1. Development and validation of a method for quantitation of cefepime/avibactam in M-H broth: application to antibacterial activity using in vitro PK/PD Model
Bingqian YAN ; You LI ; Miaomei TIAN ; Bingqian YAN ; Siwei GUO ; You LI ; Miaomei TIAN ; Bing XU ; Rong JIANG ; Xin LI ; Siwei GUO ; Bing XU ; Rong JIANG ; Xin LI
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(1):52-60
AIM: To establish a method for quantitation of cefepime and avibactam in M-H broth, and applicated in the in vitro dynamic PK/PD model. METHODS: The cefepime was also determined using the high-performance liquid chromatography method (HPLC), the avibactam was also determined using the liquid chromatography-mass spectrometry (LC-MS/MS), an in vitro dynamic PK/PD model was established to study the PK/PD relationship of cefepime/avibactam against carbapenem resistant Klebsiella pneumoniae (CRKP). RESULTS: The linear ranges of cefepime and avibactam were good at (0.5-20) and (0.1-25) μg/mL (r=0.999), and the lower limit concentrations were 0.5 and 0.1 μg/mL. The extraction recoveries of cefepime and avibactam in M-H broth were 88.0%-101.7% and 90.9%-95.2%, the relative standard deviation of intra-day precision and inter-day precision were less than 5.2%. The concentration-time curves were well simulated by the PK/PD model. All observed concentrations in each experiment were in the range of 20% of the targeted values. For the CRKP of MIC=8 μg/mL and MIC=16 μg/mL, the colony decreased to 2.783Log10 CFU/mL and 1.325Log10 CFU/mL at the cefepime/avibactam 2.5 g q8 h administration after 24 h. CONCLUSION: The determination method of cefepime and avibactam in broth established in this study has high sensitivity and good stability. For the CRKP with MIC≤8 μg/mL,cefepime/avibactam showed that good anti-CRKP activity under routine administration in vitro dynamic PK/PD model.
2.Research advances in the immunomodulatory mechanism of galectin-9 and its role in liver diseases
Jun LING ; Bing ZHU ; Weiwei CHEN ; Zhuoran WANG ; Limei YU ; Shaoli YOU
Journal of Clinical Hepatology 2024;40(1):193-198
Galectin-9 (Gal-9) is a member of the galectin family that can specifically recognize and bind to galactosides. Recent studies have shown that Gal-9 is highly expressed in the liver and can help to maintain intrahepatic immune homeostasis and perform biological functions in various liver diseases. This article reviews the immunomodulatory functions of Gal-9 and its role in different liver diseases. Studies have shown that Gal-9 has important biological functions in different liver diseases through multiple pathways. Research on the specific immunomodulatory mechanisms and functions of Gal-9 may help to discover the therapeutic role of Gal-9 in liver diseases.
3.Efficacy and safety of N-acetylcysteine in treatment of severe alcoholic hepatitis
Fangjiao SONG ; Tianjiao XU ; Yirui YIN ; Hua TIAN ; Sa LYU ; Shaoli YOU ; Shaojie XIN ; Bing ZHU
Journal of Clinical Hepatology 2024;40(12):2484-2491
ObjectiveTo investigate the efficacy and safety of N-acetylcysteine (NAC) in the treatment of severe alcoholic hepatitis (SAH), and to provide a basis for clinical medication for SAH. MethodsA prospective randomized controlled trial was conducted among 172 SAH patients with a Maddrey discriminant function score of >32 points who were recruited by The Fifth Medical Center of Chinese PLA General Hospital from June 2015 to June 2018, and these patients were divided into NAC group with 84 patients and control group with 86 patients. NAC (8 g/day, 28 days) was assessed in terms of its safety in SAH patients, its impact on 28-day biochemical parameters, and its role in improving 28- and 180-day survival rates. A further analysis was performed to investigate the effect of NAC on the 28- and 180-day survival rates of SAH patients with acute-on-chronic liver failure (ACLF-SAH patients) and those without acute-on-chronic liver failure (non-ACLF-SAH patients). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate independent influencing factors. ResultsNo serious adverse events were observed during NAC treatment, suggesting that NAC had a good safety profile. Compared with the control group, NAC did not significantly improve the 28-day biochemical parameters (all P>0.05) and survival rate of SAH patients (P=0.081), but it could improve the 180-day survival rate of SAH patients (67.4% vs 81.0%, χ2=4.280, P=0.039). NAC did not improve the 28- and 180-day survival rates of ACLF-SAH patients (both P>0.05); NAC did not improve the 28-day survival rate of non-ACLF-SAH patients (P>0.05), but it could improve the 180-day survival rate of these patients (68.4% vs 88.9%, χ2=4.883, P=0.027). The multivariate Cox regression survival analysis showed that NAC treatment (hazard ratio [HR]=2.530, 95% confidence interval [CI]: 1.334 — 4.796, P=0.004,), Maddrey discriminant function score (HR=3.852, 95%CI: 2.032 — 7.304, P<0.001), and serum sodium level (HR=1.948, 95%CI: 1.079 — 3.517, P=0.027) were independent influencing factors for 180-day survival rate in SAH patients. ConclusionNAC has a good safety profile in the treatment of SAH and can improve the 180-day survival rate of SAH patients, and in particular, non-ACLF-SAH patients can benefit from NAC treatment in terms of middle- and long-term survival rates.
4.The extreme reduction in cholinesterase caused by compound heterozygous mutations in the BCHE gene:A case report
Sa LYU ; Bing ZHU ; Tianjiao XU ; Shaoli YOU
Journal of Clinical Hepatology 2024;40(10):2075-2078
Serum cholinesterase(ChE)level is important for the diagnosis and prognostic evaluation of various diseases such as liver diseases and toxic diseases,and butyrylcholinesterase(BuChE)is an important component of ChE.Mutations in the BCHE gene can cause a significant reduction in the level of BuChE,with extensive reports in European and American populations and relatively few reports in Eastern countries,particularly China.This study describes a male patient,aged 35 years,who was misdiagnosed with organophosphorus pesticide poisoning due to an extreme reduction in ChE level and was given detoxification therapy,but such diagnosis was excluded by various biochemical examinations.Finally whole-exome sequencing and Sanger sequencing revealed the complex heterozygous mutations of c.1027dup and c.401dup at exon 2 of the BCHE gene,and hereditary BuChE deficiency due to these mutations is the cause of the extreme reduction in ChE level.
5.Research on ethical governance technology of biological identification technology:based on technology track theory
Bing LIU ; Zhichao YOU ; Fangling JIANG
Chinese Medical Ethics 2024;37(10):1125-1132
While biological identification technology has brought positive impacts to society,it has also raised ethical issues,such as privacy protection and fair application.Taking the technical dimension as the main line is the foundation of efficient and agile governance of ethical issues in biological identification technology.Based on the technology track theory,a framework for ethical governance of biological identification technology was constructed,and the track and ethical governance technology of biological identification technology were sorted out.The key to efficient governance lies in the application of ethical governance technologies such as privacy and security protection and fairness detection at the three levels of the entire lifecycle of biological identification technology,including data,algorithms,and systems.Taking Hikvision's facial recognition technology as an example,this paper elaborated that increasing the application of ethical governance technology is of great significance to ensure the trustworthy and sustainable development of biological identification technology.
6.Risk factors and predictive model of cerebral edema after road traffic accidents-related traumatic brain injury
Di-You CHEN ; Peng-Fei WU ; Xi-Yan ZHU ; Wen-Bing ZHAO ; Shi-Feng SHAO ; Jing-Ru XIE ; Dan-Feng YUAN ; Liang ZHANG ; Kui LI ; Shu-Nan WANG ; Hui ZHAO
Chinese Journal of Traumatology 2024;27(3):153-162
Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.
7.Setup error analysis during proton and heavy ion therapy for head and head neck tumor patients with fixation by thermoplastic film combined with styrofoam
Zhu-Lei LIU ; Rui-Rui BU ; Dan ZHOU ; Yao LI ; Ling-Min WU ; Dong-Peng ZHANG ; Jiang-Bing ZHANG ; Dan YOU
Chinese Medical Equipment Journal 2024;45(7):56-61
Objective To analyze the setup errors during proton and heavy ion therapy for head and head neck tumor patients fixed by thermoplastic film combined with styrofoam.Methods Totally 20 patients undergoing proton and heavy ion therapy at some hospital from January to December 2018 were selected retrospectively,of whom 10 ones had head tumors with clinical targets located in the head and the other 10 cases had head and neck tumors with clinical targets distributed in the head and neck.All the 20 patients were fixed with thermoplastic film combined with styrofoam.The head and neck images of the patients acquired after image guidance were aligned with the CT localization-based digitally reconstructed radiograph images,and the setup errors at six-dimensional directions(left-right translation,head-foot translation,forward-backward translation,isocentric rotation,pitch rotation and transverse-roll rotation)were recorded in the first five and the last five times of radiotherapy treatment.The data were processed by using the SPSS 23.0 statistical software and EXCEL.Results There were no significant differences between the head tumor patients in the setup errors at the six directions during the first and last five times of radiotherapy(P>0.05).The head and neck tumor patients did not have obvious differences in the setup errors at the the directions of left-right translation,forward-backward translation,isocentric rotation and transverse-roll rotation(P>0.05),while did at the directions of head-foot translation and pitch rotation(P<0.05).The head and head neck tumor patients with the fixation by thermoplastic film combined with styrofoam had their setup errors at the six directions meet clinical requirements after calibration by the six-dimensional treatment table.Conclusion The fixation mode by thermoplastic film and styrofoam behaves well to enhance the setup repeatability for head tumor patients at the six-dimensional directions,while not so well for head neck tumor patients at the directions of head-foot translation and pitch rotation.Proper measures have to be taken to decrease the setup errors during proton and heavy ion therapy for head and head neck tumor patients.[Chinese Medical Equipment Journal,2024,45(7):56-61]
8.Tick-borne pathogens infection of rodents at the border of China and the Democratic People's Republic of Korea
Zhuo WANG ; Qiong WU ; Xiao-Yang HUANG ; Guan-Peng HUANG ; You-Xin MA ; En-Rong MAO ; Guo-Shuang LENG ; Hong-Min ZHAO ; Bing LI ; Yi-Min WU
Chinese Journal of Zoonoses 2024;40(4):323-327
To investigate the existence of tick-borne pathogens infection of rodents at the border of China and the Demo-cratic People's Republic of Korea(DPRK).PCR was used to detect the spotted fever group rickettsiae(SFGR)ompA gene,Ehrlichia chaffeensis(Ec)and Anaplasma phagocytophilum(Ap)16S rRNA,Candidatus Neoehrlichia mikurensis(CNm)groEL gene,Bartonella(Ba)rpoB gene,and Francisella tularensis(Ft)fopA gene in rodents samples collected from Ji'an of Jilin province and Kuandian of Liaoning Province.The positivity rates of 132 wild rats spleen samples,SFGR,Ec,Ap,CNm,Ba,and Ft were 9.85%,12.88%,5.30%,3.79%,51.52%,and 6.06%,respectively,with statistical differences in in-fection rates(x2=149.236,P=0.000).The infection rate of Ba was the highest in wild rats in this area.There was no signifi-cant difference in the infection rate of SFGR,Ec,Ap,CNm,and Ft among different rats species,but there were significant differences in the infection rate of Ba(x2=13.36,P=0.010).The infection rate of Apodemus agrarius was the highest.A-mong 132 wild rats specimens,the coinfection rate of the two pathogens was 15.9%(21/132),with Ba as the main species(15/132),and two cases of coinfection with three pathogens were detected.The infection of six tick-borne pathogens is common in wild rats at the China/DPRK border.Co-infection of two or three pathogens indicates a risk of multiple tick-borne pathogens and mixed natural foci of multiple tick-borne infec-tious diseases.
9.Study on the construction of evaluation index system for multisectoral cooperation in chronic disease prevention and control under the strategy of Healthy China
Yu-Mei HUANG ; Li-Zheng GUAN ; Li-Guang SUN ; You-Li HAN ; Ning ZHANG ; Yan-Bing ZENG ; Cheng-Yu MA
Chinese Journal of Health Policy 2024;17(6):10-16
Objective:In order to construct a multisectoral cooperation evaluation index system for chronic disease prevention and control in the Healthy China strategy,so as to provide a reference for the evaluation and improvement of multisectoral cooperation work.Methods:The initial indicator system was constructed based on D'Amour's cooperative structure model.Fifteen public health experts were selected to refine the evaluation indicators through two rounds of expert consultation using the Delphi method.Then weights of indicators were assigned according to AHP.Results:Experts'positive coefficient,level of authority and coordination of opinions were confirmed.The finalized evaluation index system for multisectoral cooperation in chronic disease prevention and control contains 5 first-level indicators,12 second-level indicators and 34 third-level indicators.According to the weight,the indicators in first level were Shared Goals and Vision(0.222 8),Internalization(0.158 7),Formalization(0.252 3),Governance(0.154 5)and Cooperation effects(0.211 8).Conclusions:The evaluation index system applicable to multisectoral cooperation in the prevention and control of chronic diseases in counties(cities/districts)is preliminarily established,which is highly scientific and operable,and lays the foundation for the next step of application and promotion.
10.Preclinical study of a novel molecular probe 89Zr DFO-G4C2 for monitoring PD-1 expression levels
Yirong ZHU ; Weiwei KONG ; Jiaxi YOU ; Kairu NI ; Bing ZHANG ; Zengli LIU ; Yizhen SHI ; Zhihui HONG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(10):603-608
Objective:To design and synthesize 89Zr-deferoxamine(DFO)-G4C2, a novel molecular probe targeting programmed cell death receptor 1(PD-1), and evaluate its in vivo biodistribution and microPET/CT imaging characteristics in tumor-bearing mice. Methods:DFO-G4C2 was prepared by coupling DFO with G4C2, a monoclonal antibody targeting PD-1. The affinity and binding specificity of this amalgamation were subsequently assessed through the implementation of flow cytometry and surface plasmon resonance techniques. The molecular probe 89Zr-DFO-G4C2 was achieved by labeling DFO-G4C2 with the radioisotope 89Zr, and the labeling efficiency and in vitro stability of 89Zr-DFO-G4C2 were determined. Mouse models laden with CT26 colorectal cancer cells expressing PD-1 were established, followed by in vivo biodistribution and microPET/CT imaging studies, to explore the potential clinical value of 89Zr-DFO-G4C2. Additionally, the validity of this molecular probe was verified in 4T1 breast cancer models, affirming its efficacy as an imaging tool across different tumor models. Independent-sample t test was used to analyze the data. Results:DFO-G4C2 exhibited an affinity constant KD of (0.55±0.02) μmol/L, indicating a strong binding affinity. The binding rate to mouse PD-1 protein was determined to be (61.82±8.49)%. The labeling rate of 89Zr-DFO-G4C2 reached a high level of (98.76±0.51)%. Furthermore, the labeling rates in lysate and human serum after 144 h were measured to be (93.07±2.16)% and (83.42±3.21)%, respectively. MicroPET/CT imaging of CT26 tumor-bearing mice injected with 89Zr-DFO-G4C2 showcased pronounced radioactivity uptake in the tumor tissue. At 72 h post-injection, the tumor uptake value reached (10.47±0.34) percentage activity of injection dose per gram of tissue (%ID/g). The tumor uptake observed in the blocked experimental group, wherein an excess of unlabeled antibody was administered, was significantly lower at (6.26±1.03) %ID/g in comparison to the non-blocked group ( t=6.67, P=0.003). The in vivo biodistribution results were consistent with the observed microPET/CT imaging outcomes. MicroPET/CT imaging observations in the 4T1 breast cancer bearing mouse model were analogous to those obtained from the CT26 model. Conclusion:ImmunoPET based on the 89Zr-DFO-G4C2 molecular probe can non-invasively and visually assess the PD-1 expression level of tumors in vivo, and it is expected to be a new molecular imaging technique for immunotherapy monitoring of PD-1 inhibitors.

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