Objective:To investigate the uptake patterns of 18F-fluorodeoxy glucose ( 18F-FDG) in the endometrium using positron emission tomography (PET) imaging and to differentiate these from stage IA endometrial cancer. Methods:From September 2022 to April 2024, a prospective inclusion of 354 women without gynecological diseases and no hormone usage who underwent 18F-FDG PET-CT examinations at the affiliated hospital of Qingdao University were set as the physiological group, while a group containing 42 cases of Stage IA endometrial carcinoma was also set. The physiological group was divided into five groups based on the menstrual cycle: menstrual period, proliferative phase, ovulatory phase, secretory phase, and menopausal phase. The images were analyzed using visual and quantitative measurements; quantitative analysis indicators were standardized uptake value maximum (SUVmax) and the region of interest/liver ratio (R/L value). Receiver operating characteristic (ROCs) curve was used to determine the optimal cutoff values for SUVmax and R/L value. A clinical model was established using binary logistic regression, and ROC curves were drawn to evaluate the predictive performance of the model. Results:The uptake of 18F-FDG in the endometrium exhibited cyclical variations throughout different physiological phases, with higher uptakes observed during the menstrual and ovulation phases (SUVmax values of 6.66±3.26 and 3.89±1.21, respectively), which are significantly higher than those in the proliferative phase [median SUVmax of 2.54 (2.02, 3.47)], secretory phase (SUVmax of 2.55±0.86), and menopausal phase [SUVmax median of 2.04 (1.69, 2.29)]. During the menstrual and ovulation phases, the radiotracer accumulation patterns were triangular in 105 cases, oval in 32 cases, and round-like in 2 cases. All 42 cases of endometrial cancer showed 18F-FDG uptake, with radiotracer accumulation patterns being round-like in 17 cases, oval in 10 cases, triangular in 9 cases, and irregular in 6 cases. There were statistically significant differences in the shapes of radiotracer concentration between the menstrual, ovulatory periods, and endometrial carcinoma (both P＜0.001). The SUVmax and R/L values in menstrual period and ovulatory period were significantly lower than that in endometrial carcinoma group ( P＜0.001). During the menstrual phase, the optimal cutoff values for SUVmax and R/L in distinguishing between endometrial and endometrial cancer were 12.59 and 3.81, respectively, with corresponding AUCs of 0.885 and 0.842. After incorporating endometrial uptake morphology into the model, the AUCs was improved to 0.969 and 0.948, respectively. During the ovulatory phase, the optimal cutoff values for SUVmax and R/L were 5.96 and 2.85, respectively, with AUCs of 0.984 and 0.968. After integrating endometrial uptake morphology into the model, the AUCs were increased to 0.999 and 0.998, respectively. Conclusions:The 18F-FDG PET imaging of the endometrium shows higher uptake during the menstrual and ovulatory periods, primarily triangular in shape; endometrial carcinoma uptake is significantly higher than the physiological uptake during the menstrual and ovulatory periods, mainly in circular, oval, and irregular shapes. When SUVmax≥5.96, R/L≥2.85, combined with the physiological cycle of the subjects and the morphological characteristics of the radiotracer concentration, it is possible to effectively differentiate between physiological uptake and Stage IA endometrial carcinoma.

AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1％,PEF％),inflammatory indices(EOS,EOS％,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P＜0.05),and decreased TCM syndrome score(P＜0.05),especially for the observation group(P＜0.05);the observation group exhibited increased FEV1,FEV1％,PEF％(P＜0.05),among which FEV1,PEF％were higher than those in the control group(P＜0.05);the observation group showed decreased inflammatory indices(P＜0.05),among which FeNO was lower than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.

BACKGROUND: Physical inactivity is a significant yet underappreciated risk factor for cardiovascular disease (CVD), particularly among older adults. The aim of this study was to analyze the global burden of CVD attributable to physical inactivity in individuals aged 70 years and older from 1990 to 2021 using the Global Burden of Disease data. METHODS: We assessed trends in disability-adjusted life years (DALYs) and deaths, decomposed changes into population growth, aging, and epidemiological factors, and examined health inequalities across sociodemographic index (SDI) regions. RESULTS: From 1990 to 2021, a substantial rise in DALYs was observed, especially in low and middle SDI regions, with a 120.06% increase in the low SDI region, but a 23.10% decline in the high SDI region. Decomposition analysis identified population aging and growth as primary drivers for the burden, contributing 66.39% and 83.56% to the increase in middle and low SDI regions, respectively. By contrast, epidemiological improvements alleviated burden in the high SDI region (54.91%). Gender disparities persisted, with women experiencing a higher burden. Inequality analysis indicated a shift in CVD burden towards the low SDI region, with declining concentration indices for DALYs (-0.03 to -0.13) and deaths (-0.07 to -0.15). The Bayesian age-period-cohort projections suggest continued increases in DALYs and deaths through 2050, with women disproportionately affected. CONCLUSIONS These findings highlight the urgent need for targeted interventions promoting physical activity, improving healthcare access, and implementing region-specific prevention strategies.

AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1％,PEF％),inflammatory indices(EOS,EOS％,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P＜0.05),and decreased TCM syndrome score(P＜0.05),especially for the observation group(P＜0.05);the observation group exhibited increased FEV1,FEV1％,PEF％(P＜0.05),among which FEV1,PEF％were higher than those in the control group(P＜0.05);the observation group showed decreased inflammatory indices(P＜0.05),among which FeNO was lower than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.

Objective:To investigate the uptake patterns of 18F-fluorodeoxy glucose ( 18F-FDG) in the endometrium using positron emission tomography (PET) imaging and to differentiate these from stage IA endometrial cancer. Methods:From September 2022 to April 2024, a prospective inclusion of 354 women without gynecological diseases and no hormone usage who underwent 18F-FDG PET-CT examinations at the affiliated hospital of Qingdao University were set as the physiological group, while a group containing 42 cases of Stage IA endometrial carcinoma was also set. The physiological group was divided into five groups based on the menstrual cycle: menstrual period, proliferative phase, ovulatory phase, secretory phase, and menopausal phase. The images were analyzed using visual and quantitative measurements; quantitative analysis indicators were standardized uptake value maximum (SUVmax) and the region of interest/liver ratio (R/L value). Receiver operating characteristic (ROCs) curve was used to determine the optimal cutoff values for SUVmax and R/L value. A clinical model was established using binary logistic regression, and ROC curves were drawn to evaluate the predictive performance of the model. Results:The uptake of 18F-FDG in the endometrium exhibited cyclical variations throughout different physiological phases, with higher uptakes observed during the menstrual and ovulation phases (SUVmax values of 6.66±3.26 and 3.89±1.21, respectively), which are significantly higher than those in the proliferative phase [median SUVmax of 2.54 (2.02, 3.47)], secretory phase (SUVmax of 2.55±0.86), and menopausal phase [SUVmax median of 2.04 (1.69, 2.29)]. During the menstrual and ovulation phases, the radiotracer accumulation patterns were triangular in 105 cases, oval in 32 cases, and round-like in 2 cases. All 42 cases of endometrial cancer showed 18F-FDG uptake, with radiotracer accumulation patterns being round-like in 17 cases, oval in 10 cases, triangular in 9 cases, and irregular in 6 cases. There were statistically significant differences in the shapes of radiotracer concentration between the menstrual, ovulatory periods, and endometrial carcinoma (both P＜0.001). The SUVmax and R/L values in menstrual period and ovulatory period were significantly lower than that in endometrial carcinoma group ( P＜0.001). During the menstrual phase, the optimal cutoff values for SUVmax and R/L in distinguishing between endometrial and endometrial cancer were 12.59 and 3.81, respectively, with corresponding AUCs of 0.885 and 0.842. After incorporating endometrial uptake morphology into the model, the AUCs was improved to 0.969 and 0.948, respectively. During the ovulatory phase, the optimal cutoff values for SUVmax and R/L were 5.96 and 2.85, respectively, with AUCs of 0.984 and 0.968. After integrating endometrial uptake morphology into the model, the AUCs were increased to 0.999 and 0.998, respectively. Conclusions:The 18F-FDG PET imaging of the endometrium shows higher uptake during the menstrual and ovulatory periods, primarily triangular in shape; endometrial carcinoma uptake is significantly higher than the physiological uptake during the menstrual and ovulatory periods, mainly in circular, oval, and irregular shapes. When SUVmax≥5.96, R/L≥2.85, combined with the physiological cycle of the subjects and the morphological characteristics of the radiotracer concentration, it is possible to effectively differentiate between physiological uptake and Stage IA endometrial carcinoma.

Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:Cmax were(4 799.13±1 195.32)and(4 044.17±773.98)ng·mL-1;tmax were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC0_t were(5.59±1.19)x 104 and(5.51±1.18)x 104 ng·mL-1·h;AUC0_∞ were(5.79±1.33)x 104 and(5.74±1.32)× 104 ng·mL-1·h.Compared to the fasting state,the tmaxof the drug taken after a high fat diet was delayed by 1.25 h(P＜0.01),Cmax,AUC0_t,AUC0-∞ were less or decreased in different degrees,but the effects were small(all P＞0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.

Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.
Male ; Humans ; Androgens/therapeutic use* ; Receptors, Androgen/genetics* ; Prognosis ; Mitogen-Activated Protein Kinase 8/therapeutic use* ; Cell Line, Tumor ; Prostatic Neoplasms/pathology* ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Gene Expression Regulation, Neoplastic

OBJECTIVE: To develop and validate a nomogram for predicting outcomes of patients with gastric neuroendocrine neoplasms (G-NENs). METHODS: We retrospectively collected the clinical data from 490 patients with the diagnosis of G-NEN at our medical center from 2000 to 2021. Log-rank test was used to analyze the overall survival (OS) of the patients. The independent risk factors affecting the prognosis of G-NEN were identified by Cox regression analysis to construct the prognostic nomogram, whose performance was evaluated using the C-index, receiver-operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, DCA, and AUDC. RESULTS: Among the 490 G-NEN patients (mean age of 58.6±10.92 years, including 346 male and 144 female patients), 130 (26.5%) had NET G1, 54 (11.0%) had NET G2, 206 (42.0%) had NEC, and 100 (20.5%) had MiNEN. None of the patients had NET G3. The numbers of patients in stage Ⅰ-Ⅳ were 222 (45.3%), 75 (15.3%), 130 (26.5%), and 63 (12.9%), respectively. Univariate and multivariate analyses identified age, pathological grade, tumor location, depth of invasion, lymph node metastasis, distant metastasis, and F-NLR as independent risk factors affecting the survival of the patients (P < 0.05). The C-index of the prognostic nomogram was 0.829 (95% CI: 0.800-0.858), and its AUC for predicting 1-, 3- and 5-year OS were 0.883, 0.895 and 0.944, respectively. The calibration curve confirmed a good consistency between the model prediction results and the actual observations. For predicting 1-year, 3-year and 5-year OS, the TNM staging system and the nomogram had AUC of 0.033 vs 0.0218, 0.191 vs 0.148, and 0.248 vs 0.197, respectively, suggesting higher net benefit and better clinical utility of the nomogram. CONCLUSION The prognostic nomogram established in this study has good predictive performance and clinical value to facilitate prognostic evaluation of individual patients with G-NEN.
Humans ; Male ; Female ; Middle Aged ; Aged ; Nomograms ; Retrospective Studies ; Prognosis ; Neoplasm Staging ; Stomach Neoplasms/pathology*

Objective: To investigate the regulatory mechanisms of piwi-interacting RNA (piRNA) in bisphenol A (BPA)-induced prostate cancer cell invasion and migration. Methods: The Cancer Genome Atlas (TCGA) data was used to analyze and screen for piRNAs with significantly increased expression in prostate cancer tissues. PC-3 cells were treated with different concentrations of BPA for 12, 24, and 48 h, respectively, and the 20% inhibitory concentration (IC₂₀) was measured using a CCK-8 assay. The expression levels of piRNAs before and after BPA treatment were determined by reverse transcription-quantitative PCR. Target genes regulated by BPA and associated with prostate cancer were screened in the Comparative Toxicogenomics Database (CTD). Dual-luciferase reporter gene assay was performed to verify the relationship between piRNA and target genes, and the expression change of the piRNA target gene was detected by Western blotting. Cell migration and invasion assays were used to determine the effects of piRNA on the malignant phenotype of prostate cancer cells. Results: After treatment of PC-3 cells with 160 μmol/L BPA, the expression of piR-sno48 was most significantly increased (P<0.05). Transfection of piR-sno48 antagomir resulted in decreased expression of endogenous piR-sno48 and a significant increase in the expression of its target gene GSTP1 (P<0.05). However, the expression of GSTP1 did not change significantly in BPA-treated PC-3 cells after transfection with piR-sno48 antagomir (P>0.05). The dual-luciferase reporter gene confirmed that piR-sno48 inhibited the expression of GSTP1 by forming an inversely complementary sequence with the 3'-UTR of GSTP1. The Transwell assay results showed that treatment with BPA significantly increased the invasion and migration ability of prostate cancer cells (P<0.01), whereas piR-sno48 antagonists significantly inhibited the effects above (P<0.01). Conclusion: BPA promotes the invasion and migration of prostate cancer cells by upregulating the expression of piR-sno48 and suppressing the expression of GSTP1. Interfering with the expression of endogenous piR-sno48 may inhibit the malignant phenotype of prostate cancer cells caused by BPA.
Male ; Humans ; Prostate ; Piwi-Interacting RNA ; Antagomirs ; Prostatic Neoplasms/genetics*

Objective: To investigate the regulatory mechanisms of piwi-interacting RNA (piRNA) in bisphenol A (BPA)-induced prostate cancer cell invasion and migration. Methods: The Cancer Genome Atlas (TCGA) data was used to analyze and screen for piRNAs with significantly increased expression in prostate cancer tissues. PC-3 cells were treated with different concentrations of BPA for 12, 24, and 48 h, respectively, and the 20% inhibitory concentration (IC₂₀) was measured using a CCK-8 assay. The expression levels of piRNAs before and after BPA treatment were determined by reverse transcription-quantitative PCR. Target genes regulated by BPA and associated with prostate cancer were screened in the Comparative Toxicogenomics Database (CTD). Dual-luciferase reporter gene assay was performed to verify the relationship between piRNA and target genes, and the expression change of the piRNA target gene was detected by Western blotting. Cell migration and invasion assays were used to determine the effects of piRNA on the malignant phenotype of prostate cancer cells. Results: After treatment of PC-3 cells with 160 μmol/L BPA, the expression of piR-sno48 was most significantly increased (P<0.05). Transfection of piR-sno48 antagomir resulted in decreased expression of endogenous piR-sno48 and a significant increase in the expression of its target gene GSTP1 (P<0.05). However, the expression of GSTP1 did not change significantly in BPA-treated PC-3 cells after transfection with piR-sno48 antagomir (P>0.05). The dual-luciferase reporter gene confirmed that piR-sno48 inhibited the expression of GSTP1 by forming an inversely complementary sequence with the 3'-UTR of GSTP1. The Transwell assay results showed that treatment with BPA significantly increased the invasion and migration ability of prostate cancer cells (P<0.01), whereas piR-sno48 antagonists significantly inhibited the effects above (P<0.01). Conclusion: BPA promotes the invasion and migration of prostate cancer cells by upregulating the expression of piR-sno48 and suppressing the expression of GSTP1. Interfering with the expression of endogenous piR-sno48 may inhibit the malignant phenotype of prostate cancer cells caused by BPA.
Male ; Humans ; Prostate ; Piwi-Interacting RNA ; Antagomirs ; Prostatic Neoplasms/genetics*