AIM: To explore whether tumor necrosis factor-α (TNF-α) induces necroptosis in murine long bone osteocyte-like cell line MLO-Y4 and the possible mechanism.METHODS: The MLO-Y4 cells were divided into control group, TNF-α group, TNF-α+necrostatin-1 (Nec-1) group, TNF-α+Z-VAD group and TNF-α+receptor-interacting protein 3 (RIP3)-siRNA group.The death rate of MLO-Y4 cells was assessed by flow cytometry with Annexin V-FITC/PI staining.The morphological features of the cells were observed under transmission electron microscope (TEM).The protein levels of RIP1, RIP3 and cleaved caspase-3 were determined by Western blot.Finally, the numbers of total cells and RIP1-RIP3-positive cells were observed under laser scanning confocal microscope.The production of reactive oxygen species (ROS) in the cells was measured by DCFH-DA staining.RESULTS: Compared with control group, the apoptotic or necroptotic rate of the cells induced by TNF-α was increased significantly (P<0.01).The increased apoptotic or necroptotic rate was dramatically reduced by treating with Nec-1, Z-VAD or RIP3-siRNA transfection (P<0.01).In TNF-α group and TNF-α+Z-VAD group, a lot of MLO-Y4 cells with typical necroptotic morphological features were observed under TEM.However, obvious necroptotic cells were not found in Nec-1 or RIP3-siRNA treatment group.The protein level of RIP1 in the cells treated with Nec-1 was sharply lower than that in TNF-α group (P<0.01).However, Z-VAD did not reduce the elevated levels of RIP1 and RIP3.RIP3-siRNA effectively down-regulated the protein level of RIP3 compared with TNF-α group (P<0.01).Nec-1 effectively down-regulated the protein levels of RIP1 colocalized with RIP3 compared with TNF-α group (P<0.01).However, Z-VAD did not reduce the levels of RIP1 colocalized with RIP3.Nec-1, Z-VAD and RIP3 siRNA significantly decreased the ROS levels (P<0.01).CONCLUSION: TNF-α induces the necroptosis of MLO-Y4 cells.RIP3 play vital roles in the cell necroptotic signal pathway.ROS may be the executor of necroptosis of MLO-Y4 cells.

Objective To compare and analyze the relationship between geometric parameters of the needle of different insulin pens and their puncture force, flow rate, and pressing force. Methods The human skin tissue model and needle model were established, and the finite element simulation analysis of needle puncture was performed. Using a test platform, 25 kinds of needles with different geometric parameters were tested for the puncture force, pushing pressure, flow rate and other parameters. The influence of geometric parameters on the performance of the needles were analyzed. Results The puncture force of the needle was closely related to its section design. Compared with the three-section needle, the five-section needle increases the secondary inclination angle and the condyle angle, increases the contact area between the needle and the tissue, and make the change of the contact angle more smoothly, which reduce the needle penetration force. The smaller the outer diameter of the needle, the smaller the penetrating power. The larger the inner diameter of the needle, the greater the fluid flow rate, the smaller the pushing pressure, and the higher the injection accuracy. Conclusions Five-section, ultra-thin-walled or ultra-thin-walled needles have more excellent performance. On the basis of ensuring the strength of the needle, the needle's geometry can be optimized to reduce the puncture force. The results of this study can provide theoretical basis and experimental basis for the design of needles for insulin pens.

Objective:To conduct theoretical analysis and experimental research on peripherally inserted venous catheters, establish theoretical models of interaction between different materials catheters and simulated skin tissues, and test different catheters at the same time to provide theoretical basis and experimental basis for the optimization design.Methods:According to the mechanical properties of the catheter at 25 ℃ and 37 ℃, a finite element model of the catheter and simulate skin tissue was established. The relationship between catheter folds and material and structure during puncture was analyzed, and the stiffness, radiographic properties, etc. were tested experimentally.Results:The performance of the catheter at different temperatures is closely related to its material. The wrinkle situation of the catheter is related to the catheter material and the inclination of the wedge surface. The elastic modulus of the polyurethane (PU) catheter is about 500 MPa and 250 MPa, respectively at room temperature (25 ℃) and body temperature (37 ℃), which meets the clinical needs of high rigidity during puncture and soft material during indwelling. When the catheter structure is the same, the PU catheter is less prone to wrinkles than the fluorinated ethylene propylene copolymer (FEP) catheter. When the catheter material is the same, the smaller the inclination of the wedge surface, the less likely the catheter to wrinkle.Conclusions:Appropriately reducing the inclination of the wedge-shaped surface of the needle of peripherally inserted venous catheters can improve the success rate of puncture. The PU catheters have good mechanical properties, they are not prone to wrinkles during puncture, and their stiffness can be reduced at body temperature, which can not only increase the success rate of puncture, but also reduce the occurrence of complications. Therefore, PU catheters have a better clinical application prospect.

OBJECTIVE：To systematically e valuate the efficacy and safety of duloxetine in the improvement of pain symptoms of knee osteoarthritis （KOA），and to provide evidence-based reference for clinical treatment of KOA. METHODS ：Retrieved from PubMed，Embase，Medline，Cochrane Library ，CNKI，VIP and Wanfang database ，during the establishment of the database to Sept. 2019，RCTs about duloxetine （trial group ）vs. placebo （control group ）in the improvement of pain symptoms of KOA were collected. After data extraction and quality evaluation using Cochrane system evaluator ’s manual 5.1.0，Meta-analysis was performed by using Stata 14.0 software for WOMAC total score ，WOMAC pain score ，WOMAC stiffness score ，WOMAC function score and BPI-S score ，as well as the incidence of adverse reaction such as dry mouth ，somnolence and nausea. RESULTS：A total of 6 RCTs were included ，involving 2 059 patients. Meta-analysis results showed that WOMAC total score [MD＝－0.34，95％CI（－0.48，－0.20），P＜0.05]，WOMAC pain score [MD ＝－0.41，95％CI（－0.54，－0.29），P＜0.05]， WOMAC stiffness score [MD ＝－0.24，95％ CI（－0.37，－0.12），P＜0.05]，WOMAC function score [MD ＝－0.43，95％CI （－0.55，－0.31），P＜0.05]，BPI-S score [MD ＝－0.38，95％CI（－0.48，－0.28），P＜0.05] of trial group were significantly lower than those of control group ；the incidence of dry mouth [RR ＝3.55，95％CI（2.00，6.29），P＜0.05]，somnolence [RR ＝3.23， 95％CI（1.88，5.54），P＜0.05] and nausea [RR ＝6.95，95％CI（2.99，16.15），P＜0.05] in trial group were significantly higher than control group ，with significant difference. CONCLUSIONS ：Duloxetine can relieve the pain and improve knee function in patients with KOA ，but it is necessary to pay attention to its adverse reactions.

OBJECTIVE To systematically evaluate the efficacy and safety of denosumab versus bisphosphonates in the treatment of osteoporosis， and to provide evidence-based reference for clinical treatment. METHODS Randomized controlled trials （RCTs） about denosumab （trial group） versus bisphosphonates （control group） in the treatment of osteoporosis were retrieved from PubMed， Embase， Medline， the Cochrane Library， Chinese Journal Fulltext Database， Chinese Science and Technology Journal Database， Wanfang database from January 2012 to December 2022. After the data extraction of included clinical studies， the quality of included studies was evaluated with Cochrane Handbook for Systematic Review 5.1.0， and meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 6 RCTs were included， involving 3 145 patients. Meta-analysis showed that the improvement rate of lumbar bone mineral density （BMD） [MD＝1.78， 95%CI（1.13， 2.43）， P＜0.000 01]， femoral neck BMD [MD＝1.26， 95%CI （1.08， 1.45）， P＜0.000 01] and total hip BMD [MD＝1.16，95%CI（0.93，1.39），P＜0.000 01] in trial group were significantly better than control group. C-terminal telopeptide of type Ⅰ collagen after 6 months [MD＝－0.09， 95%CI （－0.16， －0.02）， P＝0.01] and N-terminal propeptide of type Ⅰ collagen after 12 months [MD＝－9.07， 95%CI （－11.22， －6.92）， P＜ 0.001] in trial group were significantly higher than control group. There was no statistical difference in the fracture incidence rate after 12 months [OR＝1.02， 95%CI （0.67，1.54）， P＝0.92] and the incidence of adverse reaction [OR＝0.99， 95%CI （0.67，1.46）， P＝0.97] between 2 groups. CONCLUSIONS Denosumab has more advantages in improving BMD and bone metabolism， compared with bisphosphonates.

Objective: To study the effect of long non⁃coding RNA (LncRNA) HAGLR on the expression of NODlike receptor pyrin domain⁃associated protein 3 ( NLRP3 ) inflammasome and fracture healing in tibial fracture (TF) mice and to explore the mechanism . Methods : First , HAGLR in osteoblast MC3T3 ⁃E1 was silenced by in vitro . Cell viability was detected by CCK⁃8 assay , cell apoptosis was detected by TUNEL assay , and the expressions of bone alkaline phosphatase (BALP) and osteocalcin were detected by qPCR . Western blot assay was used to detect the expressions of RUNX2 , phosphorylated RUNX2 ( p ⁃RUNX2 ) , NLRP3 , cysteine aspartic protease 1 (Caspase1) , apoptosis⁃associated spot⁃like protein ( ASC) and interleukin⁃1β . TF mouse models were established by tibial fracture operation in mice . HAGLR was overexpressed in the model mice , and RUNX2 was silenced or an inflammatory body inhibitor MCC950 was added on the basis of overexpression of HAGLR . The expressions of HAGLR and RUNX2 were detected by qPCR , and the expressions of insulin⁃like growth factor (IGF⁃1) were detected by Western blot . microCT was used to measure the volume of mouse callus (MBV) and the total tibial wet weight . Results : The apoptosis rate of MC3T3 ⁃E1 cells increased and the expression levels of RUNX2 ,p⁃RUNX2 , BALP and osteocalcin decreased ( P < 0. 05 ) . The expressions of NLRP3 , Caspase1 , ASC and IL⁃1β increased ( P <0. 05) . Compared with healthy tissue , the expressions of HAGLR and RUNX2 in TF mice decreased . Overexpression of HAGLR promoted the expressions of HAGLR and RUNX2 in TF mice , and increased the expression of MBV and tibia wet weight and IGF⁃1 (P < 0. 05) . Silencing RUNX2 on the basis of overexpression of HAGLR resulted in decreased expression of MBV , tibial wet weight and IGF⁃1 in TF mice (P < 0. 05) . However , the addition of NLRP3 inflammasome inhibitor MCC950 on top of the overexpression of HAGLR resulted in increased expressions of MBV , full⁃length tibia wet weight and IGF⁃1 (P < 0. 05) . Conclusion LncRNA HAGLR promotes the healing of tibial fractures by activating RUNX2 and inhibiting NLRP3 inflammasome .

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.