Objective To investigate the effect of4-amino-2-trifluoromethyl-phenyl retinate(ATPR)on acute liver injury induced by lipopolysaccharide(LPS)in C57BL/6 mice and its related mechanism.Methods Fifteen 6-week-old male C57BL/6 strain mice were randomly divided into normal group,model group and ATPR group,with 5 mice in each group.Mice in the ATPR group were intraperitoneally injected with ATPR(15 mg/kg·d),and normal group and model group were given solvent.After continuous administration for one week,model group and ATPR group were intraperitoneally injected with LPS(6 mg/kg),and all mice were sacrificed 6 hours later.The contents of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)in serum of mice were detec-ted.The mRNA levels of Interleukin-6(IL-6)and Tumor necrosis factor-alpha(TNF-α)were detected by qPCR.Hematoxylin-eosin(H&E)staining was used to observe the histopathological changes of liver in mice.The ultra-structural changes of mouse hepatocytes were observed by Transmission electron microscope(TEM).The expres-sion levels of mitochondrial damage-related proteins FUNDC1 and OPA1 and autophagy related proteins LC3B,P62,Beclin1 and ATG5 were detected by Western blot.Results Compared with the normal group,the content of ALT and AST in serum and the mRNA levels of IL-6 and TNF-α in liver tissue increased in the model group,and the changes were reversed in the ATPR group.H&E staining showed that the hepatic lobule structure was normal in the normal group,the hepatic cords were arranged radially,there was no hyperemia and inflammatory cell infiltra-tion,and the hepatocyte boundary was clear.In the model group,the intercellular space of liver was enlarged,the arrangement of hepatic cords was disordered,and inflammatory cells infiltrated.In the ATPR group,the intercellu-lar space of liver and the structure of hepatic cords were restored,and the inflammatory cell infiltration was less.TEM showed that the damaged mitochondria and lipid droplet accumulation in the hepatocytes of mice in the model group were compared with that in the normal group,and the morphology and quantity of mitochondria and lipid droplet in the hepatocytes of mice in the ATPR group tended to be normal.Western blot showed that compared with the normal group,the expression of FUNDC1 protein in the liver tissues of mice in the model group increased,the expression of OPA1 protein decreased,the ratio of LC3B Ⅱ to LC3B Ⅰ decreased,the expression of P62 protein in-creased,the expression of Beclin1 and ATG5 protein decreased,and the above changes were reversed in the ATPR group.Conclusion ATPR alleviates acute liver injury induced by lipopolysaccharide in mice by promoting autoph-agy.

ObjectiveTo investigate the correlation between mild cognitive impairment (MCI) and traditional Chinese medicine (TCM) body constitution types in the elderly, and to provide an evidence for the control of cognitive impairment in the elderly. MethodsThe elderly aged 65 and above who participated in the community physical examinations in a community of Changning District, Shanghai were selected as the research subjects. The cognitive function was assessed by using the Clock Drawing Test combined with the Ascertain Dementia 8-item Questionnaire (AD8), the Montreal Cognitive Assessment (MoCA) and the Mini-mental State Examination (MMSE). The diagnostic criteria for MCI was identified based on the 2018 Chinese Guidelines for the Diagnosis and Treatment of Dementia and Cognitive Disorders, along with the assessment results and clinical history information. The current investigation method was used to collect the basic information and the prevalence of chronic disease of the subjects through questionnaire inquiries. The elderly subjects’ ability to take care of themselves was evaluated based on the Elderly Self⁃Care Ability Evaluation Scale, while the TCM body constitution types were determined based on the Chinese Medicine Health Care Management Service Specification. The association of the detection rate of MCI with gender, education level, history of chronic disease and TCM body constitution types were analyzed lastly. ResultsA total of 2 351 elderly people were investigated, including 1 037 males and 1 314 females, with an average age of (74.11±6.15) years. 174 subjects, accounting for 7.40%, were identified with MCI. The highest detection rate of MCI in the elderly are those with a Qi stagnation constitution (10.8%), followed by those with a dampness-heat constitution (9.1%) and a Qi deficiency constitution (8.4%). Multivariate logistic regression analysis showed that advanced age, lower educational level, a history of tuberculosis, and TCM constitutions such as dampness-heat, Qi stagnation, and Qi deficiency were the potential risk factors for MCI. ConclusionThere is a significant association between TCM constitution types such as dampness-heat, Qi stagnation, and Qi deficiency with MCI. TCM techniques can be integrated into the health management services for the elderly population, and targeted interventions can be provided to those with imbalanced constitution types so as to reduce the risk of MCI.

Purpose The clinical and dual-layer detector spectral CT(DLCT)features of epidermal growth factor receptor(EGFR)mutation and anaplastic lymphoma kinase(ALK)rearrangement of lung adenocarcinoma were studied by DLCT multi-parameter imaging to explore a non-invasive prediction method for clinical diagnosis of lung adenocarcinoma gene expression.Materials and Methods A total of 98 cases of lung adenocarcinoma diagnosed by pathology in Gansu Provincial Hospital were prospectively collected from August 2020 to March 2022.Clinical parameters(gender,age,lesion morphology,number,mediastinal lymph node metastasis,EGFR and ALK mutations status)and DLCT parameters including slope of the spectrum curve of the arteriovenous phase(λHUA,λHUv),the standard iodine concentration of the arteriovenous phase(NICA,NICv),the 40 keV single-energy CT value of the arteriovenous phase(CTA 40 keV,CTv 40 keV),the active atomic number of the arteriovenous phases were collected,respectively.According to the expression of EGFR and ALK,all patients were divided into three groups:EGFR mutant group[EGFR(+)],ALK rearrangement group[ALK(+)],EGFR/ALK both negative group[EGFR/ALK(-)].Clinical and DLCT parameters of each group were analyzed.Results There were statistical difference in gender between the EGFR(+)group and EGFR/ALK(-)group(x2=11.010,P＜0.05).There were statistical differences in lesion morphology among the three groups(x2=12.858,P＜0.05).The value of CTv 40 keV in the EGFR(+)group was significantly higher than that in EGFR/ALK(-)group(t=1.997,P＜0.05),and the NICv in the ALK(+)group was significantly lower than that in EGFR/ALK(-)group(t=2.155,P＜0.05).The λHUv,NICv,CTv 40 keV of EGFR(+)group were significantly higher than those of ALK(+)group(t=2.613,3.149,3.218,all P＜0.05).The sensitivity and specifiicity to identify EGFR(+)and EGFR/ALK(-)adenocarcinoma were 62.7％and 70.0％,the area under curve(AUC)was 0.634(95％CI 0.516-0.756)when the CTv 40 keV value was 141.070 Hu.The sensitivity and specificity to identify ALK(+)and EGFR/ALK(-)adenocarcinoma were 76.7％and 64.2％,the AUC was 0.706(95％CI 0.536-0.853)when NICv value was 0.287.The sensitivity to identify EGFR(+)and ALK(+)adenocarcinoma were 70.6％,64.7％,72.5％and the specificity was 76.5％,76.5％,82.4％,respectively,the AUC was 0.734(95％CI 0.606-0.829),0.751(95％CI 0.610-0.832),0.773(95％CI 0.649-0.861)when the values of λHUv,NICv and CTv 40 keV were 1.335,0.320 and 132.350,respectively.Delong test showed that the AUC of CTv 40 keV and λHUv was statistically different(Z=2.327,P＜0.05),and the AUC of CTv 40 keV was 0.773.Conclusion The gender,lesion morphology and DLCT parameters(λHUv,CTv 40 keV,NICv)of lung adenocarcinoma have certain predictive value for EGFR and ALK genetic expression,which can help clinical judgment of lung adenocarcinoma gene mutation pattern.

One case of periprosthetic infection after artificial joint replacement caused by Coxiella burnetii was reported. The patient was admitted to hospital due to joint pain and sinus formation after artificial knee replacement. Through medical history, physical examination, imaging examination and gene detection, it was confirmed that the infection around the prosthesis was caused by Coxiella burnetii. The patient was treated with two-stage revision surgery combined with sensitive antibiotics. Through literature review, a total of 9 cases of Coxiella burnetii infection after artificial joint replacement were reported, including 6 cases of hip joint and 3 cases of knee joint; 4 cases had clear pathogen exposure history; only one case was found protheses loosening on imaging; 7 cases with positive IgG antibody against Coxiella burnetii; 7 cases were positive for gene detection; 8 cases were negative in etiological examination, and 1 case was not cultured. All patients were treated with doxycycline and hydroxychloroquine. The serological index of 1 case without Q fever symptom turned negative after treatment. 1 case with multiple system organ dysfunction relieved symptoms after treatment, and serological antibody indicators and nuclear medicine results turned negative. All 7 patients were cured after secondary revision surgery. Coxiella burnetii infection after total joint arthroplasty is rare and lacks typical imaging manifestations and clinical features. The diagnosis of Coxiella burnetii infection after total joint arthroplasty mainly depends on gene detection and serological detection. Two-stage revision surgery combined with sufficient and long-term sensitive antibiotics is the main method of treatment.

Objective : To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on lipopolysaccharide (LPS) -induced acute myocardial injury in C57BL/6 mice． Methods : Male mice of C57BL/6 strain were randomly divided into normal group，model group，ATRA group，and ferrostatin-1 group．Mice in the ATRA group were injected intraperitoneally with ATRA 15mg / (kg · d) ，ferrostatin-1 group received ferrostatin-1 2 mg / ( kg · d) ，the normal group and the model group were given solvent．After one week of continuous administration，the model group，ATRA group ，and ferrostatin-1 group were intraperitoneally injected with LPS 6 mg / kg． All mice were sacrificed after 6 hours．The contents of malondialdehyde ( MDA) and glutathione ( GSH) in serum of mice were detected． qPCR was used to detect mRNA levels of interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha (TNF-α) in heart tissue．Hematoxylin-eosin ( HE) staining was used to observe the changes of heart tissue in mice．Transmission electron microscopy (TEM) was used to observe the structure of mouse myocardial mitochondria．Western blot was used to detect the expression of ferroptosis markers glutathione peroxidase 4 ( GPX4) ，ferritin heavy chain 1 ( FTH1 ) ，Solute carrier family 7 member 11 ( SLC7A11 ) ，acyl-CoA synthetase long-chain family member 4 (ACSL4) and related regulatory proteins，Nuclear factor erythroid 2-related factor 2 ( NRF2 ) ，kelchlike ECH-associated protein 1 (KEAP1) . Results: Compared with the normal group，the MDA content in the serum of the model group increased and the GSH content decreased，the above changes were reversed in the ATRA group as well as in the ferrostatin-1 group．Compared with normal group，the mRNA levels of IL-6 and TNF-α in the heart tissue of model group increased steeply，the above changes were relieved in the ATRA group and the ferrostatin-1 group．There was no significant difference in HE staining of myocardial tissue among the groups of mice. Compared with the normal group，myocardial mitochondria in the model group showed the phenomenon of cristaereduction or disappearance under TEM，while myocardial mitochondrial injury was alleviated in the ATRA group and the ferrostatin-1 group．Western blot showed that GPX4，FTH1，SLC7A11，and NRF2 expression were reduced in the myocardial tissue of mice in the model group compared with the normal group，ACSL4 and KEAP1 expression increased．The above changes were reversed in the ATRA group as well as in the ferrostatin-1 group． Conclusion ATRA alleviates lipopolysaccharide-induced acute myocardial injury in mice by inhibiting ferroptosis.

Based on single-cell sequencing of the hippocampi of 5x familiar Alzheimer's disease(5x FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzheimer's disease(AD)mice.Blood brain barrier injury may also have contributed to this increase.Immune regulation by microglia plays a major role in the progression of aging and AD,according to the functions of 41 intersecting differentially expressed genes in microglia.Signaling crosstalk between C-C motif chemokine ligand(CCL)and major histocompatibility complex-1 bridges intercellular communi-cation in the hippocampus during aging and AD.The amyloid precursor protein(APP)and colony stimulating factor(CSF)signals drive 5x FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus.Microglia are involved in the progression of aging and AD can be divided into 10 functional types.The strength of the interaction among microglial subtypes weakened with aging,and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Objective To retrieve,appraise and integrate the relevant evidence of non-pharmacological sleep management measures in critically ill children.Methods We conducted a systematical search on the topic of non-pharmacological sleep management measures in critically ill children across multiple databases,including BMJ best practice,UpToDate,International Guidelines International Network,National Institute for Health and Care Excellence,Scottish Intercollegiate Guidelines Network,Registered Nurses'Association of Ontario,Joanna Briggs Institute Library,the American Academy of Sleep Medicine,International Pediatric Sleep Association,CNKI,WanFang database,VIP database,SinoMed,Cochrane Library,PubMed,Web of Science,and CINAHL.The literature retrieval time limit was from the establishment of the database to February 2023.The study design includes clinical practice guideline,evidence summary,clinical decision-making,expert consensus,and systematic review.The evidence was extracted and summarized according to the subject after the independent literature quality evaluation by 2 researchers.Results 10 relevant pieces of literature were identified,including 2 guidelines,1 consensus statement,4 systematic reviews,2 evidence summaries,and 1 top clinical decision.These sources provided a total of 28 pieces of evidence across 5 key themes,including sleep assessment,management principles and education,environmental management and sleep promotion.Conclusion This study summarizes the best available evidence on non-pharmacological sleep management measures in critically ill children.It is recommended that healthcare professionals should consider the clinical context when implementing evidence-based interventions,aiming to reduce nocturnal awakenings,extend sleep duration,and improve sleep quality in critically ill children.

Objective: To buildSERPING1-knockout porcine fetal fibroblasts(PFFs) based on CRISPR/Cas9 technology and provide cell experimental materials for the construction of hereditary angioedema models. Methods: Firstly, protein structure prediction software was used to analyze the amino acid homology between human and pigSERPING1. Secondly, the eighth exon was selected as the knockout target by screening the effective coding region of the pigSERPING1gene. A single guide RNA targeting pigSERPING1was designed, synthesized and linked to pX330 vector containing Cas9 endonuclease. G418 was used to obtain the positive monoclonal cells after transfection into PFFs. Finally, the circumstance of CRISPR/Cas9 mediated knockout was assessed by the T7 EN1 enzyme digestion assay and the genotypes of monoclonal cells were identified by sequencing analysis Results: Bioinformatic analysis revealed that theSERPING1protein of human and pig had high homology, amino acid sequence identity reached 65.87%. A vector targetingSERPING1was constructed successfully and transfected into cells. Monoclonal cells with knockoutSERPING1gene were obtained through drug screening. Sequencing confirmed the mutant genotype. Conclusion The human and pigSERPING1sequences and their protein structures are highly homologous, and it is suitable for the construction of disease model. CRISPR/Cas9 expression vectors were constructed to achieve theSERPING1gene targeting in PFFs.SERPING1-knockout monoclonal cells were obtained, which could contribute to the construction of theSERPING1knockout miniature pig model.

Although interferon