Objective To investigate the therapeutic effects of combined magnetic and electrical stimulation with an"intelligent exercise prescription"and novel matrix radiofrequency therapy in patients with pelvic organ prolapse(POP).Methods A total of 158 patients with POP who received treatment at the Gynecological Pelvic Floor Rehabilitation Center of the Eighth Affiliated Hospital of Southern Medical University between October 2022 and July 2025 were retrospectively enrolled and divided into an observation group(n=64)and a control group(n=94)based on their treatment plans.The control group underwent magnetic and electrical stimulation combined with an"intelligent exercise prescription"regimen.Specifically,patients received 10 sessions of electrical stimulation,5 sessions of magnetic stimulation,and performed 15～20 minutes of daily home exercise training guided by the"intelligent exercise prescription."The observation group received,in addition to the aforementioned treatments,four sessions of novel matrix radiofrequency therapy.Changes in the muscle strength grades of type Ⅰ and type Ⅱ pelvic floor muscles,Glazer surface electromyography(EMG)values,and POP-Q staging were compared between the two groups before and after treatment.Results After treatment,both groups demonstrated significant improvements in type Ⅰ and type Ⅱ muscle fiber strength compared to baseline(all P<0.05),with the observation group showing greater improvement in type Ⅰ muscle fiber strength than the control group(P<0.05).The muscle potential values of the observation group during rapid contraction,tense contraction,and endurance contraction stages were markedly increased compared to pre-treatment levels.Moreover,the muscle potential values during the pre-resting stage were significantly reduced after treatment(P<0.05).In the observation group,POP-Q grades of the anterior vaginal wall,uterus,and posterior vaginal wall were all significantly lower post-treatment than pre-treatment(all P<0.05).However,no statistically significant differences were observed between the observation group and the control group in these parameters(P>0.05).Both groups exhibited relatively high compliance rates(both≥75.0%),with no significant difference between them(P>0.05).The treatment cost for the observation group was significantly higher than that for the control group(P<0.05).Conclusions The combination of magneto-electrical stimulation,an"intelligent exercise prescription,"and novel matrix radiofrequency therapy can significantly improve pelvic floor muscle strength and muscle potential values in the short term,compared to pre-treatment levels.This integrated approach also effectively alleviates the prolapse of the anterior vaginal wall,uterus,and posterior vaginal wall.Furthermore,the combination of magnetic and electrical stimulation,"intelligent exercise prescription,"and matrix radiofrequency therapy demonstrates superior efficacy in enhancing type Ⅰ pelvic floor muscle fiber strength when compared to the combination of magnetic and electrical stimulation with"intelligent exercise prescription"alone.However,this treatment protocol entails a relatively high economic burden,and its clinical application should be carefully evaluated in consideration of patients'functional needs and financial conditions.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

Objective:To explore the potential of the novel fibroblast activation protein (FAP)-targeted theranostic agent 68Ga/ 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-2P (FAP inhibitor (FAPI)) 2 in microsatellite stable (MSS) colorectal cancer, and to evaluate the efficacy and underlying mechanism of 177Lu-DOTA-2P(FAPI) 2 in combination with immune checkpoint inhibitors (ICIs). Methods:This study was a randomized, parallel-group design. DOTA-2P(FAPI) 2 was labeled with 68Ga or 177Lu respectively. The binding performance of DOTA-2P(FAPI) 2 to FAP was validated through in vitro cell experiments. FAP-positive CT26-FAP tumor-bearing mouse model was constructed, and microPET imaging and biodistribution were performed. The in vivo antitumor efficacy was assessed for the 177Lu-DOTA-2P(FAPI) 2 monotherapy, α programmed death-ligand 1 (PD-L1) monotherapy, and the combination of 177Lu-DOTA-2P(FAPI) 2 with αPD-L1 therapy groups. Changes in the tumor microenvironment were analyzed using single-cell RNA sequencing to elucidate the mechanism of the combined treatment. Independent-sample t test was used to analyze data. Survival analysis was performed using the log-rank test. Results:The labeling yields of 68Ga/ 177Lu-DOTA-2P(FAPI) 2 were both >90%, with the radiochemical purities both >95%. In vitro cellular uptake and blocking assays showed that FAPI-46 significantly inhibited the binding of 68Ga-DOTA-2P(FAPI) 2 to FAP in CT26-FAP cells, with the cellular uptake values at 60min of (51.5±0.8)% and (1.0±0.3)%, respectively ( t=102.40, P<0.001). MicroPET imaging showed that the tumor uptake of 68Ga-DOTA-2P(FAPI) 2 remained stable even at 4 h post-injection, with a significantly higher uptake value compared to 68Ga-FAPI-46 ((7.3±1.6) vs (3.7±0.2) percentage activity of injection dose per gram of tissue (%ID/g); t=3.87, P=0.018). The biodistribution results indicated significant tumor uptake of 177Lu-DOTA-2P(FAPI) 2 even at 24 h post-injection ((4.30±0.52)%ID/g). The combination of 177Lu-DOTA-2P(FAPI) 2 and αPD-L1 achieved the 30-day survival rate of 100%, which was significantly superior to that of the control group (saline injection; χ2=9.53, P=0.002). Further mechanistic studies revealed that the combination therapy reprogramed the tumor microenvironment, enhanced anti-tumor intercellular communication, and activated signaling pathways such as Fas-FasL between T cells/natural killer (NK) cells and tumor cells, thereby synergistically inhibiting tumor progression. Conclusions:68Ga/ 177Lu-DOTA-2P(FAPI) 2 exhibits theranostic potential for MSS colorectal cancer. The combination of 177Lu-DOTA-2P(FAPI) 2 with ICIs may significantly prolong survival, demonstrating significant potential for clinical translation.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

Objective:To evaluate the feasibility of the novel programmed death-ligand 1 (PD-L1)-targeted PET/CT molecular probe for evaluating PD-L1 expression and tumor heterogeneity in patients with non-small cell lung cancer (NSCLC).Methods:From October 2023 to October 2024, 30 patients (21 males, 9 females; age 69(58, 75) years) with newly diagnosed NSCLC at the First Affiliated Hospital of Xiamen University were prospectively enrolled. All patients underwent PET/CT imaging 1 h after intravenous administration of 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-DK224, and SUV max was calculated. Immunohistochemical staining on biopsy samples of patients were performed and the PD-L1 tumor proportion score (TPS) was calculated. The differences of SUV max between two groups were compared by using Mann-Whitney U test. Results:Of 30 patients, 31 biopsy specimens were obtained including 24 primary lesion biopsies, 1 lymph node lesion biopsy, and 6 metastatic lesion biopsies, with 16 TPS<1%, 9 1%≤TPS<50% and 6 TPS≥50%. PD-L1-positive tumors showed relatively high uptake of 68Ga-NOTA-DK224. The SUV max of TPS≥1% group was significantly higher than that of TPS<1% group (6.9(5.1, 7.7) vs 3.8(3.1, 4.2); Z=-4.47, P<0.001), and SUV max of TPS≥50% group was significantly higher than that of TPS<50% group (8.6(7.3, 12.4) vs 4.2(3.7, 5.3); Z=-3.65, P<0.001). Of 30 patients, 24 had multiple metastatic lesions with 212 lesions in total. The median fold difference was 2.3 (range: 1.4-6.0), and the median CV was 28.3% (range: 11.7%-61.6%). Conclusion:68Ga-NOTA-DK224 PET/CT is able to accurately and comprehensively reflect PD-L1 expression and tumor heterogeneity in primary and metastatic NSCLC.

Objective To investigate the therapeutic effects of combined magnetic and electrical stimulation with an"intelligent exercise prescription"and novel matrix radiofrequency therapy in patients with pelvic organ prolapse(POP).Methods A total of 158 patients with POP who received treatment at the Gynecological Pelvic Floor Rehabilitation Center of the Eighth Affiliated Hospital of Southern Medical University between October 2022 and July 2025 were retrospectively enrolled and divided into an observation group(n=64)and a control group(n=94)based on their treatment plans.The control group underwent magnetic and electrical stimulation combined with an"intelligent exercise prescription"regimen.Specifically,patients received 10 sessions of electrical stimulation,5 sessions of magnetic stimulation,and performed 15～20 minutes of daily home exercise training guided by the"intelligent exercise prescription."The observation group received,in addition to the aforementioned treatments,four sessions of novel matrix radiofrequency therapy.Changes in the muscle strength grades of type Ⅰ and type Ⅱ pelvic floor muscles,Glazer surface electromyography(EMG)values,and POP-Q staging were compared between the two groups before and after treatment.Results After treatment,both groups demonstrated significant improvements in type Ⅰ and type Ⅱ muscle fiber strength compared to baseline(all P<0.05),with the observation group showing greater improvement in type Ⅰ muscle fiber strength than the control group(P<0.05).The muscle potential values of the observation group during rapid contraction,tense contraction,and endurance contraction stages were markedly increased compared to pre-treatment levels.Moreover,the muscle potential values during the pre-resting stage were significantly reduced after treatment(P<0.05).In the observation group,POP-Q grades of the anterior vaginal wall,uterus,and posterior vaginal wall were all significantly lower post-treatment than pre-treatment(all P<0.05).However,no statistically significant differences were observed between the observation group and the control group in these parameters(P>0.05).Both groups exhibited relatively high compliance rates(both≥75.0%),with no significant difference between them(P>0.05).The treatment cost for the observation group was significantly higher than that for the control group(P<0.05).Conclusions The combination of magneto-electrical stimulation,an"intelligent exercise prescription,"and novel matrix radiofrequency therapy can significantly improve pelvic floor muscle strength and muscle potential values in the short term,compared to pre-treatment levels.This integrated approach also effectively alleviates the prolapse of the anterior vaginal wall,uterus,and posterior vaginal wall.Furthermore,the combination of magnetic and electrical stimulation,"intelligent exercise prescription,"and matrix radiofrequency therapy demonstrates superior efficacy in enhancing type Ⅰ pelvic floor muscle fiber strength when compared to the combination of magnetic and electrical stimulation with"intelligent exercise prescription"alone.However,this treatment protocol entails a relatively high economic burden,and its clinical application should be carefully evaluated in consideration of patients'functional needs and financial conditions.

Objective:To evaluate the feasibility of the novel programmed death-ligand 1 (PD-L1)-targeted PET/CT molecular probe for evaluating PD-L1 expression and tumor heterogeneity in patients with non-small cell lung cancer (NSCLC).Methods:From October 2023 to October 2024, 30 patients (21 males, 9 females; age 69(58, 75) years) with newly diagnosed NSCLC at the First Affiliated Hospital of Xiamen University were prospectively enrolled. All patients underwent PET/CT imaging 1 h after intravenous administration of 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-DK224, and SUV max was calculated. Immunohistochemical staining on biopsy samples of patients were performed and the PD-L1 tumor proportion score (TPS) was calculated. The differences of SUV max between two groups were compared by using Mann-Whitney U test. Results:Of 30 patients, 31 biopsy specimens were obtained including 24 primary lesion biopsies, 1 lymph node lesion biopsy, and 6 metastatic lesion biopsies, with 16 TPS<1%, 9 1%≤TPS<50% and 6 TPS≥50%. PD-L1-positive tumors showed relatively high uptake of 68Ga-NOTA-DK224. The SUV max of TPS≥1% group was significantly higher than that of TPS<1% group (6.9(5.1, 7.7) vs 3.8(3.1, 4.2); Z=-4.47, P<0.001), and SUV max of TPS≥50% group was significantly higher than that of TPS<50% group (8.6(7.3, 12.4) vs 4.2(3.7, 5.3); Z=-3.65, P<0.001). Of 30 patients, 24 had multiple metastatic lesions with 212 lesions in total. The median fold difference was 2.3 (range: 1.4-6.0), and the median CV was 28.3% (range: 11.7%-61.6%). Conclusion:68Ga-NOTA-DK224 PET/CT is able to accurately and comprehensively reflect PD-L1 expression and tumor heterogeneity in primary and metastatic NSCLC.

Objective:To explore the potential of the novel fibroblast activation protein (FAP)-targeted theranostic agent 68Ga/ 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-2P (FAP inhibitor (FAPI)) 2 in microsatellite stable (MSS) colorectal cancer, and to evaluate the efficacy and underlying mechanism of 177Lu-DOTA-2P(FAPI) 2 in combination with immune checkpoint inhibitors (ICIs). Methods:This study was a randomized, parallel-group design. DOTA-2P(FAPI) 2 was labeled with 68Ga or 177Lu respectively. The binding performance of DOTA-2P(FAPI) 2 to FAP was validated through in vitro cell experiments. FAP-positive CT26-FAP tumor-bearing mouse model was constructed, and microPET imaging and biodistribution were performed. The in vivo antitumor efficacy was assessed for the 177Lu-DOTA-2P(FAPI) 2 monotherapy, α programmed death-ligand 1 (PD-L1) monotherapy, and the combination of 177Lu-DOTA-2P(FAPI) 2 with αPD-L1 therapy groups. Changes in the tumor microenvironment were analyzed using single-cell RNA sequencing to elucidate the mechanism of the combined treatment. Independent-sample t test was used to analyze data. Survival analysis was performed using the log-rank test. Results:The labeling yields of 68Ga/ 177Lu-DOTA-2P(FAPI) 2 were both >90%, with the radiochemical purities both >95%. In vitro cellular uptake and blocking assays showed that FAPI-46 significantly inhibited the binding of 68Ga-DOTA-2P(FAPI) 2 to FAP in CT26-FAP cells, with the cellular uptake values at 60min of (51.5±0.8)% and (1.0±0.3)%, respectively ( t=102.40, P<0.001). MicroPET imaging showed that the tumor uptake of 68Ga-DOTA-2P(FAPI) 2 remained stable even at 4 h post-injection, with a significantly higher uptake value compared to 68Ga-FAPI-46 ((7.3±1.6) vs (3.7±0.2) percentage activity of injection dose per gram of tissue (%ID/g); t=3.87, P=0.018). The biodistribution results indicated significant tumor uptake of 177Lu-DOTA-2P(FAPI) 2 even at 24 h post-injection ((4.30±0.52)%ID/g). The combination of 177Lu-DOTA-2P(FAPI) 2 and αPD-L1 achieved the 30-day survival rate of 100%, which was significantly superior to that of the control group (saline injection; χ2=9.53, P=0.002). Further mechanistic studies revealed that the combination therapy reprogramed the tumor microenvironment, enhanced anti-tumor intercellular communication, and activated signaling pathways such as Fas-FasL between T cells/natural killer (NK) cells and tumor cells, thereby synergistically inhibiting tumor progression. Conclusions:68Ga/ 177Lu-DOTA-2P(FAPI) 2 exhibits theranostic potential for MSS colorectal cancer. The combination of 177Lu-DOTA-2P(FAPI) 2 with ICIs may significantly prolong survival, demonstrating significant potential for clinical translation.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Objective:To develop a tetramer probe targeting fibroblast activation protein (FAP), named 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-4P(FAP inhibitor (FAPI)) 4, evaluate its biodistribution and PET image in FAP-positive-tumor bearing nude mice, and explore its feasibility as a novel radio-regent for treatment of FAP-positive tumor. Methods:FAP tetramer probe was constructed on the FAPI-46 motif with four mini-polyethylene glycol (PEG)(PEG 3) spacers between the four FAPI motifs, denoted as 4P(FAPI) 4. DOTA was used as the chelator for radiolabeling with 68Ga and 177Lu. The FAP binding characteristics were test by in vitro cell competitive binding experiment. Small-animal PET, in vivo biodistribution, and radionuclide targeting therapy were performed in HT-1080-FAP tumor bearing nude mice ( n=39). Independent-sample t test was performed to analyze tumor uptake data, and two-factor repeated measures analysis of variance was utilized to compare tumor volume data in radioactive isotope therapy. Results:Cell experiment showed that FAPI-tetramer and FAPI-monomer had similar half maximal inhibitory concentration values (3.29 and 2.15 nmol/L). 68Ga/ 177Lu radiolabeled FAPI-tetramer had better tumor uptake and retention than FAPI-monomer in small-animal PET and in vivo biodistribution experiment, with the tumor uptake for 177Lu-DOTA-4P(FAPI) 4 and 177Lu-FAPI-46 at 48 h of (18.72±1.32) vs (2.72±1.20) percentage activity of injection dose per gram of tissue (%ID/g) ( t=15.55, P<0.001). 177Lu-DOTA-4P(FAPI) 4 group showed best anti-tumor efficacy compared with 177Lu-FAPI-46 and control group in radionuclide targeting therapy. On the 2nd day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the control group (mean difference 67.19 mm 3, P=0.049); on the 14th day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the monomer treatment group (mean difference 414.33 mm 3, P=0.005). Conclusion:FAPI-tetramer can improve tumor uptake and retention ability compared with FAPI-46, and 177Lu-DOTA-4P(FAPI) 4 can be a promising radio-agent for FAP-positive tumor therapy.