BACKGROUND:Previous studies by our research group discovered that Jiawei Xiaoyao San has a significant anti-liver cancer effect,but the specific mechanism of action was unclear. OBJECTIVE:To investigate the regulatory effects of the traditional Chinese medicine formula Jiawei Xiaoyao San on the levels of miRNAs in plasma exosomes of rats with diethylnitrosamine chronically induced primary liver cancer,based on high-throughput sequencing combined with bioinformatics. METHODS:SD rats were randomly divided into a blank control group,a liver cancer model group,and a Jiawei Xiaoyao San treatment group.Liver cancer models were induced by continuous administration of diethylnitrosamine for 12 weeks.Starting from the 17th week,rats in the Jiawei Xiaoyao San treatment group were administered Jiawei Xiaoyao San once daily until the end of the 20th week,while rats in the blank control and liver cancer model groups were given an equivalent volume of saline.Anti-hepatocellular carcinoma effects were validated by assessing the morphological structure of rat liver tissues,along with the expression of the hepatocellular carcinoma markers,Glypican-3 protein and serum alpha-fetoprotein.Plasma exosomes from each group of rats were isolated using ultracentrifugation.High-throughput sequencing technology was used to screen for differentially expressed miRNAs in rat plasma exosomes.Bioinformatics was used to predict the potential biomarkers through which Jiawei Xiaoyao San exerts its anti-liver cancer effects via liver cancer-derived exosomal miRNAs,followed by functional analysis. RESULTS AND CONCLUSION:(1)Jiawei Xiaoyao San significantly improved the morphological structure of liver tissues in a rat model of liver cancer.Compared with the liver cancer model group,the expression of liver cancer markers Glypican-3 protein and serum alpha-fetoprotein was significantly reduced in the Jiawei Xiaoyao San treatment group.(2)Bioinformatics analysis showed that in the Jiawei Xiaoyao San group,upregulated miR-223-3p in the liver cancer model group had target binding sites with genes E2F1 and NCOA1,which were closely related to liver cancer survival and prognosis.Therefore,Jiawei Xiaoyao San has a therapeutic effect on liver cancer,possibly by targeting negative regulation of NCOA1/E2F1 through liver cancer plasma-derived exosomal miR-223-3p,thereby playing anti-liver cancer effect.

Objective:To develop a prediction tool for 6-year incident risk of frailty among Chinese older adults aged 65 years or above.Methods:Data from the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 was used, including 13 676 older adults aged 65 years or above who were free of frailty at baseline. Key predictors of frailty were identified via the least absolute shrinkage and selection operator (LASSO) method, and were thereafter used to predict the incident frailty based on the Cox proportional hazards regression model. The model was internally validated by 2 000 Bootstrap resamples and evaluated for the performance of discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curve, respectively. The net benefit of the developed prediction tool was evaluated by decision-curve analysis.Results:The M( Q1, Q3) age and follow-up time of the participants were 81.0 (71.0, 90.0) years and 6.0 (4.1, 9.2) years, respectively. A total of 4 126 older persons (30.2%) were recorded with frailty incidents during the follow-up, with the corresponding incidence density of 41.8/1 000 person-years. A total of 15 key predictors of frailty were selected by LASSO, namely, age, sex, race, education years, meat consumption, tea drinking, performing housework, raising domestic animals, playing cards or mahjong, and baseline status of visual function, activities of the daily living score, instrumental activities of the daily living score, hypertension, heart disease, and self-rated health. The prediction model was internally validated with an AUC of 0.802, with the max Youden's index of 0.467 at a risk threshold of 19.0%. The calibration curve showed high consistency between predicted probabilities and observed proportions of frailty events. The decision curve indicated that higher net benefits could be obtained via the prediction model than did strategies based on intervention in all or none participants for any risk threshold less than 59%, and the model-based net benefit was estimated to be 0.10 at a risk threshold of 19.0%. Conclusions:The herein developed 6-year incident risk prediction model of frailty, based on easily accessible questionnaires and physical examination variables, has good predictive performance. It has application potential in identifying populations at high risk of incident frailty.

Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.

Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.

【Objective】 To observe the penetration and biological activity of PTD4-Cu, Zn-SOD into human astrocytes and whether it can mitigate hypoxia damages. 【Methods】 ①Immunohistochemistry and fluorescence test: We labeled the Cu, Zn-SOD by a monoclonal antibody, combined it with the fluorescent secondary antibody labeled with fluorescein isothiocyanate (FITC) to observe the effect of transduced PTD4-Cu, Zn-SOD on the viability of human astrocytes. ② The experimental group: After hypoxic damage model, the cells were divided into three groups: blank control, group Cu, Zn-SOD, and group PTD4-Cu, Zn-SOD. Group blank was added with DMEM medium (excluding serum) as control; DMEM medium was added to the other two for one hour (excluding serum) with its fusion proteins (Cu, Zn-SOD and PTD4 -Cu, Zn-SOD) with the final concentration of 2 μmoL/L. After the intervention, we used SOD and MDA test kits to observe PTD4-Cu, Zn-SOD and Cu, Zn-SOD in astrocytes after fusion protein intervention. 【Results】 The PTD4-Cu, Zn-SOD fusion protein could have aggregation distribution in the nucleus by FITC fluorescently labeled. After the intervention, it could increase the SOD activity in astrocytes in group PTD4-Cu, Zn-SOD and group Cu, Zn-SOD compared with control group, but the SOD activity was more obvious in the fusion proteins PTD4-Cu, Zn-SOD group. And the dose of MDA was reduced in group PTD4-Cu, Zn-SOD compared with group Cu, Zn-SOD and control group. 【Conclusion】 PTD4-Cu, Zn-SOD fusion protein can transcellular membrane of human astrocytes. The fusion protein PTD4-Cu, Zn-SOD can increase the SOD activity and reduce the content of MDA by human astrocytes from hypoxia injury.

Objective:To explore the method of developing a canal-shaped implant template using a combined automatic pre-planning and 3D printing technology, and assess its impact on dose and efficacy improvement.Methods:Retrospective analysis of 15 patients with advanced cervical cancer admitted to the Affiliated Cancer Hospital of Guangxi Medical University from September 2020 to September 2022 was performed. Patients had characteristics such as vaginal stump recurrence, tumor eccentric growth, and previous hysterotomy, etc. Three-dimensional images were obtained by CT scan after automatic pre-planning. The PMT 3D software was used to analyze digital imaging and communications in medicine (DICOM) radiotherapy data, capture the coordinates of the pre-planned stay points to establish the implant channel, and generate the size and shape of the canal-shaped implant template based on patients' physiological structure. Dosimetric parameters, such as conformity index (CI), were evaluated. The changes of tumor size before and after treatment were analyzed by paired t-test. Results:Fifteen patients were treated with the canal-shaped implant template. The CI was 0.74±0.26, the total radiation dose (HR-CTV) D 90% (EQD 2, α/β=10) was (85.5±6.8) Gy, and the D 2 cm3 (EQD 2, α/β=3)for bladder, rectum, small intestine, and colon were (72.2±4.2), (65.8±6.1), (65.2±4.4), and (69.8±3.7) Gy, respectively, meeting clinical needs. After the treatment, the tumor volume was significantly decreased. The template had a good fit with the vaginal cavity, and a small amount of air gap on the sidewall did not affect the dose. Non-parallel needle insertion increased the utilization of the cavity space and implant needles. Conclusion:The method of developing the canal-shaped implant template using automatic pre-planning and 3D printing technology is efficient and effective, meets the requirements of modern precise radiotherapy, and has practical clinical value.

Objective:To construct and validate a predictive model for the occurrence of malignant cerebral edema(MCE)in the elderly with acute large hemispheric infarction(LHI)of the anterior cerebral artery.Methods:Clinical, laboratory and imaging data of 301 elderly patients with acute LHI of the anterior cerebral artery admitted to the Department of Neurology of the Third Affiliated Hospital of Soochow University between January 2018 and April 2023 were retrospectively analyzed.Patients were divided into a modeling group(211 cases)and a validation group(90 cases)by the simple random sampling method with a ratio of 7∶3.According to the occurrence of MCE, univariate and multivariate Logistic regression analyses were performed with data from the modeling group to screen for independent predictors of the development of MCE.Nomograms were created and internally validated using R software.Additionally, external validation was performed with data from the validation group, and the performance of the model was assessed by receiver operating characteristic(ROC)curves, calibration plots, and clinical decision curve analysis(DCA), respectively.Results:The MCE incidence and baseline data between the modeling and validation groups were not statistically significantly different and were actually comparable.Multivariate Logistic analysis in the modeling group showed that a history of atrial fibrillation( OR=3.459, 95% CI: 1.202-9.955, P=0.021), Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score( OR=1.202, 95% CI: 1.052-1.373, P=0.007), National Institutes of Health Stroke Scale(NIHSS)score( OR=1.163, 95% CI: 1.039-1.3013, P=0.008), Alberta Stroke Program Early CT Score(ASPECTS)( OR=0.782, 95% CI: 0.639-0.958, P=0.018), and collateral score(CS)( OR=0.414, 95% CI: 0.221-0.777, P=0.006)were independent predictors of the occurrence of MCE in the elderly patients with LHI.Based on the nomogram model constructed using the independent predictors, the ROC value for the risk of developing MCE was 0.912(95% CI: 0.867-0.957)in the modeling group and 0.957(95% CI: 0.902-0.997)in the validation group.The predicted probabilities from the nomograms in the modeling and validation groups were close to the actual probabilities, indicating good calibration.The DCA curves in the validation group showed that the predictive model had good clinical utility. Conclusions:The nomogram model established in this study exhibits good discrimination and calibration for the prediction of MCE, and has some predictive value.

Objective:To explore the accuracy of intelligent calculation (IC) method for risk assessment of hospitalization for patients, aiming to build a more advantageous risk assessment system.Methods:The "Search Engine" program was developed based on hospital information system (HIS) of the Fifth Center Hospital in Tianjin, which automatically captured patient information and generated nutritional risk screening 2002 (NRS 2002) score, Caprini thrombosis risk assessment model and Padua thrombosis risk assessment model for venous thromboembolism (VTE), the CHA 2DS 2-VASc for predicting stroke risk stratification in atrial fibrillation and the HAS-BLED for predicting bleeding risk in anticoagulated patients with atrial fibrillation. A randomized controlled trial was conducted. According to the applicable conditions of each risk assessment, 100 risk scores from "Search Engine" program belonged to each risk assessment were randomly selected, defined as the IC group. Manual scoring with the data of the same case at the same time, defined as the traditional calculation (TC) group, compared the consistency of the scores and the difference in time-consuming between the two groups. Results:The Bland-Altman plots showed that the 95% limits of agreement (95% LoA) of NRS 2002 score, Caprini score, Padua score, CHA 2DS 2-VASc score and HAS-BLED score was -0.46 to 0.41, -0.49 to 0.52, -0.50 to 0.41, -0.67 to 0.60, -0.44 to 0.43, respectively, all P > 0.05. In this study, the Bland-Altman plot showed that 95%, 96%, 97%, 97%, 95% plots fell within the 95% LoA in NRS 2002 score, Caprini score, Padua score, wwCHA 2DS 2-VASc score and HAS-BLED score by the two methods, respectively. The all plots of 95% LoA were within the clinically acceptable range (-0.5 to 0.5 scores). The time-consuming of NRS 2002 score, Caprini score, Padua score, CHA 2DS 2-VASc score and HAS-BLED score in IC group were significantly shorter than those in TC group [0.72 (0.71, 0.73) seconds vs. 361.02 (322.41, 361.02) seconds, 0.72 (0.72, 0.73) seconds vs. 196.68 (179.99, 291.20) seconds, 0.72 (0.72, 0.73) seconds vs. 105.75 (92.32, 114.70) seconds, 0.72 (0.71, 0.72) seconds vs. 72.66 (56.24, 84.20) seconds, 0.72 (0.71, 0.72) seconds vs. 51.30 (38.88, 57.15) seconds, respectively, all P < 0.001]. Conclusion:For the above five risk assessments, the TC method and IC method has good consistency in scores, and the IC method is faster, which has good application prospect for clinical application.

Objective:To explore the characteristics of the changes in risk score for intensive care unit (ICU) patients during hospitalization by the intelligent calculation method, and to provide evidence for the risk prevention.Methods:In this retrospective study, ICU patients of the Fifth Central Hospital in Tianjin from November 3, 2021 to March 28, 2022 were enrolled and divided into ≥ 14 days group, 10-13 days group, 7-9 days group, and 3-6 days group according to the ICU length of stay. Risk scores assessed by the intelligent calculation method of the ICU patients were collected, including nutritional risk screening 2002 (NRS 2002), Caprini score and Padua score. NRS 2002 score for all patients, Caprini score for surgical patients and Padua score for internal medicine patients were selected. Trends in change of each score were compared between patients admitted to ICU 1, 3, 7 (if necessary), 10 (if necessary), and 14 days (if necessary).Results:A total of 138 patients were involved, including 79 males and 59 females, with an average age of (61.71±18.86) years and an average hospital stay of [6.00 (4.00, 9.25)] days. ① in the group with ICU length of stay ≥ 14 days (21 cases): there was no significant change in the NRS 2002 scores of the patients within 10 days, but the NRS 2002 score was significantly decreased in 14 days as compared with 1 day [3.00 (2.50, 3.50) vs. 4.00 (3.00, 5.00), P < 0.05]; both Caprini and Padua score were increased with prolonged hospital stay and compared with 1 day, the scores at the other time points were significantly increased, especially at 14 days [Caprini score: 5.00 (3.25, 7.00) vs. 2.50 (1.25, 5.50), Padua score: 6.00 (6.00, 7.00) vs. 3.00 (1.00, 3.00), both P < 0.05].② in the group with ICU length of stay from 10-13 days (15 cases): with the prolonged hospital stay, there was no significant change in NRS 2002 score, but both Caprini and Padua score were increased at 3, 7, 10 days, especially at 10 days [Caprini score: 3.00 (2.00, 4.75) vs. 2.00 (0.25, 2.75), Padua score: 5.00 (3.50, 6.00) vs. 2.00 (0.50, 4.00), both P < 0.05].③ in the group with ICU length of stay from 7-9 days (23 cases): compared with 1 day, the NRS 2002 score at 3 days and7 days were decreased, but the Caprini and Padua score were increased, especially at 7 days [NRS 2002 score: 2.00 (1.00, 4.00) vs. 2.00 (2.00, 4.00), Caprini score: 3.00 (2.00, 5.50) vs. 2.00 (0.25, 3.00), Padua score: 5.00 (4.00, 6.00) vs. 2.00 (0, 2.00), all P < 0.05]. ④ in the group with ICU length of stay from 3-6 days (79 cases): compared with 1 day, the NRS 2002 score at 3 days was decreased [NRS 2002 score: 2.00 (1.00, 3.00) vs. 2.00 (1.00, 3.00), P < 0.05], Caprini and Padua score were significantly increased [Caprini score: 3.00 (2.00, 4.00) vs. 2.00 (1.00, 3.00), Padua score: 5.00 (4.00, 5.00) vs. 2.00 (1.00, 3.00), both P < 0.05]. Conclusion:Based on dynamic assessment of intelligent calculation methods, the risk of thrombosis in ICU patients increased with hospital length of stay, and the nutritional risk was generally flat or reducing in different hospitalization periods.

Acute kidney injury (AKI), characterized by acute renal dysfunction, is an increasingly common clinical problem and an important risk factor in the subsequent development of chronic kidney disease (CKD). Regardless of the initial insults, the progression of CKD after AKI involves multiple types of cells, including renal resident cells and immune cells such as macrophages. Recently, the involvements of macrophages in AKI-to-CKD transition have garnered significant attention. Furthermore, substantial progress has also been made in elucidating the pathophysiological functions of macrophages from the acute kidney to repair or fibrosis. In this review, we highlight current knowledge regarding the roles and mechanisms of macrophage activation and phenotypic polarization, and transdifferentiation in the development of AKI-to-CKD transition. In addition, the potential of macrophage-based therapy for preventing AKI-to-CKD transition is also discussed.
Acute Kidney Injury/drug therapy* ; Disease Progression ; Humans ; Kidney ; Macrophages ; Renal Insufficiency, Chronic