Clinical efficacy and safety of tigecycline based on therapeutic drug monitoring for carbapenem-resistant Gram-negative bacterium pneumonia in intensive care units.

BACKGROUND: We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit. METHODS: This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline's clinical efficacy and safety were performed to control confounding factors. RESULTS: For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 µg/mL in the HD group, which was higher than in the SD group (0,21 µg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005-1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755-1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline. CONCLUSIONS: Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient's age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.

Interaction between Chinese medicine and digoxin: Clinical and research update.

Background: Digoxin is one of the most widely and commonly used cardiac drug, which plays an irreplaceable role in treating heart failure and arrhythmia. The 2010 Edition of Pharmacopoeia of the People's Republic of China stipulates that the effective range of digoxin plasma concentration is 0.5-2.0 ng/mL and it is toxic at plasma concentration >2 ng/mL. Its effective plasma drug concentration is close to the toxic concentration, and large individual differences in the effects of the drug have been observed. It is often used in combination with other drugs, but drug interactions have a great impact on the plasma concentration of digoxin and lead to adverse reactions (ADRs), such as poisoning. Most of the reported drug interactions are with Western drugs. However, there are many combinations of traditional Chinese medicine (TCM) and Western drugs, TCM interacting with digoxin comprises monomer components, single medicines, and Chinese patent medicines. Aim of the study: We aimed i) to provide an overview of the TCM formulations affecting the pharmacology of digoxin and their mechanisms of action and ii) to provide a theoretical reference for the safe and rational use of digoxin in combination with TCM in clinical practice and to avoid ADRs. Methods: A literature search of electronic databases, including PubMed, MEDLINE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WANFANG Data, was performed to search for articles published between 1 January 1960, and 1 August 2022. Search terms used included "digoxin," "traditional Chinese medicine," "Chinese patent medicine," and "adverse reactions" and their combinations. Results: A total of 49 articles were obtained, including clinical reports, pharmacological experiments and in vitro experiments. The mechanisms of action affecting the pharmacology of digoxin are complex. TCM formulations may affect the pharmacology of digoxin in vivo by influencing gastrointestinal motility or gastric juice pH, regulating P-glycoprotein levels, exerting cumulative pharmacological effects, and enhancing the sensitivity of the heart to digoxin. Although studies have shown that some TCM formulations interact with digoxin, they may be influenced by the complexity of the composition and the pharmacological effects of the TCM, the sensitivity of digoxin concentration determination methods, etc. The results of existing studies are controversial and further in-depth studies are required. Conclusion: Combinations of digoxin and TCM formulations are commonly used. This article serves as a reference to understand the interactions between TCM formulations and digoxin to avoid the occurrence of ADRs and improve the efficacy and safety of digoxin.

Clinical Efficacy, Antibiotic Resistance Genes, Virulence Factors and Outcome of Hospital-Acquired Pneumonia Induced by Klebsiella pneumoniae Carbapenemase 2-Producing with Tigecycline Treatment in the ICU.

Purpose: Tigecycline is an agent for carbapenemase-producing Klebsiella pneumonia (KPC-KP), given its penetration into lung tissues. Our study focused on the molecular and clinical efficacy of tigecycline for hospital-acquired pneumonia (HAP) in the ICU. Patients and Methods: A retrospective cohort study of 52 adult KPC-KP HAP patients by searching hospital medical records from January 2018 to December 2020 was established to investigate the epidemiology of KPC-KP infections for tigecycline treatment and the associated clinical efficacy of tigecycline. The KPC-KP isolates underwent multilocus sequence typing. Molecular typing, antimicrobial resistance, and virulence profiling were also analyzed by whole-genome sequencing of KPC-KP. Results: Among 52 patients with KPC-KP, the ICU mortality rate was 14/52 (27%), and there was no significant statistical difference in mortality between the effective group and failure group (p = 0.754). However, the duration of tigecycline was statistically different between the two groups of patients (14.4 vs 10 days, p=0.046). The total bacterial clearance rate was 6/52 (11.5%). There was no significant statistical difference in both groups (p=0.416). Antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were negatively correlated with clinical efficacy (p = 0.011, OR = 1.237). Conclusions: Blakpc was the main carbapenemase in all K. pneumoniae strains. ST11-KL64 KPC-KP was the most common virulence factors in KPC-KP isolates. This study suggested that antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were independent mortality risk factors for patients with Klebsiella pneumoniae carbapenemase-2 producing K. pneumoniae infections, when during the tigecycline treatment. Molecular analysis of K. pneumoniae may provide an option when choosing the antimicrobial treatment.

Intervention effect of job rotation on wrist work-related musculoskeletal disorders of physical therapists / 中国职业医学

@#Objective - （ ） To evaluate the effect of job rotation on pain in wrist work related musculoskeletal disorders WMSDs （ ）Methods of physical therapists PTs . A total of 100 PTs from nine medical institutions were selected as the research subjects ， using judgment sampling method and they were divided into control group and intervention group by stratified random sampling ， method with 50 person in each group. The individuals in control group perform routine works. People in the intervention group were rotated between posts or added mobile shift replacements in daily work for 30 minutes. The duration of intervention was ， ， （ ） once a day five days a week for ten weeks. Visual Analogue Scale VAS score and pain duration were used as the evaluation ， indexes of intervention effect. The changes of indexes before intervention five weeks and ten weeks after intervention were Results ， compared between the two groups. Before intervention there was no significant difference in the VAS score and pain （ P ） duration between the control group and the intervention group all >0.05 . There was no significant difference in VAS score （ P ） and pain duration among the control group at three time points after intervention all >0.05 . The VAS score of PTs in the （P ）， intervention group at ten weeks was lower than that in the control group at the same time point <0.05 and it was lower than （ P ） that before intervention and at five weeks of intervention in the same group all <0.05 . The pain duration of PTs in the （ P ）， intervention group was lower than that in the control group at five and ten weeks after intervention all <0.05 and was lower （ P ） Conclusion ， than that before intervention at the same group all <0.05 . Rotating schedule can relieve WMSDs of PTs and the effect of intervention for ten weeks is more effective than that of intervention for five weeks.

Development and Application of the Placebo Response Model in Clinical Trials for Primary Sjögren's Syndrome.

This study aimed to develop a placebo response model for pharmaceutical clinical trials of primary Sjogren's syndrome,and to quantitatively analyze the distribution and related factors influencing the placebo response to further optimize the design of clinical trials and evaluate the results of single-arm clinical trials. Public databases, including PubMed, Embase, and Cochrane Library were searched for reports on randomized placebo-controlled trials for Sjögren's syndrome which used the change from baseline in ESSDAI score as the primary outcome. The model-based meta-analysis method was used to evaluate the time course and the related influencing factors of the placebo response for ESSDAI in such clinical trials. A virtual placebo control group was constructed based on the final placebo response model to determine the treatment efficacy of belimumab and cyclosporine A for primary Sjögren's syndrome in a single-arm study. A total of 12 studies involving 450 subjects were included in the analysis. The established model described the time-course characteristics of the changes in ESSDAI score from the baseline in the 48 weeks placebo group. We found that the onset time of placebo response was approximately 12 weeks, and its efficacy plateaued at 48 weeks. The baseline ESSDAI score had a significant effect on the maximum value of the placebo response; the maximum value of the placebo response decreased by 0.552 for every 1 score rise in the baseline ESSDAI score. The efficacy of belimumab and cyclosporine A in the single-arm trial was comparable to that of the placebo response at the same baseline; no significant therapeutic advantage was observed. The placebo response model established in this study could provide a basis for designing clinical trials for primary Sjogren's syndrome in the future. It may also provide a reliable external efficacy control standard for single-arm clinical trials.

Qing-Yi Decoction in the Treatment of Acute Pancreatitis: An Integrated Approach Based on Chemical Profile, Network Pharmacology, Molecular Docking and Experimental Evaluation.

Background: Qing-Yi Decoction (QYD) is a classic precompounded prescription with satisfactory clinical efficacy on acute pancreatitis (AP). However, the chemical profile and overall molecular mechanism of QYD in treating AP have not been clarified. Methods: In the present study, a rapid, simple, sensitive and reliable ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS)-based chemical profile was first established. An integration strategy of network pharmacology analysis and molecular docking based identified ingredients was further performed to screen out the potential targets and pathways involved in the treatment of QYD on AP. Finally, SD rats with acute pancreatitis were constructed to verify the predicted results through a western blot experiment. Results: A total of 110 compounds, including flavonoids, phenolic acids, alkaloids, monoterpenes, iridoids, triterpenes, phenylethanoid glycosides, anthraquinones and other miscellaneous compounds were identified, respectively. Eleven important components, 47 key targets and 15 related pathways based on network pharmacology analysis were obtained. Molecular docking simulation indicated that ERK1/2, c-Fos and p65 might play an essential role in QYD against AP. Finally, the western blot experiments showed that QYD could up-regulate the expression level of ERK1/2 and c-Fos, while down-regulate the expression level of p65. Conclusion: This study predicted and validated that QYD may treat AP by inhibiting inflammation and promoting apoptosis, which provides directions for further experimental studies.

[Research progress in the modulating effect of high-density lipoprotein on neutrophil function].

For a long period, studies about the modulating effect of high-density lipoprotein (HDL) on inflammatory cells mainly focus on cardiovascular diseases. In recent years, researchers have found the significant role of HDL in many other fields, such as diabetes, metabolic syndrome, chronic kidney disease, systemic inflammatory disease, autoimmune diseases and infectious diseases. Researches have shown that HDL can inhibit the function of activated neutrophil via disturbing the cytokine production, deformation, adhesion, transmigration and pathogen elimination. Clinical trials have discovered that serum HDL level is negatively correlated with neutrophil-to-lymphocyte ratio in healthy males with low HDL level. In addition, serum HDL level is closely associated with disease severity of severe acute pancreatitis. Consequently, understanding the effect and mechanism of the regulation of HDL on neutrophil function plays an important role in remedying the diseases resulted from excessively activated neutrophil.

[Analysis of the 4th generation outer space bred Angelica dahurica by FTIR spectroscopy].

The major components of the 4th generation outer space bred angelica and the ground group were determined and analyzed by Fourier transform infrared spectroscopy (FTIR) and second derivative spectrum, considering the large mutation of the plants with space mutagenesis. The results show that the content of the coumarin (1741 cm(-1)), which is the main active components of the space angelica dahurica increased, and the content of the protein (1 459, 1 419 cm(-1)) and the fat (930 cm(-1)) increased slightly, whereas the content of the starch and the dietary fiber reduced drastically. There are obvious differences between the peak values of the second derivative spectra of the plants, revealing that the outer space angelica dahurica contained amine component at 1 279 cm(-1). Space mutation breeding is favor of breeding angelica with better idiosyncrasy.

Discovering the distinct inhibitory effects between C4-epimeric glycosyl amino acids: new insight into the development of protein tyrosine phosphatase inhibitors.

There has been increasing interest in the development of drug candidates based on sugar templates that possess rich structural and, especially, configurational diversities. We disclose herein that the epimeric identity between methyl 3,4-bis-phenylalanyl/tyrosinyl triazolyl-alpha-D-galactopyranoside and glucopyranoside may lead to their distinct inhibitory effects on specific protein tyrosine phosphatases (PTPs). Subsequently performed molecular docking study elucidated the plausible binding behaviors of the more potent galactosyl inhibitors with their primary PTP target, i.e. Cell Division Cycle 25B (CDC25B) phosphatase.

[Application of XRF to the analysis of Scutellaria baicalensis with space mutagenesis].

X-ray fluorescence spectrum (XRF) analytic method was applied to the determination of the contents and varieties of mineral elements in the space flight mutagenesis breeding scutellaria baicalensis Georgi, and compared with the ground group which were planted and collected together under the same conditions, in an attempt to search for the influence of space environment upon mutation on scutellaria baicalensis Georgi. The result indicates that the varieties of the main mineral elements in the two samples are samely basically, therefore, the two samples have same absorption and enrichment capability of specific element, but the contents of elements Ca, Na, Zn and S increase by 0.3, 0.3, 0.04 and 0.7 times, respectively, in the space group. This modern testing method played an important role in the study. It is recommended that the testing method should be used in the selection of space bred herbal seeds for its advantages, such as quick, simple, highly sensitive, and of wide measure range. To conclude, New breeds can be selected by space breeding, it is significant for the selection and growing of space herbal medicine seeds, and it also has broad application in space breeding of medical plants.

[Comprehensive characterization of main components and microstructures in five different species of Salvia miltiorrhiza bge].

Studied with X-ray fluorescence spectrum analytic (XRF), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR) for five different species of Salvia miltiorrhiza bge grew in Anguo, the intrinsic components and microstructures were determined and comprehensive characterization was carried out. The figure of comprehensive characterization can describe characteristics of intrinsic components from elements, crystal and amorphous active component, it can give an intuitive description for the same components and subtle differences in the intrinsic components of Salvia miltiorrhiza bge, which are different idioplasmatic and same species. It is the ideal method because of the simple preparation of sample, rapid and fine accurate measurement with reproducibility and objectivity, so that it can be used for breeding of fine varieties of Chinese medicinal materials, Chinese medicinal materials GAP guidance of growing conditions, medicinal origin characteristics, the intrinsic composition and microstructure characterization, quality control and authenticity of the identification.

[Study of the fourth generation of Salvia miltiorrhiza Bge by XRF].

X-ray fluorescence spectrum (XRF) analytic method was used to analyze and compare the contents and varieties of mineral elements in the ground group Salvia miltiorrhiza Bge, and the fourth generation Salvia miltiorrhiza Bge with space flight mutagenesis breeding in order to provide important basic data for selecting high quality breed and further research. The result indicates that the varieties of the main mineral elements in the two samples are the same basically, but Cu/Zn ratio is enhanced to 1.0, the contents of microelements Cr, Mn and Fe increase by 0.6, 0.5, and 0.3 times respectively compared with the ground group. To conclude, in the space group the contents and proportions of the mineral elements are improved and optimized. Xray fluorescence spectrum analytic method has many advantages, such as quickness, simplicity, high sensitivity, wide measure range, etc. The method can be used for quantitative element analysis and study of Chinese herbal medicines.

[Research on the fourth generation of radix isatidis by FTIR].

FTIR spectra of fourth-generation space bred radix isatidis and FTIR spectra of radix isatidis in a ground group were determined on the whole. Comparative analysis was conducted on main constituents (components) to accumulate data for comprehensively understanding and thoroughly studying the inherent property, and to explore a method of evaluating the quality of space bred radix isatidis. The results showed that slight difference existed in the positions and shapes of the absorption peaks in FTIR spectra of samples between the two groups. The intensities of main absorption peaks of radix isatidis in the space group were strengthened to various degrees compared with those in the ground group. The absorption peaks were markedly enhanced at wave numbers of 1 047, 1 630 and 1 412 cm(-1), indicating that the contents of polysaccharides, sterides, triterpenes and flavanoids, particularly polysaccharides with anti-viral efficacy, increased to different extents. The absorption peak intensity of space radix isatidis at the wave number of 1 745 cm(-1) was weakened compared with that of radix isatidis in the ground group, suggesting the reduction of glycosides and organic acids. It is concluded that the contents of a plurality of active components of radix isatidis in the space group are elevated. New radix isatidis varieties with high contents of diverse active components can be harvested by spaceflight mutation breeding.

[Analysis of the 4th generation Scutellaria baicalensis Georgi with space mutagenesis via FTIR spectroscopy].

Determination and analysis for the Scutellaria baicalensis Georgi with space mutagenesis and the ground group were carried out with FTIR for the first time in order to fully understand the quality changes of the 4th generation of space mutagenesis of Scutellaria baicalensis Georgi and do further research. The result shows that for the FTIR spectra of the two samples the position and shape of main absorption peaks are approximately the same, indicating that the major components and the structures of space group remain intact, but the intensities of the absorption peaks are obviously different, with the intensities of the space group significantly enhanced compared to the ground group, especially for the flavonoid compounds (baicalin, baicalein, wogonoside, wogonin and wogonoside etc), which are the main active components of the Scutellaria baicalensis Georgi, the absorption peak intensities at 3391, 1655 and 1069 cm(-1) are obviously stronger than those of the ground group, so the contents of flavonoid compounds and other components are higher, and the amorphous active components are optimized. Space mutation breeding is conducive to breeding new varieties of highly active components, and it is also one of the ways to innovate Chinese medicines germplasm resources efficiently.

[Study of the Saposhnikovia divaricata with space mutagenesis by Fourier transform infrared spectroscopy].

The outer space Saposhnikovia divaricata of the fourth generation was studied and compared with the ground group and comparison group for the first time. The intensity of carbonyl absorption peak at 1640 cm(-1) is stronger than the other two, indicating that chromone content was enhanced obviously. The peaks at 2927 and 2856 cm(-1) were assigned to --CH2-- groups, the peak at 1050 cm(-1) was due to the C-O groups, and the intensities at 2927, 2856 and 1050 cm(-1) were stronger than other samples, indicating that polysaccharide and glycoside contents were enhanced obviously. The intensity of lactone absorption peak at 1743 cm(-1) was stronger than the ground group and weaker than the comparison, indicating that coumarin content was higher than ground group and lower than the comparison. The major components and the structures remained intact, and the effective component contents were enhanced in the outer space Saposhnikovia divaricata. Using FTIR can analyse and characterize the intrinsic quality of the outer space medicinal materials.