Objective To explore the risk factors for voriconazole-induced adverse reactions in patients with acquired immunodeficiency syndrome(AIDS)for screening the high-risk populations and safe use of voriconazole.Methods Retrospective analysis was performed on patients who received voriconazole from January 2020 to December 2023.Demographic details,medical history,laboratory tests,concomitant medications,and adverse reactions of patients were collected from the hospital information system(HIS).The potential risk factors for the adverse reactions induced by voriconazole were analyzed by univariate and logistic multivariate analysis.Receiver operating characteristic(ROC)curve was used to analyze the specificity and sensitivity of the risk factors as predictor.Results A total of 170 patients were included in this study.Adverse drug reaction was reported in 62 patients(36.5％).Central nervous system toxicity,hepatotoxicity,and visual impairment were the most common adverse reactions.Univariate analysis showed that the adverse reactions of voriconazole were significantly associated with C-reactive protein,aspartic aminotransferase,aspartic aminotransferase/alanine aminotransferase,and CD4+T lymphocytes/CD8+T lymphocytes(CD4+/CD8+).Multivariate analysis indicated that CD4+/CD8+was an independent risk factor for voriconazole-induced adverse reactions.ROC curve indicated that CD4+/CD8+had a better predictive capability(AUC=0.756).Conclusions CD4+/CD8+should be monitored closely during voriconazole treatment for fungal infection in patients with AIDS.CD4+/CD8+may be a good predictor for voriconazole-related psychiatric and visual abnormalities and hepatotoxicity.

Objective To explore the risk factors for voriconazole-induced adverse reactions in patients with acquired immunodeficiency syndrome(AIDS)for screening the high-risk populations and safe use of voriconazole.Methods Retrospective analysis was performed on patients who received voriconazole from January 2020 to December 2023.Demographic details,medical history,laboratory tests,concomitant medications,and adverse reactions of patients were collected from the hospital information system(HIS).The potential risk factors for the adverse reactions induced by voriconazole were analyzed by univariate and logistic multivariate analysis.Receiver operating characteristic(ROC)curve was used to analyze the specificity and sensitivity of the risk factors as predictor.Results A total of 170 patients were included in this study.Adverse drug reaction was reported in 62 patients(36.5％).Central nervous system toxicity,hepatotoxicity,and visual impairment were the most common adverse reactions.Univariate analysis showed that the adverse reactions of voriconazole were significantly associated with C-reactive protein,aspartic aminotransferase,aspartic aminotransferase/alanine aminotransferase,and CD4+T lymphocytes/CD8+T lymphocytes(CD4+/CD8+).Multivariate analysis indicated that CD4+/CD8+was an independent risk factor for voriconazole-induced adverse reactions.ROC curve indicated that CD4+/CD8+had a better predictive capability(AUC=0.756).Conclusions CD4+/CD8+should be monitored closely during voriconazole treatment for fungal infection in patients with AIDS.CD4+/CD8+may be a good predictor for voriconazole-related psychiatric and visual abnormalities and hepatotoxicity.

OBJECTIVE To establish a UPLC detection method for simultaneous determination of mycophenolic acid(MPA) and its glucuronide(MPAG) in plasma of rats, and to investigate gender-related pharmacokinetic characteristics of mycophenolic acid. METHODS Twelve SD rats(half male and half female) were intragastrically administrated with 90 mg·kg-1·d-1mycophenolate acetate, and blood was collected from periorbital vein at different time points after administration. Plasma samples were extracted by liquid-liquid extraction and drug concentrations of MPA and metabolite MPAG in plasma were determined using UPLC. The method was developed using Waters BEH C18 column. The gradient elution was performed at a flow rate of 0.35 mL·min-1 with the mobile phase acetonitrile solution (A)-0.1% formic acid aqueous solution(B). The detection wavelength was at 266 nm and column oven temperature was maintained at 40 ℃. The pharmacokinetic parameters were calculated by using DAS 2.0 software. RESULTS The linear relationship between peak area and concentrations of MPA and MPAG were good in the ranges of 0.31-160 µg·mL-1(R2=0.999 8) and 0.62-320 µg·mL-1(R2=0.999 4), respectively. Analytical methods of MPA and MPAG all met the requirements of the methodology. Pharmacokinetic parameters AUC0-t and Cmax of MPA and MPAG in female rats were higher than that in male rats(P<0.05 or P<0.01). In addition, the metabolic rate of genistein[UDP-glucuronosyltransferases(UGT)s substrate] and MPA in male rat liver microsomes were significantly faster than that in female rat liver microsomes. CONCLUSION This developed UPLC method is sensitive, accurate and specific, which is suitable to detect the concentrations of MPA and MPAG in the plasma. The pharmacokinetics of MPA and MPAG in rats are gender different, which may be related to the sex difference of UGTs metabolic enzyme activity.

OBJECTIVE To establish a physiologically-based pharmacokinetic （PBPK） model of amikacin in elderly patients with renal insufficiency. METHODS PK-SIM® software was adopted for model building， optimization and simulation. The physical and chemical properties and pharmacokinetic parameters related to amikacin were collected by literature review. The PBPK model on adults was established and extrapolated to the elderly population based on the built-in human model. Data from clinical PK studies were used to optimize and validate the model. The goodness of fit， relative residual， and mean folding error （MFE） were used to evaluate the performance of forecasting. The final model was employed to simulate the exposure of amikacin in the elderly population with renal insufficiency， and the efficacy and safety of commonly used clinical dosing regimens were evaluated， and the recommended regimens were proposed. RESULTS The established PBPK model of amikacin had good prediction performance in both adult and elderly populations， with the absolute mean of relative residual value of 25%； the MFE of peak concentration （cmax） and area under the plasma concentration curve （AUC0－∞） in all simulation occasions ranged ＞0.5-＜2. The simulation results showed that， compared with healthy adults， no significant clinical difference in cmax was observed in the elderly with renal insufficiency at the same dosing regimen， but the trough concentration increased significantly due to accumulation. Prolonging the administration interval of amikacin rather than reducing the dosage was more helpful to ensure the efficacy and to reduce the occurrence of nephrotoxicity. CONCLUSIONS The PBPK model for amikacin is successfully established in the elderly patient with renal insufficiency， and shows good predictive performance.

Objective:To investigate the effect of colonoscopy on intestinal microecology in healthy adults of different ages and its therapeutic strategy.Methods:A total of 128 healthy officers and soldiers of different ages and retired military personnel who underwent physical examination in the Outpatient Department of Chinese PLA Medical School from May 1, 2020 to December 30, 2020 were selected as the research subjects. They were divided into young people group (Group Y, 18 to 35 years old, n=37), middle-aged people group (Group M, 36 to 59 years old, n=44), and elderly people group (Group E, 60 years old or above, n=47) according to their age. Another 110 elderly research subjects were divided into placebo group (Control Group, n=36), Brewer’s yeast group (Yeast Group, n=35) and Bacillus subtilis combined with Enterococcus faecium group (Combined Group, n=39) according to the treatment methods. Fecal samples were collected 1 day before intestinal preparation for colonoscopy, 7 days, and 14 days after colonoscopy, respectively, and the abundance, diversity, and composition of intestinal microflora were detected by 16S rRNA sequencing technology. Steady-state changes and adverse symptoms of intestinal microflora in the elderly research subjects after treatment were observed. Results:Before intestinal preparation, there was no statistically significant difference among the three age groups in the abundance of intestinal microflora ( P>0.05); on the 7th day after colonoscopy, the abundance was all decreased significantly; on the 14th day after colonoscopy, the abundance of the Group Y and the Group M could recover to the levels before intestinal preparation, while that of the Group E was not completely recovered ( P<0.05). Compared with the 14th day after colonoscopy, there was no statistically significant difference in the diversity of intestinal microflora among the three age groups before the colonoscopy ( P>0.05). Compared with before intestinal preparation and the 14th day after colonoscopy, the diversity on the 7th day after colonoscopy was significantly decreased ( P<0.05). Regarding the phylum level, there was no statistically significant difference in the composition of microflora between the Group Y and the Group M before intestinal preparation ( P>0.05). The proportion of Firmicutes in the Group E was slightly lower than those in the Groups Y and M, while the proportion of Bacteroides was higher ( P<0.05). Regarding the family level, compared with the 14th day after colonoscopy, there was no statistically significant difference in the composition of bacteria in the Groups Y and M before intestinal preparation ( P>0.05). Compared with before intestinal preparation, the numbers of trichospiraceae in the three age groups on the 7th day after colonoscopy were all significantly decreased ( P<0.05), while the numbers of enterobacteriaceae were significantly increased ( P<0.05). The abundance of Lactobacillus in the Group E was higher than those in the Groups Y and M at three time points ( P<0.05). The abundance of intestinal microflora in the Yeast Group and the Combined Group were significantly higher than that of the Control Group. The clustering trends of the Yeast Group, the Combined Group, and the Control Group were significantly different at different treatment stages. The incidence of adverse symptoms in the Combined Group and the Yeast Group was significantly lower than that of the Control group ( P<0.05). Conclusion:Colonoscopy can cause imbalance of intestinal microbiota homeostasis, and the elderly have a longer recovery time and suffer from more complications. Probiotics can help them quickly recover intestinal microbiota homeostasis and reduce the incidence of complications.

Objective:To investigate the effect of colonoscopy on intestinal microecology in healthy adults of different ages and its therapeutic strategy.Methods:A total of 128 healthy officers and soldiers of different ages and retired military personnel who underwent physical examination in the Outpatient Department of Chinese PLA Medical School from May 1, 2020 to December 30, 2020 were selected as the research subjects. They were divided into young people group (Group Y, 18 to 35 years old, n=37), middle-aged people group (Group M, 36 to 59 years old, n=44), and elderly people group (Group E, 60 years old or above, n=47) according to their age. Another 110 elderly research subjects were divided into placebo group (Control Group, n=36), Brewer’s yeast group (Yeast Group, n=35) and Bacillus subtilis combined with Enterococcus faecium group (Combined Group, n=39) according to the treatment methods. Fecal samples were collected 1 day before intestinal preparation for colonoscopy, 7 days, and 14 days after colonoscopy, respectively, and the abundance, diversity, and composition of intestinal microflora were detected by 16S rRNA sequencing technology. Steady-state changes and adverse symptoms of intestinal microflora in the elderly research subjects after treatment were observed. Results:Before intestinal preparation, there was no statistically significant difference among the three age groups in the abundance of intestinal microflora ( P>0.05); on the 7th day after colonoscopy, the abundance was all decreased significantly; on the 14th day after colonoscopy, the abundance of the Group Y and the Group M could recover to the levels before intestinal preparation, while that of the Group E was not completely recovered ( P<0.05). Compared with the 14th day after colonoscopy, there was no statistically significant difference in the diversity of intestinal microflora among the three age groups before the colonoscopy ( P>0.05). Compared with before intestinal preparation and the 14th day after colonoscopy, the diversity on the 7th day after colonoscopy was significantly decreased ( P<0.05). Regarding the phylum level, there was no statistically significant difference in the composition of microflora between the Group Y and the Group M before intestinal preparation ( P>0.05). The proportion of Firmicutes in the Group E was slightly lower than those in the Groups Y and M, while the proportion of Bacteroides was higher ( P<0.05). Regarding the family level, compared with the 14th day after colonoscopy, there was no statistically significant difference in the composition of bacteria in the Groups Y and M before intestinal preparation ( P>0.05). Compared with before intestinal preparation, the numbers of trichospiraceae in the three age groups on the 7th day after colonoscopy were all significantly decreased ( P<0.05), while the numbers of enterobacteriaceae were significantly increased ( P<0.05). The abundance of Lactobacillus in the Group E was higher than those in the Groups Y and M at three time points ( P<0.05). The abundance of intestinal microflora in the Yeast Group and the Combined Group were significantly higher than that of the Control Group. The clustering trends of the Yeast Group, the Combined Group, and the Control Group were significantly different at different treatment stages. The incidence of adverse symptoms in the Combined Group and the Yeast Group was significantly lower than that of the Control group ( P<0.05). Conclusion:Colonoscopy can cause imbalance of intestinal microbiota homeostasis, and the elderly have a longer recovery time and suffer from more complications. Probiotics can help them quickly recover intestinal microbiota homeostasis and reduce the incidence of complications.

BACKGROUND: In recent years, immune checkpoint inhibitors (ICIs) have become a hot spot in cancer because of their remarkable survival benefits on non-small cell lung cancer (NSCLC) patients. However, the immune-related adverse events (ir-AEs) induced by ICIs have been frequently reported due to its specificity and severity. This article is to summarize and evaluate ir-AEs induced by ICIs. Hopefully it can provide guidance for advanced NSCLC patients treatment options, early recognition and management of ir-AEs. METHODS: Randomized controlled trials (RCT) which involved ICIs in the treatment of advanced NSCLC were retrieved in the Cochrane Libraby, PubMed, EMBASE and other databases. The primary outcome includes the incidence, grade and organ specificity of ir-AEs. Relative risk (RR) was used as the effect size, which was expressed as 95% confidence interval (CI). The Stata 15.0 and RevMan 5.3 software are used to conduct the meta analysis. RESULTS: A total of 17 RCTs were included. The ir-AEs were generally more than those in the traditional chemotherapy group. The risk and severity of ir-AEs induced by ICIs combined group were generally higher than that of ICI monotherapy, while the incidence of severe ir-AEs induced by ICIs combination therapy was similar to that of anti-cytotoxic T-lymphocyte-asscociated antigen 4 (CTLA-4) group. CONCLUSIONS ICIs have different toxicity profile compared with chemotherapy, and their immune-related toxicity is stronger than that of traditional chemotherapy. ICIs induced ir-AEs is organ-specific, and different ICI has specific immune-related toxicity profiles. As ICIs represent a new and distinct class of treatment for NSCLC, this article has systematically illustrated the efficacy and ir-AEs induced by ICIs, hopefully it can be useful for clinicians and patients to get a further understanding of ICIs, and facilitate early prediction, comprehensive diagnosis, and prompt management of ir-AEs by providing status reference and management suggestions, so that ICI can bring more benefit for advanced NSCLC patients.

Objective According to the changes of microcirculation in the pulmonary cancers, the treatment effect was evaluated after the vascular interventional therapy.Methods Angiography of 138 primary pulmonary carcinomas, and the feeding arteries were performed. Areas of mass blush were measured for 81 cases before and after therapy. The tumour blush was considered to be the imaging appearance of the microcirculation of the lung carcinoma. The angiographic images were collected by digital image system (DSA and movie). Results (1) The rate of the tumour blush appearance was 88.8% in this group. (2) The areas of the lung carcinoma blush in 81 cases before and after therapy were (941.4?73.2)mm 2 and (427.9? 93.8 )mm 2( P

Objective To study the effect of vasopressin (VS) on the small bowel circulation and the safety of emboliotherapy for the small intestinal hemorrhage by DSA. Methods Ten dogs were divided into three groups. Vasa recta were ligated 30min after VS infusion ended in group A( n =4), and 2h after VS infusion ended in group B( n =4), they were ligated without VS infusion in control group ( n =2). DSA were performed before and after VS infusion, before and after the ligation. The tested parts of intestine were resected to make the pathologic examination a week late. Results All branches of mesenteric arteries contracted and the contrast developed light in the intestinal wall after VS infusion. Branches contraction recovered but the contrast developed still slight in the intestinal wall about 30min after infusion ended. All manifestation of DSA recovered to normal 2h after infusion ended. In all groups, the blood vessel net can be seen but is fewer and scattered in the area of ligation. The collorate presented soon after the ligation. The pathologic examination proved that there was only mind mucosal ischemia in all groups. Conclusion The repressive effect of VS to the circulation of intestine weakened and then disappeared rapidly after the infusion ended. VS infusion had no significant effect on the safety of emboliotherapy for small intestinal bleeding when the infusion has been finished for more than 2hr. DSA can demonstrated the circulation state of the intestine before and after embolization.