BACKGROUND:Periprosthetic joint infection is the most common cause of early failure after total knee replacement.The current methods of preventing periprosthetic joint infection by improving the surface of the prosthesis have limitations to varying degrees.OBJECTIVE:To construct a coating material that can stably improve the surface of the implant,prevent the initial floating bacterial infection of periprosthetic infection,and regulate the bone transfer function around the implant.METHODS:(1)Material preparation:YGF polypeptide(which promotes bone formation),LL-37 polypeptide(with antibacterial properties)and YGF+LL-37 composite peptide were prepared by Fmoc solid phase peptide synthesis technology.The titanium-based materials were immersed in the three polypeptide solutions for 2 hours to obtain YGF coating,LL-37 coating and composite peptide coating coated titanium sheets.(2)In vitro experiment:Uncoated titanium sheets and coated titanium sheets were co-cultured with Escherichia coli(or Staphylococcus aureus)and the colonies were counted by plate method.MC3T3 cells were inoculated on the surface of uncoated titanium sheet and coated titanium sheet,respectively.Alizarin red staining was used to observe the calcium salt deposition on the surface of the material.Western blot assay was used to detect the protein expression of RUNX2,osteocalcin,osteopontin,and bone morphogenetic protein 2.(3)Animal experiment:24 SD rats were randomly divided into three groups:the blank group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal;the control group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension;the experimental group(n=8)was implanted with composite peptide coated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension.After 5 weeks of implantation,micro-CT examination,hematoxylin-eosin staining and immunohistochemical staining of femur specimens were performed.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with uncoated titanium sheet and YGF coated titanium sheet,LL-37 coated and composite peptide coated titanium sheet could significantly inhibit the growth and reproduction of Escherichia coli and Staphylococcus aureus.Compared with uncoated titanium sheets and LL-37-coated titanium sheets,YGF-coated and composite peptide-coated titanium sheets could promote calcium salt deposition in osteoblasts and increase the protein expression of RUNX2,osteocalcin,osteopontin and bone morphogenetic protein 2.(2)Animal experiment:Micro-CT test showed that the control group had less bone mass than the blank group and the experimental group.Hematoxylin-eosin staining showed that there was a large amount of fibrous tissue around the nail channel in the control group,only a small amount of tissue fibrosis around the nail channel in the blank group,and only a small amount of tissue fibrosis around the nail channel in the experimental group.Immunohistochemical staining showed that the protein expression of interleukin 1β and tumor necrosis factor α in the control group was higher than that in the blank group and the experimental group,and the expression of osteocalcin,RUNX2 and osteopontin in the experimental group was higher than that in the blank group and the control group.(3)The results show that the titanium-based material coated with YGF+LL-37 composite peptide coating has good antibacterial ability and can promote bone transfer around the implant.

BACKGROUND:Periprosthetic joint infection is the most common cause of early failure after total knee replacement.The current methods of preventing periprosthetic joint infection by improving the surface of the prosthesis have limitations to varying degrees.OBJECTIVE:To construct a coating material that can stably improve the surface of the implant,prevent the initial floating bacterial infection of periprosthetic infection,and regulate the bone transfer function around the implant.METHODS:(1)Material preparation:YGF polypeptide(which promotes bone formation),LL-37 polypeptide(with antibacterial properties)and YGF+LL-37 composite peptide were prepared by Fmoc solid phase peptide synthesis technology.The titanium-based materials were immersed in the three polypeptide solutions for 2 hours to obtain YGF coating,LL-37 coating and composite peptide coating coated titanium sheets.(2)In vitro experiment:Uncoated titanium sheets and coated titanium sheets were co-cultured with Escherichia coli(or Staphylococcus aureus)and the colonies were counted by plate method.MC3T3 cells were inoculated on the surface of uncoated titanium sheet and coated titanium sheet,respectively.Alizarin red staining was used to observe the calcium salt deposition on the surface of the material.Western blot assay was used to detect the protein expression of RUNX2,osteocalcin,osteopontin,and bone morphogenetic protein 2.(3)Animal experiment:24 SD rats were randomly divided into three groups:the blank group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal;the control group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension;the experimental group(n=8)was implanted with composite peptide coated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension.After 5 weeks of implantation,micro-CT examination,hematoxylin-eosin staining and immunohistochemical staining of femur specimens were performed.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with uncoated titanium sheet and YGF coated titanium sheet,LL-37 coated and composite peptide coated titanium sheet could significantly inhibit the growth and reproduction of Escherichia coli and Staphylococcus aureus.Compared with uncoated titanium sheets and LL-37-coated titanium sheets,YGF-coated and composite peptide-coated titanium sheets could promote calcium salt deposition in osteoblasts and increase the protein expression of RUNX2,osteocalcin,osteopontin and bone morphogenetic protein 2.(2)Animal experiment:Micro-CT test showed that the control group had less bone mass than the blank group and the experimental group.Hematoxylin-eosin staining showed that there was a large amount of fibrous tissue around the nail channel in the control group,only a small amount of tissue fibrosis around the nail channel in the blank group,and only a small amount of tissue fibrosis around the nail channel in the experimental group.Immunohistochemical staining showed that the protein expression of interleukin 1β and tumor necrosis factor α in the control group was higher than that in the blank group and the experimental group,and the expression of osteocalcin,RUNX2 and osteopontin in the experimental group was higher than that in the blank group and the control group.(3)The results show that the titanium-based material coated with YGF+LL-37 composite peptide coating has good antibacterial ability and can promote bone transfer around the implant.

Objective To investigate the impact of red blood cell suspension infusion across various perioperative periods on patients with valvular heart disease. Methods The patients with valvular heart disease admitted to Tianjin Chest Hospital from 2018 to 2020 were selected. Based on the timing of perioperative red cell suspension infusion, patients were categorized into three groups: a group 1 receiving intraoperative red cell suspension infusion, a group 2 receiving red cell suspension infusion within 24 hours after entering the ICU, and a group 3 receiving red cell suspension infusion at both time points. The laboratory results, perioperative blood component infusion volume, and other relevant parameters were retrospectively analyzed. After propensity score matching, the differences in different variables among the three groups were compared. Results After propensity score matching, 102 patients were enrolled, including 52 males and 50 females, with an average age of (61.74±10.58) years. There were 34 patients in each group. The preoperative hemoglobin (Hb) value of the group 2 was significantly higher than that of the group 1 and the group 3, and the amount of red cell suspension and autoblood transfusion was the lowest (P<0.05). Group 1 had the highest postoperative Hb, as well as the highest Hb and hematocrit (HCT) levels within 24 hours post-surgery (P<0.05). The group 1 had the lowest plasma, platelet and cryoprecipitate infusion volumes, and the shortest cardiopulmonary bypass time, aortic occlusion time, postoperative ICU stay and hospital stay, and the least blood loss and total drainage volume (P<0.05). The difference between postoperative and preoperative Hb (△Hb1) was highest in group 1 (P<0.05). Conclusion For patients with valvular heart disease, intraoperative-only infusion of red blood cell suspension is associated with a better prognosis at discharge and during follow-up.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

Objective To analyze the differences in the efficacy and safety between antibody-drug conjugate(ADC)combined with programmed cell death 1(PD-1)inhibitor and chemotherapy in the treatment of advanced bladder cancer based on real-word data, so as to provide reference for individualized treatment regimens. Methods Clinical data of 107 patients pathologically diagnosed with bladder urothelial carcinoma admitted to our hospital during Jan.13, 2022 and Dec.27, 2024 were retrospectively collected. All patients had lymph node and/or distant metastases confirmed by CT or PET/CT. Among them, 38 were treated with Disitamab Vedotin plus Toripalimab(Disitamab Vedotin group), and 69 were treated with Gemcitabine plus Cisplatin(GC, chemotherapy group). The short and long-term efficacy and treatment-related adverse events(TRAEs)were compared between the two groups. Results The objective response rate(ORR)was higher in the Disitamab Vedotin group than in the chemotherapy group(18.4% vs. 5.8%), with no statistically significant difference(P＞0.05). The disease control rate(65.8% vs. 33.3%), progression-free survival(9.35 months vs. 7.76 months)and overall survival(29.54 months vs. 12.33 months)were higher/longer in the Disitamab Vedotin group than in the chemotherapy group, with statistically significant differences(P＜0.05). TRAEs such as peripheral neuropathy(44.7%)and alopecia(36.8%)occurred in 35 patients(92.1%)in the Disitamab Vedotin group, while TRAEs including leukopenia(44.9%), nausea and vomiting(44.9%), and alopecia(42.0%)occurred in 65 patients(95.6%)in the chemotherapy group. Conclusion Compared with standardized chemotherapy, Disitamab Vedotin plus Toripalimab can significantly reduce the risk of disease progression or death in patients with advanced bladder cancer, with manageable safety.

Objective:To explore the effects of mechanical ventilation（MV）at birth transition on lung pathophysiology and pathobiology in a very preterm animal model.Methods:Based on the model of respiratory distress syndrome（RDS）in very preterm rabbits at gestational age 26（term 31）days well established by the research group using perinatal medication and lung-protective ventilation strategies（very low tidal volume 1-3 mL/kg），we conducted a secondary data analysis. The studied rabbits were re-grouped according to the MV length（≤3 h，3-6 h，6-9 h，9-12 h，and >12 h）. The changes in lung mechanics，histopathology，phospholipid biochemistry，and mRNA relative expression of inflammatory/growth factor in lung tissue were evaluated over the time course of MV. The trend of each variable was tested by ANOVA trend test（ F trend）and Jonckheere-Terpstra trend test（ J-T value）with corresponding P value. Results:With the prolonged MV length，there was improved mean dynamic compliance of respiratory system（ F trend=16.722， P trend<0.001），along with decreased mean peak inspiratory pressure（ F trend =42.226， P trend<0.001）. The content of total phospholipids，disaturated phosphatidylcholine（ J-T=1 222，1 197， P trend=0.018，0.034，respectively）and total protein（ J-T=1 247 ，P trend= 0.009）in bronchoalveolar lavage fluid gradually increased. The wet lung weight in the ≤3 h group was significantly higher than in the other groups（ F=6.819， P<0.001）. The lung injury score（total，or hemorrhage，or inflammation）had progressive exacerbation in the ≤3 h，3-6 h and 6-9 h groups. The lung tissue mRNA expression of major proinflammatory cytokines increased modestly over the time groups in contrast to decreased expression of growth factors，of which the change of keratinocyte growth factor reached statistical significance（ J-T=531， P trend =0.034）. Conclusion:In the 26-day very preterm rabbits，with prolonged MV time，the content of surfactant phospholipid in the alveolar increased gradually，the lung compliance and lung fluid clearance gradually improved. Nevertheless，ventilator-induced lung injury remained evolving. The study warrants further study on the pathogenesis and protective strategies of early postnatal acute lung injury and chronic lung disease.

This study explored whether Astragalus polysaccharide(APS)can regulate the VEGF/VEGFR signaling pathway to affect the proliferative activity of rat intestinal mucosal microvascu-lar endothelial cells(RIMMVECs).RIMMVECs were isolated from newborn rats,then purified and treated with APS at concentrations of 0.1,1.0,10.0,100.0,1 000.0,and 10 000.0 mg/L.MTT was used to determine the effect of APS on RIMMVECs proliferation and screen for the optimal concentration of APS.Subsequently,flow cytometry was used to detect the changes in cell cycle to evaluate the stage of action of APS on the cell cycle in RIMMVECs.Then,the ELISA was used to detect the changes of VEGFA in cell supernatant to evaluate the potential of cell proliferation and angiogenesis.The changes in fluorescence intensity of Fluo-8AM was observed using fluorescence microscopy to evaluate intracellular Ca2+levels.Finally,Western blot was used to detect the ex-pression of PERK in RIMMVECs to analyze the possible mechanism of APS.The results showed that 100 mg/L APS significantly enhanced the proliferative activity of RIMMVECs,increased the content of VEGFA in the cell supernatant,the intracellular Ca2+levels,and the expression of PERK protein,indicating that APS promotes the proliferation of RIMMVECs,which may be a-chieved by promoting the expression of VEGFA and activating the ERK pathway.

Objective To investigate the effect of intravenous flurbiprofen axetil on the incidence and severity of catheter-related bladder discomfort(CRBD)after transurethral resection of the prostate(TURP).Methods The elderly patients undergoing TURP under general anesthesia were enrolled,and randomly divided into two groups:flurbiprofen axetil group(group F)and control group(group C).Ten minutes before the end of surgery,group F was given 50 mg of flurbiprofen axetil intravenously,group C was given an equal amount of 0.9％sodium chloride injection.The primary outcome indicator was the incidence of moderate to severe CRBD immediately after entering the resuscitation room(T0).Secondary indicators included the incidence and severity of CRBD at 1 h(T1),2 h(T2),and 6 h(T3)after entering the resuscitation room,the amount of sufentanil used within 24 hours after surgery,postoperative NRS score,flurbiprofen axetil-related and analgesic adverse reactions 24 hours after surgery,and patient satisfaction.Results A total of 90 patients were included and each group was 45 patients.The incidence of moderate to severe CRBD at T0 was significantly lower in group F than that in group C(8.9％vs.33.3％,P=0.004).The incidence of CRBD in T1,T2,and T3 was lower in group F than in group C(P＜0.05).The incidence of mild CRBD at T3 in group F was lower than that in group C(P＜0.05).The incidence of moderate to severe CRBD at T1 and T2 in groups F was lower than that in group C(P＜0.05).The amount of sufentanil used in group F at 24 hours after surgery was significantly lower than that in group C(P=0.001).The pain scores in group F at T0,T1,T2,and T3 were lower than those in group C(P＜0.05);The postoperative patient satisfaction score in group F was higher than that in group C(P=0.001).However,there were no significant differences between the two groups in postoperative anesthesia resuscitation time and 24-hour adverse reactions incidence(P＞0.05).Conclusion Intravenous flurbiprofen axetil can safely and effectively reduce the incidence and severity of CRBD after TURP.It can significantly relieve pain,reduce sufentanil use,and have high clinical application value.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.