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.

ObjectiveTo investigate the incidence of postherpetic neuralgia （PHN） and its associated risk factors in patients aged ≥50 years with herpes zoster （HZ） who received standard antiviral therapy at the dermatology outpatient clinic of our center. MethodsHZ patients were identified by searching the medical record system using "herpes zoster" as the keyword， and those diagnosed between July 2020 and July 2021. Patients meeting the inclusion criteria were followed up via telephone to retrospectively assess the occurrence of PHN. Patients were divided into a PHN group and a non-PHN group based on the presence of PHN. General patient information （gender， age， and underlying diseases）， prodromal pain intensity， and lesion characteristics （area， location， and acute-phase pain intensity） as well as treatment modalities （pharmacotherapy， physical therapy， and combined analgesic therapy） were compared between the two groups. Intergroup comparisons and multifactorial analyses were performed to identify factors associated with the development of PHN in HZ patients. Pain intensity was assessed using the Numerical Rating Scale （NRS） for PHN pain， acute-phase HZ pain， and prodromal pain. Intergroup comparisons were conducted using the chi-square test， Mann-Whitney U test， and t-test. Binary logistic regression was used for multivariate analysis to identify independent risk factors. ResultsA total of 238 HZ patients aged ≥50 years who received standard antiviral therapy were ultimately included， of whom 76 （31.9%） developed PHN. Unifactorial analysis showed that age， lesion area， acute-phase pain intensity， and the use of gabapentin or combined analgesic therapy significantly influenced the occurrence of PHN after HZ （P<0.05）. Statistically significant indicators （P<0.05） from the unifactorial analysis and the different analgesic regimens adopted by patients were included in the multifactorial analysis. Multifactorial analysis revealed that lesion area ≥1% （OR=2.501； 95%CI=1.408-4.443； P=0.002<0.05） and acute-phase pain score （OR=1.160； 95%CI=1.028-1.309； P=0.016<0.05） were independent risk factors for PHN. Age and the use of gabapentin or combined analgesic therapy showed no statistically significant association with the occurrence of PHN （P>0.05）. ConclusionsIn HZ patients aged ≥50 years receiving standard antiviral therapy， the incidence of PHN is 31.9%. A lesion area ≥1% and higher acute-phase pain NRS scores are identified as independent risk factors for the development of PHN in these patients.

ObjectiveTo investigate the incidence of postherpetic neuralgia （PHN） and its associated risk factors in patients aged ≥50 years with herpes zoster （HZ） who received standard antiviral therapy at the dermatology outpatient clinic of our center. MethodsHZ patients were identified by searching the medical record system using "herpes zoster" as the keyword， and those diagnosed between July 2020 and July 2021. Patients meeting the inclusion criteria were followed up via telephone to retrospectively assess the occurrence of PHN. Patients were divided into a PHN group and a non-PHN group based on the presence of PHN. General patient information （gender， age， and underlying diseases）， prodromal pain intensity， and lesion characteristics （area， location， and acute-phase pain intensity） as well as treatment modalities （pharmacotherapy， physical therapy， and combined analgesic therapy） were compared between the two groups. Intergroup comparisons and multifactorial analyses were performed to identify factors associated with the development of PHN in HZ patients. Pain intensity was assessed using the Numerical Rating Scale （NRS） for PHN pain， acute-phase HZ pain， and prodromal pain. Intergroup comparisons were conducted using the chi-square test， Mann-Whitney U test， and t-test. Binary logistic regression was used for multivariate analysis to identify independent risk factors. ResultsA total of 238 HZ patients aged ≥50 years who received standard antiviral therapy were ultimately included， of whom 76 （31.9%） developed PHN. Unifactorial analysis showed that age， lesion area， acute-phase pain intensity， and the use of gabapentin or combined analgesic therapy significantly influenced the occurrence of PHN after HZ （P<0.05）. Statistically significant indicators （P<0.05） from the unifactorial analysis and the different analgesic regimens adopted by patients were included in the multifactorial analysis. Multifactorial analysis revealed that lesion area ≥1% （OR=2.501； 95%CI=1.408-4.443； P=0.002<0.05） and acute-phase pain score （OR=1.160； 95%CI=1.028-1.309； P=0.016<0.05） were independent risk factors for PHN. Age and the use of gabapentin or combined analgesic therapy showed no statistically significant association with the occurrence of PHN （P>0.05）. ConclusionsIn HZ patients aged ≥50 years receiving standard antiviral therapy， the incidence of PHN is 31.9%. A lesion area ≥1% and higher acute-phase pain NRS scores are identified as independent risk factors for the development of PHN in these patients.

[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.

[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.

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.

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］

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

OBJECTIVE: To explore the current research status and hotspots in the field of biomechanics of diabetic foot by bibliometric analysis methods. METHODS: Literatures related to biomechanics of diabetic foot published in the Web of Scienc Core Collection (WoSCC) from 1981 to 2024 were searched. CiteSpace software and R language bibliometrics plugin were used to conduct a visual analysis of annual publication volume of the literature, including publication volume of each country and region, the publication situation of authors and institutions, the citation situation of individual literature, and the co-occurrence network of keywords. RESULTS: Totally 996 literatures were included, and the number of published papers increased steadily. The United States (261 papers) and China (89 papers) were the top two countries in terms of the number of published papers. The mediating centrality of the United States was 0.94, and that of China was 0.01. Scholars such as Cavanagh and institutions like the Cleveland Clinic were at the core of research in this field. High-frequency keywords include plantar pressure (plantar pressure), diabetic foot (diabetic foot), ulceration (ulcer), etc. The research focuses on plantar pressure, ulcer formation and prevention, etc. CONCLUSION Biomechanical research on diabetic foot mainly focuses on the pressure distribution on the sole of the foot, callus formation, mechanical analysis of soft tissues on the sole of the foot, and the study of plantar decompression caused by Achilles tendon elongation. The research trend has gradually shifted from focusing on joint range of motion to gait and the design of braces and assistive devices, and has begun to pay attention to muscle strength, gait imbalance and proprioception abnormalities.
Humans ; Diabetic Foot/physiopathology* ; Biomechanical Phenomena ; Bibliometrics