Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

BackgroundNon-suicidal self-injury （NSSI） behaviors are prevalent among adolescents， significantly affecting their physical and mental well-being. Understanding the risk factors associated with adolescent NSSI is crucial for prevention. Previous studies have identified mobile phone dependence as a risk factor for NSSI in adolescents. However， as a key form of mobile phone dependence， the evidence regarding the impact of mobile phone social media dependence on adolescent NSSI behavior remains insufficient. ObjectiveTo explore the impact of mobile phone social media dependence and its associated factors on adolescent NSSI behavior， so as to provide references for intervention strategies targeting NSSI in adolescents. MethodsA total of 100 adolescents diagnosed with NSSI according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， and receiving treatment at Tongde Hospital of Zhejiang Province from January 2022 to December 2023 were included in the study group. Concurrently， 100 age- and sex-matched students from Hangzhou were recruited as the control group. Assessments were conducted using Ottawa Self-injury Inventory（OSI） Function Subscale and Addiction Features Subscale， Adolescents Self-Harm Scale（ASHS）， and Mobile Phone Social Media Dependence Questionnaire. Multiple linear regression was used to analyze the factors influencing NSSI behaviors. ResultsThe research group had a total of 99 patients （99.00%） who completed the study， while the control group consisted of 97 （97.00%） adolescents who finished this research.The study group had statistically significantly higher total scores on the Mobile Phone Social Media Dependence Questionnaire， as well as higher scores on the conflict and withdrawal dimensions， compared with control group（t=-3.061， -2.874， -2.368， P<0.05 or 0.01）. The study group also scored significantly higher on the OSI Function Subscale for internal emotion regulation， social influence， external emotion regulation， and sensation-seeking factors， as well as on the OSI Addiction Features Subscale scores， compared to the control group（t=-22.249， -8.854， -17.968， -10.591， -20.157， P<0.01）. OSI Function Subscale scores were positively correlated with Mobile Phone Social Media Dependence Questionnaire scores （r=0.321， P<0.01）， and OSI Addiction Features Subscale scores were positively correlated with Mobile Phone Social Media Dependence Questionnaire scores （r=0.282， P<0.01）. ASHS scores were positively correlated with Mobile Phone Social Media Dependence Questionnaire scores （r=0.145， P<0.05）. Multiple linear regression analysis showed that compulsivity （β=0.416， P<0.01） and conflict （β=0.256， P<0.05） were significant predictors for adolescent NSSI behaviors. ConclusionAdolescent NSSI behaviors are associated with mobile phone social media dependence. The compulsivity and conflict dimension of mobile phone social media dependence are influencing factors for adolescent NSSI behaviors. The higher level of the compulsivity and conflict are associated with an increased risk of the NSSI behaviors in adolescents. ［Funde by Zhejiang Medical and Health Science and Technology Plan Project in 2022 （number， 2022KY704］

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

[Objective] To investigate the protective effect of Salvia miltiorrhiza injection (SMI) on the kidneys of HBOC-CHP01 resuscitated haemorrhagic shock rats. [Methods] A 50% haemorrhagic shock rat model was established, with 12 rats divided into two groups: SMI + HBOC-CHP01 group and HBOC-CHP01 group, with 6 rats in each group. The rats in the SMI+ HBOC-CHP01 group were given an equal volume of HBOC-CHP01 for resuscitation after haemorrhagic shock, and an 8 mL/kg dose of SMI. Rats in the HBOC-CHP01 group were resuscitated by administering an equilibrium blood loss volume of HBOC-CHP01 and given an 8 mL/kg dose of 0.9% NaCl solution. Blood was taken from rats at five points: before bloodletting (baseline), during haemorrhagic shock (HS), immediately after resuscitation (RS0h), 1 h after resuscitation (RS1h), and 24 h after resuscitation (RS24h). A blood gas analyser was used to detect the lactate level (Lac), glucose content (Glu), residual base (BEecf), pH, bicarbonate (HCO3-), high iron haemoglobin (MetHb). White blood cells (WBC), platelets (PLT), haemoglobin content (Hb), carboxyhaemoglobin (COHb) were detected using a quintuple classification. Blood creatinine (SCr), uric acid (UA), kidney-related indexes were detected using biochemistry instrument. Kidney tissues of the rats were taken after 24 h of resuscitation and after execution, and the inflammation of kidneys of the rats of the two groups was analyzed using HE staining. Fluorescence staining was used to detect the level of ROS in the kidneys of rats in both groups. [Results] At RS 0h, the Beecf, Glu and Lac levels of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group, and the pH level of rats in the SMI+HBOC-CHP01 group was significantly higher than that of rats in the HBOC-CHP01 group, and the Glu levels of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group at RS 1h. At RS 0h, the WBC, PLT and COHb contents of rats in the SMI+HBOC-CHP01 group were all significantly higher than those of rats in the HBOC-CHP01 group, and at RS 1h, the WBC content of rats in the SMI+HBOC-CHP01 group was significantly higher than that of rats in the HBOC-CHP01 group; at RS 1h, the UA content of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC-CHP01 group; at RS 24h, the SCr content of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC-CHP01 group; at RS 24h, the inflammation level of kidney tissues of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC -CHP01 group rats, and the ROS and MPO levels in the kidney tissues of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group. [Conclusion] The combination of Salvia miltiorrhiza injection during the resuscitation of rats with severe haemorrhagic shock by HBOC-CHP01 can alleviate renal injury by reducing inflammatory response and oxidative stress.

Objective To investigate the effects of joint function screening and correction on intervention efficacy of prevention and assessment score of training injuries in new recruits.Methods A randomized controlled study was conducted on 265 new recruits subjected from two organizational units of an army unit with cluster sampling.Based on entire organizational unit,the participants were randomly divided into a control group(n=132)and an experimental group(n=133).The experimental group received joint function screening and corrective movement training,which was subsequently applied in the new recruit training,while the control group underwent training according to conventional methods.Joint function were collected before and after training.The demographic data,assessment score of training,and incidence of training injuries were collected through the participant's own organizational unit.Receiver operating characteristic(ROC)curve was plotted to evaluate the efficacy of joint function screening in predicting training injuries,and binary logistic regression and general linear regression analyses were applied to verify the correlation of joint function screening score with training injuries and assessment score of training.Results After new training,the score of joint function screening was significantly higher in the experimental group than the control group(16.62±1.87 vs 14.92±2.58,P<0.001).And the score was obviously increased in the experimental group(16.62±1.87 vs 12.82±1.98,P<0.001)and the control group(14.92±2.58 vs 12.95±1.81,P<0.001)when compared with the corresponding score before training.The area under the ROC curve(AUC)of joint function screening in predicting training injuries was 0.762(95%CI:0.694～0.830),indicating good predictive efficacy.During the new training process,the incidence of training injuries in the experimental group(13.53%)was significantly lower than that in the control group(24.24%,Chi-square=4.963,P=0.026).Binary logistic regression analysis showed that the pre-training assessment score of joint function screening was an important influencing factor for training injuries in new recruits(OR=0.552,95%CI:0.413～0.660,P<0.001).The experimental group obtained notably higher mean assessment score than the control group[733.00(716.00,752.75)vs 728.79(710.46,744.28),P=0.027].Linear regression analysis revealed a correlation between post-training score of joint function screening and the assessment score of newly trained personnel(P<0.001).Conclusion Joint function screening and correction for newly trained personnel can effectively prevent training-related injuries during the new training period,and correcting joint function through training can effectively improve the assessment score of newly trained personnel.

OBJECTIVE To evaluate the effect of bundled property management under multidisciplinary coopera-tion mode on prevention and control of multidrug-resistant organisms(MDROs)in intensive care units(ICUs)and explore the evidence-based methods for prevention and control of MDROs.METHODS A control study before and after the same time period was designed,the post-intervention period was 2024 when the bundled measures were fully implemented,and the pre-intervention period was 2023.Totally 8 ICUs of general and special depart-ments of a three-A hospital in Hubei Province were recruited as research subjects,the multidisciplinary coopera-tion team was established,the bundled management measures were introduced to optimize the quality of property cleaning work.The quality of service of the property cleaning work was evaluated through surveillance of hospital-associated infections and environmental hygiene surveillance before and after the bundled measures were imple-mented.RESULTS The isolation rate of MDROs from object surfaces of ICU environment declined from 0.34％to 0.10％after the bundled management measures under multidisciplinary cooperation model were implemented(P＜0.05).The incidence of MDROs hospital-associated infections was reduced from 0.07％to 0.03％(P＜0.05);the isolation rate of MDROs from patients decreased from 14.68％to 12.69％(P＜0.05);the performance as-sessment score of the cleaning staff was raised from(85.56±7.21)points to(91.06±3.07)points,however,there was no significant difference.The hand hygiene compliance rate of the cleaning staff was raised from 42.86％to 68.52％(P＜0.05).The positive rate of random ATP fluorescent test for environmental object surfaces de-clined from 25.41％to 10.05％(P＜0.05).Other environmental hygiene indexes for the cleaning and disinfection effects were improved in varying degrees.CONCLUSION The bundled management measures under multidiscipli-nary cooperation mode boost the property service quality,enhance the cleaning staff's awareness of disinfection,prevention and control,reduce the isolation rate of MDROs in environment,and thus decrease the incidence of MDROs hospital-associated infections and prevent the transmission.

[Objective] To extract hemoglobin (Hb) from red blood cells using osmotic pressure swelling method, expected to achieve a hemoglobin dissolution rate of ≥80% and a cell membrane integrity rate of ≥70%. [Methods] Human umbilical cord blood red blood cells were used as raw materials and phosphate buffer solution was used as the swelling solution for red blood cells. A three factor three-level orthogonal experiment (n=3) was conducted to determine the optimal matching conditions for selecting the osmolality molar concentration of phosphate buffer solution, pH value of hypotonic phosphate buffer solution and volume ratio of hypotonic phosphate buffer solution to washed red blood cells. Red blood cell swelling solution samples (n=6) were prepared by the optimal matching conditions and the original process conditions. The hemoglobin dissolution rate and cell membrane integrity rate were checked. In the expanded comparative experiment, red blood cell swelling solution samples (n=6) were prepared by the optimal matching conditions and the original process conditions, which was filtered by ultrafiltration membranes. The filtration time and hemoglobin yield were checked. [Results] The optimal matching conditions for preparing red blood cell swelling solution were obtained through orthogonal experiment as follows: osmotic pressure molar concentration was 30 mOsmol/Kg, pH was 7.8, and phosphate buffer to red blood cell volume ratio was 6∶1. On the basis of the above conditions, the red blood cell swelling solution sample was compared with the original process sample: the hemoglobin dissolution rate was (82.4±1.8)% vs (78.6±3.0)% (P<0.05), and the cell membrane integrity rate was (65.8±4.0)% vs (28.7±2.3)% (P<0.05). In the expanded comparative experiment, the optimal matching conditions were compared with the original process conditions: filtration time(s) (327±9) vs (434±13) (P<0.05), and hemoglobin yield was (72.3±1.2)% vs (66.0±1.4)% (P<0.05). [Conclusion] Compared with the original preparation process, the hemoglobin extraction process which optimized through orthogonal experiments greatly reduces the cell membrane fragmentation rate and minimizes the entry of cell membrane matrix into the target solution, ensuring a slightly higher hemoglobin dissolution rate, and reducing the preparation difficulty for the subsequent cell membrane separation and further purification.

Prosthesis loosening is the leading cause of postoperative revision in unicompartmental knee arthroplasty (UKA). The deviation of medial and lateral translational installation of the prosthesis during surgery is a common clinical phenomenon and an important factor in increasing the risk of prosthesis loosening. This study established a UKA finite element model and a bone-prosthesis fixation interface micromotion prediction model. The predicted medial contact force and joint motion of the knee joint from a patient-specific lower extremity musculoskeletal multibody dynamics model of UKA were used as boundary conditions. The effects of 9 femoral component medial and lateral translational installation deviations on the Von Mises stress of the proximal tibia, the contact stress, and the micro-motion of the bone prosthesis fixation interface were quantitatively studied. It was found that compared with the neutral position (a/A of 0.492), the lateral translational deviation of the femoral component significantly increased the tibial Von Mises stress and the bone-prosthesis fixation interface contact stress. The maximum Von Mises stress and the maximum contact stress of the fixation interface increased by 14.08% and 143.15%, respectively, when a/A was 0.361. The medial translational deviation of the femoral component significantly increased the bone-prosthesis fixation interface micro-motion. The maximum value of micromotion under the conditions of femoral neutral and medial translation deviation was in the range of 20-50 μm, which is suitable for osseointegration. Therefore, based on considerations such as the micromotion range suitable for osseointegration reported in the literature, the risk of reducing prosthesis loosening, and factors that may induce pain, it is recommended that clinicians control the mounting position of the femoral component during surgery within the safe range of 0-4 mm medial translation deviation.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Finite Element Analysis ; Biomechanical Phenomena ; Knee Prosthesis ; Tibia/surgery* ; Femur/surgery* ; Stress, Mechanical ; Prosthesis Failure ; Knee Joint/surgery* ; Prosthesis Design

Although metal blocks have been widely used for reconstructing uncontained tibial bone defects, the influence of their elastic modulus on the stability of tibial prosthesis fixation remains unclear. Based on this, a finite element model incorporating constrained condylar knee (CCK) prosthesis, tibia, and metal block was established. Considering the influence of the post-restraint structure of the prosthesis, the effects of variations in the elastic modulus of the block on the von Mises stress distribution in the tibia and the block, as well as on the micromotion at the bone-prosthesis fixation interface, were investigated. Results demonstrated that collision between the insert post and femoral prosthesis during tibial internal rotation increased tibial von Mises stress, significantly influencing the prediction of block elastic modulus variation. A decrease in the elastic modulus of the metal block resulted in increased von Mises stress in the proximal tibia, significantly reduced von Mises stress in the distal tibia, decreased von Mises stress of the block, and increased micromotion at the bone-prosthesis fixation interface. When the elastic modulus of the metal block fell below that of bone cement, inadequate block support substantially increased the risk of stress shielding in the distal tibia and fixation interface loosening. Therefore, this study recommends that biomechanical investigations of CCK prostheses must consider the post-constraint effect, and the elastic modulus of metal blocks for bone reconstruction should not be lower than 3 600 MPa.
Knee Prosthesis ; Humans ; Finite Element Analysis ; Tibia/surgery* ; Elastic Modulus ; Arthroplasty, Replacement, Knee/methods* ; Stress, Mechanical ; Metals ; Prosthesis Design ; Knee Joint/surgery* ; Biomechanical Phenomena