Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Stroke is an important challenge for the healthy survival of humans and is characterized by high disability， mortality， and recurrence rates， which brings huge burden to family and society and affects social development. Due to the rapid progression of stroke， the monitoring and treatment of this disease has become an important part of medical research. Thromboelastography （TEG） is a rapid coagulation detection method， and as a newly developed platform for coagulation function detection， it can fully reflect abnormalities in the activity of coagulation factors and the coagulation-related factors such as platelet and fibrinogen function， which is convenient for clinicians to conduct disease monitoring， treatment evaluation， and prognosis prediction. This article reviews the basic concepts， main parameters， and clinical significance of TEG and its application in the diagnosis， treatment， and prognosis of stroke.
Stroke

Objective:To determine the predictive value of serum neurofilament light chain (NfL) on neurologic function in out-of-hospital cardiac arrest (OHCA) patients.Methods:The clinical data of 96 OHCA patients admitted to Cangzhou Central Hospital from January 2018 to March 2022 were retrospectively analyzed. According to the Glasgow-Pittsburgh cerebral performance category (CPC) upon hospital discharge, the patients were divided into the favorable neurologic function (grade 1-2) and poor neurologic function (grade 3-5) groups. The difference of serum NfL was compared between the two groups, and the relationship between serum NfL and neurologic function was assessed using correlation analysis and logistic regression analysis. The area under the curve (AUC), sensitivity, and specificity of serum Nfl were calculated by receiver operating characteristic (ROC) curve. Hanley & McNeil method test was used to compare the difference of AUCs between serum NfL and neuron specific enolase (NSE).Results:Twenty-six percent (25/96) patients were discharged with favorable neurologic function. Serum NfL in the favorable neurological function group was significantly lower than that in the poor neurologic function group (47.6 pg/mL vs. 261.4 pg/mL, P<0.001). Correlation analysis showed that serum NfL was positively correlated with neurologic function ( r=0.69, P<0.001). Logistic regression analysis showed that serum NfL was independently associated with neurological function ( OR=0.92, 95% CI: 0.86-0.98; P=0.010). ROC curve indicated that the AUC of serum NfL in predicting poor neurologic function was 0.95 (95% CI: 0.92-0.99), with a sensitivity of 84.5% and a specificity of 100% at the cutoff value of 80.0 pg/mL. The AUC of serum NSE in predicting poor neurologic function was 0.79 (95% CI: 0.69-0.89), with a sensitivity of 67.6% and a specificity of 80.0% at the cutoff value of 45.1 ng/mL. A pairwise comparison using Hanley & McNeil method showed that the AUC of serum NfL in predicting poor neurologic function was higher than that of NSE ( Z=3.22, P=0.001). Conclusions:Serum NfL is helpful for clinician to predict neurologic function in OHCA patients.

ObjectiveTo observe the clinical efficacy and safety of traditional Chinese medicine （TCM） external therapeutic protocol of enriching pus for tissue growth （EPTG） in the treatment of Wagner 2-3 diabetic foot ulcer. MethodThe randomized controlled trial （RCT） design was adopted. Patients receiving basic treatment were divided into the EPTG group and the control group （debridement and change of nano-silver medical antibacterial dressing）. Ulcer healing rate， ulcer area， ulcer depth， TCM symptom score， visual analogue scale（VAS）， transcutaneous partial pressure of oxygen， wound blood flow， inflammatory factors ［C-reactive protein （CRP）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）］， growth factors ［vascular endothelial growth factor （VEGF）， transforming growth factor-β₁ （TGF-β₁）， and fibroblast growth factor-β （FGF-β）］， adverse events， and outcome events of the two groups before and after treatment were observed. ResultCompared with the conditions before treatment， the ulcer healing rate， ulcer area， ulcer depth， TCM symptom score， VAS score， transcutaneous partial pressure of oxygen， wound blood flow， CRP， IL-6， TNF-α， VEGF， TGF-β₁， and FGF-β were significantly improved （P<0.01）. In terms of the improvement in the ulcer healing rate， ulcer area， ulcer depth， VAS score， transcutaneous partial pressure of oxygen， wound blood flow， CRP， IL-6， TNF-α， VEGF， TGF-β₁， and FGF-β， the EPTG group was superior to the control group （P<0.01）. There were no statistically significant differences in adverse events and outcome events between the two groups. ConclusionThe TCM external therapeutic protocol of EPTG is safe and effective in the treatment of Wagner 2-3 diabetic foot ulcer. It can greatly reduce the area and depth of diabetic foot ulcer， improve the ulcer healing rate and TCM symptom score， relieve the pain of patients， and improve the microcirculatory blood supply in the local ulcer. Its mechanism of action may be related to the reduction of the local inflammatory response of the wound and the improvement of the proliferation of fibroblasts and vascular endothelial cells.

Objective:To investigate the sensitivity of the Catalyst HD in monitoring different skin colors, and assess the effect of skin color on the setup uncertainties using this system in radiotherapy.Methods:The standard cards guiding skin color and the cylinder model guiding quality control in radiotherapy were utilized to simulate the patients’ positioning. During the first monitoring, Catalyst HD was employed to acquire the image of the phantom as the reference image after conventional positioning (indoor laser+ phantom marking). When it was not the first monitoring, the couch was moved (-5 to 5 mm, step length of 2 mm) and Catalyst HD was adopted to obtain the surface image after conventional positioning. The bed deviation and corresponding setup errors monitored by Catalyst HD for different skin colors were recorded in the anterior-posterior (AP), superior-inferior (SI) and left-right (LR) direction, respectively.Results:During Catalyst HD monitoring, the integration time and gain were increased with the darker color. The logarithm of integration time and gain was significantly linearly negatively correlated with the same color ( R2>0.9). When the color difference with 1Y01SP was ΔE≤189, there was a significant correlation between the bed deviation and corresponding setup errors monitored by Catalyst HD in the SI and LR directions (R SI>0.5, R LR>0.5, R AP>0.9). The Catalyst HD monitoring was rapid and stable. When 218≤ΔE≤253, the correlation coefficients of them in the LR were R LR<0.3 and the Catalyst HD monitoring was stable. When 254≤ΔE≤285, the Catalyst HD failed to monitor stably. When ΔE>318, it failed to monitor this skin color. Conclusions:Gain, integration time and color have a certain correlation. The Catalyst HD can accurately monitor the setup errors within a specific range of skin color.

Objective:To report our experience in treatment of patients with orthopaedic trauma during COVID-19 epidemic.Methods:We retrospectively analyzed the 67 patients with orthopedic trauma who had been treated at Department of Orthopaedics, Peking Union Medical College Hospital from February 1 to March 31, 2020. After screening for COVID-19 infection was performed under strict protection, the patients were diagnosed and assigned to outpatient emergency treatment or hospitalization according to their specific condition. Twenty-six patients were treated at the outpatient emergency department. They were 8 males and 18 females with an average age of 69.5 years. Of them, 6 with vertebral compression fracture were placed on bed brakes, 14 with limb fracture immobilized after close reduction, 2 with skin laceration treated with debridement and suture, and 4 with hip fracture immobilized in bed. In the 41 hospitalized patients, there were 14 males and 27 females with an average age of 68.5 years. In them, hemiarthroplasty was performed for 7 femoral neck fractures, kyphoplasty for 5 vertebral compression fractures, total elbow arthroplasty for one humeral intercondylar fracture, exploration and suture for one case of Achilles tendon rupture, and internal fixation surgery for the remaining 27 cases.Results:Most of the patients had osteoporotic fractures which accounted for 61.5% (16/26) of the outpatients and 68.3% (28/41) of the inpatients, respectively. The duration from injury to surgery averaged 2.3 days and the length of hospitalization 4.5 days for the 41 hospitalized patients, decreased compared with the corresponding data (3.1 days and 11.5 days) for the similar inpatients in the same period last year. In the 41 inpatients, fever was observed upon hospitalization in 4 cases and after operation in 26 cases, and related to their primary injury or surgical trauma in all. Acute pulmonary embolism happened during operation in one patient with femoral shaft fracture.Conclusions:The prevention and control of COVID-19 should be continued. The awareness and behavior of health care providers are expected to be enhanced by strict screening protocol, protection and supervision. The proportion of elderly patients with osteoporotic fracture increased during the COVID-19 pandemic. Shortage of blood was the major problem affecting the treatment. Timely surgical treatment should be indicated for the patients with orthopedic trauma, especially those with lower extremity fracture.