BACKGROUND:Irisin,a myokine isolated from the transmembrane protein FNDC5 by muscle cells during exercise,has the function of inducing the browning of white adipose tissue,but its effect on lipotoxicity-induced osteogenic differentiation and the mechanism is unclear. OBJECTIVE:To investigate the effect of irisin on the osteogenic ability of palmitic acid-induced bone marrow mesenchymal stem cells and the mechanism of action. METHODS:CCK-8 assay was used to detect the effect of different concentrations of palmitic acid on the proliferation of mouse bone marrow mesenchymal stem cells and the effect of irisin on the proliferation of mouse bone marrow mesenchymal stem cells in the presence of palmitic acid.After pretreatment with irisin and palmitic acid for 24 hours,osteogenic differentiation of mouse bone marrow mesenchymal stem cells was induced by alkaline phosphatase staining as well as qRT-PCR was performed to detect the expression of osteogenesis-related genes on day 7 of osteogenic induction culture.The expression of proteins related to the AMPK/BMP2/SMAD signaling pathway was detected by western blot assay.Alizarin red staining was conducted on day 21 to detect osteogenic differences. RESULTS AND CONCLUSION:(1)The CCK-8 assay results suggested that the amplification of bone marrow mesenchymal stem cells was inversely proportional to the concentration of palmitic acid,but at 0.02 mmol/L concentration,palmitic acid had no significant effect on the amplification of bone marrow mesenchymal stem cells,and irisin did not affect the proliferation of bone marrow mesenchymal stem cells when its mass concentration was in the range of 0.1-20 μg/L.(2)Alkaline phosphatase staining and alizarin red staining showed that palmitic acid inhibited the osteogenic differentiation ability of bone marrow mesenchymal stem cells.Irisin improved palmitic acid-induced osteogenic inhibition of bone marrow mesenchymal stem cells.qRT-PCR results showed that palmitic acid could cause the downregulation of osteogenic-related genes,and irisin could inhibit this trend.(3)Western blot assay results showed that compared with the palmitic acid intervention group,irisin treatment enhanced AMPK/BMP2/SMAD signal transduction in bone marrow mesenchymal stem cells.It is found that irisin can improve the osteogenic differentiation ability of bone marrow mesenchymal stem cells pretreated with palmitic acid,and proposed that the specific mechanism might be mediated by AMPK/BMP/SMAD signaling pathway.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective Evaluate the performance of the encephalon state index(ESI)in depth of anesthesia monitoring during clinical surgery,compared with the bispectral index(BIS).Methods ESI and BIS data were collected from 60 patients in a single-center clinical trial to compare their efficacy in measuring the depth of anesthesia.Results Consistency analysis revealed mean differences and standard deviations of-0.18±5.42 and-0.11±6.51 between ESI and BIS for awake and anesthetized states,respectively.Correlation analysis showed a correlation coefficient of 0.92 throughout the operative period.Prediction probability analysis indicated that both ESI and BIS had prediction probabilities of 0.97,effectively predicting anesthesia status.Conclusion ESI and BIS show good equivalence in monitoring depth of anesthesia during clinical surgery,which meet the requirements of clinical anesthesia.

Replantation of traumatic amputation in children has its own characteristics. This consensus primarily focuses on the issues related to the treatment of traumatically amputated limb injuries in children. Organised along a timeline, the consensus summarises domestic and international clinical experiences in emergency care and injury assessment of traumatic limb amputation limbs, indications and contraindications for replantation surgery, principles and procedures of replantation surgery, postoperative medication and management, as well as rehabilitation in children. The aim of this consensus is to propose standardise the treatment protocols for limb replantation for children therefore to serve as a reference for clinical practitioners in medical practices, and further improve the treatment and care for the traumatic limb amputations in children.

Purpose: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). Materials and Methods: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. Results: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). Conclusion GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Objective:To explore the effect of Xingnao Kaiqiao acupuncture treatment on brain network reorganization for the patients with stroke recovery, and therefore understand the neural mechanism underlying Xingnao Kaiqiao acupuncture treatment.Methods:Prospective case series study. Thirteen acute ischemia stroke patients were recruited from the Department of Neurology, Shanghai Minhang Hospital of Integrated Traditional Chinese and Western Medicine from Aug 2018 to Oct 2019. They were treated with Xingnao Kaiqiao acupuncture once a day for 10 consecutive days in addition to routine treatments, and received clinical assessments before treatment and 14 days after treatment onset. EEG signals were recorded during the first acupuncture treatment, from before inserting the needles (the baseline), during needle retention, to after removal of the needles. The brain network was constructed using phase locking index, and its clustering coefficient (CC), characteristic path length (PL) and small-worldness (S) were analyzed using one-way repeated ANOVA.Results:Compared with the baseline, the CC of delta-band network (sparsity=0.10: t=3.306, P=0.006; 0.12: t=2.909, P=0.013; 0.14: t=2.331, P=0.038) and the PL of delta-band (sparsity=0.12: t=3.236, P=0.007; 0.14: t=2.754, P=0.017, 0.18: t=2.878, P=0.014) and alpha-band (sparsity=0.10: t=2.432, P=0.032) networks were significantly decreased during the needle retention stage. Clinical assessments demonstrated a significant treatment efficacy of Xingnao Kaiqiao acupuncture, and its efficacy which was indicated by improved NIHSS score, was significantly correlated with the CC changes in the delta band network from baseline to needle retention. The correlation was strongest when the network sparsity was 0.12 ( r=0.78, P=0.002). Conclusion:Xingnao Kaiqiao acupuncture can regulate the brain network of stroke patients in real time, and this immediate regulation maybe associated with its treatment effect.

Objective:To investigate the application value of the Nottingham Hip Fracture Score (NHFS) in China and establish a formula specifically designed to assess the risk for 30-day mortality after surgery for hip fracture patients in China.Methods:A retrospective study was conducted to analyze the clinical data of 824 hip fracture patients who had been treated at Department of Orthopaedics, The First Hospital Affiliated to Zhengzhou University from August 2019 to May 2022. There were 312 males and 512 females with a median age of 73 (63, 82) years. The clinical data were compared between patients with different survival outcomes. The 30-day mortality was calculated by the formula according to the patients' NHFS, and compared with the actual one to validate the effectiveness of the original prediction model. The patients were divided into a training group ( n=577) and a validation group ( n=247). Binary logistic regression analysis was performed to establish a new prediction model for the patients in the training group. The discrimination, calibration, and clinical effectiveness of the predictive model were assessed in both the training and validation groups. Results:Multivariate logistic regression analysis showed that advanced age (≥86 years old) ( OR=3.775, 95% CI: 1.099 to 12.972, P=0.035), male ( OR=3.151, 95% CI: 1.574 to 6.306, P=0.001), admission hemoglobin concentration ≤100 g/L ( OR=2.402, 95% CI: 1.189 to 4.850, P=0.015), dependence on others for care before admission ( OR=2.673, 95% CI: 1.298 to 5.505, P=0.008), and comorbidities ≥2 ( OR=4.988, 95% CI: 1.874 to 13.274, P=0.001) were identified as risk factors for postoperative 30-day mortality (all P<0.05). In validation of the original prediction model, the C-index was found to be 0.764, indicating good discrimination. However, there was a significant discrepancy between the mortality forecast by the original prediction model and the actual mortality ( P<0.05), indicating poor calibration. After the prediction model was recalibrated, 30-day mortality (%) = 100/[1 + e (5.818-NHFS×0.599)]. After the new prediction model was validated in both the training and validation groups, the C-indexes were 0.762 and 0.780, indicating a good level of discrimination. The predicted 30-day mortality by the prediction model was closely aligned with the actual mortality ( P>0.05), demonstrating good calibration. When the threshold probabilities of the training and the validation groups were 0 to 26% and 0 to 35%, respectively, the patients might benefit from clinical intervention, showing clinical effectiveness of the model. Conclusions:The NHFS can predict the risk for 30-day mortality after hip fracture surgery. The new NHFS prediction model after calibration has a good predictive value for 30-day mortality after hip fracture surgery in Chinese population.