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.

Adenosine monophosphate-activated protein kinase(AMPK),acting as a"molecular switch"for cellular energy status,regulates multiple metabolic pathways to maintain energy balance and plays a crucial role in the development of various ocular diseases.This article summarizes the mechanisms of AMPK in several ophthalmic diseases and the pro-gress of related research,with a focus on age-related macular degeneration,diabetic retinopathy,and ocular surface disea-ses.By reviewing the pathogenesis of these diseases and the regulatory role of the AMPK signaling pathway,we explore the potential applications of the AMPK signaling pathway in the treatment of ophthalmic diseases and analyze the limitations and deficiencies of current research.With further investigation,regulatory strategies targeting the AMPK signaling pathway are expected to provide new ideas and potential therapies for the treatment of ophthalmic diseases in the future.

Adenosine monophosphate-activated protein kinase(AMPK),acting as a"molecular switch"for cellular energy status,regulates multiple metabolic pathways to maintain energy balance and plays a crucial role in the development of various ocular diseases.This article summarizes the mechanisms of AMPK in several ophthalmic diseases and the pro-gress of related research,with a focus on age-related macular degeneration,diabetic retinopathy,and ocular surface disea-ses.By reviewing the pathogenesis of these diseases and the regulatory role of the AMPK signaling pathway,we explore the potential applications of the AMPK signaling pathway in the treatment of ophthalmic diseases and analyze the limitations and deficiencies of current research.With further investigation,regulatory strategies targeting the AMPK signaling pathway are expected to provide new ideas and potential therapies for the treatment of ophthalmic diseases in the future.

Objective:To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer.Methods:A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate.Results:Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side ( P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion:For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

Objective:To evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

Objective:Sepsis is a life-threatening organ dysfunction caused by the host's imbalanced response to infection.Due to lack of effective treatments,it has always been the difficulty and focus of clinical treatment of sepsis.Studies have shown that pro-brain-derived neurotrophic factor(proBDNF)binds to the high-affinity total neurotrophic factor p75 neurotrophin receptor(p75NTR),which activates downstream signaling cascades and disrupts immunological inflammation and plays an important role in the progression of sepsis.This study aims to explore the expression changes of lymphocyte-derived proBDNF/p75NTR in patients with sepsis and its effect on lymphocyte differentiation. Methods:From the healthy donors(control group,n=40)and sepsis patients(sepsis group,n=40)admitted to the hospital for the first time,peripheral blood samples and blood routine clinical detection indicators were obtained.By using flow cytometry,the proportion of lymphocyte subsets and their expression of proBDNF/p75NTR were examined.The peripheral blood lymphocytes were isolated from the control group and incubated with lipopolysaccharide(LPS).Flow cytometry analysis technology was used to detect the expression of proBDNF/p75NTR on LPS-treated lymphocyte subsets.On this basis,we investigated the effects on lymphocyte differentiation by inhibiting p75NTR. Results:White blood cell count,neutrophil count,and neutrophil percentage of the patients in the sepsis group at admission were significantly higher than those in the control group;on the contrary,lymphocyte count and lymphocyte percentage in the sepsis group were lower than those in the control group(all P＜0.001).The patients in the sepsis group had considerably greater neutrophil/lymphocyte and monocyte/lymphocyte ratios than those in the control group(both P＜0.05).In the peripheral blood of sepsis patients,proBDNF expression was upregulated on CD19+ B cells,whereas p75NTR expression was elevated on B cells,CD4+ T cells,and CD8+ T cells(all P＜0.05).ProBDNF/p75NTR expression was upregulated by LPS stimulation in vitro in peripheral blood cells of the control group(P＜0.05),and this tendency was similar to the expression alterations in peripheral lymphocytes of the sepsis group.Inhibition of p75NTR increased CD4+ T cell and CD19+ B cell percentages,cytokine expression of IL-4 and IL-10,and reduced IL-1β and IL-6 production(all P＜0.05). Conclusion:The immunosuppressive state of sepsis patients is indicated by a reduction in lymphocyte count and an increase in the proportion of inactive neutrophils.ProBDNF/p75NTR expression is upregulated in the peripheral blood lymphocytes of sepsis patients,and p75NTR inhibition may control lymphocyte differentiation involved in sepsis progression.

Objective::The purpose of this study was to determine the relationship between remnant-like particle cholesterol (RLP-C) and major adverse cardiovascular events (MACEs) in patients with different levels of proprotein convertase subtilisin/kexin 9 (PCSK9).Methods::From September 2007 to January 2009, 1,859 subjects in Pingguoyuan communities in Beijing were initially screened. After excluding those with bedridden status, mental illness, severe systemic diseases, and missing data, 1,680 subjects were recruited for follow up. All recruited subjects were followed up from February 2013 to September 2013 (181 subjects were lost to follow-up) and from June 2017 to September 2018 (174 subjects were lost to follow up). Finally, 1,325 subjects were included in the study. General demographic characteristics, lifestyle and behaviors, disease history and use of medication was collected. Levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fast blood glucose, RLP-C, low-density lipoprotein triglycerides and PCSK9 were measured. The levels of RLP-C (low: RLP-C ≤ 157 mg/L; high: RLP-C > 157 mg/L) and PCSK9 (low: PCSK9 ≤ 135.87 μg/L; high: PCSK9 > 135.87 μg/L) were represented using quartiles. Subjects were categorized into 4 groups according to their RLP-C and PCSK9 levels: Q4, high levels of RLP-C with high levels of PCSK9; Q3, high levels of RLP-C with low levels of PCSK9; Q2, low levels of RLP-C with high levels of PCSK9; and Q1, low levels of RLP-C with low levels of PCSK9. The association of RLP-C with MACEs in subjects with different PCSK9 levels was evaluated.Results::After a median follow-up of 9.5 years, 1,325 subjects were included in the study and a total of 191 MACEs had occurred. The incidence of MACEs was higher in the RLP-C > 157 mg/L group than the RLP-C ≤ 157 mg/L group (18.40% vs. 10.42%). Cox proportional hazards regression model analysis showed that increased RLP-C levels were associated with an increased risk of MACEs (hazard ratio: 1.405; 95% confidence interval: 1.005-1.964; P < 0.005). The incidence of MACEs was higher in the high RLP-C/PCSK9 group vs. the low RLP-C/PCSK9 group (20.68% vs. 8.76%). Cox proportional hazards regression model analysis showed that RLP-C was associated with an increased risk of MACEs in subjects with high PCSK9 levels independent of traditional risk factors (hazard ratio: 1.791; 95% confidence interval: 1.168-2.825; P = 0.001), but not in those with low PCSK9 levels. Conclusions::RLP-C was identified as a risk factor for MACEs, particularly in subjects with high PCSK9 levels. Lowering PCSK9 levels may reduce residual risk in subjects with elevated plasma RLP-C levels.

Objective::The purpose of this study was to determine the relationship between remnant-like particle cholesterol (RLP-C) and major adverse cardiovascular events (MACEs) in patients with different levels of proprotein convertase subtilisin/kexin 9 (PCSK9).Methods::From September 2007 to January 2009, 1,859 subjects in Pingguoyuan communities in Beijing were initially screened. After excluding those with bedridden status, mental illness, severe systemic diseases, and missing data, 1,680 subjects were recruited for follow up. All recruited subjects were followed up from February 2013 to September 2013 (181 subjects were lost to follow-up) and from June 2017 to September 2018 (174 subjects were lost to follow up). Finally, 1,325 subjects were included in the study. General demographic characteristics, lifestyle and behaviors, disease history and use of medication was collected. Levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fast blood glucose, RLP-C, low-density lipoprotein triglycerides and PCSK9 were measured. The levels of RLP-C (low: RLP-C ≤ 157 mg/L; high: RLP-C > 157 mg/L) and PCSK9 (low: PCSK9 ≤ 135.87 μg/L; high: PCSK9 > 135.87 μg/L) were represented using quartiles. Subjects were categorized into 4 groups according to their RLP-C and PCSK9 levels: Q4, high levels of RLP-C with high levels of PCSK9; Q3, high levels of RLP-C with low levels of PCSK9; Q2, low levels of RLP-C with high levels of PCSK9; and Q1, low levels of RLP-C with low levels of PCSK9. The association of RLP-C with MACEs in subjects with different PCSK9 levels was evaluated.Results::After a median follow-up of 9.5 years, 1,325 subjects were included in the study and a total of 191 MACEs had occurred. The incidence of MACEs was higher in the RLP-C > 157 mg/L group than the RLP-C ≤ 157 mg/L group (18.40% vs. 10.42%). Cox proportional hazards regression model analysis showed that increased RLP-C levels were associated with an increased risk of MACEs (hazard ratio: 1.405; 95% confidence interval: 1.005-1.964; P < 0.005). The incidence of MACEs was higher in the high RLP-C/PCSK9 group vs. the low RLP-C/PCSK9 group (20.68% vs. 8.76%). Cox proportional hazards regression model analysis showed that RLP-C was associated with an increased risk of MACEs in subjects with high PCSK9 levels independent of traditional risk factors (hazard ratio: 1.791; 95% confidence interval: 1.168-2.825; P = 0.001), but not in those with low PCSK9 levels. Conclusions::RLP-C was identified as a risk factor for MACEs, particularly in subjects with high PCSK9 levels. Lowering PCSK9 levels may reduce residual risk in subjects with elevated plasma RLP-C levels.

Objective:To analyze the association between thyroglobulin antibody (TgAb) and differentiated thyroid cancer (DTC) metastases detected by post-radioactive iodine (RAI) therapy scan, when stimulated thyroglobulin (sTg) <1 μg/L.Methods:A total of 314 (68 males, 246 females, age (44.5±12.5) years) post-thyroidectomy DTC patients whose sTg <1 μg/L between March 2013 and May 2017 in Henan Cancer Hospital were enrolled retrospectively. Patients underwent 131I whole-body planar imaging ( 131I-WBS) and SPECT/CT imaging 5 d after 131I administration. Iodine avid metastases were compared between TgAb-positive group and TgAb-negative (TgAb<4 kU/L) group. Logistic regression analysis was conducted to assess odds ratio ( OR) for iodine avid metastases in each subgroup (Q1: 4 kU/L≤TgAb≤9.27 kU/L; Q2: 9.27 kU/L101.43 kU/L) of TgAb-positive patients, with the TgAb-negative patients as the reference. χ2 test was used to analyze the data. Results:Iodine avid metastases were found in 16.9% (53/314) of DTC patients and were more frequently in TgAb-positive group with TgAb>26.75 kU/L than TgAb-negative group (26.0%(19/73) vs 13.7%(23/168); χ2=5.382, P=0.02). Most metastases (92.5%, 49/53) occurred in cervical and mediastinal lymph nodes. The OR for iodine avid metastases was obviously high in TgAb-positive patients with 26.75 kU/L

Objective:To investigate the diagnostic efficacy of 99Tc m-MIBI SPECT dual-phase imaging combined with rapid parathyroid hormone detection in thyroid cancer with suspected parathyroid mass. Methods:Data of 76 cases of thyroid cancer with suspected cervical parathyroid gland tumors receiving colorectal ultrasonography or CT examination in Thyroid Surgery Department of the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. Blood samples were taken before surgery to detect parathyroid hormone. Parathyroid hormone was quickly detected after clamping the tumor blood vessels during surgery. Based on the postoperative pathological results, the sensitivity, specificity, accuracy and consistency of various diagnostic methods were evaluated. The ROC curve was drawn by measuring the value of the parathyroid gland concentration after reduction of the tumor blood vessels by clamping the tumor.Results:The sensitivity and accuracy of the 99Tc m-MIBI SPECT dual-phase imaging combined with the rapid detection of parathyroid hormone in diagnosis of suspected parathyroid tumors were (96.5%, 93.4%) better than the 99Tc m-MIBI SPECT dual-phase imaging methods (77.6%, 78.9%) and intraoperative rapid detection methods (86.2%, 82.8%) , and had a high consistency with the results of pathological examination, Kappa value of 0.81. The combined detection rate of suspected parathyroid tumors was significantly higher than that of 99Tc m-MIBI SPECT dual-phase imaging and rapid intraoperative detection, but there was no significant difference between 99Tc m-MIBI SPECT dual-phase imaging and intraoperative rapid detection. The area under the ROC curve of the reduction ratio a value after clamping the blood vessels of the tumor was 0.774, and the standard error was 0.073. The difference was statistically significant ( P<0.001,95% CI:0.631-0.918) . According to the results obtained by the ROC, the index (sensitivity + specificity-1) was plotted on the ordinate and a was the abscissa. The maximum value of the Jordan index was 0.584. The a value corresponding to this point was 0.52. 0.52 is the DCP value. The corresponding sensitivity, specificity, accuracy was 86.2%,72.2%,and 82.9%. Conclusion:99Tc m-MIBI SPECT dual-phase imaging combined with rapid parathyroid hormone detection during surgery has good diagnostic value for thyroid cancer with suspected parathyroid mass, and is completely consistent with pathological diagnosis.