Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.

Objective To explore the effect of electromyographic perception-assisted robotic training combined with paired associa-tion stimulation on upper limb function in hemiplegic patients after stroke.Methods From December,2023 to December,2024,120 hemiplegic patients after stroke in Nanjing Pukou People's Hos-pital(Liangjiang Hospital,Southeast University)were randomly assigned to control group(n=60)and experi-mental group(n=60)using random envelope method.Both groups received medication and routine rehabilita-tion training,the control group received traditional muscle strength training combined with paired associative stimulation,and the experimental group received electromyographic perception robot-assisted training combined with paired association stimulation.Fugl-Meyer Assessment-Upper Extremities(FMA-UE),modified Barthel In-dex(MBI),and modified Ashworth Scale(MAS)were conducted before and four weeks after treatment.The sur-face electromyography(sEMG)was used to detect the root mean square(RMS)and integrated electromyography(iEMG)of the biceps and triceps brachii,and to calculate the corresponding co-activation ratio(CR).Results Nine cases in the control group and four cases in the experimental group dropped down.After treatment,RMS of triceps,CR of flexion elbow,the scores of FMA-UE and MBI increased in both groups(|t|>2.219,P<0.001),and were better in the experimental group than in the control group(|t|>2.084,P<0.05);the biceps RMS and CR of elbow extension significantly increased in experimental group(|t|>3.863,P<0.001),and were better in the experimental group than in the control group(|t|>2.498,P<0.05).The MAS score of biceps improved in experi-mental group after treatment(Z=-4.097,P<0.001),and was better in the experimental group than in the con-trol group(Z=-3.459,P<0.01).Conclusion Electromyographic perception robot-assisted training combined with paired association stimulation can im-prove the upper limb motor function and the ability of daily living in hemiplegic patients after stroke.

Objective To investigate the proportions of myeloid-derived suppressor cells(MDSCs)and their subsets,including poly-morphonuclear MDSCs(PMN-MDSCs),early-stage MDSCs(e-MDSCs),monocytic MDSCs(M-MDSCs),and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)positive PMN-MDSCs,in the peripheral blood of ovarian cancer(OC)patients and ana-lyze their correlations with clinicopathological parameters of the patients.Methods The proportions of MDSCs and their subsets in the peripheral blood of 38 OC patients(OC group)and 46 healthy individuals(healthy control group)were detected by flow cytometry.The levels of serum IL-10 and TGF-β were detected using ELISA.The OC group was further divided into LOX-1 high and low expres-sion subgroups based on the median proportion of LOX-1+PMN-MDSCs in MDSCs.Results The proportions of MDSCs,PMN-MDSCs,and LOX-1+PMN-MDSCs in the peripheral blood mononuclear cells(PBMCs)of the OC group were significantly higher than those in the healthy control group(U=492,P＜0.001;t=8.741,P＜0.000 1;U=223,P＜0.000 1).The proportions of M-MDSCs and e-MDSCs in the OC group were significantly lower than those in the healthy control group(t=4.366,P＜0.000 1;t=6.927,P＜0.000 1).The proportion of LOX-1+PMN-MDSCs in the lymph node metastasis group of OC patients was significantly higher than that in the non-metastasis group(t=2.249,P＜0.05).The levels of serum IL-10 and TGF-β in the OC group were significantly higher than those in the healthy control group(P＜0.05).In addition,the level of serum TGF-β in the LOX-1 high expression group was significantly higher than that in the LOX-1 low expression group(t=2.302,P＜0.05).Conclusion The proportion of LOX-1+PMN-MDSCs in the peripheral blood of OC patients is significantly increased and closely related to lymph node metastasis.

Objectives:To investigate the predictive value of epicardial fat volume(EFV)and atrioventricular groove fat thickness(AVGT)—morphological biomarkers of epicardial adipose tissue—for major adverse cardiovascular events(MACE)in patients with dilated cardiomyopathy(DCM).Methods:This study enrolled 216 DCM patients.EFV and AVGT were obtained from cardiac magnetic resonance imaging(CMR).Patients were divided into event-free group(n=142)and event group(n=74)based on MACE occurrence during follow-up.Receiver operating characteristic(ROC)curve analysis was used to determine optimal cutoff values.Survival differences were assessed using Kaplan-Meier analysis,Cox proportional hazards regression analysis was used to identify independent risk factors,and restricted cubic spline(RCS)models were used to evaluate dose-response relationships.Results:AVGT and EFV were significantly higher in the event group than in event-free group(both P<0.05).ROC analysis identified optimal MACE-predicting cutoffs as follows:AVGT≥7.74 mm(area under the curve[AUC]=0.57)and EFV≥78.6 ml(AUC=0.62).Kaplan-Meier analysis revealed significantly lower MACE-free survival rates in patients with AVGT≥7.74 mm and EFV≥78.6 ml(both P<0.05).Cox regression analysis confirmed that AVGT(HR=2.18,95%CI:1.34-3.54)and EFV(HR=1.81,95%CI:1.11-2.96)were independent MACE risk factors(both P<0.05)in this patient cohort.RCS models demonstrated the significant linear associations between EFV/AVGT and MACE risk(bothoverall P<0.05).Conclusions:EFV and AVGT,the non-invasive imaging biomarkers quantifying and characterizing fat distribution,are independently correlated with elevated MACE risk in DCM patients.These metrics serve as potential prognostic indicators,enriching risk stratification indicators for early identification of high-risk patients and guiding personalized medication strategies.

Objective To explore the effect of electromyographic perception-assisted robotic training combined with paired associa-tion stimulation on upper limb function in hemiplegic patients after stroke.Methods From December,2023 to December,2024,120 hemiplegic patients after stroke in Nanjing Pukou People's Hos-pital(Liangjiang Hospital,Southeast University)were randomly assigned to control group(n=60)and experi-mental group(n=60)using random envelope method.Both groups received medication and routine rehabilita-tion training,the control group received traditional muscle strength training combined with paired associative stimulation,and the experimental group received electromyographic perception robot-assisted training combined with paired association stimulation.Fugl-Meyer Assessment-Upper Extremities(FMA-UE),modified Barthel In-dex(MBI),and modified Ashworth Scale(MAS)were conducted before and four weeks after treatment.The sur-face electromyography(sEMG)was used to detect the root mean square(RMS)and integrated electromyography(iEMG)of the biceps and triceps brachii,and to calculate the corresponding co-activation ratio(CR).Results Nine cases in the control group and four cases in the experimental group dropped down.After treatment,RMS of triceps,CR of flexion elbow,the scores of FMA-UE and MBI increased in both groups(|t|>2.219,P<0.001),and were better in the experimental group than in the control group(|t|>2.084,P<0.05);the biceps RMS and CR of elbow extension significantly increased in experimental group(|t|>3.863,P<0.001),and were better in the experimental group than in the control group(|t|>2.498,P<0.05).The MAS score of biceps improved in experi-mental group after treatment(Z=-4.097,P<0.001),and was better in the experimental group than in the con-trol group(Z=-3.459,P<0.01).Conclusion Electromyographic perception robot-assisted training combined with paired association stimulation can im-prove the upper limb motor function and the ability of daily living in hemiplegic patients after stroke.

Objective To investigate the proportions of myeloid-derived suppressor cells(MDSCs)and their subsets,including poly-morphonuclear MDSCs(PMN-MDSCs),early-stage MDSCs(e-MDSCs),monocytic MDSCs(M-MDSCs),and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)positive PMN-MDSCs,in the peripheral blood of ovarian cancer(OC)patients and ana-lyze their correlations with clinicopathological parameters of the patients.Methods The proportions of MDSCs and their subsets in the peripheral blood of 38 OC patients(OC group)and 46 healthy individuals(healthy control group)were detected by flow cytometry.The levels of serum IL-10 and TGF-β were detected using ELISA.The OC group was further divided into LOX-1 high and low expres-sion subgroups based on the median proportion of LOX-1+PMN-MDSCs in MDSCs.Results The proportions of MDSCs,PMN-MDSCs,and LOX-1+PMN-MDSCs in the peripheral blood mononuclear cells(PBMCs)of the OC group were significantly higher than those in the healthy control group(U=492,P＜0.001;t=8.741,P＜0.000 1;U=223,P＜0.000 1).The proportions of M-MDSCs and e-MDSCs in the OC group were significantly lower than those in the healthy control group(t=4.366,P＜0.000 1;t=6.927,P＜0.000 1).The proportion of LOX-1+PMN-MDSCs in the lymph node metastasis group of OC patients was significantly higher than that in the non-metastasis group(t=2.249,P＜0.05).The levels of serum IL-10 and TGF-β in the OC group were significantly higher than those in the healthy control group(P＜0.05).In addition,the level of serum TGF-β in the LOX-1 high expression group was significantly higher than that in the LOX-1 low expression group(t=2.302,P＜0.05).Conclusion The proportion of LOX-1+PMN-MDSCs in the peripheral blood of OC patients is significantly increased and closely related to lymph node metastasis.

OBJECTIVE To explore the mechanism of Shaoyao gancao decoction in improving intestinal motility in rats with slow transit constipation(STC)by regulating acid-sensitive ion channel 3(ASIC3)/extracellular signal-regulated kinase(ERK)signaling pathway.METHODS SD rats were used to construct an STC model by gavage with compound diphenoxylate.The successfully modeled rats were randomly divided into model group,Shaoyao gancao decoction group(1.5 g/mL),lactulose group(208.4 mg/mL,positive control),and combined inhibition group(Shaoyao gancao decoction 1.5 g/mL+amiloride hydrochloride 20 μg/kg),with 12 rats in each group.Additionally,12 healthy rats were selected as the blank group.They were given relevant medicine once a day and continuously intervened for 14 days.After intervention,the intestinal propulsion function and visceral sensitivity of the model rats were detected.The expression of ASIC3 in the colon tissue of rats was observed by immunohistochemical staining.mRNA expressions of ASIC3,ERK1 and ERK2 as well as protein expressions of ASIC3,ERK1/2 and phosphorylated ERK1/2(p-ERK1/2)in colon tissue of rats were detected;the ultrastructural changes of the enteric nervous system(ENS)-interstitial cell of Cajal(ICC)-smooth muscle cell(SMC)network in the rat colon were observed under electron microscopy.RESULTS Compared with the model group,the intestinal propulsion rate of the Shaoyao gancao decoction group was significantly increased,while the visceral pain threshold was significantly decreased.The proportion of the positive area of ASIC3 in the colonic tissue was significantly increased.The relative mRNA expression levels of ERK1,ERK2,and ASIC3,as well as the relative protein expression levels of p-ERK1/2 and ASIC3,and the p-ERK1/2 to ERK1/2 in the colonic tissue,were all significantly increased(P＜0.05 or P＜0.01).Additionally,there was marked repair of the morphological structure of ICC and SMC,with closer gap junctions observed.Compared with the Shaoyao gancao decoction group,the combined inhibition group exhibited a diminished improvement in intestinal motility of rats,with statistically significant differences in the levels of some indicators(P＜0.05 or P＜0.01);the repairing of the morphological structure of ICC and SMC was notably attenuated.CONCLUSIONS Shaoyao gancao decoction can effectively improve the intestinal transmission function and promote intestinal repair in STC rats,and its mechanism may be related to regulating the balance of the ENS-ICC-SMC network mediated by the ASIC3/ERK signaling pathway,thus promoting intestinal motility and reducing visceral sensitivity.

Objectives:To investigate the predictive value of epicardial fat volume(EFV)and atrioventricular groove fat thickness(AVGT)—morphological biomarkers of epicardial adipose tissue—for major adverse cardiovascular events(MACE)in patients with dilated cardiomyopathy(DCM).Methods:This study enrolled 216 DCM patients.EFV and AVGT were obtained from cardiac magnetic resonance imaging(CMR).Patients were divided into event-free group(n=142)and event group(n=74)based on MACE occurrence during follow-up.Receiver operating characteristic(ROC)curve analysis was used to determine optimal cutoff values.Survival differences were assessed using Kaplan-Meier analysis,Cox proportional hazards regression analysis was used to identify independent risk factors,and restricted cubic spline(RCS)models were used to evaluate dose-response relationships.Results:AVGT and EFV were significantly higher in the event group than in event-free group(both P<0.05).ROC analysis identified optimal MACE-predicting cutoffs as follows:AVGT≥7.74 mm(area under the curve[AUC]=0.57)and EFV≥78.6 ml(AUC=0.62).Kaplan-Meier analysis revealed significantly lower MACE-free survival rates in patients with AVGT≥7.74 mm and EFV≥78.6 ml(both P<0.05).Cox regression analysis confirmed that AVGT(HR=2.18,95%CI:1.34-3.54)and EFV(HR=1.81,95%CI:1.11-2.96)were independent MACE risk factors(both P<0.05)in this patient cohort.RCS models demonstrated the significant linear associations between EFV/AVGT and MACE risk(bothoverall P<0.05).Conclusions:EFV and AVGT,the non-invasive imaging biomarkers quantifying and characterizing fat distribution,are independently correlated with elevated MACE risk in DCM patients.These metrics serve as potential prognostic indicators,enriching risk stratification indicators for early identification of high-risk patients and guiding personalized medication strategies.

Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.

OBJECTIVE To observe the effects of Modified shaoyao gancao decoction on intestinal transit function,intestinal flora and the contents of metabolites[γ aminobutyric acid(GABA)and 5-hydroxytryptamine(5-HT)]in slow transit constipation(STC)rats.METHODS SD rats were randomly divided into blank group(10 rats)and modeling group(30 rats),with half male and half female.The STC model was established by intragastric administration of Compound diphenoxylate tablets in the modeling group.The successfully modeled rats were randomly divided into model group,Modified shaoyao gancao decoction group[56 g/(kg·d),calculated by crude drug]and positive control group[lactulose 2.09 g/(kg·d)],with 10 rats in each group.Each administration group was given relevant medicine intragastrically,the blank group and model group received an equivalent volume of normal saline,once a day,for 14 consecutive days.During the experiment,the general situation of rats was observed in each group.After the last medication,the body weight was measured,and the Bristol score was used to evaluate the fecal characteristics.The fecal moisture content,intestinal propulsion rate,and the contents of GABA and 5-HT in intestinal content were detected;the diversity of intestinal flora in intestinal contents was investigated,and the correlation between the contents of GABA,5-HT and relative abundance of microbiota was analyzed.RESULTS Compared with the model group,general conditions such as small body shape,sparse and rough fur,and slow movement were all improved in Modified shaoyao gancao decoction group;body weight,Bristol score,fecal moisture content,intestinal propulsion rate,5-HT content,Chao1 index and Shannon index were increased significantly,while GABA content and Simpson index were decreased significantly(P＜0.05).The intestinal flora of rats in the Modified shaoyao gancao decoction group could be classified as the same as the blank group,but was far from the model group;the relative abundances of Desulfobacterota,Firmicutes and Bacteroidota in this group showed a tendency of pull back,but the differences were not statistically significant compared to model group(P＞0.05).Desulfobacterota was an intergroup differential factor(P＜0.05).The content of GABA was negatively correlated with the relative abundance of Bacteroidota,Cyanobacteria,Patescibacteria and Actinobacteriota(P＜0.05).The content of 5-HT was positively correlated with the relative abundance of Campilobacterota(P＜0.05).CONCLUSIONS Modified shaoyao gancao decoction can improve the fecal properties and intestinal motility of STC rats.Its mechanism may be related to improving intestinal flora and then affecting the contents of GABA and 5-HT in intestinal contents.In addition,the contents of GABA and 5-HT may be significantly correlated with the relative abundance of specific bacterial phyla such as Bacteroidota and Campilobacterota.