Objective To investigate the mechanism by which miR-148a affects M2 macrophage polarization and inhibits liver cancer cell proliferation through Wnt3a/β-catenin. Methods The mRNA expression levels of miR-148a, CD206 and interleukin-10 (IL-10) in tumor tissues and adjacent non-tumor liver tissues of 84 patients with liver cancer were detected by real-time quantitative PCR. THP-1 cells were separated into blank group (conventional culture), M2 group (200 nmol/L phorbol ester, 20 ng/mL IL-4, 20 ng/mL IL-13), M2 combined with negative control (miR-NC) group (transfected with miR-NC on the basis of M2 group), M2 combined with miR-148a mimics (transfected with miR-148a mimics on the basis of M2 group) group, M2 combined with miR-148a mimics combined with Wnt3a (treated with 100 μg/L Wnt3a on top of M2 combined with miR-148a mimics group) group. The proliferation of HuH7 cells was detected by CCK-8 and EdU methods. Apoptosis and M2 macrophage marker CD206 was detected by flow cytometry. The level of IL-10 in cell supernatant was detected by chemiluminescence method; The mRNA levels of miR-148a, CD206 and IL-10 were detected by real-time quantitative PCR. The protein levels of Wnt3a and β-catenin were detected by Western blot. Results The expressions of CD206, IL-10 mRNA, Wnt3a and β-catenin in tumor tissue were higher than those in non-tumor liver tissues, and the miR-148a level was decreased. The mRNA expression of M2 macrophage markers CD206 and IL-10 were significantly increased. Compared with the blank group, the OD450 value, EdU positive rate, the mRNA expressions of CD206 and IL-10, the level of IL-10 in the supernatant, and the expressions of Wnt3a and β-catenin were increased in M2 group, while the apoptotic rate and miR-148a level were decreased. Compared with M2 group and M2 combined with miR-NC group, the OD₄₅₀ value, EdU positive rate, the mRNA expressions of CD206 and IL-10, the level of IL-10 in the supernatant, and the expressions of Wnt3a and β-catenin were decreased in M2 combined with miR-148a mimics group, while the apoptotic rate and miR-148a level were increased. Wnt3a reversed the inhibitory effect of miR-148a overexpression on the proliferation of liver cancer cells. Conclusion Overexpression of miR-148a inhibits M2 polarization of macrophages and prevents the proliferation of liver cancer cells, which may be related to the inhibition of the Wnt3a/β-catenin pathway.
Humans ; MicroRNAs/metabolism* ; Wnt3A Protein/metabolism* ; Liver Neoplasms/metabolism* ; Cell Proliferation/genetics* ; beta Catenin/genetics* ; Macrophages/metabolism* ; Interleukin-10/metabolism* ; Apoptosis/genetics* ; Cell Line, Tumor ; Female ; Male ; Mannose Receptor ; Lectins, C-Type/metabolism* ; Mannose-Binding Lectins/metabolism* ; Middle Aged ; Receptors, Cell Surface/metabolism*

Objective:To analyze and predict the incidence and mortality rate condition from 1990 to 2021 and 2022 to 2045 in China so as to evaluate the impact of different ages, periods, and birth cohorts on liver cancer.Methods:The 2021 Global Burden of Disease Study database was used. The variation trend of standardized incidence and mortality of liver cancer was analyzed using the Joinpoint regression model. The age, period, and cohort effects were used to explore liver cancer incidence and mortality rates based on the age-period-cohort model. The Nordpred prediction model was used to fit the trend of standardized incidence and mortality rates in liver cancer. Simultaneously, the standardized incidence and mortality rates were predicted from 2022 to 2045 for liver cancer. Joinpoint regression analysis was performed using the GBDASR_aapc package.Results:The standardized incidence and mortality rate from 1990 to 2021 of liver cancer showed an overall downward trend year by year in China ( P<0.01). Age, period, and cohort effects were all risk factors for the incidence of liver cancer. The incidence and mortality rates both increase with age, reaching a peak in the 85～89 age group. The risk of HCC morbidity and mortality was higher in the population of early-stage birth cohorts. Although the period effect showed a slight upward trend over time, the change in the period effect was relatively small. The incidence and mortality rates after the age of 40 were significantly higher in males than those of females. The prediction results showed that the standardized incidence and mortality rates from 2022 to 2045 of liver cancer have had a downward trend in China. Conclusion:The standardized incidence and mortality rates of liver cancer show an overall downward trend in China, but the burden in males is still high. Therefore, liver cancer prevention and control work in the future should continue to strengthen intervention in high-risk groups.

Objective:To analyze and predict the incidence and mortality rate condition from 1990 to 2021 and 2022 to 2045 in China so as to evaluate the impact of different ages, periods, and birth cohorts on liver cancer.Methods:The 2021 Global Burden of Disease Study database was used. The variation trend of standardized incidence and mortality of liver cancer was analyzed using the Joinpoint regression model. The age, period, and cohort effects were used to explore liver cancer incidence and mortality rates based on the age-period-cohort model. The Nordpred prediction model was used to fit the trend of standardized incidence and mortality rates in liver cancer. Simultaneously, the standardized incidence and mortality rates were predicted from 2022 to 2045 for liver cancer. Joinpoint regression analysis was performed using the GBDASR_aapc package.Results:The standardized incidence and mortality rate from 1990 to 2021 of liver cancer showed an overall downward trend year by year in China ( P<0.01). Age, period, and cohort effects were all risk factors for the incidence of liver cancer. The incidence and mortality rates both increase with age, reaching a peak in the 85～89 age group. The risk of HCC morbidity and mortality was higher in the population of early-stage birth cohorts. Although the period effect showed a slight upward trend over time, the change in the period effect was relatively small. The incidence and mortality rates after the age of 40 were significantly higher in males than those of females. The prediction results showed that the standardized incidence and mortality rates from 2022 to 2045 of liver cancer have had a downward trend in China. Conclusion:The standardized incidence and mortality rates of liver cancer show an overall downward trend in China, but the burden in males is still high. Therefore, liver cancer prevention and control work in the future should continue to strengthen intervention in high-risk groups.

Objective This paper aims to construct a scientific and standardized index system for evaluating the applica-tion effect of Diagnosis-Intervention Packet(DIP)in medical institutions.It seeks to determine the weights of indicators at all lev-els to provide a basis for evaluating the effectiveness of DIP used in various regions as well as a reference for improving DIP poli-cy.Methods This paper used literature analysis to develop an indicator pool preliminarily.The Delphi method was used to con-duct a questionnaire survey with 22 experts to establish the index system.It also used the Analytic Hierarchy Process(AHP)to determine the weight of each index.Results A total of two rounds of expert consultation questionnaires were conducted.The questionnaire exhibited high expert positive coefficients by 91.00％and 100.00％and higher authority coefficients of both 0.91 for two rounds.The coordination coefficients of the two rounds of expert consultation met the standard,and the expert opinions reached a consistence.Additionally,the questionnaire established comprised three primary indicators(efficiency of medical in-surance fund,medical service management,patient benefit,and satisfaction),9 secondary indicators,and 38 tertiary indicators.The AHP was used to determine the weight of indicators at all levels.Among the primary indicators,patient benefit and satisfac-tion had the highest weight(0.446 9).Among the secondary indicators,patients'medical cost burden had the highest weight(0.287 6).Among the tertiary indicators,the inpatient satisfaction had the highest weight(0.1592).The Cronbach's α coeffi-cients of the two rounds were＞0.7.Conclusion This paper utilized Delphi method and AHP to establish the evaluation system for assessing the implementation effectiveness of DIP.The approach is highly scientific and authoritative.It can be used to evalu-ate the application effect of DIP and provide an effective tool for medical insurance and hospital managers at all levels to assess DIP payment policies.

Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

The construction of smart hospital is an important part of modern hospital management system,and it is also the key way to build the new system of high-quality hospital development.In terms of building smart hospitals,multi-campus hos-pitals face more difficulties and challenges than single campus hospitals,such as the lack of top-level design,the difficulty of in-tegrated management,the uneven development of hospitals and the widespread phenomenon of information islands.This study summarizes and analyzes the difficulties encountered in the construction and application of smart hospitals in multi-hospital areas.Guided by problems,it puts forward countermeasures and suggestions for the construction of refined and high-quality smart hospi-tals in multi-campus hospitals,including strengthening overall and forward-looking awareness,integrating management according to hospital conditions,characteristic development under demand guidance,establishing a data integration center for smart hospi-tals,scientific planning of talent reserve and discipline layout,etc.

Objective:To assess the association between warm ischemia time (WIT) and renal function in patients undergoing laparoscopic partial nephrectomy.Methods:A total of 344 patients treated with laparoscopic partial nephrectomy in Peking University People’s Hospital were included. There were 240 males (69.8%) and 104 females (30.2%) with a median age of 57 (23-89) years.The median BMI was 25.6 (16.7-36.0) kg/m 2.213 cases (61.9%) were associated with hypertension.There were 66 (19.2%) patients with diabetes mellitus. There were 92 cases (26.7%) with smoking history. The median preoperative creatinine was 73 (32-170) μmol/L. The median preoperative estimated glomerular filtration rate (eGFR) was 95 (33-142) ml/(min·1.73m 2). The maximum diameter of the tumor was 2.5 (7-9) cm.314 (91.3%) patients with renal cancer stage T 1. All patients underwent warm ischemia during the operation. The patients were divided into three groups for analysis. Restricted cubic spline regression analysis was used to assess the association between WIT as a continuous variable and percentage change of eGFR. Analysis of covariance was used to compare postoperative eGFR among the three groups, and to adjust for preoperative eGFR and tumor diameter. Results:There were statistically significant differences in the percentage change of postoperative eGFR ( P=0.009) and tumor diameter ( P<0.001) among the three groups. Restricted cubic spline regression analysis showed that with the prolongation of WIT, the percentage change of postoperative eGFR gradually decreased, and the curve began to stabilize after 30 minutes (R 2=0.044, P=0.015). The results of covariance analysis showed that after adjusting for baseline preoperative eGFR and tumor size, the effect of WIT on postoperative eGFR was significantly different among the three groups ( F=3.864, P=0.022). The postoperative eGFR in the WIT<20 min group was significantly higher than that in 20 min≤WIT<30 min group( P=0.009) and WIT≥30 min group( P=0.017). There was no significant difference in postoperative eGFR between the two groups with longer WIT( P=0.806). Conclusions:In partial nephrectomy, patients with WIT less than 20 minutes had higher postoperative eGFR levels than those with WIT greater than 20 minutes. However, when WIT exceeded 20 minutes, prolonged ischemia time did not lead to further decline in renal function.

Objective To investigate the protective effect of adult human liver-derived stem cell exosomes (HLSC-exo) intravenously injected at different time points against acute liver injury induced by concanavalin A (ConA) in mice. Methods HLSC-exo was extracted by differential centrifugation. Western blot was used to measure the expression of the marker proteins CD9 and CD63, and nanoparticle tracking analysis was used to investigate particle size distribution. A total of 56 male C57BL/6 mice were randomly divided into blank control group, ConA model group, and HLSC-exo treatment group. The ConA model group and the HLSC-exo treatment group were further divided into 3-, 6-, and 12-hour subgroups according to the interval between phosphate buffer or HLSC-exo injection and ConA injection. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) were measured, and the gross morphology and histopathology of the liver were compared between groups. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results HLSC-exo was a membranous vesicle with a diameter of 90-110 nm, with a clear saucer-like structure under an electron microscope and marked expression of its specific marker proteins CD9 and CD63. In the blank control group, the levels of ALT and AST were 31.81±6.74 U/L and 69.75±8.30 U/L, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had significant increases in the levels of ALT and AST (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had significant reductions in the levels of ALT and AST (225.58±115.59 U/L vs 1989.32±347.67 U/L, 1174.71±203.30 U/L vs 2208.33±349.96 U/L, 303.53±126.68 U/L vs 2534.27±644.72 U/L, 1340.70±262.56 U/L vs 2437.13±288.13 U/L, all P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had significantly greater reductions ( P < 0.001). In the blank group, the levels of IL-10 and TNF-α were 313.51±10.97 pg/ml and 476.05±7.31 pg/ml, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant reduction in the level of IL-10 (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant increase in the level of IL-10(331.61±10.46 pg/ml vs 266.20±8.15 pg/ml, 288.13±10.74 pg/ml vs 264.41±9.12 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater increase ( P < 0.001). Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant increase in the level of TNF-α (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the level of TNF-α (478.26±12.99 pg/ml vs 551.31±17.70 pg/ml, 515.58±7.18 pg/ml vs 556.21±11.15 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater reduction ( P < 0.001). Compared with the 3-and 6-hour ConA model groups in terms of the gross morphology and histopathology of the liver, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the degree of hepatocyte necrosis, and the 3-hour HLSC-exo treatment group had a basically complete lobular structure, with sporadic spotty necrosis; the 12-hour HLSC-exo treatment group had no significant improvement in hepatocyte necrosis compared with the 12-hour ConA model group. Conclusion Intravenous injection of adult HLSC-exo can alleviate acute liver injury induced by ConA in mice, and injection at 3 hours in advance has the most significant protective effect. Regulation of cytokines is one of the important mechanisms for HLSC-exo to alleviate liver injury.

Objective:To establish the Chinese version of Medication Appropriateness Index (MAI) and evaluate the appropriateness of medication in elderly inpatients on trial.Methods:According to Brislin′s translation model for cross-cultural research, the MAI was translated into Chinese through 4 steps: translation, back translation, cultural adaptation, and pre-survey. Using convenient sampling method, 300 elderly inpatients in the Department of Geriatrics, Nanjing Drum Tower Hospital from July to December 2019 were selected as the research subjects, and the Chinese version of MAI was used to evaluate the appropriateness of medication. Reliability of the Chinese version of MAI was evaluated using Cronbach′s α coefficient and intraclass correlation coefficient (ICC); the content validity and structural validity of the Chinese version of MAI were evaluated using 4-level scoring method and exploratory factor analysis, respectively. The appropriateness of medication in 300 elderly inpatients was evaluated by analyzing the MAI scores and the distribution of irrational items.Results:The Chinese version of MAI contained 10 items. The evaluation results of 300 elderly inpatients were statistically analyzed. The Cronbach′s α coefficient of the scale was 0.892 and the ICC of the scale was 0.876 when 20 patients were selected for re-testing 14 days later. The item-level content validity index (I-CVI) of the Chinese version of MAI was 0.86 to 1.00 and the scale-level content validity index/average (S-CVI/Ave) was 0.96. A total of 4 common factors were extracted by exploratory factor analysis, the cumulative variance contribution rate was 58.132%, and the factor loading of 8 items was more than 0.4. The evaluation results of appropriateness of medication showed that the average MAI score in 300 patients was 2.6, of which 198 patients did not score 0; inappropriate medication counted 66.00% and the average MAI score of each drug was 0.2. The top 3 items with more inappropriate medication were drug-disease/abnormal condition interaction (88 cases, 29.3%), duplication (69 cases, 23.0%), and incorrect dosage (67 cases, 22.3%).Conclusions:The Chinese version of MAI had good reliability and validity. The items with more inappropriate medication in elderly inpatients in the Department of Geriatrics, Nanjing Drum Tower Hospital were mainly drug-disease/abnormal condition interaction, duplication, and incorrect dose.

Medication rationality index (MAI) scale sets up 10 items to evaluate the rationality of prescription medication, including indication, effectiveness, dosage, correct direction, practical direction, drug-drug interaction, drug-disease interaction, duplication, duration, and cost. MAI scale has good reliability, which can be used to evaluate the rationality of drug use and the non-essential drug use, the potential inappropriate medication in elderly patients, verify the reliability and effect of irrational drug use detection software, quantify clinical intervention measures, and predict adverse events and quality of life. Since MAI scale application involves subjective judgment, evaluators should be trained before use.