Objective To investigate the effect of mitochondrial unfolded protein response(UPRmt)on lipid metabolism in human kidney 2(HK-2)cells.Methods Lipid accumulation was induced by palmitic acid(PA)in HK-2 cells.The cells were pretreated with siRNA or CDDO respectively.The intracellular lipid accumulation was observed by oil red staining;mitochondrial membrane potential(MMP)was measured by JC-1.The contents of reactive oxygen species(ROS)in mitochondria were measured by Mito-SOX,and the expressions of HSP60,LONP1,CLPP,ACOX1,PPARα,PGC1α and CPT1α were detected by Western blotting.Results PA induced lipid aggregation,MMP decrease,ROS generation in mitochondria and the decreased expression of UPRmt proteins(e.g.,HSP60 and LONP1)in HK-2 cells.Pretreatment of HK-2 cells with siRNA could aggravate lipid aggregation,MMP decrease and ROS generation induced by PA,and further decrease the expression of HSP 60and LONP1.Pretreatment of HK-2 cells with CDDO alleviated lipid aggregation,MMP decrease,ROS generation and decreased HSP60 and LONP1 expressions induced by PA.Conclusion Lipid aggregation in HK-2 cells induced by PA may be related to mitochondrial dysfunction and UPRmt has a protective effect on HK-2 cells in the process.

Objective To study the mechanical response of tibial prostheses and the distal tibial cancellous bone after implantation of radial and axial functionally graded materials(FGM)into the ankle joint.Methods Three FGM were used:titanium alloy-bioactive glass composite FGM(FGM-Ⅰ),titanium(Ti)alloy-ideal bone elastic composite FGM(FGM-Ⅱ),and Ti alloy-hydroxylapatite composite FGM(FGM-Ⅲ).A three-dimensional finite element model of total ankle arthroplasty(TAA)was established,and the simulation software ABAQUS was used for secondary development based on Fortra.By changing the volume fraction,the mechanical properties of the FGM tibial prosthesis can be adjusted both axially and radially.The stress distributions of the tibial prosthesis and cancellous bone after FGM axial and radial tibial component implantation in the standing position were analyzed.Results Compared with Ti alloy tibial prosthesis,three kinds of FGM could effectively reduce the stress concentration on the tibial prosthesis,and the overall effect of FGM-Ⅲ tibial prosthesis was better than that of FGM-Ⅰ and FGM-Ⅱ tibial prosthesis;the radial distribution of FGM could effectively reduce the maximum von Mises stress of the prosthesis.For the tibial cancellous bone,the three types of FGM radial tibial prostheses and FGM-Ⅲ axial tibial prostheses could effectively increase the distal stress,thus,relieving the stress shielding on the cancellous bone;the FGM-Ⅲ radial tibial prosthesis was the most effective in improving the stress level of the cancellous bone.Conclusions FGM-Ⅲ radial ankle prosthesis can effectively reduce the stress concentration phenomenon and the stress shielding effect on the prosthesis to prolong its life,with potential application prospects.

Objective·To further clarify the mechanism of podocyte damage by studying the expression of cartilage oligomeric matrix protein(COMP)in glomerular podocytes and its relationship with podocyte autophagy under high glucose environment.Methods·The gene expression dataset GSE104948 was downloaded from the GENE EXPRESSION OMNIBUS(GEO)database,and differentially expressed genes(DEGs)were obtained via GEO2R.The molecular functions and signaling pathways related to differential genes were summarized.The most correlated key genes(hub genes)were acquired by Weighted Gene Co-Expression Network Analysis(WGCNA)and the protein-protein interaction network(PPI)of DEGs was constructed with STRING database.The enrichment analysis was performed again.Conditionally immortalized mouse podocyte cells were cultured in vitro.After being fully differentiated,they were stimulated with high glucose,and the expressions of COMP,mammalian target of rapamycin(mTOR),microtubule-associated protein 1 light chain3(LC3)and other proteins in podocytes were detected by Western blotting.The shRNA constructed by lentiviral vector was further used to infect podocytes to inhibit the expression of COMP,and the stable cell strains were screened by puromycin.The expression of COMP,mTOR,and LC3 of stable strains were detected by Western blotting,in order to observe the effect of COMP on autophagy.Results·A total of 362 DEGs were filtered for subsequent analysis.Among these DEGs,284 genes were up-regulated and 78 genes were down-regulated.The results of Gene Onotology(GO)term analysis showed that DEGs in diabetic nephropathy(DN)were mainly enriched in cell surface receptor signaling pathway,receptor binding,etc.The main enriched Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways included phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/AKT)signaling pathway,extracellular matrix(ECM)-receptor interaction,etc.Sixty-four hub genes were refined through the intersection of WGCNA and PPI hub genes,and the hub genes with significantly increased or decreased expression were sifted.The hub genes were annotated with KEGG again,and it was found that most of the hub genes were enriched in"ECM-receptor interaction"and"PI3K/AKT signaling pathway".The PI3K/AKT/mTOR signaling pathway is a classic autophagy pathway,and COMP was absolutely overexpressed(logFC>2)in the 64 hub genes,suggesting that it may affect autophagy through this pathway.Western blotting showed that compared with the mannitol control group and the low glucose group,the expression of COMP in podocytes was significantly increased under high glucose stimulation.Compared with the control group,the expression of LC3-Ⅱ in the high glucose group was significantly decreased,indicating that the autophagy initiation of podocytes was inhibited under the high glucose environment.Compared with the negative control,the expression of LC3-Ⅱ in renal podocytes of mice with knockdown of COMP was significantly increased,and the mTOR decreased with the decrease of the expression of COMP,indicating that inhibiting COMP contributed to the recovery of autophagy in podocytes.Conclusion·COMP is highly expressed in DN patients and highly enriched in ECM receptor and PI3K/AKT signaling pathway.Autophagy in mouse renal podocytes is inhibited under high glucose conditions,and the high expression of COMP induced by high glucose may be a key factor in autophagy inhibition.Inhibiting COMP helps to restore autophagy in mouse renal podocytes.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

The simulator testing in vitro and computational simulation of the artificial knee joint wear are important methods to evaluate the wear performance of the prosthesis in vitro and to predict the clinical performance of knee joint products. Based on the method of literature search, this paper compares the mechanical and kinematic loading input curves carried out by Chinese scholars in recent years, standard curves, and Chinese measurement curves of two typical movements of gait. Data of vitro simulator test and computational simulation model are compared, summarized, and analyzed. The results show that the measured data of motion and load cannot be directly used as the loading conditions for the simulator wear test and computational simulation. The mechanics and kinematics data of Chinese people are different from the international standards. The domestic artificial knee joint in vitro simulator wear test methods are similar but the results of different test institutions are somewhat different. The computation wear prediction research is basically synchronized with foreign countries, but the problem that the calculated wear results are lower than that in vitro test is still unsolved. The artificial knee joint wear performance evaluation system based on Chinese knee joint mechanics and kinematics data is the forward direction of the research.

Early brain injury (EBI) refers to the direct damage and secondary pathophysiological changes of brain tissue within 72 h after aneurysmal subarachnoid hemorrhage. Studies have shown that a variety of signaling pathways are involved in the mechanism of EBI, such as ecoxy chloropropane Kelch sample related protein-1 (Keap1)-nuclear factor E2 related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, Toll-like receptor 4 (TLR4)/nuclear factor-κB pathway, phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway. This article reviews the mechanisms of action of different signaling pathways involved in EBI.

Objective To clarify the characteristics and postoperative benefit of gallbladder carcinoma in elderly patients (≥ 65 years old).Methods Two hundred and seventy-three patients of gallbladder carcinoma were collected,who were treated intent resection from January 2004 to December 2012 in the Department of Hepatobiliary Surgery,Eastern Hepatobiliary Hospital,Second Military Medical University.More than 65 years old was defined as the elderly,else was defined as the younger.The clinical-pathological features and prognosis of 85 elderly patients(elderly group) and 188 younger patients (younger group) were retrospectively analyzed.The survival of patients were followed up by telephone or outpatient.The incidence of hypertension,incidence of diabetes,TNM staging,and median CA19-9 were compared between the two groups.Continuous variables using a two-sample t test or Mann-Whitney U test.Categorical variables were compared by the Chi-square test or Fisher probability method.The survival curve was drawn by the Kaplan-Meier method.The univariate analysis and multivariate analysis of prognosis were respectively done using the Log-rank test and COX regression model.Results The incidence of hypertension,incidence of diabetes,TNM stage ratio (Ⅲ + Ⅳ/Ⅰ + Ⅱ),and CA19-9 median in the elderly group were 30.6％,11.8％,27.6 and 69.3 U/ml,respectively.The differences in the younger group were 13.8％,4.8％,7.9 and 28.2 U/ml,respectively,with statistically significant difference between the two groups (all P ＜ 0.05).The incidence of complications was 54.1％ in the elderly group and 48.9％ in the younger group,with no significant difference between the two groups (P =0.302).The median survival of the elderly group was 28.01 months,and the median survival of the younger group was 36.20 months,with no statistical difference between the two groups (P =0.131).Cox analysis showed that independent prognostic risk factors for the elderly patients with gallbladder cancer included liver invasion (HR =2.386,95％ CI:1.379-4.127,P =0.002) and lymph node metastasis (HR =1.866,95 ％ CI:1.100-3.167,P =0.021).Conclusions Radical resection is safe and feasible for elderly patients with gallbladder carcinoma.Age is not a contraindication for surgery.Radical resection can get the same benefits as young people.Liver invasion and lymph node metastasis are independent risk factors affecting the prognosis of the elderly patients with gallbladder carcinoma.

Objective To examine the prognostic value of flow diversion (FD) presented on transcranial Doppler ultrasound (TCD) in patients with large hemispheric infarction (LHI) caused by the unilateral middle cerebral artery (MAC) occlusion.Methods Seventy-three consecutive LHI patients who had occlusion in M1 segment of MAC and were admitted to neurological intensive care unit at Xijing Hospital from January 2012 to June 2016 were reviewed.All the participants had TCD examination after admission,and were grouped according to the presence or absence of FD into FD+ and FD-.Three-month,six-month,and twelve-month functional outcomes of all the participants were collected and analyzed.Long-term survival rates were compared using Kaplan-Meier survival analysis.Receiver operating characteristic curve (ROC) was used to examine the predictive power of FD in patients with LHI.Results Among 73 LHI patients,28 (38.36％) patients were presented with FD.The incidence rates of cerebral herniation,usage of mechanical ventilation,mortality during hospitalization and incidence rates of three-month,six-month and twelve-month poor outcomes were much higher in patients without FD than those with FD.Multivariate analyses demonstrated that FD was independently associated with cerebral herniation (OR=28.943,95％CI 1.922-435.918,P=0.015),usage of mechanical ventilation (OR=11.151,95％CI 1.614-77.018,P=0.014),three-month (OR=20.163,95％CI 3.048-133.362,P=0.002),six-month (OR=3.525,95％CI 1.153-10.773,P=0.027),and twelve-month (OR=4.400,95％CI 1.387-13.960,P=0.012) poor outcomes.FD yielded an area under the ROC of 0.756,allowing for prediction of three-month outcomes of LHI.Conclusion FD presented on TCD is an early predictor of outcomes in patients with LHI.

Objective To investigate the energy intake and complications of continuous and intermittent pump feeding in acute stroke patients and provide a theoretical evidence to support for clinical treatment.Methods From April 2012 to June 2016,69 acute srtoke patients on the nasogastric tube feeding and admitted in the Department of Neurology intensive care unit in Xijing Hospital were enrolled and randomly assigned to have continuous or intermittent pump feeding.The primary endpoint was the efficacy in supplying the desired amount of nutrients by the fifth day and complications(hospital-acquired pneumonia,diarrhea,gastric retention,gastrointestinal bleeding)during the first week.The secondary endpoint was nutritional assessments(albumin,prealbumin,transferrin,hypersensitive c-reactive protein)in the first week.Results Both groups were comparable in acute physiology and chronic health evaluation Ⅱ(13.3±4.7 vs.12.9±4.5),Glasgow coma scale[10(7.2,14)vs.9.5(7.7,12)],National Institute of Health stroke scale[17(15,19)vs.16(13,20)],and Barthel scores[5(0,12.5)vs.10(5,15)](all P>0.05).It was no significantly different in the achievement percentage of the energy determined in the fifth day [93.9％(77.9％,99.8％)in continuous group and 84.8％(75.7％,93.9％)in intermittent group(U=0.144,P>0.05).Intermittent pump feeding significantly reduced the rate of hospital-acquired pneumonia in the first week when compared with continuous pump feeding(58.3％vs.33.3％,X2=4.327,P=0.038),and both groups displayed a moderate number of digestive complications without significant differences,including diarrhea(30.6％vs.27.3％,X2=0.09,P=0.764),gastric retention(2.78％vs.3.03％,X2=0.001,P=1.000),and gastrointestinal bleeding(5.56％vs.9.10％,X2=0.010,P=0.920).No difference could be demonstrated in serum protein markers between two groups in the first week,including prealbumin[0.17(0.13,0.20)g/L vs.0.18(0.15,0.24)g/L,P=0.195),transferrin[1.90(1.52,2.20)g/L vs.1.94(1.65,2.06)g/L,P=0.747),and hypersensitive C-reactive protein[22.5(8.3,50.1)mg/L vs.14.6(6.5,30.5)mg/L,P=0.205].Conclusions Both continuous and intermittent pump feeding can reach the target predictive nutrition(100％of calculated caloric requirements)without statistical differences in the incidences of gastrointestinal complications,and the rate of HAP is lower in intermittent group.Intermittent enteral nutrition can be used as an appropriate method of enteral nutrition support to improve the nutritional status in critically acute stroke patients.