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 provide a reference for clinical pharmacists to participate in the treatment of rare and complex cases of CTLA-4 haploid deficiency combined with severe malnutrition. METHODS The clinical pharmacist participated in the diagnosis and treatment of a complex case of CTLA-4 haploid deficiency with severe malnutrition， type 1 diabetes， blood coagulation abnormalities with gastrointestinal bleeding and virus infection， assisted the doctor to develop an individualized parenteral nutrition program， and dynamically adjusted the ratio of glucose and insulin （from 3.9∶1 to 15.6∶1）. When patient had severe coagulation abnormalities and gastrointestinal bleeding， the clinical pharmacist recommended discontinuing fat emulsion and switching to glucose amino acid dual energy supply； when the patient had a high fever accompanied by a sudden drop in platelets， the clinical pharmacist recommended to improve the second-generation sequencing of plasma metagenomics. Based on positive results for both EB virus and cytomegalovirus， the clinical pharmacist recommended to discontinue meropenem and switch to ganciclovir for antiviral treatment； when the patient experienced systemic itching and mental excitement， the clinical pharmacist quickly diagnosed as an adverse reaction of ganciclovir and recommended to switch to acyclovir for antiviral treatment. The clinical pharmacist simultaneously carried out parenteral nutrition medication education， and standardized infusion speed， and continuously monitored bleeding-related indicators. RESULTS The physician adopted the advice of the clinical pharmacist. After comprehensive intervention， the patient’s body temperature returned to normal， gastrointestinal bleeding stopped， coagulation indicators significantly improved， blood sugar control reached the standard， and the condition improved and the patient was discharged. CONCLUSIONS Clinical pharmacists rely on comprehensive pharmaceutical services to balance the benefits and risks of treatment for rare and complex cases. They play a key role in individualized nutrition planning， refined blood glucose control， infection identification and anti-infection optimization， and identification and treatment of adverse drug reactions to ensure patient medication safety and efficacy.

Objective To explore the clinical value of serum stromal cell-derived factor-1(SDF-1)and macro-phage inflammatory protein-1α(MIP-1α)in predicting biliary tract infection after endoscopic retrograde cholangiopancreatography(ERCP)stone removal in patients with common bile duct stones.Methods From January 2022 to January 2024,100 patients with common bile duct stones who underwent ERCP stone removal surgery in Pingdingshan First People's Hospital were collected.They were grouped into an infection group(12 cases)and a non-infection group(88 cases)based on whether biliary tract infection occurred after surgery.The general information of patients in the two groups was compared.ELISA method was used to measure the levels of serum SDF-1 and MIP-1α.Spearman method was applied to analyze the correlation between the severity of infec-tion and serum level of SDF-1 and MIP-1α.ROC curve was applied to analyze the value of serum SDF-1 and MIP-1α to predict biliary tract infection after ERCP stone removal in patients with common bile duct stones.Results A total of 36 strains of pathogenic bacteria were detected in the biliary drainage fluid samples of the infection group,among which Gram-negative bacteria accounted for 55.56%and Gram-positive bacteria accounted for 44.44%.The infection group showed significantly higher serum levels of SDF-1 and MIP-1α(P＜0.05).As the infection wors-ened,SDF-1 and MIP-1α levels progressively increased(P＜0.05).The severity of biliary tract infection was sig-nificantly positively correlated with both serum SDF-1 and MIP-1α levels(P＜0.05).For predicting biliary tract in-fection,SDF-1 and MIP-1α exhibited AUC values of 0.761 and 0.825,sensitivities of 63.33%and 66.67%,and specificities of 83.33%and 83.33%,respectively.When combined,the predictive AUC reached 0.977,with a sensitivity of 83.33%and a specificity of 98.33%.Conclusions Serum level of SDF-1 and MIP-1α are significant-ly elevated in patients with common bile duct stones and biliary tract infections after ERCP stone removal surgery,showing a positive correlation with the severity of the infection.The combination of these two biomarkers demon-strates excellent predictive efficacy for postoperative infection.

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.

Objective:To investigate the clinical efficacy of stamp skin grafting combined with vacuum sealing drainage in the treatment of diabetic foot ulcers.Methods:A prospective study was conducted involving 80 patients with diabetic foot ulcers admitted to Lishui Central Hospital from January 2020 to December 2022. The patients were divided into an observation group and a control group, with 40 patients in each group, using a random number table method. The control group received treatment with vacuum-sealing drainage technology, while the observation group was treated with stamp skin grafting combined with vacuum sealing drainage. The two groups were compared based on several perioperative indicators, including wound healing time, length of hospital stay, number of dressing changes, and progress of granulation tissue growth. Pain levels were assessed using the Visual Analog Scale. Additionally, dorsalis pedis blood flow dynamics were evaluated, focusing on the diameter of the dorsalis pedis artery and arterial blood flow velocity. Foot function was assessed using the Maryland Foot Function Scale. The occurrence of postoperative complications was recorded.Results:The wound healing time and length of hospital stay in the observation group were (21.54 ± 5.32) days and (27.08 ± 5.97) days, respectively, which were significantly shorter than those in the control group [(26.69 ± 5.66) days, (31.49 ± 6.80) days, t = 4.19, 3.08, both P < 0.05]. The number of dressing changes in the observation group was (5.11 ± 1.14), which was significantly fewer than that in the control group [(8.07 ± 1.59), t = 9.56, P < 0.001]. The progress of granulation tissue growth in the observation group [(3.12 ± 0.64) mm] was faster that in the control group [(2.09 ± 0.48) mm, t = 8.14, P < 0.001]. At 1, 2, and 3 months post-surgery, the Visual Analog Scale scores for the observation group were (3.52 ± 0.65), (2.33 ± 0.42), and (1.40 ± 0.26), respectively, which were significantly lower than those in the control group [(3.96 ± 0.71), (2.74 ± 0.44), (1.78 ± 0.34), t = 2.89, 4.26, 5.615, all P < 0.05). At 3 months post-surgery, the diameter of the dorsalis pedis artery and arterial blood flow velocity in the observation group were (2.64 ± 0.44) mm and (36.42 ± 6.28) cm/s, respectively, which were greater than those in control group [(2.18 ± 0.41) mm, (30.97 ± 5.33) cm/s, t = 4.83, 4.18, both P < 0.001]. At 3 months post-surgery, the scores for pain, foot function, appearance, and range of motion in the observation group were (39.28 ± 6.70), (48.10 ± 7.22), (7.94 ± 1.54), and (12.15 ± 2.35), respectively, which were significantly higher than those in the control group [(33.46 ± 6.89), (43.08 ± 6.68), (5.38 ± 1.06), and (10.69 ± 2.16), t = 3.83, 3.22, 8.66, 2.89, all P < 0.05]. There was no statistically significant difference in the overall incidence of postoperative complications, including skin flap necrosis/dislocation, hematoma accumulation, infection, and ulcer recurrence, between the two groups ( P > 0.05). Conclusions:Stamp skin grafting combined with vacuum sealing drainage can significantly accelerate wound healing in patients with diabetic foot ulcers, reduce postoperative pain, improve dorsalis pedis blood flow dynamics, enhance foot function, and demonstrate good safety.

Objective:To optimize the image quality of PET/CT following 90Y-selective internal radiation therapy ( 90Y-SIRT) using block-sequential regularized expectation maximization (BSREM) reconstruction algorithm, and to evaluate its impact of different β values on image quality and quantitative analysis. Methods:A retrospective study was conducted on 8 male patients with hepatic tumors (age: 62(52, 71) years) treated at Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine Tsinghua University, between June 2024 and January 2025. All patients were treated with 90Y resin microspheres (2.6(0.9, 3.6)GBq) and underwent post-treatment 90Y PET/CT liver imaging. Imaging data were reconstructed using BSREM with different noise penalty weighting factors ( β values: 0, 300, 1000, 1500, 2500, 3500, 4000, 6000, 8000, 10000). Visual assessment was independently performed by two nuclear medicine physicians, using a 4-point scale (1=worst, 4=best). The mean score was considered as the final score. The consistency of the 2 reviewers was calculated and analyzed by Kappa test. Visual scores of different β value groups were compared by Friedman test. The β value demonstrating highest mean score and optimal consistency was selected as the optimal. Quantitative analysis was performed using MIM software to calculate the maximum absorbed dose ( Dmax) and the mean absorbed dose ( Dmean) for tumor, normal liver, and whole liver regions, and the CV was used to evaluate the impact of β values. Results:The visual assessment consistency of reviewers in 3 β value groups (0, 3500, 6000) were the highest (7/8) (all kappa=0.88, all P<0.05). Visual scores of the 10 β value groups were significantly different ( χ2=28.74, P<0.001), and the visual scores of 2 β value groups (3500, 4000) were the highest, both of which were 4.0(4.0, 4.0). Overall, visual assessment identified β=3500 as the optimal. Quantitative analysis revealed that, (1) Dmax in all regions (tumor, normal liver, whole liver) decreased with the increasing β values, stabilizing when β>1000 ( CV 56%-67%); (2) Dmean remained stable across different β values ( CV 0.04%-5.00%). Conclusions:In BSREM reconstruction, β=3500 is the optimal parameter for improving 90Y-PET image quality. β values significantly affect Dmax (stabilizing at β > 1000), but have no significant impact on Dmean, suggesting that reconstruction parameters primarily influence dose distribution morphology rather than average dose assessments.

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 evaluate the clinical efficacy of intervertebral disc radiofrequency(RF)ablation combined with dorsal medial branch(DMB)neurotomy in elderly patients suffering from chronic low back pain.Methods:A retrospective analysis was conducted on patients aged 60 years and older with chronic low back pain admitted to Beijing Hospital from March 2023 to September 2024.The combined treatment group underwent intervertebral disc radiofrequency ablation combined with radiofrequency treatment of the dorsal medial branch of the spinal nerve.The single treatment group underwent intervertebral disc radiofrequency ablation alone.Pain visual analogue scale(VAS)scores were assessed before treatment and on the first day, 3 months, and 6 months post-treatment.The Oswestry Disability Index(ODI)and Barthel Index were evaluated before treatment and at 3 months and 6 months post-treatment.Clinical efficacy was compared between the two groups.Results:A total of 115 elderly patients with chronic low back pain were enrolled, aged 61 to 72 years(mean 66.5 ± 5.6 years), with 44 males.The combined therapy group consisted of 71 patients, and the monotherapy group consisted of 44 patients.All patients were followed up continuously for 6 months.At all-time points post-treatment, the VAS scores in the combined therapy group were significantly lower than those in the monotherapy group( t=-4.887, -10.095, -7.687, all P<0.05); at 3 and 6 months post-treatment, the combined therapy group showed significantly greater improvements in ODI( t=-3.645, -9.451, both P<0.001)Barthel Index improvement were significantly greater than those in the monotherapy group( t=6.578, 8.530, both P<0.001); the overall good-to-excellent rate in the combined therapy group was 88.7%, higher than the 72.7% in the monotherapy group( χ2=4.85, P<0.05). Conclusions:Combined disc RF ablation and DMB neurotomy provide superior pain relief, functional recovery, and improvement in daily activities compared to single disc ablation in elderly patients with CLBP.This minimally invasive approach represents a safe and effective therapeutic strategy for managing chronic low back pain in the geriatric population.