Objective To systematically evaluate the risk factors for postoperative delirium (POD) in patients undergoing pneumonectomy. Methods PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP databases were searched from the inception to November 7, 2024 for cross-sectional studies, case-control studies, and cohort studies on POD in patients undergoing pneumonectomy. Two researchers independently screened the literature, extracted data, and evaluated the quality of the literature. RevMan 5.4.1 software was used for meta-analysis. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the literature. Results A total of 12 studies were included, with 5 574 patients. The NOS scores of the literature were all≥6 points. Meta-analysis results showed that age (≥60 years) [OR=2.43, 95%CI (2.01, 2.93), P<0.01], American Society of Anesthesiologists (ASA) classification (Ⅳ) [OR=8.74, 95%CI (5.23, 14.61), P<0.01], history of diabetes [OR=12.81, 95%CI (10.45, 15.71), P<0.01], history of cerebrovascular disease [OR=3.00, 95%CI (2.46, 3.67), P<0.01], depression [OR=7.27, 95%CI (5.46, 9.67), P<0.01], squamous cell carcinoma [OR=4.79, 95%CI (1.83, 12.51), P<0.01], malnutrition [OR=5.25, 95%CI (3.35, 8.25), P<0.01], sleep disorders [OR=2.79, 95%CI (2.28, 3.42), P<0.01], and duration of one-lung ventilation during surgery [OR=1.32, 95%CI (1.11, 1.57), P<0.01] were all risk factors for POD, while high body mass index (BMI) [OR=0.96, 95%CI (0.95, 0.97), P<0.01] was a protective factor for POD. Conclusion Age (≥60 years), ASA classification (Ⅳ), history of diabetes, history of cerebrovascular disease, depression, squamous cell carcinoma, malnutrition, sleep disorders, and duration of one-lung ventilation during surgery are independent risk factors for POD, while high BMI is a protective factor.

This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

BACKGROUND:Traditional Chinese medicine has been proved to have a significant role in anti-osteoporosis,and the effectiveness and mechanism of Ligustri Lucidi Fructus and its the active ingredients against osteoporosis have gradually gained the attention of scholars.OBJECTIVE:To analyze and summarize the research progress of Ligustri Lucidi Fructus and its active ingredients against osteoporosis in vitro and in vivo.METHODS:We searched the relevant literature included in CNKI and PubMed databases using the search terms of"Osteoporosis,Bone marrow mesenchymal stem cells,Osteoblast,Osteoclast,Ligustri Lucidi Fructus,Signal path"in Chinese and English,respectively.According to the needs of the research,we established the corresponding criteria and screened the literature.A total of 82 papers were included in the final review.RESULTS AND CONCLUSION:(1)The active ingredients of Ligustri Lucidi Fructus that exert anti-osteoporotic effects in vitro and in vivo mainly involve the following:Salidroside activates the Wnt/β-catenin signaling pathway by inhibiting the expression of Sclerostin and Dickkopf-related protein 1.This activation process enhances the expression of phosphorylated low-density lipoprotein receptor-related protein 6 in ovariectomized rats and primary osteoblasts,while decreasing the expression of glycogen synthase kinase 3β.Further,it promotes the expression of β-catenin,runt-related transcription factor 2 and cellular myelocytomatosis oncogene in the nucleus,thereby promoting the bone formation capacity of osteoblasts.The advantage is that it acts directly on osteoblasts to promote bone formation,which provides a new strategy for the treatment of osteoporosis.(2)Olive bittersweet significantly increases bone mineral density and regulates bone metabolism by decreasing terminal interleukin-6 and alkaline phosphatase concentrations in Sprague-Dawley rats.In vitro experiments showed that olive bittersweet promotes the proliferation of osteoblasts and up-regulates the protein and mRNA expression of osteoprotegerin,while inhibiting the protein and mRNA expression of receptor activator of nuclear factor-κB ligand.This mechanism of action is closely related to the regulation of the balance of the osteoprotegerin/receptor activator of nuclear factor-κB ligand system,demonstrating the advantage of increasing bone mineral density and maintaining bone health by regulating factors related to bone metabolism,but there is no significant effect on Ca2+concentration,which may limit its use in some specific types of osteoporosis.(3)By decreasing the expression of phosphatidylinositol 3 kinase,reducing the phosphorylation of protein kinase B and the expression of osteoclast-specific marker protein c-Fos,pineconiferin effectively inhibits the activation of phosphatidylinositol 3 kinase/protein kinase B/c-Fos pathway in osteoclasts.This inhibition reduces the proliferation and maturation of osteoclasts,which can help to reduce bone resorption.The advantage of this inhibition is that it can directly target osteoclasts,which provides a new target for osteoporosis treatment.However,the specific regulatory mechanism of osteoclasts needs to be studied in depth,and its long-term effect and safety need to be further evaluated.(4)The active ingredients of Ligustri Lucidi Fructus have shown good therapeutic effects on osteoporosis,but their mechanism of action is complex,involving the interaction of multiple genes,proteins and signaling pathways.In the future,large-scale clinical trials need to be carried out to verify its effectiveness and safety,and the strategy of combining the active ingredients of Ligustri Lucidi Fructus with other drugs needs to be further explored in order to obtain better therapeutic effects.

BACKGROUND:In most species,a bone defect that is longer than 1.5 or 2 times its diameter can be considered a critical bone defect,and when the bone defect volume reaches the critical value,it cannot heal on its own.Currently,there is no uniform standard for the size of critical-sized defects in the osteoporotic femoral condyle of rabbits.OBJECTIVE:To establish a rabbit model with different sizes of bone defects in the osteoporotic femoral condyle and to determine the critical-sized defects of osteoporotic femoral condyle in rabbits.METHODS:Thirty-six 3-month-old female New Zealand white rabbits were randomly divided into ovariectomy group(n=30)and sham operation group(n=6).Rabbits in the ovariectomy group underwent bilateral ovariectomy to establish an osteoporosis model,and then femoral condyle bone defect models of different diameters(diameters were 4,5,6,and 7 mm,and depths were 8 mm)were further established;rabbits in the sham operation group did not undergo ovariectomy.At 8 and 12 weeks after modeling,3 rats were randomly selected from each group for CT scanning and three-dimensional reconstruction to evaluate the healing of bone defects.Afterwards,samples were taken for gross observation and hematoxylin-eosin staining to observe the growth of new bone in the femoral condyle bone defect area.RESULTS AND CONCLUSION:(1)All rabbits survived and moved well after modeling of osteoporosis and femoral condyle bone defect.(2)At 12 weeks after osteoporosis modeling,dual-energy X-ray absorptiometry results showed that the bone mineral density of lumbar vertebrae in ovariectomy group was significantly lower than that in sham operation group(P＜0.05).Hematoxylin-eosin staining showed that the bone trabeculae in the ovariectomy group became thinner and sparse.The proportion of bone tissue area in the ovariectomy group was significantly lower than that in the sham operation group(P=0.00).Micro-CT results showed that the bone tissue parameters of the femoral condyle in the ovariectomy group were significantly different from those in the sham operation group(P＜0.05),and the ovariectomy group showed obvious characteristics of osteoporosis.(3)CT showed that the bone defect in the 4 mm and 5 mm diameter groups was basically completely repaired at 12 weeks after surgery.There was more new bone tissue in the 6 mm diameter group,but the central part of the bone defect was not completely repaired.A small amount of new bone tissue grew in the 7 mm diameter group,and the bone defect was obvious.(4)Gross observation at 12 weeks after surgery showed that the femoral condyle bone defect in the 4 mm and 5 mm diameter groups was completely repaired.Obvious depression was seen in the bone defect area of the 6 mm and 7 mm diameter groups,and the bone defect was not completely repaired.(5)Histological observation at 12 weeks after surgery showed that the bone defect area of the 4 mm and 5 mm diameter groups was completely filled with new bone,and the trabecular structure was irregular;while there were new trabeculae in the periphery of the 6 mm and 7 mm diameter groups,and the bone defect in the central area was still obvious.(6)The results showed that during the 12-week experimental observation period of osteoporotic femoral condyle defects in rabbits,under the condition of the same defect depth of 8 mm,femoral condyle defects with a diameter ≥ 6 mm could not heal on their own,while femoral condyle defects with a diameter＜6 mm were completely repaired.A diameter of 6 mm and a depth of 8 mm can be used as the critical bone defect value of osteoporotic femoral condyle in rabbits.

BACKGROUND:In most species,a bone defect that is longer than 1.5 or 2 times its diameter can be considered a critical bone defect,and when the bone defect volume reaches the critical value,it cannot heal on its own.Currently,there is no uniform standard for the size of critical-sized defects in the osteoporotic femoral condyle of rabbits.OBJECTIVE:To establish a rabbit model with different sizes of bone defects in the osteoporotic femoral condyle and to determine the critical-sized defects of osteoporotic femoral condyle in rabbits.METHODS:Thirty-six 3-month-old female New Zealand white rabbits were randomly divided into ovariectomy group(n=30)and sham operation group(n=6).Rabbits in the ovariectomy group underwent bilateral ovariectomy to establish an osteoporosis model,and then femoral condyle bone defect models of different diameters(diameters were 4,5,6,and 7 mm,and depths were 8 mm)were further established;rabbits in the sham operation group did not undergo ovariectomy.At 8 and 12 weeks after modeling,3 rats were randomly selected from each group for CT scanning and three-dimensional reconstruction to evaluate the healing of bone defects.Afterwards,samples were taken for gross observation and hematoxylin-eosin staining to observe the growth of new bone in the femoral condyle bone defect area.RESULTS AND CONCLUSION:(1)All rabbits survived and moved well after modeling of osteoporosis and femoral condyle bone defect.(2)At 12 weeks after osteoporosis modeling,dual-energy X-ray absorptiometry results showed that the bone mineral density of lumbar vertebrae in ovariectomy group was significantly lower than that in sham operation group(P＜0.05).Hematoxylin-eosin staining showed that the bone trabeculae in the ovariectomy group became thinner and sparse.The proportion of bone tissue area in the ovariectomy group was significantly lower than that in the sham operation group(P=0.00).Micro-CT results showed that the bone tissue parameters of the femoral condyle in the ovariectomy group were significantly different from those in the sham operation group(P＜0.05),and the ovariectomy group showed obvious characteristics of osteoporosis.(3)CT showed that the bone defect in the 4 mm and 5 mm diameter groups was basically completely repaired at 12 weeks after surgery.There was more new bone tissue in the 6 mm diameter group,but the central part of the bone defect was not completely repaired.A small amount of new bone tissue grew in the 7 mm diameter group,and the bone defect was obvious.(4)Gross observation at 12 weeks after surgery showed that the femoral condyle bone defect in the 4 mm and 5 mm diameter groups was completely repaired.Obvious depression was seen in the bone defect area of the 6 mm and 7 mm diameter groups,and the bone defect was not completely repaired.(5)Histological observation at 12 weeks after surgery showed that the bone defect area of the 4 mm and 5 mm diameter groups was completely filled with new bone,and the trabecular structure was irregular;while there were new trabeculae in the periphery of the 6 mm and 7 mm diameter groups,and the bone defect in the central area was still obvious.(6)The results showed that during the 12-week experimental observation period of osteoporotic femoral condyle defects in rabbits,under the condition of the same defect depth of 8 mm,femoral condyle defects with a diameter ≥ 6 mm could not heal on their own,while femoral condyle defects with a diameter＜6 mm were completely repaired.A diameter of 6 mm and a depth of 8 mm can be used as the critical bone defect value of osteoporotic femoral condyle in rabbits.

BACKGROUND:Traditional Chinese medicine has been proved to have a significant role in anti-osteoporosis,and the effectiveness and mechanism of Ligustri Lucidi Fructus and its the active ingredients against osteoporosis have gradually gained the attention of scholars.OBJECTIVE:To analyze and summarize the research progress of Ligustri Lucidi Fructus and its active ingredients against osteoporosis in vitro and in vivo.METHODS:We searched the relevant literature included in CNKI and PubMed databases using the search terms of"Osteoporosis,Bone marrow mesenchymal stem cells,Osteoblast,Osteoclast,Ligustri Lucidi Fructus,Signal path"in Chinese and English,respectively.According to the needs of the research,we established the corresponding criteria and screened the literature.A total of 82 papers were included in the final review.RESULTS AND CONCLUSION:(1)The active ingredients of Ligustri Lucidi Fructus that exert anti-osteoporotic effects in vitro and in vivo mainly involve the following:Salidroside activates the Wnt/β-catenin signaling pathway by inhibiting the expression of Sclerostin and Dickkopf-related protein 1.This activation process enhances the expression of phosphorylated low-density lipoprotein receptor-related protein 6 in ovariectomized rats and primary osteoblasts,while decreasing the expression of glycogen synthase kinase 3β.Further,it promotes the expression of β-catenin,runt-related transcription factor 2 and cellular myelocytomatosis oncogene in the nucleus,thereby promoting the bone formation capacity of osteoblasts.The advantage is that it acts directly on osteoblasts to promote bone formation,which provides a new strategy for the treatment of osteoporosis.(2)Olive bittersweet significantly increases bone mineral density and regulates bone metabolism by decreasing terminal interleukin-6 and alkaline phosphatase concentrations in Sprague-Dawley rats.In vitro experiments showed that olive bittersweet promotes the proliferation of osteoblasts and up-regulates the protein and mRNA expression of osteoprotegerin,while inhibiting the protein and mRNA expression of receptor activator of nuclear factor-κB ligand.This mechanism of action is closely related to the regulation of the balance of the osteoprotegerin/receptor activator of nuclear factor-κB ligand system,demonstrating the advantage of increasing bone mineral density and maintaining bone health by regulating factors related to bone metabolism,but there is no significant effect on Ca2+concentration,which may limit its use in some specific types of osteoporosis.(3)By decreasing the expression of phosphatidylinositol 3 kinase,reducing the phosphorylation of protein kinase B and the expression of osteoclast-specific marker protein c-Fos,pineconiferin effectively inhibits the activation of phosphatidylinositol 3 kinase/protein kinase B/c-Fos pathway in osteoclasts.This inhibition reduces the proliferation and maturation of osteoclasts,which can help to reduce bone resorption.The advantage of this inhibition is that it can directly target osteoclasts,which provides a new target for osteoporosis treatment.However,the specific regulatory mechanism of osteoclasts needs to be studied in depth,and its long-term effect and safety need to be further evaluated.(4)The active ingredients of Ligustri Lucidi Fructus have shown good therapeutic effects on osteoporosis,but their mechanism of action is complex,involving the interaction of multiple genes,proteins and signaling pathways.In the future,large-scale clinical trials need to be carried out to verify its effectiveness and safety,and the strategy of combining the active ingredients of Ligustri Lucidi Fructus with other drugs needs to be further explored in order to obtain better therapeutic effects.

This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

Objective:To investigate the effect and underlying mechanism of isoliquiritigenin (ISL) on chondrocyte ferroptosis in a rat model of knee osteoarthritis (KOA).Methods:Sixty male SD rats were randomly divided into a sham group, KOA group, celecoxib group, ISL low-dose group, and ISL high-dose group. Except for the sham group, KOA models were induced in the other groups using the modified Hulth method. The ISL low-dose and high-dose groups received intraperitoneal injections of 10 mg/kg and 40 mg/kg ISL, respectively; the celecoxib group was orally administered 24 mg/kg celecoxib; the sham and KOA groups received equivalent doses of saline via intraperitoneal injection. Interventions were administered once daily for 8 weeks. Behavioral changes in the open field test, histopathological observations of cartilage, inflammatory cytokine detection, ferroptosis-related indicators, and Sirt1/Nrf2/GPX4 pathway protein expression were measured to determine the optimal ISL dose. Another 60 male SD rats were randomly divided into sham, KOA, ISL high-dose, Sirt1 inhibitor (EX-527), and ISL high-dose + EX-527 groups. KOA models were established in all groups except the sham group. The ISL high-dose group received 40 mg/kg ISL, the EX-527 group received 10 mg/kg EX-527, and the combination group received both. The sham and KOA groups were given saline. Interventions lasted 8 weeks. Histopathological staining evaluated cartilage damage and scoring; ELISA measured tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels in synovial fluid; iron deposition, Fe 2+, malonaldehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) levels were assessed; Western blot analyzed Sirt1/Nrf2/GPX4 pathway proteins; immunohistochemistry detected Collagen II, Aggrecan, MMP-3, and MMP-13 expression. Results:The joint cartilage tissue damage in the ISL low-dose and high-dose rat groups was alleviated compared to the KOA group. The OARSI score, levels of TNF-α, IL-1β and IL-6 in joint fluid, iron deposition in cartilage tissue, Fe 2+, MDA and ROS levels were 8.33±1.86 and 4.50±1.52, respectively. 67.24±7.25 pg/ml, 42.06±5.12 pg/ml; 37.97±4.9 pg/ml, 23.75±4.12 pg/ml; 31.67±4.16 pg/ml, 20.91±3.28 pg/ml; 2.00±0.20, 1.53±0.14; 2.84±0.19 μmol/mg, 1.87±0.16 μmol/mg; 9.11±1.08 nmol/ml, 5.49±1.05 nmol/ml; 759.15±59.80 μmol/ml and 610.85±44.23 μmol/ml were lower than those in KOA group ( P<0.05), and the serum SOD and GSH contents were 12.12±1.52 U/ml and 16.79±2.14 U/ml, respectively. Compared with KOA group, the protein expressions of Sirt1, Nrf2, GPX4 and SLC7A11 were 0.70±0.11 and 0.96±0.13, 0.69±0.10 and 0.95±0.14, 0.51±0.06 and 0.87±0.12, 0.56±0.06 and 0.83±0.10, which were higher than those in KOA group ( P<0.05). The expressions of Acetyl-H4K16, ACSL4, MMP-3 and MMP-13 were 1.68±0.17 and 1.30±0.10, 1.39±0.12 and 0.97±0.10, 1.70±0.14 and 1.10±0.10, 1.64±0.15 and 1.28±0.10, which were lower than those of KOA group ( P<0.05). And the changes of these indexes were higher in Sirt1 inhibitor group. Compared with the ISL high-dose group, the ferroptosis-related indexes were significantly increased in the ISL high-dose+Sirt1 inhibitor group. Conclusion:ISL alleviates articular cartilage injury in KOA rats, and its mechanism is related to activating the Sirt1/Nrf2/GPX4 pathway and inhibiting ferroptosis.

Objective To find and select stable and specific identification indexes in chest CT images,to establish mathematical models and provide a systematic and scientific identification method.Methods Medical imaging analysis and processing technology were applied to compare the image indexes such as lung apical shadow,double lung texture,trachea,sternum,thoracic morphology,liver,spleen,interlobular fissure morphology,first rib,aorta and thoracic vertebrae morphology of 600 serial chest CT scans of of the same adults at different periods and 600 scans of different adults.Consistency test(Kappa analysis)was applied to determine the consistency of different identification indexes,and to screen out the image identification indexes that were not easily affected by subjective factors and had high consistency;the cumulative exclusion probability method was applied to calculate the combined identification ability of the observation indexes,and select optimal indexes to establish the identification index system.Results Five indexes-left lung texture,right lung texture,interlobular fissure of the liver,first rib on the left side,and first rib on the right side demonstrated high consistency across age groups and minimal subjective interference.A combination of any three indexes achieved＞99.99％discrimination probability for homologous versus non-homologous sources identification.Conclusion The independent or combined use of the indexes of left lung texture,right lung texture,interlobular fissure of the liver,first rib on the left side,and first rib on the right side enables individual identification in adult chest CT under different imaging conditions.

It is believed that the occurrence and development of squamous cell carcinoma （SCC） is closely associated with inflammatory responses. The theory of fire and heat， advocated by LIU Wansu， provides significant clinical guidance for understanding the pathogenesis and treatment of SCC. Based on this theory， the pathological mechanisms and clinical characteristics of SCC at different stages were analyzed. In the precancerous and early stages， the primary pathogenesis is qi stagnation leading to internal generation of constrained heat； in post-surgery， the condition shifts to qi deficiency with latent yin fire； during the treatment phase， the pathogenesis involves accumulation of pathogenic factors， excess toxins， and severe heat toxicity； in the late stage， the main pathology is yin deficiency with toxic heat， and phlegm-stasis obstruction of the internal organs. Corresponding stage-based treatment strategies are proposed. In the early stage， regulating qi movement to dissipate constrained heat； for post-surgery， tonifying qi and raising yang to dispel latent fire； during treatment stage， clearing heat and detoxifying to eliminate cancerous toxins； and in the late stage， nourishing yin and unblocking the bowels to clear deficiency heat.