Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective To investigate the diagnostic value of serum soluble growth stimulation expressed gene 2(sST2),decoy receptor 3(DcR3)and dynamic electrocardiogram(DCG)for asymptomatic myocardial ischemia(SMI).Methods Eighty-five patients with coronary heart disease were selected as observation subjects(the observation group).Sixty-one SMI patients were confirmed by coronary angiography(the SMI group).Among them,there were 24 cases with symptomatic myocardial ischemia(the symptomatic myocardial ischemia group).During the same period,84 patients with unexplained chest pain who were examined in our hospital and without coronary heart disease were selected as the control group.ELISA was applied to detect serum levels of sST2 and DcR3.ROC was used to analyze the diagnostic value of serum sST2,DcR3 and DCG for SMI.Multivariate Logistic regression was applied to analyze the influencing factors of SMI.Results The serum level of sST2 was higher in the observation group than that in the control group[(55.61±7.12)μg/L vs.(14.22±3.64)μg/L],while the level of DcR3 was lower than that in the control group[(0.68±0.11)μg/L vs.(1.24±0.21)μg/L](P＜0.05).The serum level of sST2 was higher in the SMI group than that in the symptomatic myocardial ischemia group[(59.28±7.12)μg/L vs.(46.28±8.15)μg/L],while the level of DcR3 was lower than that in the symptomatic myocardial ischemia group[(0.63±0.11)μg/L vs.(0.81±0.14)μg/L](P＜0.05).The heart rate of the SMI group was higher than that of the symptomatic myocardial ischemia group,and the duration of ischemia and the decrease in ST segment were lower than those of the symptomatic myocardial ischemia group(P＜0.05).ROC curve results showed that the AUC values of serum sST2,DcR3 and DCG alone and in their combination for diagnosing SMI in patients with coronary heart disease were 0.826,0.882,0.773,and 0.958,respectively,and the combined diagnosis of SMI was superior to individual diagnosis(Z=3.188,2.225,2.770,P＜0.05).sST2 and DcR3 were influencing factors of SMI occurrence(P＜0.05).Conclusion The increased serum sST2 and the decreased DcR3 are closely related to the occurrence of SMI,and the combination of serum sST2 and DcR3 with DCG has certain diagnostic value for SMI.

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

The phenomenon that the listener's reception,perception,and understanding of a sound are dis-turbed by an irrelevant sound is called the auditory masking effect.In the auditory masking effect,the human audi-tory nervous system is able to screen and extract target sounds from different sound sources based on different cues,and filter out unwanted masked sounds.The auditory masking effect is not a simple processing from separation to integration however it is,with a complex internal mechanism.Under energetic masking,acoustic information such as frequency and intensity of target and masher generates coding competition in the auditory periphery.Under infor-mational masking,target sound and masher competes with perceptive and cognitive information in the auditory cen-ter.Informational masking is the focus of masking research,but its mechanism is still controversial.This study studies the neural mechanism of informational masking effect from three factors,including similarity,uncertainty and intelligibility.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective To investigate the diagnostic value of serum soluble growth stimulation expressed gene 2(sST2),decoy receptor 3(DcR3)and dynamic electrocardiogram(DCG)for asymptomatic myocardial ischemia(SMI).Methods Eighty-five patients with coronary heart disease were selected as observation subjects(the observation group).Sixty-one SMI patients were confirmed by coronary angiography(the SMI group).Among them,there were 24 cases with symptomatic myocardial ischemia(the symptomatic myocardial ischemia group).During the same period,84 patients with unexplained chest pain who were examined in our hospital and without coronary heart disease were selected as the control group.ELISA was applied to detect serum levels of sST2 and DcR3.ROC was used to analyze the diagnostic value of serum sST2,DcR3 and DCG for SMI.Multivariate Logistic regression was applied to analyze the influencing factors of SMI.Results The serum level of sST2 was higher in the observation group than that in the control group[(55.61±7.12)μg/L vs.(14.22±3.64)μg/L],while the level of DcR3 was lower than that in the control group[(0.68±0.11)μg/L vs.(1.24±0.21)μg/L](P＜0.05).The serum level of sST2 was higher in the SMI group than that in the symptomatic myocardial ischemia group[(59.28±7.12)μg/L vs.(46.28±8.15)μg/L],while the level of DcR3 was lower than that in the symptomatic myocardial ischemia group[(0.63±0.11)μg/L vs.(0.81±0.14)μg/L](P＜0.05).The heart rate of the SMI group was higher than that of the symptomatic myocardial ischemia group,and the duration of ischemia and the decrease in ST segment were lower than those of the symptomatic myocardial ischemia group(P＜0.05).ROC curve results showed that the AUC values of serum sST2,DcR3 and DCG alone and in their combination for diagnosing SMI in patients with coronary heart disease were 0.826,0.882,0.773,and 0.958,respectively,and the combined diagnosis of SMI was superior to individual diagnosis(Z=3.188,2.225,2.770,P＜0.05).sST2 and DcR3 were influencing factors of SMI occurrence(P＜0.05).Conclusion The increased serum sST2 and the decreased DcR3 are closely related to the occurrence of SMI,and the combination of serum sST2 and DcR3 with DCG has certain diagnostic value for SMI.

The phenomenon that the listener's reception,perception,and understanding of a sound are dis-turbed by an irrelevant sound is called the auditory masking effect.In the auditory masking effect,the human audi-tory nervous system is able to screen and extract target sounds from different sound sources based on different cues,and filter out unwanted masked sounds.The auditory masking effect is not a simple processing from separation to integration however it is,with a complex internal mechanism.Under energetic masking,acoustic information such as frequency and intensity of target and masher generates coding competition in the auditory periphery.Under infor-mational masking,target sound and masher competes with perceptive and cognitive information in the auditory cen-ter.Informational masking is the focus of masking research,but its mechanism is still controversial.This study studies the neural mechanism of informational masking effect from three factors,including similarity,uncertainty and intelligibility.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective: To explore a standard procedure for the treatment of combined dorsal and palmar internal fixation for complex four part distal radius fractures and assess its clinical results. Methods: From May 2009 to October 2016, 38 patients(39 sides)who suffered from complex four part distal radius fractures were performed operatively with open reduction and internal fixation via combined dorsal and palmar approach in Department of Orthopaedic Trauma, Qilu Hospital of Shandong University(Qingdao). The series included 22 males(22 sides) and 16 females(17 sides). Age of the patients was 53.5 years ranging from 25 to 79 years.According to Melone classification, there were 34 sides of type of Ⅳ, 5 of type Ⅴ.According to Frykman classification, there were 15 sides of type Ⅶ, 24 sides of type Ⅷ, and all the cases were type C3 according to AO/OTA classification.Preoperatively, the key articular fragments in four part distal radius fractures were identified and the individual fracture patterns from conventional X-ray and CT-scan were analyzed. All the patients were performed combined volar and dorsal fixation.Firstly, a palmar approach which gave access to and fix the palmar-ulnar fragment and the radial styloid fragment was performed.Then a limited dorsal approach across the third extensor compartment which gave access to the dorso-ulnar fragment and a limited dorsal arthrotomy to visualize the radiocarpal joint when necessary were performed.Through dorsal approach, we can address the dorso-ulnar fragment, free intra-articular fragment and direct visualize the joint.Use of a retinacular flap was routinely advocated to help prevent against tendon irritation and rupture.The follow-up control included conventional X-ray, range of motion(ROM), grip strength, and the disabilities of the arm, shoulder and hand index(DASH), as well as the patient-rated wrist evaluation(PRWE) score for functional outcome at 6 and 12 months. Results: Thirty-three patients(34 sides) were followed up for at least 12 months.The would healed well in all cases 2 weeks postoperatively, and no soft tissue infections, necrosis or neurovascular complications occurred.All the fractures of 38 cases(39 sides)healed averaged 3.6 months(ranging from 2.5-5.7 months), and no loss of reduction occurred postoperatively.Anatomic reconstruction with a step or gap of <1 mm was achieved in 37 cases(38 sides), Whereas 5 patients were lost to follow-up at 12 months postoperatively.ROM and grip strength were all recovered to over 85% of the unaffected side(exception of the bilateral patient). Median DASH-index and PRWE were 6.5(0-17) and 9.3(0-20)respectively. Conclusion Combined volar and dorsal approaches allow achieving anatomic reconstruction in complex four part intra-articular distal radius fractures and reveal good functional outcomes at intermediate follow-up.