OBJECTIVE: To evaluate the effect of biodegradable magnesium alloy materials in promoting tendon-bone healing during rotator cuff tear repair and to investigate their potential underlying biological mechanisms. METHODS: Forty-eight 8-week-old Sprague Dawley rats were taken and randomly divided into groups A, B, and C. Rotator cuff tear models were created and repaired using magnesium alloy sutures in group A and Vicryl Plus 4-0 absorbable sutures in group B, while only subcutaneous incisions and sutures were performed in group C. Organ samples of groups A and B were taken for HE staining at 1 and 2 weeks after operation to evaluate the safety of magnesium alloy, and specimens from the supraspinatus tendon and proximal humerus were harvested at 2, 4, 8, and 12 weeks after operation. The specimens were observed macroscopically at 4 and 12 weeks after operation. Biomechanical tests were performed at 4, 8, and 12 weeks to test the ultimate load and stiffness of the healing sites in groups A and B. At 2, 4, and 12 weeks, the specimens were subjected to the following tests: Micro-CT to evaluate the formation of bone tunnels in groups A and B, HE staining and Masson staining to observe the regeneration of fibrocartilage at the tendon-bone interface after decalcification and sectioning, and Goldner trichrome staining to evaluate the calcification. Immunohistochemical staining was performed to detect the expressions of angiogenic factors, including vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2), as well as osteogenic factors at the tendon-bone interface. Additionally, immunofluorescence staining was used to examine the expressions of Arginase 1 and Integrin beta-2 to assess M1 and M2 macrophage polarization at the tendon-bone interface. The role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in tendon-bone healing was further analyzed using real-time fluorescence quantitative PCR. RESULTS: Analysis of visceral sections revealed that magnesium ions released during the degradation of magnesium alloys did not cause significant toxic effects on organs such as the heart, liver, spleen, lungs, and kidneys, indicating good biosafety. Histological analysis further demonstrated that fibrocartilage regeneration at the tendon-bone interface in group A occurred earlier, and the amount of fibrocartilage was significantly greater compared to group B, suggesting a positive effect of magnesium alloy material on tendon-bone interface repair. Additionally, Micro-CT analysis results revealed that bone tunnel formation occurred more rapidly in group A compared to group B, further supporting the beneficial effect of magnesium alloy on bone healing. Biomechanical testing showed that the ultimate load in group A was consistently higher than in group B, and the stiffness of group A was also greater than that of group B at 4 weeks, indicating stronger tissue-carrying capacity following tendon-bone interface repair and highlighting the potential of magnesium alloy in enhancing tendon-bone healing. Immunohistochemical staining results indicated that the expressions of VEGF and BMP-2 were significantly upregulated during the early stages of healing, suggesting that magnesium alloy effectively promoted angiogenesis and bone formation, thereby accelerating the tendon-bone healing process. Immunofluorescence staining further revealed that magnesium ions exerted significant anti-inflammatory effects by regulating macrophage polarization, promoting their shift toward the M2 phenotype. Real-time fluorescence quantitative PCR results demonstrated that magnesium ions could facilitate tendon-bone healing by modulating the PI3K/AKT signaling pathway. CONCLUSION Biodegradable magnesium alloy material accelerated fibrocartilage regeneration and calcification at the tendon-bone interface in rat rotator cuff tear repair by regulating the PI3K/AKT signaling pathway, thereby significantly enhancing tendon-bone healing.
Animals ; Rotator Cuff Injuries/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Wound Healing/drug effects* ; Alloys/pharmacology* ; Rats ; Proto-Oncogene Proteins c-akt/metabolism* ; Rotator Cuff/metabolism* ; Macrophages/metabolism* ; Magnesium/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Male ; Biocompatible Materials ; Bone Morphogenetic Protein 2/metabolism*

Objective To establish an expert consensus on in-hospital transfer safety management for patients undergoing invasive mechanical ventilation,providing guidance for clinical medical teams to conduct standardized transfers,reduce transfer risks,and ensure patient safety.Methods Through systematic searching,screening,evaluation,and summary of evidence related to in-hospital transfer safety management for patients on invasive mechanical ventilation,we extracted recommendations to form a preliminary draft of the expert consensus.From July to October 2024,totally 2 rounds of expert consultations,and 2 rounds of expert reviews were conducted,and the content was refined and finalized based on expert feedback.Results The final consensus encompasses 9 aspects,including transfer assessment and decision-making,pre-transfer preparation of medical staff,pre-transfer patient preparation,pre-transfer equipment preparation,pre-transfer medication preparation,monitoring and intervention during transfer,emergency events and management,transfer handover and documentation,and post-transfer management.Conclusion This consensus demonstrates strong practicality and operability,offering professional guidance for enhancing the safety of in-hospital transfers for patients on invasive mechanical ventilation.

Objective To evaluate the value of molecular markers of thrombine-antithrombin complex(TAT),soluble thrombomodulin(sTM),tissue-plasminogen activator-inhibitor complex(t-PAIC)in the early diagnosis of disseminated intravascular coagulation(DIC)in sepsis patients.Methods Thirty patients diagnosed with DIC secondary to hemoinfect-induced sepsis were selected as the DIC group in the intensive care unit(ICU)of the First Hospital of Lanzhou University from July to September 2023.Thirty patients with sepsis caused by bloodstream infection without DIC were randomly selected as the sepsis group.General data and procalcitonin(PCT),platelet count(PLT),white blood cell count(WBC),the levels of traditional clotting indexes activated partial thromboplastin time(APTT),prothrombin time(PT),fibrinogen(Fib),D-dimer and new clotting indexes(TM,TAT,t-PAIC)were collected.The indicators with statistical significance in univariate analysis were included in multivariate Logistic regression analysis to screen the independent risk factors for DIC in sepsis patients.Receiver operator characteristic curve(ROC curve)was drawn to analyze the diagnostic value of TM,TAT,t-PAIC and their combination in the occurrence of DIC in sepsis patients.Results A total of 60 patients with sepsis were included.There was no significant difference in gender,age,PCT,PLT and WBC between the DIC group and the sepsis group.In terms of traditional coagulation indexes,the PT level in sepsis DIC group was significantly lower than that in sepsis group,and the Fib level was significantly higher than that in sepsis group(both P<0.05).There were no statistically significant differences in APTT and D-dimer levels between the two groups.In terms of new coagulation indexes,TAT,sTM and t-PAIC levels in sepsis DIC group were significantly higher than those in sepsis group(all P<0.05).Multivariate Logistic regression analysis showed that TAT,sTM were independent risk factors for DIC in sepsis patients(both P<0.05).ROC curve analysis showed that TAT,sTM,t-PAIC combined detection had certain value in diagnosis of DIC in sepsis patients,area under the curve(AUC)was 0.735;when the cut-off value was 0.73,the sensitivity was 100.0%and specificity was 43.3%.Conclusion TAT,sTM and t-PAIC could help to predict DIC in sepsis.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Aluminum adjuvants are widely used in the field of vaccines due to their ability to induce efficient and long-lasting immune responses and good safety profile. With the development of immunology, the requirements for adjuvants have gradually increased, and traditional aluminum adjuvants can no longer meet all the needs of application. The development of novel aluminum adjuvants has become a hot research topic in order to achieve good immunity-enhancing effects and induce specific types and strengths of immune responses. This review briefly introduces the mechanism of action and safety of aluminum adjuvants, with focus on the research progress of novel aluminum adjuvants in recent years, mainly including nano-aluminum adjuvants and composite aluminum adjuvants (aluminum adjuvants compounded with immunity-stimulating molecules or delivery carriers), and a prospect of their future research direction, aiming to provide some reference for the further development and clinical application of aluminum adjuvants.

Objective To explore the effect of PCSK9 inhibitor combined with atorvastatin on carotid atherosclerosis and its anti-inflammatory effect in patients with hypertension complicated with type 2 diabetes mellitus.Methods A total of 100 patients with hypertension complicated with type 2 diabetes mellitus who were treated in Nanchang Third Hospital from October 2022 to August 2023 were selected as the research subjects.They were divided into the control group and the study group by the random number table method,with 50 cases in each group.Both groups of patients received conventional antihypertensive,hypoglycemic,and antiplatelet therapy.The control group took 20 mg of atorvastatin calcium tablets orally,once a night.On the basis of the control group,the study group was additionally given 150 mg of evolocumab injection(a PCSK9 inhibitor)by subcutaneous injection,once every two weeks.Both groups of patients were followed up for 24 weeks.The levels of blood lipids,blood glucose,inflammatory cytokines,carotid intima-media thickness(IMT),atherosclerotic plaque score and adverse reactions of the patients in the two groups before and after treatment were detected and compared.Results The levels of TC,TG and LDL-C in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜0.05).The levels of IL-1,IL-6,TNF-α,hs-CRP,as well as the ca-rotid IMT and atherosclerotic plaque score in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜O.05).During the treatment period,there was no significant difference in the occurrence of adverse reac-tions between the two groups(P＞0.05).Conclusion The combination of PCSK9 inhibitor and atorvastatin can effectively regulate the blood lipid levels of patients with hypertension complicated and type 2 diabetes mellitus,alleviate the inflammatory response,and improve the degree of carotid atherosclerosis in these pa-tients.

Objective To establish an expert consensus on in-hospital transfer safety management for patients undergoing invasive mechanical ventilation,providing guidance for clinical medical teams to conduct standardized transfers,reduce transfer risks,and ensure patient safety.Methods Through systematic searching,screening,evaluation,and summary of evidence related to in-hospital transfer safety management for patients on invasive mechanical ventilation,we extracted recommendations to form a preliminary draft of the expert consensus.From July to October 2024,totally 2 rounds of expert consultations,and 2 rounds of expert reviews were conducted,and the content was refined and finalized based on expert feedback.Results The final consensus encompasses 9 aspects,including transfer assessment and decision-making,pre-transfer preparation of medical staff,pre-transfer patient preparation,pre-transfer equipment preparation,pre-transfer medication preparation,monitoring and intervention during transfer,emergency events and management,transfer handover and documentation,and post-transfer management.Conclusion This consensus demonstrates strong practicality and operability,offering professional guidance for enhancing the safety of in-hospital transfers for patients on invasive mechanical ventilation.

Objective To evaluate the value of molecular markers of thrombine-antithrombin complex(TAT),soluble thrombomodulin(sTM),tissue-plasminogen activator-inhibitor complex(t-PAIC)in the early diagnosis of disseminated intravascular coagulation(DIC)in sepsis patients.Methods Thirty patients diagnosed with DIC secondary to hemoinfect-induced sepsis were selected as the DIC group in the intensive care unit(ICU)of the First Hospital of Lanzhou University from July to September 2023.Thirty patients with sepsis caused by bloodstream infection without DIC were randomly selected as the sepsis group.General data and procalcitonin(PCT),platelet count(PLT),white blood cell count(WBC),the levels of traditional clotting indexes activated partial thromboplastin time(APTT),prothrombin time(PT),fibrinogen(Fib),D-dimer and new clotting indexes(TM,TAT,t-PAIC)were collected.The indicators with statistical significance in univariate analysis were included in multivariate Logistic regression analysis to screen the independent risk factors for DIC in sepsis patients.Receiver operator characteristic curve(ROC curve)was drawn to analyze the diagnostic value of TM,TAT,t-PAIC and their combination in the occurrence of DIC in sepsis patients.Results A total of 60 patients with sepsis were included.There was no significant difference in gender,age,PCT,PLT and WBC between the DIC group and the sepsis group.In terms of traditional coagulation indexes,the PT level in sepsis DIC group was significantly lower than that in sepsis group,and the Fib level was significantly higher than that in sepsis group(both P<0.05).There were no statistically significant differences in APTT and D-dimer levels between the two groups.In terms of new coagulation indexes,TAT,sTM and t-PAIC levels in sepsis DIC group were significantly higher than those in sepsis group(all P<0.05).Multivariate Logistic regression analysis showed that TAT,sTM were independent risk factors for DIC in sepsis patients(both P<0.05).ROC curve analysis showed that TAT,sTM,t-PAIC combined detection had certain value in diagnosis of DIC in sepsis patients,area under the curve(AUC)was 0.735;when the cut-off value was 0.73,the sensitivity was 100.0%and specificity was 43.3%.Conclusion TAT,sTM and t-PAIC could help to predict DIC in sepsis.

Objective To evaluate the physical activities of the patients under haemodialysis(HD)with triaxial accelerometers so as to provide data for development of interventional exercise programs for the HD patients.Methods A total of 38 patients who underwent HD in our hospital between March 2021 and July 2021 were included in the study group.Further 38 healthy subjects without chronic disease with matched gender and age to the HD patients in the study group,were recruited from local communities as a control group.The subjects in both groups were asked to wear an Altigraph GT3X+ accelerometer on waist after getting up in the morning for 12 hours a day for 7 consecutive days.The average number of steps and the standard rate of exercise time in the 7 days were compared between the groups.Durations of the exercises,standing,walking,sitting,and lying down were also compared between the groups.Results Both groups had completed the study.The number of daily steps in the HD group was found significantly lower than that in the control group(5684.3±1238.5 step/day vs.8792.2±2870.8 step/day,P<0.001).The rate of sedentariness in the HD group was significantly higher than that in the control group(47.4%vs.10.5%,P<0.001).In comparison with the control group,HD patients spent more time for lying down per day(195.6±77.8 min/day vs.47.8±15.5 min/day,P<0.001)and sitting(369.3±79.8 min/day vs.301.2±77.1 min/day,P<0.001).For intragroup comparison,on the days of dialysis,the HD patients spent more time for lying down[250.1±71.1 min/day vs.152.1±40.6 min/day,P<0.001],sitting(371.2±76.9 min/day vs.332.2±88.6 min/day,P<0.05)and with less walking(4362.3±1084.5 steps/day vs.7007.6±2437.8 steps/day,P<0.001),in comparison with those on the non-dialysis days.Conclusions HD patients spend less time on physical activities,but more time on sitting and lying down.The situation is even worse on the days of dialysis treatment.The HD patients should be advised and encouraged to take more physical activities.