Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7％of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.

Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7％of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.

Objective:To summarize the scope of research status and progress of midway abandonment of electronic health records.Methods:Articles on the application of community electronic health records were retrieved through computers in China Biology Medicine disc, Wanfang Data, China National Knowledge Infrastructure, PubMed. The retrieval time limit was from January 1, 2010 to June 1, 2022. The basic features of the articles were retrieved, screened and extracted independently by 2 researchers.Results:A total of 19 articles were included. The influencing factors of midway abandonment of electronic health records included 4 categories, namely the imbalance of perceived and actual learning costs and benefits, exposure to undesirable content during participation in electronic health records community, concerns about privacy infringement, demographic and sociological characteristics of users.Conclusions:The imbalance of perceived and actual learning costs and benefits, exposure to undesirable content during participation in electronic health records community, concerns about privacy infringement, and demographic and sociological characteristics of users can lead users abandon electronic health records. Relevant departments should pay attention to the needs of users, strengthen information supervision and privacy protection, formulate appropriate health education programs, standardize the electronic health records management process, so as to improve the utilization rate of electronic health records.

Objective:To investigate the effects of high-energy shock and vibration on cortex injury and peripheral blood immune cells in goats.Methods:Seventeen Boer goats without gender preference were selected. By using random number tables, the goats were divided into normal control group ( n=5) and shock and vibration injury group ( n=12). The goats in the normal control group were anatomized routinely and their brain was collected after being sacrificed without any other treatment. The goats in the high-energy shock and vibration model group were placed on a loading table (part of the BY10-100 instant shock and vibration simulation platform) in a restrained state, and made into a high-energy shock and vibration injury model induced by a vertical impact waveform generator. The intravenous blood samples were taken from the goats in the shock and vibration injury group before and at 0, 3, 6 and 24 hours after injury.Then, the goats were sacrificed and the following procedures were the same as the normal control group. At 24 hours after injury, the brain injury and the histopathological changes of the cerebral cortex in the normal control group and shock and vibration injury group were observed by gross pathological and anatomical examination and HE staining. The mRNA expression of zonula occludens 1 (ZO-1), tight junction protein 5 (Claudin-5), glial fibrillary acidic protein (GFAP), ionized calcium binding adaptor molecule 1 (IBA-1), interleukin (IL)-1β, IL-6 and cluster of differentiation antigen 177 (CD177) of the cerebral cortex in the normal control group and shock and vibration injury group were measured through fluorogenic quantitative polymerase chain reaction. The expression of ZO-1 and Claudin-5 proteins of the cerebral cortex in the normal control group and shock and vibration injury group were detected by Western blotting. Hematology analyzer and coagulation analyzer were used to detect white blood cell count, neutrocyte, lymphocyte, monocyte, prothrombin time 1 (PT-1), prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin activity (PTA) and fibrinogen (FIB) levels in goats of the shock and vibration injury group before and at 0, 3, 6 and 24 hours after injury, respectively. Results:At 24 hours after injury, no visible contusion or necrosis was found in goat brain tissue in the shock and vibration injury group; the cerebral micro-vessels presented with a local dilation, hyperemia, edema, aggregation of inflammatory cells, disruption of vessel walls and leakage of red blood cells. These changes were not observed in the normal control group. In the shock and vibration injury group, ZO-1 and Claudin-5 mRNA expressions in the cerebral cortex were 0.25±0.10 and 0.09(0.04, 0.44) respectively, which were significantly lower than those of the normal control group [1.00±0.15 and 0.99(0.80, 1.20)]; GFAP, IBA-1, IL-1β, IL-6 and CD177 mRNA expression levels were 4.40(3.88, 6.75), 2.60±1.07, 3.04±0.51, 2.71±0.45 and 2.93±0.62 respectively, which were significantly higher than those of the normal control group [1.00(0.78, 1.22), 1.00±0.37, 1.00±0.27, 1.00±0.57 and 1.00±0.35]; ZO-1 and Claudin-5 protein expression levels were 0.41±0.06 and 0.42±0.11 respectively, which were significantly lower than those of the normal control group (1.08±0.12 and 0.91±0.23) (all P<0.01). In the shock and vibration injury group, the levels of white blood count, neutrocyte, and lymphocyte in peripheral blood were (13.7±3.3)×10 9/L, (35.3±14.8)% and (57.2±15.1)% respectively before injury, (19.4±3.1)×10 9/L, (60.5±12.5)% and (33.6±14.2)% respectively at 3 hours after injury, and (20.6±3.6)×10 9/L, (63.6±13.0)% and (30.9±15.0)% respectively at 6 hours after injury. By contrast, the levels of white blood count and neutrocyte were significantly increased but the level of lymphocyte was significantly decreased at 3 and 6 hours after injury ( P<0.05 or 0.01); the levels of the above indicators showed no significant changes at 0 and 24 hours after injury (all P>0.05); the level of monocyte did not change significantly at all time points before and after injury (all P>0.05). The levels of PT-1, PT-INR, APTT, TT, PTA and FIB in the shock and vibration injury group did not change significantly at each time point before and after injury (all P>0.05). Conclusion:Cerebral cortex microvascular injury and disruption of blood-brain barrier can be initiated in the early stage of high-energy shock and vibration injury in goats, accompanied by the presence of central and peripheral inflammatory response.

Exposure to antineoplastics is a potential health threat. If improperly disposed, it will also cause environmental pollution, which is a medical safety issue worthy of attention. In order to improve the protection awareness of healthcare professionals exposed to antineoplastic drugs (medical personnels, drug transportation staffs, patients and their caregivers, etc.), standardize exposure protection operations, and reduce the risk and harm of occupational exposure, the Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society, the Hospital Pharmacy Professional Committee of Chinese Pharmaceutical Association, the Oncology Society of Chinese Medical Association, the Nursing Branch of China International Exchange and Promotive Association for Medical and Healthcare, and Chinese Pharmacological Society Professional Committee of Drug-induced Diseases formulated the Management guidelines for preventing exposure to antineoplastics, which was published in the 1st issue of Chinese Journal of Cancer Research in 2023. The guideline was developed referring to the World Health Organization handbook for guideline development and other international methodologies and focused on the full-process management of antineoplastics in hospitals. Using the Delphi method, clinical questions and 14 recommendations were formulated. This paper interprets 14 recommendations, hoping to help promote the implementation of the guideline.

Exposure to antineoplastics is a potential health threat. If improperly disposed, it will also cause environmental pollution, which is a medical safety issue worthy of attention. In order to improve the protection awareness of healthcare professionals exposed to antineoplastic drugs (medical personnels, drug transportation staffs, patients and their caregivers, etc.), standardize exposure protection operations, and reduce the risk and harm of occupational exposure, the Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society, the Hospital Pharmacy Professional Committee of Chinese Pharmaceutical Association, the Oncology Society of Chinese Medical Association, the Nursing Branch of China International Exchange and Promotive Association for Medical and Healthcare, and Chinese Pharmacological Society Professional Committee of Drug-induced Diseases formulated the Management guidelines for preventing exposure to antineoplastics, which was published in the 1st issue of Chinese Journal of Cancer Research in 2023. The guideline was developed referring to the World Health Organization handbook for guideline development and other international methodologies and focused on the full-process management of antineoplastics in hospitals. Using the Delphi method, clinical questions and 14 recommendations were formulated. This paper interprets 14 recommendations, hoping to help promote the implementation of the guideline.

Objective To evaluate a new biodegradable inferior vena cava(IVC) filter by in vitro and in vivo experiments.Methods The biodegradable filter consisted of metal stent and absorbable suture,which acts as a degradable deformable switch of the filter.When the suture of the proximal metal filter degrades and lost its tension,the metal filter will change into a stent.In vitro experiments were performed to test the influence of the sterilization method and the tension of absorbable sutures to the filter's selfconvertible time,animal experiments were conducted to evaluate the effectiveness of emboli capture and to observe the in vivo self-convertible time of the filter.IVC stenosis,pulmonary embolus and intimal hyperplasia and inflammation were evaluated.Results Ethylene oxide sterilization did not have an adverse effect on the self-convertible time of the filters.The tension did not affect the degradation rates of the suture significantly.In animal experiments,the VCFs were successfully implanted via femoral vein approach.Not any tilt,migration or structural damage of the filters was found during the follow-up time.Postoperative fluoroscopy and autopsy confirmed that there was no stenosis or thrombosis,IVC perforation.After implantation large thrombi were captured.The sutures degraded and filters transformed into stents in 3 weeks.After 90 days IVC was patent with mild intimal hyperplasia and no thrombosis.Conclusions This study demonstrated the effectiveness and safety of the biodegradable filter we designed.

Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson's disease (PD), respectively, which manifested with the selective vulnerability of neuronal cells in substantia nigra (SN) and striatum (STR) regions. However, the underlying molecular mechanism linking parkin with the etiology of PD remains elusive. Here we report that p62, a critical regulator for protein quality control, inclusion body formation, selective autophagy and diverse signaling pathways, is a new substrate of parkin. P62 levels were increased in the SN and STR regions, but not in other brain regions in parkin knockout mice. Parkin directly interacts with and ubiquitinates p62 at the K13 to promote proteasomal degradation of p62 even in the absence of ATG5. Pathogenic mutations, knockdown of parkin or mutation of p62 at K13 prevented the degradation of p62. We further showed that parkin deficiency mice have pronounced loss of tyrosine hydroxylase positive neurons and have worse performance in motor test when treated with 6-hydroxydopamine hydrochloride in aged mice. These results suggest that, in addition to their critical role in regulating autophagy, p62 are subjected to parkin mediated proteasomal degradation and implicate that the dysregulation of parkin/p62 axis may involve in the selective vulnerability of neuronal cells during the onset of PD pathogenesis.
Adaptor Proteins, Signal Transducing ; chemistry ; metabolism ; Animals ; HEK293 Cells ; Heat-Shock Proteins ; chemistry ; metabolism ; Humans ; Lysine ; metabolism ; Mice ; Neurons ; metabolism ; pathology ; Oxidopamine ; pharmacology ; Parkinson Disease ; metabolism ; pathology ; Proteasome Endopeptidase Complex ; metabolism ; Protein Stability ; Proteolysis ; drug effects ; Sequestosome-1 Protein ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitination ; drug effects

Objective To explore the experimental methods and conditions of 131I-labeled anti-epidermal growth factor receptor (EGFR) vⅢ preparation,and to evaluate the targeting distribution of 131I-Anti-EGFRvⅢ in malignant glioma-loading nude mice.Methods The 131I labeling on anti-EGFRvⅢ was performed by Iodogen method.The labeling rate was determined after separation and purification and paper chromatography was used for the determination of radioactive chemical purity.Twenty-eight U87-EGFRvⅢ malignant glioma-loading nude mice with glioma average diameter of 10-15 mm were chosen and randomly divided into group of 131I-Anti-EGFRvⅢ intravenous injection,group of Na131I intravenous injection,group of 131I-Anti-EGFRvⅢ intratumor injection and group of Na131I intratumor injection;7.5 MBq/0.1 mL labeled products with 131I-Anti-EGFRvⅢ or Na131I were injected in the veins or the tumors to observe the changes of the radioactivity distribution of malignant glioma-loading nude mice with SPECT imaging.Results The rate of 131I-labeled anti-EGFRvⅢ was (68.12±6.19)％,and the immediate rate of radiochemieal purity was (95.12±0.59)％,and (87.78 ±5.35)％ in room temperature and (85.12±3.58)％ in 37 ℃ serum placed for 24 h.SPECT scan showed that the tumor site had significantly stronger imaging than the thyroid gland with the labeled products either by intravenous or intratumor injection.Conclusions It is applicable to the 131I-labeled Anti-EGFRvⅢ with Iodogen method.131I-Anti-EGFRvⅢ has good radiation chemical purity and stability in vitro and in vivo,and could be combined with tumor tissue specificity.

To screen potential hamster chymase 2 inhibitors, a high-throughput screening (HTS) model was established. Recombinant hamster chymase 2 with active form was cloned and expressed in E. coli. The HTS model with total volume of 50 microL in 384-well microplate was based on fluorescence analysis and was proved sensitive as well as specific (Z' = 0.84). A total of 40 080 samples (including 28 060 compounds and 12 020 natural products) were screened, and 613 samples with inhibition greater than 90% were selected for further rescreening. Finally, compounds J16647 and J16648 were identified with high inhibitory activity on chymase 2, and whose IC50 values were 0.823 and 0.690 micromol x L(-1), respectively.