OBJECTIVE To investigate the efficacy and safety of ropivacaine combined with oxycodone for the analgesia of iliac fascia nerve block in patients undergoing hip replacement. METHODS Sixty-six patients who underwent hip replacement at the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from October 2023 to April 2024 were selected and randomly divided into observation group and control group， with 33 cases in each group. Before induction of anesthesia， ultrasound-guided iliac fascial nerve block was performed. Patients in the observation group were treated with 0.33% ropivacaine+0.1 mg/kg oxycodone injection mixture 30 mL， and patients in the control group were treated with 0.33% ropivacaine injection 30 mL. The time of first postoperative rescue analgesia， 24 h postoperative analgesic drug consumption， sensory block and motor block effective and maintenance time， satisfaction degree， numerical rating scale （NRS） pain score， Ramsay sedation score， muscle strength score， heart rate （HR）， mean arterial pressure （MAP）， oxygen saturation（SpO2）， sleep score， anxiety score， and the occurrence of adverse reactions in the two groups were all recorded. RESULTS Compared with the control group， the first rescue analgesia time after operation was significantly prolonged in the observation group， and 24 h postoperative analgesic drug consumption after operation decreased； the effective time of sensory block was significantly shortened， and the maintenance time of sensory block was significantly prolonged， and the satisfaction score was higher； the NRS pain score after iliac fascia nerve block was lower， HR and MAP were lower， and the anxiety score and sleep score 24 and 48 h after operation were lower （P＜0.05）. In terms of safety， patients in both groups had adverse reactions after operation， such as hypertension， nausea， vomiting， and dizziness， but there was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS Oxycodone combined with ropivacaine shows good efficacy and safety for iliac fascial nerve block analgesia in patients undergoing hip replacement， can significantly prolong the analgesic time of ropivacaine， reduce postoperative analgesic drug consumption， improve the sleep quality of patients， and promote the rapid recovery of patients.

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.

Objective This study investigated the protective effects of Corni Fructus ethanol extract on β-amyloid protein 25-35 (Aβ25-35)-induced Alzheimer's disease (AD) mice by regulating histone lysine-specific demethylase 1 (LSD1) / postsynaptic density protein 95 (PSD95) on synapses and neuroinflammation. Methods Specifically, according to the body weight, 40 C57BL/6N mice were randomized into four groups: the sham operation group, the model group, the low-dose (0.1mg/g) and the high-dose (0.3 mg/g) Corni Fructus ethanol extract groups. Aβ25-35 was injected into the hippocampus of mice in three groups except for the sham operation group to established AD model. All mice were orally administered with either Corni Fructus ethanol extract or vehicle by gavage for 7 days before molding and continued 5 days after surgery for a total of 60 days. Morris water maze, Y maze and open field tests were performed to evaluate the recognition memory and space exploration ability of mice. The expression of LSD1, PSD95, synaptophysin (SYN), interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α) and H3K9me2 level were measured by Western blotting. Chromatin immunoprecipitation (CHIP) combined with qPCR was used to detect H3K9me2 modification of PSD95 promoter region and mRNA levels of PSD95. The correlation between the expression of H3K9me2 and PSD95 and the expression of IBA1 in the hippocampus were detected by immunofluorescence assay.Results The result showed that Corni Fructus ethanol extract significantly reversed Aβ25-35-induced learning and memory impairment in AD mice. Compared with the model group, Corni Fructus ethanol extract demonstrated shorter escape latency, increased number and time of autonomous activities and the rate of autonomous alternation. Moreover, it increased the expression of LSD1 in hippocampus of AD mice(P<0.05), and reduced H3K9me2 modification level in the promoter region of PSD95 gene, and then promoted the mRNA transcription and protein expression of PSD95. Immunofluorescence staining indicated the reduction of H3K9me2 modification level in hippocampus was accompanied by the enhancement of PSD95 expression. Corni Fructus ethanol extract could also inhibit the activation of microglia and reduce the expression of proinflammatory factors IL-1β and TNF-α.Conclusion Corni Fructus ethanol extract may regulate PSD95 gene transcription by up-regulating the expression of LSD1 and reducing the H3K9me2 modification level in its promoter region, thereby increasing the expression of PSD95, a key protein in synaptic plasticity regulation, which alleviate neuroinflammatory response, improve learning and memory dysfunction in AD model mice, and thus play a protective role in Aβ25-35-induced nerve damage.

Purpose To construct a benign and malignant prediction model of thyroid nodules based on ultrasound image features and clinical features,and to evaluate its diagnostic efficacy.Materials and Methods The data of 121 patients diagnosed with thyroid nodules admitted to the General Hospital of Northern Theater Command from September 2020 to March 2022 were retrospectively analyzed.Taken surgical pathology as the gold standard,there were 70 benign nodules and 51 malignant nodules.Logistic regression was used to analyze the ultrasound image characteristics and clinical data of thyroid nodules,and the characteristic indexes with statistical differences were obtained and a comprehensive prediction model was established.Results There were significant differences in the maximum diameter,morphology,calcification,capsule continuity,blood flow grade,elastography score and contrast-enhanced ultrasound characteristics between benign and malignant thyroid nodules(χ2=11.709,17.707,6.901,12.785,16.984,57.095,98.854,all P<0.05).There were significant differences in age,free thyroxine/free thyroxine ratio,and free thyroxine between the two groups(χ2/t=5.944,2.519,-2.468,all P<0.05).The sensitivity,specificity and accuracy of the clinical model,ultrasonic characteristic model and ultrasonic-clinical combined model were 55.7%,98.6%and 97.0%;72.5%,94.1%and 96.1%;and 61.9%,95.1%and 95.9%,respectively.The area under the curve of the three models were 0.619,0.991 and 0.994,respectively.The diagnostic efficiency of the ultrasonic characteristic model and the combined model was superior to the clinical model,and the difference was statistically significant(Z=-1.75,-2.25,P=0.039,0.012).The area under the curve of the combined model was greater than that of the multi-modal ultrasound model,however,the difference was not statistically significant(Z=-1.60,P=0.054).Conclusion Both the multimodal ultrasound model and the clinical model have certain diagnostic value in predicting benign and malignant thyroid nodules.The diagnostic efficiency of the multimodal ultrasound model is higher than that of the clinical model,and the combined prediction model of the two can improve the diagnostic value.

Objective:To investigate the diagnostic efficacy of ultrasound in pregnancy associated breast cancer (PABC) under different breast ultrasound background echotextures.Methods:The ultrasonic images of 269 female patients with breast diseases who underwent breast surgery in Fudan University Shanghai Cancer Center from January 2016 to September 2023 and were pregnant or within one year postpartum at the time of onset were retrospectively reviewed. Breast ultrasound background echotextures were classified according to two criteria: the first classification was homogeneous-fat, homogeneous-fibroglandular, and heterogeneous; the other classification was hypoechoic dominated and hyperechoic dominated. The comparison of the diagnostic value of ultrasound in PABC under different backgrounds was conducted by the receiver operating characteristic(ROC) curves.Results:Among 269 patients, 67 patients(24.91%)were during pregnancy and 202 patients(75.09%) were within one year postpartum. Pathologically, 47 patients (17.47%) were confirmed as benign, 222 patients (82.53%) were malignant. According to the first classification, 138 patients were homogeneous-fibroglandular and 131 patients were heterogeneous, with the diagnostic sensitivity of ultrasound in PABC were 88.70% and 59.81% respectively, and the specificity were 91.30% and 83.33% respectively, the areas under the ROC curves were 0.940 and 0.826 respectively ( P=0.022). According to the second classification, 119 were hypoechoic dominated and 150 patients were hyperechoic dominated, the sensitivity were 60.21% and 85.27% respectively, the specificity 84.62% and 90.48% respectively, the areas under the ROC curves were 0.826 and 0.925 ( P=0.042). Conclusions:The heterogeneous background echotextures of the breast may cause decrease of the diagnostic efficiency of ultrasound in PABC, and hypoechoic dominated background was more unfavorable for the diagnosis of PABC compared to the hyperechoic dominated background.

Objective:To investigate the application effect of production-oriented approach (POA) for consulting ability teaching in general practice standardized residency training.Methods:Eighteen third-year general practice residents in the Second Affiliated Hospital of Harbin Medical University received a special training course on the consulting ability based on POA with the situational simulation teaching from September 2021 to March 2022. The consulting ability of residents was evaluated with Objective Structured Clinical Examination (OSCE) and Leichester Assessment Package (LAP) before and after the training, and the results were compared. Meanwhile, a questionnaire survey and semi-structured interviews were conducted to assess residents′ satisfaction with the course.Results:All 18 resident trainees (11 females and 7 males) aged 25 to 34 (27.3±2.4) years successfully completed the training. Both OSCE scores and LAP scores after the training were significantly higher than those before training (66.25±5.84 vs. 44.44±12.80, t=8.46, P<0.001; 65.78±7.05 vs. 38.33±14.2, t=1.47, P<0.001, respectively). The ability of medical history collection, physical examination, patient management, problem solving, doctor-patient relationship, preventive care and medical record writing were all significantly improved after the training compared with those before training ( t=2.464, 4.278, 8.997, 2.385, 10.35, 5.212, 7.578, all P<0.05). The questionnaire survey showed that all the 18 residents were satisfied with the reasonableness of the teaching content, the class time arrangement, the teaching progress arrangement and the instructors. In the dimension of training effectiveness, 18 participants all believed that the course was helpful to improve their humanistic quality and confidence in reception. In terms of self-promotion, all respondents believed that this course was able to promote their reflection ability and stimulate their learning interest. By coding and analyzing the contents of the semi-structured interviews with the residents, nine main themes were constructed, namely course deficiencies, course characteristics, course advantages, course suggestions, trainees′ deficiencies, trainees′ gains, trainees′ goals, previous teaching deficiencies, and instructor′s role. The results showed that all residents had a high degree of satisfaction with the course, and they thought the course was vivid and interesting and it is able to mobilize the enthusiasm of learning, promote learner to reflect. The residents also suggested to increase the teaching hours and to enrich teaching cases. Conclusion:The consulting ability training of general practice based on POA can effectively improve consulting ability, stimulate learning interest and improve independent learning ability of residents, which gains recognition from both faculty and trainees.

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Circular RNA(circRNA)represents a unique class of closed-loop structured non-coding RNAs involved in various biological processes such as cell proliferation,differentiation,and apopto-sis.They play a significant role in the development of numerous diseases,and also serve as poten-tial biomarkers and therapeutic targets.To explore the impact of circRNA on viral replication,this study performed an omics measurement and analysis of circRNA differential expression in MC38 cells infected with HY12 enterovirus.It was found that,following HY12 virus infection,the ex-pressionlevels of 570 circRNAs were upregulated,while 381 circRNAs were downregulated.A-mong the upregulated circRNAs,the significantly upregulated circRNA mmu_circ_0001083 was selected for further investigation into its association with HY12 infection and its impact on viral replication.The results indicated that after HY12 virus infection,the expression of host circRNA mmu_circ_0001083 significantly increased,and its expression level was dependent on the virus dos-age and time.Compared to normal MC38 cells infected with the HY12 virus,cells with knocked down expression of circRNA mmu_circ_0001083 showed reduced expression of the 2C protein and significantly lower viral titers.Conversely,after HY12 virus infection in MC38 cells with overexpressed circRNA mmu_circ_0001083,there was an increase in the expression of the 2C pro-tein and a significant rise in viral titers.These results suggest that the upregulation of host cir-cRNA mmu_circ_0001083 is significantly positively correlated with the replication of HY12 virus,meaning mmu_circ_0001083 plays a positive regulatory role in the replication of HY12.This find-ing lays a foundation for future in-depth studies on the regulatory mechanisms of circRNA on viral replication.

The NMGCF-19 strain is an E.coli strain isolated and identified in our laboratory from lambs manifesting severe diarrhea and meningitis.Previous analysis of the genome sequence of NMGCF-19 strain showed that the outer membrane protein A(ompA)gene was a potential viru-lent gene.In order to determine whether the ompA gene is associated with the pathogenicity of NMGCF-19 strain and the underlying mechanism,the NMGCF-19 strain with ompA knockout(NMGCF-19△ompA)was generated in this study using CRISPR/Cas9 technology and used to de-termine the role of ompA gene in mediating the encephalitis by NMGCF-19 infection and the un-derlying mechanism using the mouse model system.The results showed that the neuronal cell nec-rosis in the hippocampus in mice infected by NMGCF-19△ompA was significantly reduced and was not focal compared with that of mice infected with the wild-type NMGCF-19 strain.The number of bacteria in brain of mice infected by NMGCF-19 △ompA was significantly reduced in comparison to that of mice infected by NMGCF-19.Simultaneously,the mRNA and protein expression levels of the tight junction proteins ZO-1 and Occludin were both increased in mice infected by NMGCF-19 △ompA strain compared with the mice infected by NMGCF-19 strain.These results suggest that the ompA gene is a virulent gene and plays an important role in the invasion of the blood-brain barrier by NMGCF-19 strain in mice.