The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective:To investigate the role and mechanism of IL-17 in hypertensive heart failure in rats.Methods:The spon-taneously hypertensive(SHR)model of hypertensive heart failure was established by abdominal aortic ligation.IL-17+IgG and IL-17 protein were injected intraperitoneally into the rats with hypertensive heart failure.After 4 weeks,cardiac structure and function were monitored,and peripheral blood and myocardial tissue were collected.The role and mechanism of IL-17 in hypertensive heart failure were studied by HE staining,immunohistochemistry,Western blot,qRT-PCR and ELISA.Results:After intraperitoneal injection of exogenous IL-17,the levels of IL-17,NT-proBNP,P38 and MK2 protein expressions were increased,and the levels of VEGF and Cav1.2 protein expression were decreased.Exogenous intraperitoneal injection of IL-17+IgG blocked IL-17,increased VEGF level and Cav1.2 protein expression,and decreased NT-proBNP level,P38 and MK2 protein expressions.Conclusion:IL-17 can be activated P38 lightning/MK2-Cav1.2 signaling pathways involved in high blood pressure,heart failure and cardiac function in rats damage;inhi-bition of IL-17 can effectively improve the cardiac function damage caused by hypertensive heart failure.

Objective:To investigate any effect of aerobic exercise on the functioning of endothelial progenitor cells (EPCs) and on the Akt/eNOS signaling pathway in type 2 diabetes.Methods:Forty-five 6-week-old Sprague-Dawley rats free of specific pathogens were randomly divided into a normal control group, a diabetic model group and an exercise group. Type 2 diabetes mellitus was induced in the model and exercise groups by feeding a high-fat diet and streptozotocin injection. After successful modeling, the exercise group underwent 8 weeks of non-weight-bearing swimming training after which blood was collected from their abdominal aortas to measure EPCs, serum nitric oxide and the level of vascular endothelial growth factor (VEGF). Bone marrow-derived EPCs were isolated from the rats′ femurs and tibias for in vitro culture. The cells′ tube formation capacity was assessed using Matrigel assays, while the expression of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) were determined using western blotting.Results:Compared with the normal group, the model group exhibited significantly reduced counts of EPCs in their peripheral blood. Serum NO and VEGF were also significantly lower, on average, and tube formation capacity was significantly impaired. p-Akt and p-eNOS protein expression were significantly downregulated. In contrast, the exercise group showed significantly increased EPC counts, elevated serum NO and VEGF levels, improved tube formation, and upregulated p-Akt and p-eNOS expression compared with the model group.Conclusions:Aerobic exercise improves EPC functioning in diabetic rats, and its mechanism may be associated with the regulation of the Akt/eNOS signaling pathway.

Objective:To analyze the clinical characteristics, distribution of common pathogenic bacteria and drug resistance in children with non-chronic osteomyelitis, to provide a basis for empirical antimicrobial drug selection.Methods:This study was a retrospective analysis cohort study. Clinical data, pathogenic bacteria and drug sensitivity test results of 289 children aged 0 to 18 years with non-chronic osteomyelitis who were hospitalized in the Pediatrics Hospital of Fudan University from January 2013 to June 2023 were collected retrospectively. Statistical analyses were performed using chi-square test.Results:Of the 289 children, 188(65.1%) were male, with a male to female ratio of 1.86∶1, and the age was 3.00(0.66, 8.00) years. The age less than six years amounted 65.1% (188/289). The incidence was the highest from December to February of the following year, reaching 32.5%(94/289). The clinical manifestations were fever in 193 cases (66.8%), fever with localized pain in 47 cases (16.3%), and fever with localized swelling and fever with localized swelling and pain in 39 cases (13.5%) each. Single bone involvement was observed in 242(83.7%) cases, including 88(36.4%) femur, 47(19.4%) tibia, and 37(15.3%) humerus. Of the 130 pathogen-positive cases, 102(78.5%) were Staphylococcus aureus (SA) including 45(44.1%) methicillin-resistant Staphylococcus aureus (MRSA), 10(7.7%) were Pseudomonas aeruginosa, and 3(2.3%) each were Klebsiella pneumoniae and Staphylococcus mansoni. The rate of MRSA detection in SA fluctuated each year from 2013 to 2023, with the highest in 2017, when eight out of 13 SA cases were MRSA. The resistance rates of all SA to vancomycin, linezolid, moxifloxacin, ciprofloxacin, gentamicin, rifampicin, ceflorin, tigecycline, ticlosporin, fosfomycin, daptomycin, furotoxin, quinupristin/dalfopristin were all zero, and the differences in resistance rates of methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA to cefazolin, cefuroxime, benzoxiline, ampicillin/sulbactam, and clindamycin were all statistically significant ( χ2=68.91, 68.91, 82.00, 68.91 and 9.20, respectively, all P<0.05). Intravenous anti-infective treatment was administered for 24(35, 47) days in 289 children with osteomyelitis, for a total duration of 42.00(35.00, 47.00) days. After treatment, 287 cases (99.3%) were discharged with improvement, while two cases (0.7%) died. One death was due to phagocytosis syndrome and septic shock, and the other death was due to septic shock and multiple organ dysfunction. Conclusions:Non-chronic osteomyelitis in children is most common in male children under six years old, and the most common sites are femur, tibia and humerus. The main clinical manifestations are fever, localized swelling and pain. SA was the most common causative agent. No SA strain resistant to vancomycin, linezolid, moxifloxacin, ciprofloxacin, gentamicin, rifampicin, ceflorin, tigecycline, ticlosporin, fosfomycin, daptomycin, furotoxin, quinupristin/dalfopristin is found.

Objective:To investigate any effect of aerobic exercise on the functioning of endothelial progenitor cells (EPCs) and on the Akt/eNOS signaling pathway in type 2 diabetes.Methods:Forty-five 6-week-old Sprague-Dawley rats free of specific pathogens were randomly divided into a normal control group, a diabetic model group and an exercise group. Type 2 diabetes mellitus was induced in the model and exercise groups by feeding a high-fat diet and streptozotocin injection. After successful modeling, the exercise group underwent 8 weeks of non-weight-bearing swimming training after which blood was collected from their abdominal aortas to measure EPCs, serum nitric oxide and the level of vascular endothelial growth factor (VEGF). Bone marrow-derived EPCs were isolated from the rats′ femurs and tibias for in vitro culture. The cells′ tube formation capacity was assessed using Matrigel assays, while the expression of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) were determined using western blotting.Results:Compared with the normal group, the model group exhibited significantly reduced counts of EPCs in their peripheral blood. Serum NO and VEGF were also significantly lower, on average, and tube formation capacity was significantly impaired. p-Akt and p-eNOS protein expression were significantly downregulated. In contrast, the exercise group showed significantly increased EPC counts, elevated serum NO and VEGF levels, improved tube formation, and upregulated p-Akt and p-eNOS expression compared with the model group.Conclusions:Aerobic exercise improves EPC functioning in diabetic rats, and its mechanism may be associated with the regulation of the Akt/eNOS signaling pathway.

Objective:To analyze the clinical characteristics, distribution of common pathogenic bacteria and drug resistance in children with non-chronic osteomyelitis, to provide a basis for empirical antimicrobial drug selection.Methods:This study was a retrospective analysis cohort study. Clinical data, pathogenic bacteria and drug sensitivity test results of 289 children aged 0 to 18 years with non-chronic osteomyelitis who were hospitalized in the Pediatrics Hospital of Fudan University from January 2013 to June 2023 were collected retrospectively. Statistical analyses were performed using chi-square test.Results:Of the 289 children, 188(65.1%) were male, with a male to female ratio of 1.86∶1, and the age was 3.00(0.66, 8.00) years. The age less than six years amounted 65.1% (188/289). The incidence was the highest from December to February of the following year, reaching 32.5%(94/289). The clinical manifestations were fever in 193 cases (66.8%), fever with localized pain in 47 cases (16.3%), and fever with localized swelling and fever with localized swelling and pain in 39 cases (13.5%) each. Single bone involvement was observed in 242(83.7%) cases, including 88(36.4%) femur, 47(19.4%) tibia, and 37(15.3%) humerus. Of the 130 pathogen-positive cases, 102(78.5%) were Staphylococcus aureus (SA) including 45(44.1%) methicillin-resistant Staphylococcus aureus (MRSA), 10(7.7%) were Pseudomonas aeruginosa, and 3(2.3%) each were Klebsiella pneumoniae and Staphylococcus mansoni. The rate of MRSA detection in SA fluctuated each year from 2013 to 2023, with the highest in 2017, when eight out of 13 SA cases were MRSA. The resistance rates of all SA to vancomycin, linezolid, moxifloxacin, ciprofloxacin, gentamicin, rifampicin, ceflorin, tigecycline, ticlosporin, fosfomycin, daptomycin, furotoxin, quinupristin/dalfopristin were all zero, and the differences in resistance rates of methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA to cefazolin, cefuroxime, benzoxiline, ampicillin/sulbactam, and clindamycin were all statistically significant ( χ2=68.91, 68.91, 82.00, 68.91 and 9.20, respectively, all P<0.05). Intravenous anti-infective treatment was administered for 24(35, 47) days in 289 children with osteomyelitis, for a total duration of 42.00(35.00, 47.00) days. After treatment, 287 cases (99.3%) were discharged with improvement, while two cases (0.7%) died. One death was due to phagocytosis syndrome and septic shock, and the other death was due to septic shock and multiple organ dysfunction. Conclusions:Non-chronic osteomyelitis in children is most common in male children under six years old, and the most common sites are femur, tibia and humerus. The main clinical manifestations are fever, localized swelling and pain. SA was the most common causative agent. No SA strain resistant to vancomycin, linezolid, moxifloxacin, ciprofloxacin, gentamicin, rifampicin, ceflorin, tigecycline, ticlosporin, fosfomycin, daptomycin, furotoxin, quinupristin/dalfopristin is found.

Objective:To investigate the role and mechanism of IL-17 in hypertensive heart failure in rats.Methods:The spon-taneously hypertensive(SHR)model of hypertensive heart failure was established by abdominal aortic ligation.IL-17+IgG and IL-17 protein were injected intraperitoneally into the rats with hypertensive heart failure.After 4 weeks,cardiac structure and function were monitored,and peripheral blood and myocardial tissue were collected.The role and mechanism of IL-17 in hypertensive heart failure were studied by HE staining,immunohistochemistry,Western blot,qRT-PCR and ELISA.Results:After intraperitoneal injection of exogenous IL-17,the levels of IL-17,NT-proBNP,P38 and MK2 protein expressions were increased,and the levels of VEGF and Cav1.2 protein expression were decreased.Exogenous intraperitoneal injection of IL-17+IgG blocked IL-17,increased VEGF level and Cav1.2 protein expression,and decreased NT-proBNP level,P38 and MK2 protein expressions.Conclusion:IL-17 can be activated P38 lightning/MK2-Cav1.2 signaling pathways involved in high blood pressure,heart failure and cardiac function in rats damage;inhi-bition of IL-17 can effectively improve the cardiac function damage caused by hypertensive heart failure.

Objective:To compare the antiosteoporosis effect of conventional treatment and conventional treatment combined with Denosumab after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 211 patients with OVCF admitted to the Second Affiliated Hospital of Soochow University from September 2020 to September 2022. All the patients were female, aged 56-90 years [(71.4±8.1)years]. The bone mineral density T-score of the lumbar spine was (-2.6±1.0)SD before operation. Fracture segments included T 1-T 9 in 45 patients, T 10-L 2 in 146, and L 3-L 5 in 69. Of all, 174 patients were treated with single-segment surgery, 25 with two-segment surgery and 12 with surgery involving three or more segments. According to the wishes of the patients, 107 patients were treated with daily oral administration of calcium and active Vitamin D after PKP (conventional treatment group) and 104 patients with Denosumab combined with the conventional treatment after PKP (Denosumab therapy group). The bone mineral density T-scores of the lumbar spine of the two groups were compared before surgery and at the last follow-up. The visual analogue scale (VAS) and Oswestry disability index (ODI) before surgery, at 3 days, 6 months after surgery, and at the last follow-up were evaluated and the refracture rate after surgery was detected. Possible adverse effects after medication during anti-osteoporosis treatment were observed in two the groups. Results:All the patients were followed up for 12-24 months [(13.5±2.0)months]. Before surgery, the bone mineral density T-score of the lumbar spine was (-2.7±1.1)SD in the Denosumab therapy group and (-2.5±0.8)SD in the conventional treatment group ( P>0.05). At the last follow-up, the bone mineral density T-score of the lumbar spine was (-2.1±1.1)SD in the Denosumab therapy group, significantly higher than (-2.5±0.9)SD in the conventional treatment group ( P<0.05). In the Denosumab therapy group, the bone mineral density T-score of the lumbar spine at the last follow-up was significantly increased compared to that before surgery ( P<0.01), while there was no significant difference in the conventional treatment group ( P<0.05). Before surgery and at 3 days after surgery, the VAS scores and ODI values were (8.5±0.9)points, (2.8±0.8)points, 48.7±4.8 and 25.6±4.0 in the Denosumab therapy group, which was not statistically different from those in the conventional treatment group [(8.5±1.3)points and (2.8±0.9)points, 47.9±7.0 and 25.9±3.7] ( P>0.05). At 6 months after surgery and at the last follow-up, the VAS scores and ODI values were (2.2±0.8)points, (1.7±0.8)points, 24.2±3.6 and 23.2±4.1 in the Denosumab therapy group, significantly lower than those of the conventional treatment group [(2.8±0.9)points, (2.8±1.1)points, 26.4±3.2 and 27.3±4.0] ( P<0.01). The VAS scores at each time point after surgery in both groups decreased significantly compared with those before surgery ( P<0.05). The VAS scores continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while no significant difference was found among those at different time points in the conventional treatment group ( P>0.05). The ODI values at each time point after surgery in both groups significantly decreased compared to those before surgery ( P<0.05). The ODI values continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while in the conventional treatment group, no significant difference was found between those at 6 months after surgery and those at 3 days after surgery ( P>0.05) and they were improved at the last follow-up compared with those at 3 days after surgery ( P<0.05). The refracture rate after surgery was 6.7% (7/104) in the Denosumab therapy group, significantly lower than 16.8% (18/107) in the conventional treatment group ( P<0.05). No serious complications were observed during the antiosteoporosis period in either group. Conclusion:Compared with daily oral administration of Calcium and active Vitamin D after PKP, the conventional treatment combined with Denosumab after PKP can effectively increase the bone density, relieve pain continuously, improve functional restoration, and reduce the risk of refracture in OVCF patients.

OBJECTIVE: To investigate the anti-adhesive effect and underlying mechanism of dynamic and static stress stimulation on the early healing process of rat Achilles tendon injury. METHODS: Achilles tendon tissues of 15 male Sprague Dawley (SD) rats aged 4-6 weeks were isolated and cultured by enzyme digestion method. Rat Achilles tendon cells were treated with tumor necrosis factor α to construct the Achilles tendon injury cell model, and dynamic stress stimulation (dynamic group) and static stress stimulation (static group) were applied respectively, while the control group was not treated. Live/dead cell double staining was used to detect cell activity, ELISA assay was used to detect the expression of α smooth muscle actin (α-SMA), and real-time fluorescence quantitative PCR was used to detect the mRNA expression of collagen type Ⅰ (COL1A1), collagen type Ⅲ (COL3A1), and Scleraxis (SCX). Thirty male SD rats aged 4-6 weeks underwent Achilles tendon suture and were randomly divided into dynamic group (treated by dynamic stress stimulation), static group (treated by static stress stimulation), and control group (untreated), with 10 rats in each group. HE staining and scoring were performed to evaluate the healing of Achilles tendon at 8 days after operation. COL1A1 and COL3A1 protein expressions were detected by immunohistochemical staining, α-SMA and SCX protein expressions were detected by Western blot, and maximum tendon breaking force and tendon stiffness were detected by biomechanical stretching test. RESULTS: In vitro cell experiment, when compared to the static group, the number of living cells in the dynamic group was higher, the expression of α-SMA protein was decreased, the relative expression of COL3A1 mRNA was decreased, and the relative expression of SCX mRNA was increased, and the differences were all significant ( P<0.05). In the in vivo animal experiment, when compared to the static group, the tendon healing in the dynamic group was better, the HE staining score was lower, the expression of COL1A1 protein was increased, the expression of COL3A1 protein was decreased, the relative expression of SCX protein was increased, the relative expression of α-SMA protein was decreased, and the tendon stiffness was increased, the differences were all significant ( P<0.05). CONCLUSION Compared with static stress stimulation, the dynamic stress stimulation improves the fibrosis of the scar tissue of the rat Achilles tendon, promote the recovery of the biomechanical property of the Achilles tendon, and has obvious anti-adhesion effect.
Animals ; Achilles Tendon/injuries* ; Male ; Rats ; Rats, Sprague-Dawley ; Collagen Type I/metabolism* ; Collagen Type III/metabolism* ; Tendon Injuries/therapy* ; Wound Healing ; Stress, Mechanical ; Actins/metabolism* ; Cells, Cultured ; Tissue Adhesions/prevention & control* ; Tumor Necrosis Factor-alpha/metabolism* ; RNA, Messenger/genetics* ; Disease Models, Animal ; Collagen Type I, alpha 1 Chain/metabolism* ; Biomechanical Phenomena ; Basic Helix-Loop-Helix Transcription Factors

Objective:To evaluate the efficacy of Qingqi Huatan Decoction combined with conventional western medicine therapy in the treatment of severe pneumonia with phlegm-heat obstructing the lung syndrome.Methods:A total of 84 patients with severe pneumonia with phlegm-heat obstructing lung syndrome admitted to Zhangjiagang Hospital of Traditional Chinese Medicine from February 2018 to June 2020 were randomly divided into two groups, 42 in each group. The control group was treated with bronchoalveolar lavage (BAL) on the basis of routine treatment, and the combined group was treated with Qingqi Huatan Decoction on the basis of the control group. Both groups were treated for 7 days. The Clinical Pulmonary Infection Score (CPIS) was used to evaluate the degree of pulmonary infection, and the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) was used to evaluate the severity of the disease. The Serum CRP and IL-6 levels were detected by ELISA, and procalcitonin (PCT) levels were detected by electrochemiluminescence method to evaluate clinical efficacy.Results:The total effective rate was 88.1% (37/42) in the combined group and 69.0% (29/42) in the control group, with a statistically significant difference between the two groups ( χ2=4.53, P=0.033). After treatment, the CPIS (2.19±0.42 vs. 3.66±0.69, t=11.79) and APACHE Ⅱ (9.84±1.31 vs. 11.25±3.22, t=2.63) in the combination group were significantly lower than those in the control group. The serum CRP, PCT, and IL-6 levels in the combination group were significantly lower than those in the control group ( t=30.32, 8.59, 6.08, all Ps<0.001). During the treatment period, there was no obvious abnormality of liver and kidney function in both groups. Conclusion:Qingqi Huatan Decoction combined with conventional western medicine therapy can reduce the degree of pulmonary infection in patients with severe pneumonia with phlegm-heat obstructing the lung syndrome, reduce the level of inflammatory cytokines, and improve clinical efficacy.