Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Objective To analyze the single nucleotide polymorphism (SNP) and copy number variation (CNV) of cardiac myxoma to find the SNP sites and CNV events that may play important roles in the occurrence of tumors. Methods The patients with myxoma admitted to our hospital from 2015 to 2019 were randomly selected. The SNP analysis and the CNV test in gene level were performed through whole exome sequencing (WES). The samples were divided into two groups according to the mean size of the tumor: a diameter≤5.7 cm group and a diameter>5.7 cm group. The analysis results were compared between the two groups. Results A total of 14 patients were enrolled, including 8 females and 6 males with a mean age of 61.4 (41-79) years. Thirty-seven cancer-genes with SNP were detected, among which 18 mutated sites had a mutation rate of>10%; and TP53, EP300 and CREBBP played a core binding role in protein-protein interaction-network. The GO enrichment results showed significant differences in the regulation of cell secretion of the mutated genes, and the KEGG enrichment results showed significant differences in the PI3K-AKT and JAK-STAT signaling pathways in the occurrence of myxoma. In addition, 17 new mutation sites of tumor genes with high mutation effect were found in SNP detection. The WES results of 14 samples showed that the CNV events were detected in 120 tumor genes of the samples, 10 of which were included in two tumor databases. The GO enrichment results showed significant differences in the tube development and regulation of cell proliferation, and the KEGG enrichment results showed significant differences in the comprehensive tumor signaling pathway. Statistical differences of ERCC6L and INTS6L in CNV test were found (P=0.030). Conclusion There may be multiple tumor gene site mutations in the process of tumor generation, among which there are multiple core tumor genes such as TP53, EP300 and CREBBP, regulating tumor cells through PI3K-AKT and JAK-STAT signaling pathways and playing an important role in tumor generation. The CNV of ERCC6L and INTS6L genes may be related to tumor growth.

Objective To observe the safety and efficacy of levosimendan in the perioperative pe-riod for patients with pulmonary hypertension associated with valvular heart disease undergoing heart valve replacement surgery.Methods A total of 90 patients with pulmonary hypertension associated with valvular heart disease who underwent valve replacement surgery from April 2023 to May 2024 were enrolled.Based on the use of levosimendan,patients were divided into low-dose group,high-dose group,and control group,with 30 patients in each group.The control group received conventional drug therapy;the low-dose group received one dose of levosimendan from 3 days before surgery to 3 days after surgery combined with conventional drug therapy;the high-dose group received two doses of levosimendan from 3 days before surgery to 3 days after surgery combined with conventional drug therapy.Data on brain natriuretic peptide(BNP),left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),creatinine(Cr),mean pulmonary artery pressure(mPAP),PH related to left heart disease(PH-LHD)status,postoperative ICU stay,postoperative hospital stay,and cardiac function classification were collected and recorded at admission and before discharge.Results There were no statistically significant differences in gender,age,and body mass among the control group,low-dose group,and high-dose group(P＞0.05).There was no sta-tistically significant difference in the increase in Cr among the three groups(P＞0.05).There were statistically significant differences in postoperative ICU stay between the control group and the high-dose group,and between the control group and the low-dose group(P=0.017,0.028).However,there was no statistically significant difference in postoperative ICU stay between the low-dose group and the high-dose group(P=0.839).There were statistically significant differences in postopera-tive hospital stay between the control group and the high-dose group,and between the control group and the low-dose group(P=0.001,0.009),but no statistically significant difference was found between the low-dose group and the high-dose group(P=0.463).No serious complications oc-curred in any of three groups,and no patients withdrew from the study.Only one patient in the high-dose group experienced hypotension during the postoperative use of levosimendan,which nor-malized after fluid replacement.There was no statistically significant difference in the decrease in mPAP among the three groups(P＞0.05).There was a statistically significant difference in the de-crease in BNP between the control group and the high-dose group(P=0.025);however,there were no statistically significant differences in the decrease in BNP between the control group and the low-dose group,or between the low-dose group and the high-dose group(P=0.068,0.970).There was a statistically significant difference in the increase in LVEF between the control group and the high-dose group(P=0.019);however,there were no statistically significant differences in the increase in LVEF between the control group and the low-dose group,or between the low-dose group and the high-dose group(P=0.055,0.652).There were statistically significant differences in the decrease in LVEDD between the control group and the low-dose group,and between the control group and the high-dose group(P=0.019,0.033);however,there was no statistically significant difference between the low-dose group and the high-dose group(P=0.829).In the control group,18 patients(60.0％)had clinically effective treatment,22 patients(73.3％)in the low-dose group,and 24 patients(80.0％)in the high-dose group.There was no statistically significant differ-ence in clinical efficacy among the three groups(P=0.220).Conclusion Levosimendan is safe and effective in the perioperative period for patients with pulmonary hypertension associated with valvular heart disease,and high-dose use can more significantly improve LVEF and reduce BNP levels.

Objective:To analyze the disease characteristics, diagnosis and treatment methods of venous pulsatile tinnitus treated by intervention of sigmoid sinus.Methods:Fifty patients (from Shandong Provincial ENT Hospital, Shandong University between February 2014 and July 2020) with venous pulsatile tinnitus treated by sigmoid sinus surgery were analyzed retrospectively. The tinnitus characteristics, imaging findings, surgical methods, intraoperative findings and postoperative tinnitus changes were recorded. The patients were followed up for 6-12 months. The sign rank sum test was used to analyze the difference in tinnitus grading before and after surgery. There were 50 patients with unilateral venous pulsatile tinnitus, including 49 females and 1 male. The age ranged from 17 to 67 years, with a median age of 44 years. There were 45 cases of right tinnitus and 5 cases of left tinnitus. The degree of tinnitus before operation was grade Ⅱ or above, including 4 cases of gradeⅡ, 11 cases of grade Ⅲ, 22 cases of grade Ⅳ and 13 cases of grade Ⅴ.Results:Thirty-seven cases were cured, 8 cases were ineffective (no change in tinnitus), 3 cases were markedly effective (tinnitus grade decreased by 3 in 2 cases, 4 in 1 case), and 2 cases were effective (tinnitus grade decreased by 1). The difference of tinnitus grade before and after operation was statistically significant ( Z=-5.70, P<0.05). Temporal bone CT showed 36 cases of sigmoid diverticulum (including 17 cases with sigmoid sinus dehiscence), 12 cases of sigmoid sinus dehiscence and 2 cases of absence of the temporal bone cortex abutting to sigmoid sinus. Thirty-five cases were performed with closure of sigmoid sinus diverticulum, 4 cases were performed with resurfacing of the sigmoid plate, 5 cases were performed with narrowing of sigmoid sinus, 4 cases were performed with simple opening of pre sigmoid mastoid air chamber, 1 case of opening was performed with pre sigmoid mastoid air chamber combined with narrowing of sigmoid sinus, and 1 case was performed with opening of pre sigmoid mastoid air chamber combined with closure of sigmoid sinus diverticulum. Conclusions:Venous pulsatile tinnitus is common in women. The common causes may be sigmoid sinus wall abnormalities such as sigmoid sinus diverticulum and perisigmoid bone defect. Imaging examinations are helpful for diagnosis. Venous pulsatile tinnitus can be treated with surgery.

BACKGROUND:Nowadays,posterior cruciate ligament injury caused by a sports injury or vehicle injury is more common than people think.Posterior cruciate ligament reconstruction is one of the main treatment methods,but there are still a lot of controversies about the surgical method and ligament selection of posterior cruciate ligament reconstruction. OBJECTIVE:To comprehensively analyze the global application trend of posterior cruciate ligament reconstruction and identify promising research hotspots of posterior cruciate ligament reconstruction based on bibliometrics and visual analysis. METHODS:Publications(articles and reviews)related to posterior cruciate ligament reconstruction from 2000 to 2022 were retrieved from the Web of Science(WOS).The country,institution,publication year,author,journal,average citations per item,H index,title,keywords of publication,and the top 25 cited articles were extracted and analyzed in detail.The VOSviewer/citespace/Pajek software was used to analyze the co-occurrence result of keywords to predict the hotspots of posterior cruciate ligament reconstruction. RESULTS AND CONCLUSION:A total of 664 articles were included.(1)In the past 22 years,the number of posterior cruciate ligament reconstruction articles has shown an increasing trend in general.The top 3 countries(the USA,China,and South Korea)accounted for 65.51%of all articles published.The USA has the largest number of publications.The University of Pittsburgh is the largest contributor.Knee Surgery Sports Traumatol Arthrosc and American Journal of Sports Medicine are the most influential journals.Laprade,Robert F.is the professor who has published the most articles in the field of posterior cruciate ligament reconstruction,and Fanelli,GC is the professor who has the highest total chain strength in the field of posterior cruciate ligament reconstruction.(2)The research direction can be divided into the following five clusters:"posterior cruciate ligament anatomical and biomechanical studies","posterior cruciate ligament reconstruction prognosis,outcome,and complications","posterior cruciate ligament reconstruction surgical method and tendon selection","surgical technique",and"posterior cruciate ligament tear combined with multiple ligament injury".(3)It is concluded that in terms of the trend of previous years,an increasing number of articles related to posterior cruciate ligament reconstruction will be published in the future.The USA is a world leader in the field of posterior cruciate ligament reconstruction.China and South Korea presented great potential in this area.Anatomical and biomechanical research of posterior cruciate ligament and posterior cruciate ligament reconstruction methods and the selection of tendons may be the future hotspots in the field of posterior cruciate ligament reconstruction.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

Objective:To construct a primary nanobody library for human papillomavirus 16(HPV16)L1 protein and obtain a nanobody specific to HPV16 L1 through selection and identification.Methods:HPV16 L1 protein was used as antigen to immunize alpaca,and a primary antibody library was constructed using phage display technology.After three rounds of screening,positive clones were identified by ELISA.The VHH sequence of the strongest positive clone was used for eukaryotic expression.The target nanobody was obtained after affinity purification,gel filtration chromatography,SDS PAGE and WB identification.The affinity between the nanobody and HPV16 L1 protein was evaluated using surface plasmon resonance(SPR)technology.The cytotoxicity of the nanobody was detected using CCK-8 assay.The neutralizing activity of nanobody against HPV16 pseudovirus was detected using a luciferase reporter gene assay.Results:The primary library was constructed with a capacity of 1.304×1010 and an abundance of 6.5×109 clones/mL.ELISA identified 36 positive clones.Protein monomer and dimers were expressed and purified,and the target nanobody(designated as"Nb")was successfully identified.The binding affinity of Nb to HPV16 L1 protein was 35.41 nmol/L.There was no significant difference in HaCat cell proliferation activity between Nb group and blank group(P>0.05).Compared to the negative group,both 0.1 and 1 μmol/L Nb inhibited pseudovirus infection in 293FT cells(all P<0.01).Conclusion:This study successfully obtained a nanobody with high purity and strong affinity that exhibited no cytotoxicity to epithelial cells and effectively inhibited HPV16 pseudovirus infection in 293FT cells.The nanobody provides a promising candidate antibody-based drug for the prevention and treatment of HPV 16 infection.

Objective:To evaluate a wound diagnosis and treatment mode with integrated medical care in the repair of chronic infectious wounds plus bone exposure at lower extremities.Methods:A retrospective analysis was conducted of the 64 patients with chronic infectious wound plus bone exposure at the lower 1/3 of the leg who had been admitted to Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University from January 2019 to December 2021. The patients were divided into 2 groups according to the wound diagnosis and treatment mode. In the observation group of 31 patients subjected to the wound diagnosis and treatment mode with integrated medical care led by specialist nurses, there were 24 males and 7 females with an age of (53.6±12.4) years, the wound was located at the tibial side in 15 cases and at the fibular side in 16 cases, the wound areas averaged [28.27 (23.56, 37.70) cm 2], and the time from injury to treatment was (27.3±4.1) d. Evaluation of the patient's condition, wound diagnosis and formulation of treatment protocols were performed jointly by a doctor-nurse team after the patients were admitted, and continuous diagnosis and treatment of the wounds were carried out mainly by specialist nurses during the doctors' follow-up. In the control group of 33 patients subjected to the conventional wound diagnosis and treatment mode led by doctors, there were 25 males and 8 females with an age of (51.3±14.3) years, the wound was located at the tibial side in 17 cases and at the fibular side in 16 cases, the wound areas averaged [27.49 (17.84, 40.45) cm 2], and the time from injury to treatment was (27.6±4.0) d. The 2 groups were compared in the wound healing rate, wound recurrence rate, hospitalization time and patients' satisfaction. Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The observation group achieved a significantly higher wound healing rate within 1 month after treatment [83.87% (26/31)] than the control group [60.61% (20/33)], a significantly lower wound recurrence rate within 6 months after treatment [0% (0/31)] than the control group [18.18% (6/33)], significantly shorter hospitalization time [18.0 (15.1, 20.9) d] than the control group [26.8 (18.4, 40.1) d], and significantly higher patients' satisfaction [50 (50, 50) points] than the control group [50 (42, 50) points] (all P<0.05). Conclusion:In the repair of chronic infectious wounds plus bone exposure at lower extremities, the wound diagnosis and treatment mode with integrated medical care led by specialist nurses may result in a higher wound healing rate, a lower wound recurrence rate, a shorter hospital stay and higher patients' satisfaction than the conventional wound diagnosis and treatment mode led by doctors.