Lipopolysaccharide (LPS) was used to induce mouse mononuclear macrophages (RAW 264.7 cells) to establish the inflammation model for investigating the effect and mechanism of Mailuoning oral liquid on arteriosclerosis occlusion (ASO) in vitro. RAW264.7 cells viability was measured by MTT assay. NO concentration was determined by Griess. mRNA levels and protein expressions of NFAT5/NLRP3 signaling pathway were detected by Q-PCR and Western blot. The relationship between NFAT5 and NLRP3 was explored by cellular transfection of NFAT5-siRNA combined with Western blot. Nuclear translocation of NFAT5 was detected by immunofluorescence. The results showed that Mailuoning oral liquid decreased the NO release induced by LPS in RAW264.7 cells. The mRNA levels of NFAT5, NLRP3, caspase1, IL-18 and MMP9, the protein expressions of NFAT5, NLRP3, cleaved-caspase1 (p20) and the phosphorylation of NF-κB-P65 were decreased after administration of Mailuoning oral liquid. NFAT5-siRNA significantly reversed the increase in protein expressions of NLRP3 induced by LPS in RAW264.7 cells. Both Mailuoning oral liquid and KRN2 (NFAT5 inhibitor) could inhibit the expressions and nuclear translocation of NFAT5. In conclusion, Mailuoning oral liquid exert significant anti-inflammatory effects in vitro by inhibiting the NFAT5/NLRP3 signaling pathway, and NFAT5 might be involved in regulating the expressions of NLRP3.

Objective To investigate the trends in the global burden due to cystic echinococcosis from 1990 to 2021, and to predict the global burden of cystic echinococcosis from 2022 to 2035, so as to provide insights into formulation of the cystic echinococcosis control strategy. Methods The global age-standardized prevalence, mortality, disability-adjusted life years (DALYs) rates and their 95% uncertainty intervals (UI) of cystic echinococcosis from 1990 to 2021 were captured from the Global Burden of Disease Study 2021 (GBD 2021) database, and the trends in the global burden of cystic echinococcosis from 1990 to 2021 were analyzed using the Joinpoint regression model. The associations between the global burden of cystic echinococcosis and socio-demographic index (SDI) were examined using a smoothing spline model and frontier analysis, and the global burden of cystic echinococcosis was projected from 2022 to 2035 using the Bayesian age-period-cohort (BAPC) model. Results The global agestandardized prevalence, mortality and DALYs rates of cystic echinococcosis were 7.69/10⁵ [95% UI: (6.27/10⁵, 9.51/10⁵)], 0.02/10⁵ [95% UI: (0.01/10⁵, 0.02/10⁵)], and 1.32/10⁵ [95% UI: (0.99/10⁵, 1.69/10⁵)] in 2021. The global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a rise by 0.14% per year from 1990 to 2021, and the global age-standardized mortality and DALYs rates of cystic echinococcosis appeared a tendency towards a decline by 4.68% and 4.01% per year from 1990 to 2021, respectively. Joinpoint regression analysis showed that global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a decline from 1990 to 2000 [annual percent change (APC) = −0.66%, 95% confidence interval (CI): (−0.70%, −0.61%)] and from 2005 to 2015 [APC = −0.88%, 95% CI: (−0.93%, −0.82%)], and towards a rise from 2000 to 2005 [APC = 3.68%, 95% CI: (3.49%, 3.87%)] and from 2015 to 2021 [APC=0.30%, 95%CI: (0.19%, 0.40%)].Theagestandardized prevalence (r = −0.17, P < 0.05), mortality (r = −0.67, P < 0.05) and DALYs rates of cystic echinococcosis (r = −0.60, P < 0.05) all correlated negatively with SDI across 21 geographical regions from 1990 to 2021, and the age-standardized mortality (r = −0.61, P < 0.05) and DALYs rates (r = −0.44, P < 0.05) both correlated negatively with SDI across 204 countries and territories in 2021. Frontier analysis revealed that the age-standardized DALYs rate of cystic echinococcosis was still not in line with the frontier in some high-SDI countries or territories. In addition, the global age-standardized prevalence was projected with the BAPC model to appear a tendency towards a rise among both men [estimated annual percent change (EAPC) = 0.18%, 95% CI: (0.13%, 0.23%)] and women [EAPC = 0.29%, 95% CI: (0.24%, 0.34%)] from 2022 to 2035, and the global age-standardized mortality [men: EAPC = −4.71%, 95% CI: (−4.71%, −4.37%); women: EAPC = −4.74%, 95% CI: (−4.74%, −4.74%)] and DALYs rates [men: EAPC = −3.35%, 95% CI: (−3.36%, −3.34%); women: EAPC = −3.17%, 95% CI: (−3.18%, −3.16%)] were projected to appear a tendency towards a decline among both men and women. Conclusions The global burden of cystic echinococcosis appeared an overall tendency towards a decline from 1990 to 2021; however, the global prevalence of cystic echinococcosis is projected to appear a tendency towards a rise from 2022 to 2035. Intensified cystic echinococcosis control programmes are recommended.

Objective:To observe the impact of ultra early neurorehabilitation combined with cognitive intervention training on the psychological state,neurological function,and quality of life of stroke patients.Methods:89 stroke patients who were admitted to our hospital from April 2023 to May 2024 were divided into control group(conventional rehabilitation intervention combined with cognitive intervention training,44 cases)and study group(control group combined with ultra early neurological rehabilitation,45 cases)by using random number table method.The neurological function,daily self-care ability,psychological state,quality of life,and satisfaction between two groups were compared.Results:14 d after intervention,the study group had lower scores on the national institutes of health stroke scale(NIHSS),self rating anxiety scale(SAS),and self rating depression Scale(SDS)compared to the control group,had higher scores of the comprehensive quality of life evaluation questionnaire-74(CQOLI-74)and the modified barthel index(MBI)(P＜0.05).The overall satisfaction rate of the study group was higher than that of the control group(P＜0.05).Conclusion:Ultra early neurorehabilitation combined with cognitive intervention training can effectively improve the neurological function and daily self-care ability of stroke patients,reduce anxiety and depression,improve their quality of life,and achieve good patient satisfaction.

Objective To investigate the effects of angelica polysaccharides on diabetic retinopathy(DR)and possi-ble mechanisms of action.Methods DR mouse models were established by injecting streptozotocin into 18 C57BL/6J mice.The mice were then divided randomly into an Angelica polysaccharide group(given 289 mg·kg-1 Angelica polysac-charides),a positive control group(given 217 mg·kg-1 calcium hydroxybenzenesulfonate),and a model group(given an equal volume of saline),6 mice in each group.6 normal mice were selected as a blank group(given an equal volume of sa-line).The drug was administered by gavage once a day for 28 consecutive days.ARPE-19 cells were exposed to a high-glu-cose(25 mmol·L-1)culture medium to establish DR cell models,which were divided into a negative control group(con-trol vector),a lncRNA MEG3 group(lncRNA MEG3 overexpression vector),and a model group(DR cells without vector transfection).Cells not treated with 25 mmol·L-1glucose were taken as a blank group.All cells were cultured for 24 h.Fasting blood glucose levels were detected in mice.Hematoxylin-Eosin(HE)staining was performed to study the his-topathological changes in the retinal tissue of mice.Quantitative polymerase chain reaction(qPCR)was performed to de-tect the expression level of lncMEG3 mRNAs in the retinal tissue of mice.CCK-8 assay was used to measure the activity of ARPE-19 cells.Enzyme linked immunosorbent assay(ELISA)was used to detect IL-1β and IL-6 levels in mouse retinal tis-sues and ARPE-19 cells.The Western blot analysis was made to detect the levels of cellular pyroptosis-related proteins(in-cluding Caspase-1,Cleaved-Caspase-1,GSDMD,GSDMD-N,NLRP3,IL-1 β,and IL-18)in mouse retinal tissues and ARPE-19 cells.Results Blood glucose levels in the mice of the model group were higher than those in the mice of the blank group and lower than those in the mice of Angelica polysaccharide and positive control groups(all P＜0.05).HE staining results showed that compared with those of the blank group,the mice in the mode group had significantly damaged retinal tissues and disordered and loose cell arrangement.The retinal tissue of the mice in Angelica polysaccharide and positive control groups was arranged more orderly and densely and suffered less damage,compared with that of the mice in the model group.The relative expression levels of lncMEG3 mRNAs in the retinal tissue of mice in the blank,model group,An-gelica polysaccharide,and positive control groups were 1.005±0 114,0.423±0.054,0.701±0.101 and 0.593±0.084,re-spectively.The retinal expression levels of lncMEG3 mRNAs in the mice of Angelica polysaccharide and positive control groups were significantly higher than those in the mice of the model group(both P＜0.01).CCK-8 results showed that the survival rates of ARPE-19 cells in the lncRNA MEG3 group at 48 and 72 h were higher than those in the negative control group(both P＜0.05).ELISA and Western blot results showed that the retinal expression levels of IL-1 β,IL-6 and cellular pyroptosis-related proteins in the mice of the model group were significantly higher than those in the mice of the blank group(all P＜0.01)and higher than those in the mice of Angelica polysaccharide group and positive control group(all P＜0.05).The expression levels of IL-1 β,IL-6,and cellular pyroptosis-related proteins in ARPE-19 cells of the model group were significantly higher than those in the blank group(all P＜0.01).The expression levels of IL-1 β,IL-6,and cellular py-roptosis-related proteins in ARPE-19 cells of the lncRNA MEG3 group were lower than those in the negative control group(all P＜0.05).Conclusion Angelica polysaccharides can improve DR by promoting lncRNA MEG3 expression and down-regulating IL-1 β,IL-6,Caspase-1,Cleaved-Caspase-1,GSDMD,GSDMD-N,NLRP3,IL-1β,and IL-18 protein ex-pression.

Objective:To establish venetoclax-resistant acute myeloid leukemia(AML)cell lines,assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family,and investigate their resistance mechanisms.Methods:CCK-8 method was used to screen AML cell lines(MV4-11,MOLM13,OCI-AML2)that were relatively sensitive to venetoclax.Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines.Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry.BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients.Results:Venetoclax-resistant cell lines of MV4-11,MOLM13,and OCI-AML2 were successfully established,with IC50 values exceeding 10-fold.Under the same concentration of venetoclax,the apoptosis rate of resistant cells decreased significantly(P＜0.05).BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins(such as BIM,BID and NOXA).RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines.Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results.Conclusion:The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax.The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM,BID,and NOXA,which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.

Medication reconciliation plays a key role in improving patient medication safety,reducing inappropriate polypharmacy,and promoting the high-quality development of pharmaceutical services.Compared to advanced international guidelines,China's medication reconciliation service standards have deficiencies in areas such as definition and process design,and multidisciplinary team building.There is a need to establish a comprehensive medication reconciliation effect evaluation index system,develop pharmacist-led multidisciplinary teams,promote the advancement of artificial intelligence and big data technologies,and strengthen outpatient and community medication reconciliation coverage,thereby contributing to the high-quality development of pharmaceutical services in China.

Objective:To investigate the predictive value of 18F-FDG PET related metabolic parameters on microsatellite instability-high (MSI-H) and human epidermal growth factor receptor-2(HER2) expression in colorectal cancer (CRC). Methods:The 18F-FDG PET imaging, clinical and pathological data of 101 CRC patients (58 males, 43 females; age 68.0(58.0, 75.0) years) admitted to Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2016 to March 2024 were retrospectively collected, including 17 cases in MSI-H group, 84 cases in microsatellite stability/microsatellite instability-low (MSS/MSI-L) group, 23 cases in HER2 expression group, 34 cases in non-HER2 expression group, and 44 patients without HER2 detection. Univariate analyses (independent-sample t test, Mann-Whitney U test, χ2 test) and multivariate logistic regression analysis were used to screen out independent risk factors, and ROC curve was used to evaluate the predictive efficacy. Bootstrap method was used to verify the model internally. Results:There were significant differences in metabolic tumor volume (MTV) 80% between MSI-H group and MSS/MSI-L group (2.1(1.6, 4.0) vs 1.4(1.0, 2.7) cm 3;Z=-2.10, P=0.036), and total lesion glycolysis (TLG) 80% and carcinoembryonic antigen (CEA) were significantly different between those 2 groups ( Z=-2.27, χ2=6.40, both P<0.05). There were significant differences in TLG 80% (29.0(16.1, 41.0) vs 14.3(9.4, 22.9) g; Z=-2.80, P=0.005) between HER2 expression group and non-HER2 expression group, and significant differences were also found in MTV 80%, heterogeneity index (HI) and CV ( Z=-2.24, t values: -2.26, 2.54, all P<0.05). The independent risk factors for MSI-H were MTV 80% (odds ratio ( OR)=1.326, 95% CI: 1.015-1.733, P=0.038) and CEA ( OR=0.200, 95% CI: 0.056-0.706, P=0.012), with the AUC for the combined model of 0.730 (95% CI: 0.605-0.856), and the concordance index (C-index) of 0.716. The independent risk factors for HER2 expression were TLG 80% ( OR=1.037, 95% CI: 1.001-1.073, P=0.041) and CV ( OR=1.467, 95% CI: 1.073-2.005, P=0.016), with the AUC for the combined model of 0.775 (95% CI: 0.645-0.875), and the C-index of 0.757. Conclusions:18F-FDG PET can be used as a noninvasive tool to evaluate CRC microsatellite status and HER2 gene amplification. MTV 80% and CEA are independent risk factors for MSI-H; TLG 80% and CV are independent risk factors for HER2 expression.

Objective:To evaluate the clinical prognostic value of intratumoral metabolic heterogeneity parameters of baseline 18F-FDG PET/CT in primary cutaneous malignant melanoma (CMM). Methods:From October 2015 to July 2023, the clinical data of 35 patients (24 males, 11 females, age (66.6±13.1) years) diagnosed with primary CMM who underwent baseline 18F-FDG PET/CT in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School were retrospectively analyzed. Conventional metabolic parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG)) and PET intratumoral metabolic heterogeneity parameters (area under the cumulative SUV histograms curve (AUC-CSH), linear regression slope, SUV max/ SUV mean) were assessed. Using thresholds of 30%, 40%, 50%, 60%, 70%, and 80% SUV max or thresholds of 40%, 60%, and 80% SUV max to delineate MTV, linear regression was performed, with the slopes being heterogeneity index-1 (HI-1) and heterogeneity index-2 (HI-2), respectively. Using SUV thresholds of 2.5, and 40%, 50%, 60%, and 70%SUV max to calculate AUC-CSH and SUV max/SUV mean. Kaplan-Meier survival curves and Cox proportional hazards models were used to analyze the prognostic value of primary lesion PET metabolic parameters on overall survival (OS) and progression-free survival (PFS). Results:The median follow-up time of 35 patients was 20 months, with 25 patients (71%) experiencing disease progression and 16 patients (46%) deceased. Multivariate Cox regression analysis revealed that HI-1, HI-2, MTV, SUV max/SUV mean2.5, and SUV max were the independent prognostic factors for PFS (hazard rate ( HR) (95% CI): 0.32(0.13-0.82), 0.32(0.13-0.82), 3.86(1.34-11.12), 4.61(1.33-16.02), 4.06(1.55-10.61), all P<0.05), whereas SUV max and SUV max/SUV mean2.5 were the independent prognostic factors for OS ( HR: 8.04(1.96-32.87), 2.87(1.09-7.51), P values: 0.004, 0.032). Conclusion:HI-1, HI-2, and SUV max/SUV mean2.5 have prognostic value for CMM, while the value of AUC-CSH heterogeneity parameters are not significant.

Objective:To establish a combined model of tumor heterogeneity metabolic parameters using 18F-FDG PET/CT and explore its value in differentiating benign from malignant pulmonary lesions. Methods:A total of 251 patients (157 males, 94 females; age 15-88 years) who were diagnosed with malignant lung lesions by 18F-FDG PET/CT and with definitive pathological results at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from February 2017 to February 2024 were retrospectively enrolled. Analysis was conducted on clinical data, traditional parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG)) of primary lesions on 18F-FDG PET/CT, and intra-tumoral metabolic heterogeneity index (HI; such as cumulative SUV volume histogram AUC (AUC-CSH), linear regression slope, CV). AUC-CSH and CV were calculated using SUV thresholds of 2.5 and 40%SUV max. Logistic univariate and multivariate regression analyses were used to extract independent predictors in clinical features and PET/CT parameters for the differential diagnosis of pulmonary lesions. A multi-parameter combined model was established through logistic regression and validated for diagnostic efficacy using ROC curve analysis. Results:Among 251 patients, 101 were benign and 150 were malignant. In univariate analysis, gender, age, tumor markers, spiculation sign, lobulation sign, vessel convergence sign, air bronchogram, long diameter, short diameter, SUV max, AUC-CSH 2.5, AUC-CSH 40%, CV2.5, and CV40% were predictive factors for the diagnosis of benign and malignant tumors (odds ratio ( OR): 0.57-17.39, all P<0.05). In multivariate analysis, gender, age, tumor markers, lobulation sign, vessel convergence sign, SUV max, AUC-CSH 40%, and CV40% were independent predictors for the diagnosis of benign and malignant tumors ( OR: 2.30-13.18, all P<0.05). The AUC, sensitivity, specificity, and accuracy of the multi-parameter combined model established with the above independent predictors were 0.89, 77.33%(116/150), 84.16%(85/101), 80.08%(201/251), respectively. Conclusion:18F-FDG PET/CT multi-parameter combined model has high value in the differentiation of benign and malignant pulmonary lesions.

Objective:To explore the value of preoperative 18F-fluorodeoxyglucose ( 18F-FDG) positron emission tomography (PET) metabolic heterogeneity parameters in predicting tumor deposits (TD) in colorectal cancer (CRC). Methods:A retrospective analysis was conducted on 91 CRC patients who underwent surgical treatment at the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from February 2013 to March 2024. All patients underwent preoperative 18F-FDG PET/CT examination. The LIFEx-7.5.15 software was used to delineate the primary lesion with 40% of maximum standardized uptake value (SUV max) as the relative threshold, and metabolic parameters were extracted. Intratumoral metabolic heterogeneity parameters included cumulative SUV histogram area under the curve (AUC-CSH), heterogeneity index (HI), heterogeneity factor (HF), and coefficient of variation (CV). The presence of TD was confirmed by postoperative pathological examination. Differences in data between the TD group and non-TD (NTD) group were compared. Binary logistic regression analysis was used to identify independent risk factors for TD, and receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of each parameter for TD. Results:Postoperative pathological diagnosis showed that 27 patients were included in the TD group and 64 in the NTD group. There were statistically significant differences between the TD group and NTD group in CV ( Z=-3.145, P=0.002) and the proportion of patients with carcinoembryonic antigen (CEA) >10 ng/ml (χ 2=10.751, P=0.001), while no statistically significant differences were found in HI, HF, or AUC-CSH (all P>0.05). Binary logistic regression analysis showed that CV was an independent risk factor for TD. ROC curve analysis showed that the area under the ROC curve (AUC) of CV for predicting TD was 0.709(95% CI: 0.593-0.826), which was higher than that of other metabolic heterogeneity parameters. Conclusions:The preoperative 18F-FDG PET/CT metabolic heterogeneity parameter CV has value in predicting TD in CRC patients.