BACKGROUND:Periprosthetic joint infection is the most common cause of early failure after total knee replacement.The current methods of preventing periprosthetic joint infection by improving the surface of the prosthesis have limitations to varying degrees.OBJECTIVE:To construct a coating material that can stably improve the surface of the implant,prevent the initial floating bacterial infection of periprosthetic infection,and regulate the bone transfer function around the implant.METHODS:(1)Material preparation:YGF polypeptide(which promotes bone formation),LL-37 polypeptide(with antibacterial properties)and YGF+LL-37 composite peptide were prepared by Fmoc solid phase peptide synthesis technology.The titanium-based materials were immersed in the three polypeptide solutions for 2 hours to obtain YGF coating,LL-37 coating and composite peptide coating coated titanium sheets.(2)In vitro experiment:Uncoated titanium sheets and coated titanium sheets were co-cultured with Escherichia coli(or Staphylococcus aureus)and the colonies were counted by plate method.MC3T3 cells were inoculated on the surface of uncoated titanium sheet and coated titanium sheet,respectively.Alizarin red staining was used to observe the calcium salt deposition on the surface of the material.Western blot assay was used to detect the protein expression of RUNX2,osteocalcin,osteopontin,and bone morphogenetic protein 2.(3)Animal experiment:24 SD rats were randomly divided into three groups:the blank group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal;the control group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension;the experimental group(n=8)was implanted with composite peptide coated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension.After 5 weeks of implantation,micro-CT examination,hematoxylin-eosin staining and immunohistochemical staining of femur specimens were performed.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with uncoated titanium sheet and YGF coated titanium sheet,LL-37 coated and composite peptide coated titanium sheet could significantly inhibit the growth and reproduction of Escherichia coli and Staphylococcus aureus.Compared with uncoated titanium sheets and LL-37-coated titanium sheets,YGF-coated and composite peptide-coated titanium sheets could promote calcium salt deposition in osteoblasts and increase the protein expression of RUNX2,osteocalcin,osteopontin and bone morphogenetic protein 2.(2)Animal experiment:Micro-CT test showed that the control group had less bone mass than the blank group and the experimental group.Hematoxylin-eosin staining showed that there was a large amount of fibrous tissue around the nail channel in the control group,only a small amount of tissue fibrosis around the nail channel in the blank group,and only a small amount of tissue fibrosis around the nail channel in the experimental group.Immunohistochemical staining showed that the protein expression of interleukin 1β and tumor necrosis factor α in the control group was higher than that in the blank group and the experimental group,and the expression of osteocalcin,RUNX2 and osteopontin in the experimental group was higher than that in the blank group and the control group.(3)The results show that the titanium-based material coated with YGF+LL-37 composite peptide coating has good antibacterial ability and can promote bone transfer around the implant.

BACKGROUND:Periprosthetic joint infection is the most common cause of early failure after total knee replacement.The current methods of preventing periprosthetic joint infection by improving the surface of the prosthesis have limitations to varying degrees.OBJECTIVE:To construct a coating material that can stably improve the surface of the implant,prevent the initial floating bacterial infection of periprosthetic infection,and regulate the bone transfer function around the implant.METHODS:(1)Material preparation:YGF polypeptide(which promotes bone formation),LL-37 polypeptide(with antibacterial properties)and YGF+LL-37 composite peptide were prepared by Fmoc solid phase peptide synthesis technology.The titanium-based materials were immersed in the three polypeptide solutions for 2 hours to obtain YGF coating,LL-37 coating and composite peptide coating coated titanium sheets.(2)In vitro experiment:Uncoated titanium sheets and coated titanium sheets were co-cultured with Escherichia coli(or Staphylococcus aureus)and the colonies were counted by plate method.MC3T3 cells were inoculated on the surface of uncoated titanium sheet and coated titanium sheet,respectively.Alizarin red staining was used to observe the calcium salt deposition on the surface of the material.Western blot assay was used to detect the protein expression of RUNX2,osteocalcin,osteopontin,and bone morphogenetic protein 2.(3)Animal experiment:24 SD rats were randomly divided into three groups:the blank group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal;the control group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension;the experimental group(n=8)was implanted with composite peptide coated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension.After 5 weeks of implantation,micro-CT examination,hematoxylin-eosin staining and immunohistochemical staining of femur specimens were performed.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with uncoated titanium sheet and YGF coated titanium sheet,LL-37 coated and composite peptide coated titanium sheet could significantly inhibit the growth and reproduction of Escherichia coli and Staphylococcus aureus.Compared with uncoated titanium sheets and LL-37-coated titanium sheets,YGF-coated and composite peptide-coated titanium sheets could promote calcium salt deposition in osteoblasts and increase the protein expression of RUNX2,osteocalcin,osteopontin and bone morphogenetic protein 2.(2)Animal experiment:Micro-CT test showed that the control group had less bone mass than the blank group and the experimental group.Hematoxylin-eosin staining showed that there was a large amount of fibrous tissue around the nail channel in the control group,only a small amount of tissue fibrosis around the nail channel in the blank group,and only a small amount of tissue fibrosis around the nail channel in the experimental group.Immunohistochemical staining showed that the protein expression of interleukin 1β and tumor necrosis factor α in the control group was higher than that in the blank group and the experimental group,and the expression of osteocalcin,RUNX2 and osteopontin in the experimental group was higher than that in the blank group and the control group.(3)The results show that the titanium-based material coated with YGF+LL-37 composite peptide coating has good antibacterial ability and can promote bone transfer around the implant.

OBJECTIVE To explore the mechanism of Chaiqi yigan granules （CQYG） against liver cancer through the ferroptosis pathway. METHODS Network pharmacology combined with ferroptosis-related database was used to screen key targets and main effective components of CQYG against liver cancer via regulating ferroptosis； molecular docking technology was employed to analyze the binding ability of main active components to key targets. Human liver Huh-7 cells were divided into blank serum control （CON） group， CQYG drug-containing serum （CQYGKL） group， ferroptosis inducer （RSL3） group， mammalian target of rapamycin complex 1 （mTORC1） inhibitor （RMC-5552） group， mTORC1 agonist （CCT007093） group， and CCT007093+CQYGKL group. The levels of Fe 2+ ， malondialdehyde （MDA）， and glutathione （GSH） in the cells were detected in the former three groups； mRNA expressions of mammalian target of rapamycin （mTOR）， sterol regulatory element-binding protein 1 （SREBP1）， and stearoyl-CoA desaturase 1 （SCD1）， protein expressions of SREBP1 and SCD1 as well as phosphorylation levels of mTOR and ribosomal S6 kinase （S6K） proteins were detected in all groups. RESULTS Key targets of CQYG for anti-liver cancer through the ferroptosis pathway were mTOR， SREBP1， SCD1，etc. The main active components included quercetin， tanshinone Ⅱ A ， baicalein， etc. The binding energies of main active components to key targets were all less than －5 kJ/mol. Compared with CON group， the levels of Fe 2+ and MDA in the cells in CQYGKL group and RSL3 group were significantly increased， while the levels of GSH were significantly decreased （ P ＜0.05）. mRNA expressions of mTOR， SREBP1 and SCD1， protein expressions of SREBP1 and SCD1， as well as the phosphorylation levels of mTOR and S6K proteins were significantly decreased in the CQYGKL group， RSL3 group， and RMC-5552 group， whereas all the above indicators were significantly increased in the CCT007093 group （ P ＜0.05）. Compared with CCT007093 group， the changes in all the above indicators were significantly suppressed in the CCT007093+CQYGKL group （ P ＜0.05）. CONCLUSIONS CQYG may induce ferroptosis by inhibiting mTORC1/SREBP1/SCD1 axis， thereby exerting anti-liver cancer effects.

Objective To analyze the current status and influencing factors of occupational stress, job burnout and sleep quality among workers in the secondary industry in Jinshan District, Shanghai City. Methods A total of 1 418 workers from six key industries in Jinshan District, Shanghai City were selected as the study subjects by the stratified cluster sampling method. The Occupational Stress Core Scale, Maslash Burnout Inventory General Survey and Pittsburgh Sleep Quality Index were used to investigate occupational stress, job burnout and sleep quality of the workers. Results The detection rates of occupational stress, job burnout and sleep disturbance among the study subjects were 33.6%, 65.4% and 23.3%, respectively. Multivariate logistic regression analysis showed that the workers with a monthly income <5 000 yuan had a higher risk of occupational stress than those with a monthly income ≥5 000 yuan (P<0.01). The workers with ≥5.0 years of service had a higher risk than those with <1.0 year (P<0.05). Lack of physical exercise, employment in medium- and large-sized enterprises, and shift work were risk factors of occupational stress in the workers (all P<0.01). The workers aged 18-<30 years had a higher risk of job burnout than those aged 45-<60 years (P<0.05). The workers monthly income <5 000 yuan was associated with a higher risk of job burnout than those with ≥9 000 yuan (P<0.05). The workers with 1.0-<10.0 years or ≥15.0 years of service had higher job burnout risks than those with <1.0 year (all P<0.05). Being unmarried, lack of physical exercise, and employment in medium- and large-sized enterprises were risk factor of job burnout in the workers (all P<0.05). The workers with an educational level of high school or above had a higher risk of sleep disturbance than those with junior school or below (P<0.05). The workers who work >56 hours per week had a higher risk than those working ≤40 hours per week (P<0.01). Conclusion There is a high detection rate of occupational stress, job burnout, and sleep disturbance in the secondary industry workers in Jinshan District, Shanghai City. Special attention should be given to workers with low income, lack of physical exercise, employment in medium- and large-sized enterprises, shift work, long service duration, and long weekly working hours to protect their physical and mental health.

Carbon dioxide(CO2),a colorless,odorless,low-density negative contrast agent with no nephrotoxicity or allergic reactions,has seen increasingly widespread application in the field of vascular imaging in recent years,particularly in patients with iodine allergy or renal insufficiency.When combined with digital subtraction angiography,CO2 angiography has demonstrated high-quality imaging in various arterial and venous sites such as the abdominal aorta,renal arteries,iliac arteries,lower limb arteries,and inferior vena cava.It has also shown safety and efficacy in clinical scenarios such as peripheral arterial disease,dialysis access evaluation,and transjugular intrahepatic portosystemic shunt procedures.This review systematically summarizes domestic and international research progress on CO2 angiography,outlines its physicochemical properties,injection dosages and parameters,clinical indications,and imaging characteristics,and compares its image quality with that of iodine-based contrast agents.Common complications,their mechanisms,and preventive measures are also discussed.Although the image quality of CO2 is slightly inferior to that of iodine agents,it remains sufficient for most diagnostic and therapeutic needs,with a low overall incidence of mainly mild and transient adverse effects.With the development of automated injection systems and digital variance angiography technology,CO2 imaging quality is expected to continue improving,and its application scope is likely to expand further.Future efforts should focus on strengthening multicenter clinical research and establishing standardized operational protocols to promote the broader adoption and regulated use of this technology.

AIM:To investigate the impact of Kir2.1 channels on abnormal spontaneous pacemaker activities induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:Human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)were transfected with lentiviral particles containing sequences for human Kir2.1,the Kir2.1-E224G mutant,or Kir4.1.Patch clamp techniques were employed to examine the effects of low extracellular potassium concentration([K+]e)of 1 mmol/L on the resting membrane potentials and whole-cell currents of the cells in each group,assessed via both current and voltage clamp modes.RESULTS:Under conditions of 1 mmol/L[K+]e,cur-rent clamp data revealed that hiPSC-CMs overexpressing Kir2.1 channels exhibited both hyperpolarized and depolarized resting membrane potentials,with the depolarized state triggering abnormal pacemaker activities.In contrast,cells overex-pressing the Kir2.1-E224G mutant or Kir4.1 channels displayed only hyperpolarized resting membrane potentials.Voltage clamp analysis indicated that hiPSC-CMs overexpressing Kir2.1 channels produced"N"-shaped whole-cell currents,whereas cells expressing the Kir2.1-E224G mutant or Kir4.1 exhibited typical K+currents.CONCLUSION:Kir2.1 channels play a crucial role in mediating hypokalemia-induced abnormal spontaneous pacemaker activities in human car-diomyocytes through their inward rectification properties.

Objective: To screen and identify the key active molecules, signaling pathways, and therapeutic targets of Shuxuening (SXN) injection for treating liver cirrhosis (LC) and to evaluate its therapeutic potential using a mouse model. Methods: Target genes of SXN and LC were retrieved from public databases, and enrichment analysis was performed. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and hub genes were identified using Molecular Complex Detection (MCODE). LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride (CCl4) for 12 weeks. Starting at week 7, SXN was administered intraperitoneally to the mice in the treatment group. Serum and liver tissues of the mice were collected for the detection of indicators, pathological staining, and expression analysis of hub targets using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 368 overlapping genes (OLGs) between SXN and LC targets. These OLGs were subsequently used to build a PPI network and to screen for hub genes. Enrichment analysis showed that these genes were associated with cancer-related pathways, including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes, such as responses to chemicals and metabolic regulation. In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition. Furthermore, qRT-PCR demonstrated that SXN regulated the expression of MAPK8, AR and CASP3 in the livers of LC mice. Conclusion This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods. The observed effect was associated with modulation of hub gene expression, particularly MAPK8, and CASP3.

Objective To compare the efficacy of 2 L and 3 L polyethylene glycol(PEG)electrolyte solution for bowel preparation in a real-world setting.Methods A real-world,single-center cohort study was conducted on the individuals undergoing colonoscopy in Department of Gastroenterology of Chengdu Third People's Hospital between May and October 2023.Based on our inclusion and exclusion criteria,they were given 2 L(n=4 684)and 3 L(n=3 700)PEG electrolyte solution for bowel preparation.The primary outcome indicator was the adequacy of bowel preparation by Boston bowel preparation score(BBPS).Secondary outcome indicators included the BBPS score,polyp detection rate(PDR),tolerability,compliance,and incidence of adverse events.Results The adequacy rate of bowel preparation was 94.35％in the 3 L group,significantly higher than that of the 2 L group(91.29％,P＜0.001).The 3 L group obtained a higher BBPS score then the 2 L group(6.92±1.06 vs 6.81±1.14,P＜0.001).But there was no statistical difference in the PDR between the 2 groups(P=0.073).And the rate of PEG completion(P=0.810),administration of low residue diet as required(P=0.094)or use of dimethicone(P=0.072)were comparable between the 2 groups.However,the incidences of vomiting(4.5％vs 3.2％,P=0.002),abdominal discomfort(5.0％vs 3.9％,P=0.011)and sleep disturbance(18.0％vs 14.6％,P＜0.001)were obviously higher in the 3 L group than the 2 L group.Conclusion In a real-world setting,2 L PEG is a considerably safe and effective regimen for bowel preparation.

Objective:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

Objective:To determine the best scoring system for assessing the severity of perioperative aortic dissection.Methods:All data were obtained from the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ) database in the United States. The predictive value of the Acute Physiology Score Ⅲ(APS Ⅲ), Oxford Acute Severity of Illness Score (OASIS), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score Ⅱ(SAPS Ⅱ), and Charlson Comorbidity Index (CCI) scoring systems were evaluated using the receiver operating characteristic ( ROC) curve. The area under the curve ( AUC) was used to determine the best predictive score, and the ideal cutoff value of the score was calculated based on the Youden index. Patients were divided into high and low groups according to the cutoff value. The Kaplan- Meier curve was used to show the impact on the survival rate of patients with aortic dissection. Results:ROC curve analysis showed that APS Ⅲ( AUC: 0.803, 95% CI: 0.721-0.885) was superior to SAPS Ⅱ( AUC: 0.767, 95% CI: 0.654-0.880), OASIS( AUC: 0.760, 95% CI: 0.635-0.885), SOFA( AUC: 0.753, 95% CI: 0.649-0.857), and CCI( AUC: 0.670, 95% CI: 0.524-0.817) in assessing in-hospital mortality. Based on the ROC curve and the Youden index calculation, the ideal cutoff value of the APS Ⅲ score was 57.5. Kaplan- Meier survival analysis showed that patients in the high group of APS Ⅲ had a shorter 28-day survival time. Patients in the high group of APS Ⅲ had a higher incidence of postoperative complications, and correlation analysis showed that patients in the high group of APS Ⅲ had a longer hospital stay. Conclusion:The APS Ⅲ scoring system is more valuable in predicting the 28-day mortality and prognosis of patients with aortic dissection.