve the utilization rate of intravenous infusion in inpatients and enhance the level of rational drug use. METHODS PDCA cycle method was used to formulate and implement countermeasures from the aspects of institution， system， person and management. The utilization rate of intravenous infusion and the average daily number of bags （bottles） per bed for intravenous infusion were used as indicators to evaluate the implementation effect of PDCA. RESULTS The utilization rate of intravenous infusion decreased from （92.58±0.11）% 3 months before PDCA cycle to （89.72±0.62）% 3 months after PDCA cycle， and the average daily number of bags （bottles） per bed from intravenous infusion decreased from 5.20±0.09 to 4.64±0.24 （P＜ 0.05）. The utilization rate of intravenous infusion decreased from 92.55% 6 months before PDCA cycle to 89.98% 6 months after PDCA cycle （P＜0.05）； but average daily number of bags （bottles） per bed for intravenous infusion decreased from 5.36±0.26 6 months before PDCA cycle to 4.97±0.39 6 months after PDCA cycle， without statistical significance （P＞0.05）. CONCLUSIONS PDCA cycle method can effectively reduce the utilization rate and average daily number of bags （bottles） per bed for intravenous infusion in the inpatients and improve the level of rational drug use.

Purpose: The purpose of this study was to optimize a peptide (nABP284) that binds to programmed cell death protein 1 (PD-1) by a computer-based protocol in order to increase its affinity. Then, this study aimed to determine the inhibitory effects of this peptide on cancer immune escape by coculturing improving cytokine-induced killer (ICIK) cells with cancer cells. Materials and Methods: nABP284 that binds to PD-1 was identified by phage display technology in our previous study. AutoDock and PyMOL were used to optimize the sequence of nABP284 to design a new peptide (nABPD1). Immunofluorescence was used to demonstrate that the peptides bound to PD-1. Surface plasmon resonance was used to measure the binding affinity of the peptides. The blocking effect of the peptides on PD-1 was evaluated by a neutralization experiment with human recombinant programmed death-ligand 1 (PD-L1) protein. The inhibition of activated lymphocytes by cancer cells was simulated by coculturing of human acute T lymphocytic leukemia cells (Jurkat T cells) with human tongue squamous cell carcinoma cells (Cal27 cells). The anticancer activities were determined by coculturing ICIK cells with Cal27 cells in vitro. Results: A high-affinity peptide (nABPD1, KD=11.9 nM) for PD-1 was obtained by optimizing the nABP284 peptide (KD=11.8 μM). nABPD1 showed better efficacy than nABP284 in terms of increasing the secretion of interkeulin-2 by Jurkat T cells and enhancing the in vitro antitumor activity of ICIK cells. Conclusion nABPD1 possesses higher affinity for PD-1 than nABP284, which significantly enhances its ability to block the PD-1/PD-L1 interaction and to increase ICIK cell-mediated antitumor activity by armoring ICIK cells.

Objective · To investigate the prevalence of passive smoking among pregnant women in Shanghai and to analyze its influencing factors and to provide the basis and suggestion for making related intervention measures to reduce the harm of secondhand smoke on the health of pregnant women. Methods · From July to October 2014, pregnant women and their spouses were recruited for a questionnaire investigation at the antenatal care clinics of 3 maternity hospitals and 3 community hospitals in Shanghai. The questionnaire included demographic information, family basic situation and cognitive status of passive smoking. Results · The passive smoking rate before pregnancy in the 2831 pregnant women, who were involved in the investigation, was 17.1%. The passive rate during pregnancy was 7.8%. The difference between these two rates was statistically significant (P<0.05). 71.0% of the pregnant women have passive smoking for 15~59 min each day. Relative to home and work place, the passive smoking rate of pregnant women in public place was the highest (P<0.05). The passive smoking rate of pregnant women was significantly associated with the educational level of smoking spouses and the attitude of pregnant women when they faced the smokers. Conclusion · The passive smoking rate of pregnant women is influenced by the educational level of their spouses and the pregnant women's feedback to the smokers face to face. Public places are the most important exposure places to secondhand smoke for pregnant women. In order to reduce the harm from passive smoking to pregnant women and their fetuses, the related measures of smoking control at home education and smoking ban in public place should be made.

OBJECTIVE:To establish a method for the determination of drug loading and encapsulation efficiency of Epirubi-cin hydrochloride-sorafenib-loaded Polylactic Acid-glycolic Acid Polymer(PLGA)embolic microspheres. METHODS:HPLC meth-od was adopted to determine the contents of epirubicin hydrochloride and sorafenib in the preparation,and then drug loading and encapsulation efficiency were calculated by formula. The determination was performed on Phenomenex Luna 5u C8(2) 100A col-umn with mobile phase consisted of methanol-water(containing 0.05% trifluoroacetic acid and 0.14% dium dodecyl sulfate)(75:25,V/V)at the flow rate of 1.0 mL/min. The detection wavelength was set at 252 nm,and the column temperature was maintained at 25℃. The injection volume was 10μL. RESULTS:The linear ranges were 2.020-101.00μg/mL for epirubicin hydrochloride(r=0.9998)and 2.048-102.40 μg/mL for sorafenib(r=0.9997),respectively. The limits of quantification were 3.2970,2.5468 μg/mL, respectively. The detection limits were 0.9891,0.7641 μg/mL,respectively. RSDs of precision,stability and repeatability tests were all less than 2.0%. The recoveries were 96.41%-101.80%(RSD=1.64%,n=9),99.46%-101.45%(RSD=0.70%,n=9),re-spectively. Drug loading of two components in 3 batches of samples were no lower than 1.17%,encapsulation efficiency no lower than 58%. CONCLUSIONS:The method is simple,accurate,can be used to determine drug loading and encapsulation efficiency of Epirubicin hydrochloride-sorafenib PLGA embolic microspheres.

Objective: To explore the safety and feasibility of associating diaphragm resection and liver-diaphragmatic metastasis lesions resection for patients with advanced ovarian cancer. Methods: Retrospectively analysis 83 cases(98 times) of advanced ovarian cancer with liver-diaphragmatic metastasis between January 2012 and December 2016 at Department of Liver Surgery, Peking Union Medical College Hospital.The patients were aged from 19 to 75 years.Surgical procedure included metastatic lesions resection(43 times) and stripping(55 times). Operation status, post-operative complications, pathology results and follow-up of the patients were analyzed. Results: Fifteen patients received twice surgical treatment and 68 patients received one time surgical treatment. Postoperative hemorrhage in chest and between liver and diaphragm was not occurred in all cases.Dyspnea and low oxygen saturation were occurred in two cases of stripping patients and 1 case of metastatic lesions resection patients.Results of CT examination indicated that there was medium to large amount of ascites in right chests.The symptoms were relieved after placing thoracic closed drainage.Other patients were recovered smoothly.All patients were diagnosed as ovarian cancer by pathological examination. Conclusion Associating diaphragm resection is safe and feasible for liver-diaphragmatic metastasis lesions from ovarian cancer.

A method of derivatization at injection port following three phase hollow fiber microextraction with tetramethylammonium hydroxide (TMAH) as a dual-function reagent, for the simultaneous determination of salicylic acid, p-hydroxybenzoic acid, cinnamic acid, vanillic acid, p-coumaric acid and ferulic acid in beers by gas chromatography was developed. Phenolic acids were extracted from aqueous samples to a thin layer of organic solvent ( hexyl acetate) phase impregnated into the pores of the hollow fiber wall, and then back extracted to an acceptor solution (TMAH) located inside the lumen of the hollow fiber. Upon injection, the phenolic acids were derivatized to their methyl esters in the GC injection port. Several parameters related to the derivatization and extraction efficiency were optimized. The optimized conditions were as follows: hexyl acetate was used as the extraction solvent, an aqueous solution of TMAH (5% W/ V) was used as the derivatization reagent and acceptor phase, the pH value of donor phase was 2. 0, the concentrations of NaCl was 25% W/ V, the stirring rate was 500 r/ min, the extraction time was 40 min. Under the optimal conditions, the linear range of phenolic acids was 0. 50 -15. 00 mg / L, the limits of detection were 0. 05 -0. 18 mg / L. The proposed method was applied to the determination of the phenolic acids in beers. Vanillic acid, p-coumaric acid and ferulic acid were found in the beer samples, others were not detected. The spiked average recoveries were 90. 1% -106. 8% and RSD% was less than 5. 9% (n =3). The method is suitable for the determination of phenolic acids in beers.

OBJECTIVETo optimize a compound prescription for treatment of liver fibrosis with an improved therapeutic effect and low toxicity.

METHODSIn rat models of liver fibrosis induced by thioacetamide (TAA), the optimized prescription was screened based on a uniform design with 2-factor 5-level table using Uniform Design 3.0 software and tested using liver content of Hyp as the screening index. To verify the efficacy of the optimized prescription, the rat models of liver fibrosis were randomized into normal control group, model group, colchicine group and optimized prescription group, and the changes of hepatic Hyp content, serum HA, ALT, AST, and ALB levels, and the pathology liver fibrosis were observed after corresponding treatments.

RESULTSThe optimized prescription, which contained 70 mg/kg glycyrrhizin and 70 mg/kg matrine, showed a significant therapeutic effect against liver fibrosis in rats (Plt;0.05), and the effect was equivalent to that of colchicine (P>0.05).

CONCLUSIONUniform design is a valuable method in prescription optimization. The optimized compound prescription of matrine and glycyrrhizin has a significant effect in inhibiting liver fibrosis.

Alkaloids ; administration & dosage ; Animals ; Drug Therapy, Combination ; Female ; Glycyrrhizic Acid ; administration & dosage ; Liver Cirrhosis ; chemically induced ; drug therapy ; Male ; Phytotherapy ; Quinolizines ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Thioacetamide