Druggability evaluation is one of the core processes in new drug development, yet the inaccuracy and high cost of existing in vitro liver models have been a major technical bottleneck, leading to an increasing demand from the pharmaceutical industry for reliable in vitro liver models to enhance the efficiency of new drug research and development. Traditional animal models and in vitro 2D culture models have their limitations in simulating in vivo physiological and pathological conditions, making it challenging to accurately predict drug efficacy and safety. With the advancement of microfluidic technology, in vitro cell culture, and biosensor technology, liver-on-a-chip (LOC) has garnered increasing attention in the field of new drug development in recent years, and is expected to become a powerful tool for addressing the challenges in druggability evaluation. While introducing the construction technology of LOC, this article mainly summarizes the research and application of existing LOC from the perspectives of disease model construction, drug metabolism research, and drug safety evaluation. Furthermore, it analyzes the role of LOC in druggability evaluation and discusses the current challenges and prospects in this field.

Methods: CHB patients and healthy volunteers were enrolled from Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between August 21, 2018 and December 31, 2020. They were divided into three groups: healthy group, LGDHS group, and latent syndrome (LP) group. Proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify differentially expressed proteins (DEPs). Metabolomic profiling via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to serum samples to detect differentially regulated metabolites (DMs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment were employed to explore dysregulated pathways. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to visualize group separation and identify key metabolites and proteins contributing to LGDHS differentiation. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic performance of key biomarkers, while logistic regression models assessed their predictive accuracy. P values were corrected for multiple tests using the Benjamini-Hochberg method to control the false discovery rate (FDR). Validation of potential biomarkers was conducted using independent microarray data and real-time quantitative polymerase chain reaction (RT-qPCR). Results: A total of 150 participants were enrolled, including healthy group (n = 45), LGDHS group (n = 60), and LP group (n = 45). 254 DEPs from proteomics data and 72 DMs from metabolomic profiling were identified by PCA and OPLS-DA. DEPs were mainly enriched in immune and complement pathways, while DMs involved in amino acid and energy metabolism. The integrated analysis identified seven key biomarkers: α1-acid glycoprotein (ORM1), asparagine synthetase (ASNS), solute carrier family 27 member 5 (SLC27A5), glucosidase II alpha subunit (GANAB), hexokinase 2 (HK2), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and maltase-glucoamylase (MGAM). Microarray validation confirmed the diagnostic potential of these genes, with area under the curve (AUC) values for ROC analysis ranging from 0.536 to 0.759. Among these, ORM1, ASNS, and SLC27A5 showed significant differential ability in differentiating LGDHS patients (P = 0.016, P = 0.035, and P < 0.001, respectively), with corresponding AUC of 0.749, 0.743, and 0.759, respectively. A logistic regression model incorporating these three genes demonstrated an AUC of 0.939, indicating a high discriminatory power for LGDHS. RT-qPCR further validated the differential expression of ORM1 and SLC27A5 between LGDHS and LP groups (P = 0.011 and P = 0.034, respectively), with ASNS showing a consistent trend in expression (P = 0.928). Conclusion This study integrates multi-omics approaches to uncover the molecular mechanisms underlying LGDHS in CHB. The identification of biomarkers ORM1, ASNS, and SLC27A5 offers a solid basis for the objective diagnosis of LGDHS, contributing to the standardization and modernization of TCM diagnostic practices.

Objective To investigate the role and mechanism of milk fat globule-EGF factor 8(MFG-E8)in neuroprotection in glaucoma rats.Methods A glaucoma rat model was constructed,and MFG-E8 or D89E was injected into the vitreous cavity of the rats.The intraoc-ular pressure of the rats was measured.HE staining,TUNEL staining and immunofluorescence staining were used to detect the patholog-ical injury,apoptosis and microglia activation of the retina.The protein expressions of cleaved caspase-3,caspase-3,cleaved caspase-9,caspase-9 and Bax were detected by Western blotting,and the expression levels of IL-10,TGF-βand NGFwere detected by ELISA and RT-qPCR.Results Compared with the control group,the intraocular pressure of glaucoma rats significantly increased,the retinal GCC layer became thinner,the apoptotic cells increased,the levels of cleaved caspase-3/caspase-3,cleaved caspase-9/caspase-9 and Bax increased,and the number of IBA1 positive cells increased,after treatment with MFG-E8,retinal GCC layer thickness increased,and the levels of cleaved caspase-3/caspase-3,cleaved caspase-9/caspase-9,Bax decreased,the number of IBA1 positive cells and the levels of IL-10,TGF-β,NGFincreased,but the progression of glaucoma was aggravated after the treatment of MFG-E8 inactivated isomer D89E.Conclusion MFG-E8 can mediate microglia activation,inhibit apoptosis of ganglion cells,and slow down the progression of glaucoma in rats.

Objective:To translate the Nurse Delirium Care Competency Scale (NDCCS) into Chinese and test the validity and reliability of Chinese version of NDCCS among ICU nurses.Methods:According to Brislin translation model, the Chinese version of NDCCS was developed by forward translation, back translation, cross-cultural adaptation and pre-survey. From October to December of 2023, 338 ICU nurses from Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were selected by cross-sectional survey to test the reliability and validity of Chinese version of NDCCS.Results:A total of 329 valid questionnaires were collected. There were 50 males and 279 females, aged 20-53 years old. The Chinese version of NDCCS included 6 dimensions and 27 items. The scale-level content validity value was 0.985, and the item-level content validity value was 0.800-1.000. Exploratory factor analysis showed a six-factor structure, the cumulative variance contribution rate was 75.700%, the Cronbach′s α coefficients of the scale amount table were 0.952, and the Cronbach′s α coefficients of the dimensions were 0.811- 0.936,and the retest reliability was 0.932.Conclusions:The Chinese version of the NDCCS has good reliability and validity, and it is suitable for assessing the delirium care competence of ICU nurses in China.

Nursing information security is an essential component of providing high-quality nursing services and is an important guarantee for the construction of large-scale health care data application systems. This article reviewed the concept, assessment tools, and influencing factors of nursing information security, aiming to provide references for hospital nursing managers to effectively assess information security and improve nurses′ information literacy.

Objective:To optimize the accuracy of the intelligent hand hygiene system to monitor the hand hygiene timing warning, and provide a reference basis for healthcare workers to apply the intelligent hand hygiene system.Methods:Using a single-sample diagnostic pilot study method, 62 clinical nurses wearing smart badges working in the intensive care unit of Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine in Hangzhou, from December 1, 2020 to December 31, 2021 were selected by convenience sampling methods. Direct observation was used as the gold standard. The accuracy of the warning timing of the intelligent hand hygiene monitoring system was optimized through adjusting the bed sensing rang,adjusting the time setting, adjusting the time settings according to the physical space of the ward and adding posture recognition.Results:The sensitivity of adjusting the bed sensing range was 0.935 (95% CI 0.918-0.949); the specificity was 0.008 (95% CI 0.001-0.074). The sensitivity of the temporal setting based on the physical space of the ward was 0.932(95% CI 0.915-0.946); the specificity was 0.205 (95% CI 0.087-0.410). The false positive rate with gesture recognition turned on was 86.1% higher than the false positive rate without gesture recognition which was 79.5%. The diagnostic OR based on the temporal setting of the physical space of the ward was the largest at 3.517(95% CI 1.213-10.193). Conclusions:The intelligent hand hygiene system exhibits high accuracy in monitoring hand hygiene timing. Adjusting the bed sensing range and individualizing the timing settings according to the physical space of the ward can improve the accuracy. Further optimization is needed for posture recognition to improve the accuracy.

Objective:To explore the effects of tyrosine kinase inhibitors (TKI) on SARS-CoV-2 infection, the related symptoms, and recovery in patients with chronic myeloid leukemia (CML) during the SARS-CoV-2 epidemic.Methods:A retrospective case series study was conducted. The information including general data and SARS-CoV-2 infection of 319 CML patients treated in the First Affiliated Hospital of Soochow University from January 2021 to December 2021 and 547 co-residents during the SARS-CoV-2 epidemic was collected by telephone follow-up from December 2022 to January 2023. The differences in clinical characteristics, infection rate, symptom severity, and recovery time of the SARS-CoV-2 between CML patients and their co-residents, between patients whether getting vaccine for SARS-CoV-2, between patients whether receiving TKI and among CML patients receiving different types of TKI were compared. The multivariate logistic regression analysis was used to analyze the factors influencing the infection rate, symptom severity, and recovery time of SARS-CoV-2.Results:The median age [ M ( Q1, Q3)] of CML patients was 46 years (36 years, 57 years) and all 319 CML patients included 188 (59.0%) males and 131 (41.0%) females; the median age of co-residents of CML patients was 41 years (22 years, 55 years), and all 547 co-residents included 266 (48.6%) males and 281 (51.4%) females. There were statistically significant differences in age, gender, vaccination against SARS-CoV-2 or not, infection rate [83.7% (267/319) vs. 90.5% (495/547)], distribution of symptomatic patients at different severity levels (mild, moderate, severe, and fatal), and recovery time [7 d (5 d, 14 d) vs. 6 d (2 d, 8 d)] between CML patients and co-residents (all P < 0.05). There were statistically significant differences in age, gender, SARS-CoV-2 infection rate, distribution of symptomatic patients at different severity levels and recovery time between CML patients (143 cases) and their co-residents (517 cases) who received the SARS-CoV-2 vaccine (all P < 0.05); there were no statistically significant differences in age, gender, infection rate, distribution of symptomatic patients at different severity levels and recovery time between vaccinated and unvaccinated CML patients with SARS-CoV-2 vaccine (all P > 0.05). There were 297 (93.1%) CML patients who took TKI and 22 patients who did not take TKI. There were no statistically significant differences in age and gender distribution between patients taking TKI and those not taking TKI (all P > 0.05). The infection rate of SARS-CoV-2 in patients taking TKI was lower than that of patients not taking TKI [82.5% (245/297) vs. 100.0% (22/22)], and the difference was statistically significant ( P = 0.032); however, there were no significant differences in distribution of symptomatic patients at different severity levels and recovery time between patients taking TKI and those not taking TKI (all P > 0.05). The results of multivariate logistic regression analysis showed that TKI therapy was an independent protective factor for SARS-CoV-2 infection in CML patients (taking TKI vs. not taking TKI: OR = 1.970, 95% CI: 1.093-3.554, P = 0.024), and was an independent risk factor for severe symptoms of SARS-CoV-2 infection (assigning mild, moderate, severe and fatal levels the value of 0, 1, 2, 3; OR = 0.042, 95% CI: 0.004-0.421, P = 0.007) and recovery time exceeding 7 d (> 7 d vs. ≤ 7 d, OR = 0.649, 95% CI: 0.426-0.988, P = 0.044). The third TKI therapy was given in 1 patient, and there were no statistically significant differences in SARS-CoV-2 infection rate, the symptoms at different severity levels and recovery time > 7 d between CML patients receiving first generation TKI (63 cases) and those receiving second generation TKI (77 cases) who were vaccinated against SARS-CoV-2 (all P > 0.05). Conclusions:TKI can reduce the infection rate of SARS-CoV-2 in CML patients, but will aggravate the severity of symptoms and prolong the recovery time. TKI types may have no impact on whether infected with SARS-CoV-2, the severity level of symptoms after infection and recovery time.

Hepatolithiasis is a common biliary tract disease in China and other Asian countries.It has insidious onset,recurrent disease,and may lead to biliary cirrhosis or even cancer in the late stage without inter-vention.At present,surgery is considered to be the best choice for treatment.In the 21st century of minimally inva-sive surgery,traditional procedures such as partial hepatectomy,choledochotomy,cholangioenterostomy and liver transplantation can be performed with the assistance of laparoscopy and da Vinci robots,and emerging endoscopic techniques such as endoscopic retrograde cholangiopancreatography(ERCP)and percutaneous transhepatic cho-ledochoscopic lithotripsy(PTCSL)have also been developed,bringing better treatment for patients with hepatoli-thiasis.As treatment options are becoming more varied,there are also some clinical problems that need to be addressed.In this article,we would like to briefly review the current surgical treatment modalities in order to provide a theoretical basis for optimizing the treatment modalities.

Objective:To investigate the protective effect of ulinastatin on sepsis-acute kidney injury (SA-AKI) by NF-κB signaling pathway.Methods:Total of 60 mice were randomly(random number) divided into sham group, cecal ligation puncture group (CLP group) and ulinastatin treatment group (CLP+UTI group). Ulinastatin treatment group was intraperitoneally injected with ulinastatin 50 000 U/kg once a day. 24 hours after operation, five mice were sacrificed, the kidney tissues were collected to observe renal histopathology by HE staining. The macrophage infiltration was observed by immunohistochemistry. The remaining mice in each group were used to calculate the survival rate of 7-day after operation. HK-2 cells were stimulated by LPS to obtain the SA-AKI model, and the cells were divided into control group, LPS group and LPS + UTI group. CCK-8 assay was used to detect cell viability, EdU assay was used to detect cell proliferation, and JC-1 assay was used to detect mitochondrial damage. The phosphorylation degree of NF-κB was detected by western blot. Inflammatory factors concentrations of cellular supernatant were detected by ELISA assay.Results:Compared with the sham group, the kidney tissue of mice in CLP group showed that kidney pathological obvious changed, the infiltration of macrophages increased, and the survival rate of mice decreased. CLP+ UTI group reduced the pathological changes and the infiltration of macrophages, improved the survival rate of mice. Compared with control group, LPS group obviously inhibited the cells activity and proliferation of HK-2 cells, damaged the mitochondrial membrane potential of HK-2 cells. Compared with LPS group, LPS+ UTI group attenuated the phosphorylation of NF-κB, decreased the secretion of inflammatory factors, rescued the activity and proliferation of HK-2 cells, and reduced the damage of HK-2 mitochondrial membrane potential.Conclusions:Ulinastatin can reduce mitochondrial damage, inhibit the secretion of inflammatory factors and improve the function of renal tubular epithelial cells through regulating NF-κB signaling pathway.

Objective:To explore the effect of pediatric critical illness score (PCIS), pediatric risk of mortality Ⅲ score (PRISM Ⅲ), pediatric logistic organ dysfunction 2 (PELOD-2), pediatric sequential organ failure assessment (p-SOFA) score and Glasglow coma scale (GCS) in the prognosis evaluation of septic-associated encephalopathy (SAE).Methods:The data of children with SAE admitted to the Pediatric Intensive Care Unit (PICU), Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences from January 2010 to December 2020 were retrospectively analyzed. They were divided into the survival and death groups according to the clinical outcome on the 28th day after admission. The efficiency of PCIS, PRISM Ⅲ, PELOD-2, p-SOFA and GCS scores for predicting death were evaluated by the area under the ROC curve (AUC). The Hosmer-Lemeshow goodness-of-fit test assessed the calibration of each scoring system.Results:Up to 28 d after admission, 72 of 82 children with SAE survived and 10 died, with a mortality rate of 12.20%. Compared with the survival group, the death group had significantly lower GCS [7 (3, 12) vs. 12 (8, 14)] and PCIS scores [76 (64, 82) vs. 82 (78, 88)], and significantly higher PRISM Ⅲ [14 (12, 17) vs. 7 (3, 12)], PELOD-2 [8 (5, 13) vs. 4 (2, 7)] and p-SOFA scores [11 (5, 12) vs. 6 (3, 9)] ( P<0.05). The AUCs of PCIS, PRISM Ⅲ, PELOD-2, p-SOFA and GCS scores for predicting SAE prognosis were 0.773 ( P=0.012, AUC>0.7), 0.832 ( P=0.02, AUC>0.7), 0.767 ( P=0.014, AUC>0.7), 0.688 ( P=0.084, AUC<0.7), and 0.692 ( P=0.077,AUC<0.7), respectively. Hosmer-Lemeshow goodness-of-fit test showed that PCIS ( χ2=5.329, P=0.722) predicted the mortality and the actual mortality in the best fitting effect, while PRISM Ⅲ ( χ2=12.877, P=0.177), PELOD-2 ( χ2=8.487, P=0.205), p-SOFA ( χ2=9.048, P=0.338) and GCS ( χ2=3.780, P=0.848) had poor fitting effect. Conclusions:The PCIS, PRISM Ⅲ and PELOD-2 scores have good predictive ability assessing the prognosis of children with SAE, while the PCIS score can more accurately evaluate the fitting effect of SAE prognosis prediction.