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.

Objective To explore the effect of improved total cavity endoscopy on lung function,postoperative feeding and complications in patients with chronic lung disease of esophageal cancer.Methods 120 esophageal cancer patients with chronic lung disease admitted to our hospital from September 2022 to June 2023 were randomly divided into two groups.The observation group consisted of 60 patients who underwent improved total cavity endoscopy assisted esophageal cancer resection,while the control group consisted of 60 patients who underwent traditional open surgery.The perioperative related indexes,lung function indexes[forced expiratory volume in the first second(FEV1),forced vital capacity(FVC),maximum ventilation volume(MVV)],inflammatory level[interleukin-6(IL-6),interleukin-8(IL-8),tumor necrosis factor(TNF-α)]were compared between the two groups.Results The blood loss,operation time,number of lymph node dissection and drainage time in the observation group were(329.51±78.84)ml,(175.47±10.41)min,(29.67±17.86)pieces per case and(3.14±0.98)d respectively.In the control group,the intraoperative blood loss,operation time,number of lymph node dissection and drainage time were(372.31±99.23)ml,(148.54±10.68)min,(28.36±18.15)pieces and(6.37±1.23)d,respectively,there was statistical significance between the two groups(P＜0.05).The FEV,,FVC and MVV of the observation group were(1.88±0.53)L,(2.33±0.46)L and(32.59±11.84)L,respectively.Two weeks after operation,the control group was(1.37±0.31)L,(1.75±0.38)L and(23.68±9.41)L respectively,there was statistical significance between the two groups(P＜0.05).The inflammatory factors IL-6,IL-8 and TNF-α in the observation group were(2.17±1.62)ng/ml,(2.09±1.52)ng/ml and(1.32±0.57)ng/ml,respectively.The control group were(3.06±1.52)ng/ml,(2.75±1.29)ng/ml and(1.73±0.75)ng/ml respectively,there was statistical significance between the two groups(P＜0.05).The incidence of postoperative complications in the observation group and the control group were 6.67％and 20.00％respectively,and patients in the observation group ate earlier than those in the control group(P＜0.05).Conclusion Compared with the traditional open surgery,the improved total laparoscopic surgery has the advantages of less trauma,simpler operation,less damage to lung function,significantly lower incidence of postoperative complications,and shorter postoperative eating time.

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.

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.

A recombinant enzyme-mediated nucleic acid amplification(RAA)technology combined with colloidal gold test strips was developed for the rapid detection of bovine enterovirus(BEV).Using the highly conserved BEV 5'UTR as the target sequence,the primers were designed and screened.Downstream primer labeled with biotin at the 5'end and the probe labeled with 6-FAM at the 5'end were used to establish the RT-RAA method.The test strips were assembled by using mouse-derived anti-6-FAM monoclonal antibody as the gold standard antibody,with a streptavidin encapsulated in the detection line and sheep anti-mouse IgG encapsulated in the quality control line.A RT-RAA-LFD method was established by combing RAA technique with the prepared later-al flow device test strips for the detection of bovine enterovirus nucleic acids.The specificity,sensi-tivity,repeatability,and clinical application of the method are also evaluated.The results showed that the optimal primer concentration of this method was 5 μmol/L,and the amplification of BEV nucleic acids was accomplished by reacting at 35 ℃ for 8 min with the lowest detection limit of 101 copies/μL.No cross-reactivity with bovine viral diarrhea virus,bovine parvovirus,and foot-and-mouth disease virus was observed.The efficacy for the prepared test strips was at least for 90 d kept at 4 ℃.Detection of 74 clinical samples yielded a similar result compared with RT-PCR method.The above results demonstrated that the BEV RT-RAA-LFD method established in this study has high sensitivity,specificity,and more convenient to use,which is suitable for clinical de-tection on-site and provides a new technical tool for the diagnosis and epidemiological investigation of BEV infection.

Objective To explore the correlation between rs207663 mutation in PARK9 gene and response to cognitive improvement in early Parkinson's disease(PD).Methods A total of 100 pa-tients with early PD treated in Department of Neurology of Handan Fourth Hospital from Octo-ber 2020 to October 2023 were enrolled and subjected as the study group,and another 100 healthy individuals taking physical examinations during the period were assigned into the control group.Their rs207663 polymorphisms of PARK9 gene were detected,and the alleles and genotype distri-bution were compared between the two groups,and the therapeutic effects of the patients with different genotypes were analyzed.Results There were three genotypes in rs207663 of PARK9 gene:GG,GA and AA.The frequencies of GG genotype and G allele were significantly higher in the study group than the control group(40.0％vs 26.0％,P＜0.05;63.0％vs 50.0％,P＜0.01).After treatment,the mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)scores of the GG,GA and AA genotypes showed an increasing trend,the GG genotype had significantly lower MMSE score[(22.95±1.34)vs(23.89±1.68),P＜0.05]and MoCA score[(24.86±1.83)vs(25.12±1.48),P＜0.05]when compared with the GA genotype.The GA geno-type had notably higher total assets,larger number of safe options and elevated utilization rate of negative feedback than the GG genotype[(-1541.50±537.24)Yuan vs(-3102.00±1274.38)Yuan,P＜0.01;(9.24±3.27)vs(7.11±2.14),P＜0.05;(0.51±0.23)vs(0.35±0.15),P＜0.05].While the AA genotype obtained smaller number of risk options than the GA genotype,and the GA genotype got lower number of risk options than the GG genotype(P＜0.05).Conclusion The rs207663 polymorphism of PARK9 gene is significant associated with the response to improve-ment treatment for early PD.The patients carrying GG genotype have poor response to treatment,the patients carrying GG genotype prefer high-risk and high-reward options,and have low utiliza-tion rate of negative feedback.

Objective:To summarize the clinical and genetic characteristics of children with Menkes disease(MD).Methods:The clinical manifestations, auxiliary examinations and genetic testing results of 15 MD children admitted to the Department of Pediatrics of the Third Affiliated Hospital of Zhengzhou University, Children′s Hospital Affiliated of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University from June 2016 to October 2022 were analyzed retrospectively.These children were followed up.Results:All the 15 children were male.The age at onset was ranging from 9 days to 5.5 months.White skin, curly hair, skin laxity, hypotonia and severe developmental delay were found in all children, with epilepsy in 13 children, anemia in 11 children and granulocytopenia in 4 children.The concentration of ceruloplasmin in the serum of MD children was lower than that in healthy children of the same age.The concentration of ceruloplasmin in MD children younger than 3 months was significantly lower than that in healthy children of the same age and MD children older than 3 months.The brain magnetic resonance imaging showed abnormalities in all 15 children.Twelve children showed tortuous intracranial vessels in brain magnetic resonance angiography examinations.All the 15 children had ATP7A gene pathogenic variants, including 4 missense variants(2 cases with c. 2179G>A), 3 frameshift variants, 3 nonsense variants, 3 exon deletions and 2 splice site variants.Among these children, 1 had a novel gene variant that had not been reported so far(c.2968C>T). Conclusions:MD has early onset age and diverse clinical manifestations, but also has characteristic clinical manifestations and applicable auxiliary examinations.Its diagnosis depends on genetic testing.The c. 2179G>A and exon deletions may be hot mutations in Chinese MD patients.