BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Objective:To analyze the efficacy of laparoscopic partial splenectomy and devascularization (LPSPD), open partial splenectomy and devascularization (OPSPD), laparoscopic total splenectomy and devascularization (LTSPD), and open total splenectomy and devascularization (OTSPD) in the treatment of portal hypertension.Methods:Clinical data of 128 patients with portal hypertension admitted to the Department of Hepatobiliary and Pancreatic Surgery of the Affiliated Hospital of Qinghai University and the General Surgery Department of the Fifth Medical Center of the Chinese PLA General Hospital from May 2018 to May 2022 were retrospectively analyzed, including 69 males and 59 females, aged 51.0±10.9 years. According to different surgical methods, patients were divided into four groups, namely the LPSPD group ( n=30), the OPSPD group ( n=32), the LTSPD group ( n=31), and the OTSPD group ( n=35). Operation time, postoperative hospitalization time, postoperative complications such as newly occurred PVT, etc of the four groups of patients were compared. Results:The operation times of the LPSPD, OPSPD, LTSPD and OTSPD group were 240.0 (180.0, 399.0), 209.5 (169.0, 259.0), 207.0 (175.3, 297.5) and 200.0 (162.0, 264.0) minutes, respectively. The postoperative hospital stays were 8.0 (7.0, 12.0), 10.0 (8.3, 11.8), 11.0 (9.0, 13.0) and 13.0 (11.0, 15.0) days, respectively. The incidences of newly occurred PVT after surgery were 3.3% (1/30), 3.1% (1/32), 19.4% (6/31), and 20.0% (7/35), respectively. The above indicators were compared among the four groups respectively, and the differences were statistically significant (all P<0.05). The postoperative hospital stay of the LPSPD group was shorter than that of the LTSPD group [8.0 (7.0, 12.0) vs 11.0 (9.0, 13.0), d, Z=-3.93], and the postoperative hospital stay of the OPSPD group was also shorter than that of the OTSPD group [10.0 (8.3, 11.8) vs 13.0 (11.0, 15.0), d, Z=-3.56; all P<0.001]. The incidence of newly occurred PVT after surgery in the partial splenectomy group (LPSPD and OPSPD) was 3.2% (2/62), which was lower than that in the total splenectomy group [LTSPD and OTSPD, 19.7% (13/66), χ2=8.38, P=0.004]. Conclusion:Compared to total splenectomy, partial splenectomy might be favorable for the shortened postoperative hospital stay and lower incidence of newly occurred portal vein thrombosis.

Objective:To explore the value of quantitative parameters of diffusion weighted imaging (DWI) combined with dynamic enhanced magnetic resonance imaging (DCE-MRI) in predicting the efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) .Methods:A total of 97 patients with LABC admitted to the hospital from Mar. 2020 to Mar. 2023 were studied and received neoadjuvant chemotherapy to evaluate the therapeutic effect, and DWI and DCE-MRI scans were performed before and after treatment. The difference of DWI and DCE-MRI quantitative parameters before treatment in patients with different therapeutic effects was compared, and the correlation between the difference of DWI and DCE-MRI quantitative parameters and therapeutic effect was analyzed. The predictive value of quantitative parameters of DWI and DCE-MRI before treatment was analyzed. The quantitative parameters of DWI and DCE-MRI in patients with different pathological reactions were compared before treatment, and the quantitative parameters of DWI and DCE-MRI were compared before and after treatment.Results:The apparent diffusion coefficient (ADC) of patients with effective chemotherapy before treatment was higher, but transport constant (Ktrans) , extracellular space volume percentage (Ve) and rate constant (Kep) were lower ( t=5.0, 3.27, 3.55, 3.89, P < 0.05) ; Spearman correlation analysis showed that ADC was positively correlated with chemotherapy efficacy before treatment (r=0.66; P < 0.05) , while Kep, Ve, Ktrans were negatively correlated with it (r=-0.58, -0.47, -0.60; P < 0.05) ; ROC curves showed that the area under the curve (AUC) values of ADC, Kep, Ve and Ktrans in predicting chemotherapy efficacy before treatment were 0.771, 0.797, 0.664 and 0.715, respectively, while the combined AUC value of each indicator was 0.832; Compared with patients with non-significant pathological response, ADC before treatment was higher in patients with significant pathological response, Kep, Ve and Ktrans were lower ( t=4.46, 3.32, 3.60, 3.95, P < 0.05) ; Compared with before treatment, ADC value increased after treatment, while Kep, Ve and Ktrans decreased ( t=8.77, 6.22, 9.34, 10.26, P < 0.05) . Conclusion:Quantitative parameters of DWI and DCE-MRI can reflect the changes in the condition of patients with locally advanced neoadjuvant chemotherapy, and the combination of the two can help to improve the predictive value of chemotherapy efficacy in patients.

Objective:To explore the value of quantitative parameters of diffusion weighted imaging (DWI) combined with dynamic enhanced magnetic resonance imaging (DCE-MRI) in predicting the efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) .Methods:A total of 97 patients with LABC admitted to the hospital from Mar. 2020 to Mar. 2023 were studied and received neoadjuvant chemotherapy to evaluate the therapeutic effect, and DWI and DCE-MRI scans were performed before and after treatment. The difference of DWI and DCE-MRI quantitative parameters before treatment in patients with different therapeutic effects was compared, and the correlation between the difference of DWI and DCE-MRI quantitative parameters and therapeutic effect was analyzed. The predictive value of quantitative parameters of DWI and DCE-MRI before treatment was analyzed. The quantitative parameters of DWI and DCE-MRI in patients with different pathological reactions were compared before treatment, and the quantitative parameters of DWI and DCE-MRI were compared before and after treatment.Results:The apparent diffusion coefficient (ADC) of patients with effective chemotherapy before treatment was higher, but transport constant (Ktrans) , extracellular space volume percentage (Ve) and rate constant (Kep) were lower ( t=5.0, 3.27, 3.55, 3.89, P < 0.05) ; Spearman correlation analysis showed that ADC was positively correlated with chemotherapy efficacy before treatment (r=0.66; P < 0.05) , while Kep, Ve, Ktrans were negatively correlated with it (r=-0.58, -0.47, -0.60; P < 0.05) ; ROC curves showed that the area under the curve (AUC) values of ADC, Kep, Ve and Ktrans in predicting chemotherapy efficacy before treatment were 0.771, 0.797, 0.664 and 0.715, respectively, while the combined AUC value of each indicator was 0.832; Compared with patients with non-significant pathological response, ADC before treatment was higher in patients with significant pathological response, Kep, Ve and Ktrans were lower ( t=4.46, 3.32, 3.60, 3.95, P < 0.05) ; Compared with before treatment, ADC value increased after treatment, while Kep, Ve and Ktrans decreased ( t=8.77, 6.22, 9.34, 10.26, P < 0.05) . Conclusion:Quantitative parameters of DWI and DCE-MRI can reflect the changes in the condition of patients with locally advanced neoadjuvant chemotherapy, and the combination of the two can help to improve the predictive value of chemotherapy efficacy in patients.

Objective:To analyze the efficacy of laparoscopic partial splenectomy and devascularization (LPSPD), open partial splenectomy and devascularization (OPSPD), laparoscopic total splenectomy and devascularization (LTSPD), and open total splenectomy and devascularization (OTSPD) in the treatment of portal hypertension.Methods:Clinical data of 128 patients with portal hypertension admitted to the Department of Hepatobiliary and Pancreatic Surgery of the Affiliated Hospital of Qinghai University and the General Surgery Department of the Fifth Medical Center of the Chinese PLA General Hospital from May 2018 to May 2022 were retrospectively analyzed, including 69 males and 59 females, aged 51.0±10.9 years. According to different surgical methods, patients were divided into four groups, namely the LPSPD group ( n=30), the OPSPD group ( n=32), the LTSPD group ( n=31), and the OTSPD group ( n=35). Operation time, postoperative hospitalization time, postoperative complications such as newly occurred PVT, etc of the four groups of patients were compared. Results:The operation times of the LPSPD, OPSPD, LTSPD and OTSPD group were 240.0 (180.0, 399.0), 209.5 (169.0, 259.0), 207.0 (175.3, 297.5) and 200.0 (162.0, 264.0) minutes, respectively. The postoperative hospital stays were 8.0 (7.0, 12.0), 10.0 (8.3, 11.8), 11.0 (9.0, 13.0) and 13.0 (11.0, 15.0) days, respectively. The incidences of newly occurred PVT after surgery were 3.3% (1/30), 3.1% (1/32), 19.4% (6/31), and 20.0% (7/35), respectively. The above indicators were compared among the four groups respectively, and the differences were statistically significant (all P<0.05). The postoperative hospital stay of the LPSPD group was shorter than that of the LTSPD group [8.0 (7.0, 12.0) vs 11.0 (9.0, 13.0), d, Z=-3.93], and the postoperative hospital stay of the OPSPD group was also shorter than that of the OTSPD group [10.0 (8.3, 11.8) vs 13.0 (11.0, 15.0), d, Z=-3.56; all P<0.001]. The incidence of newly occurred PVT after surgery in the partial splenectomy group (LPSPD and OPSPD) was 3.2% (2/62), which was lower than that in the total splenectomy group [LTSPD and OTSPD, 19.7% (13/66), χ2=8.38, P=0.004]. Conclusion:Compared to total splenectomy, partial splenectomy might be favorable for the shortened postoperative hospital stay and lower incidence of newly occurred portal vein thrombosis.

Objective:To explore the core issues in the implementation of"packaged payment"in China's compact county medi-cal community,in order to provide useful references for the innovative reform of medical insurance payment methods in compact coun-ty medical community.Methods:By constructing the problem system through the macro model of the health system,analyzing the re-lated literature using multidimensional scale analysis and social network analysis,and comprehensively evaluating the results using the entropy-weighted TOPSIS method,it summarizes the core issues of"packaged payment"in compact county medical community.Results:There are core issues in China's compact county medical community,such as inadequate distribution of benefits and incen-tive and constraint mechanisms within the medical community(Ci= 1.000),lack of effective supervision and assessment mechanism for medical communities(Ci= 0.732),suppressed quality and efficiency of medical services(Ci= 0.652),lagging medical informatiza-tion construction(Ci= 0.595),and incomplete supporting policy measures(Ci= 0.579).Conclusion:The"packaged payment"of com-pact county medical community can be optimized from the following three aspects:a multi-level collaborative incentive mechanism should be improved to ensure the service quality and efficiency;optimize the total amount calculation method and improve the de-tailed supporting measures;accelerate information construction and strengthen supervision and assessment management.

Objective:To explore the leading role and influence path of the coordinated development of the tight medical community service capacity and the high level of county economy,so as to provide a basis for its deepening reform and long-term development.Methods:Taking 39 pilot compact medical communities in Guangxi in 2022 as research samples,from the perspective of set and whole,the coupling coordination degree model and fuzzy set qualitative comparative analysis were used to analyze the coordinated development status and influence mechanism of their service capacity and county economic level.Results:High-level county economic structure is a necessary condition to promote coupling and coordinated development.Among the six configuration paths that affect the improvement of coupling and coordination degree,the core conditions are stable county economic foundation and sufficient health human resources or(and)health financial resources.The overall solution consistency is 0.996(≥0.8),and the coverage is 0.780(≥0.5).The model has strong explanatory power.Conclusion:Multi-factor internal and external cooperation to promote the coordinated development of the service capacity of the compact medical community and the county economy should focus on the county economic foundation and structure,further improve the income of the compact medical community and pay attention to the optimization and expansion of the talent team.

Objective:To explore the leading role and influence path of the coordinated development of the tight medical community service capacity and the high level of county economy,so as to provide a basis for its deepening reform and long-term development.Methods:Taking 39 pilot compact medical communities in Guangxi in 2022 as research samples,from the perspective of set and whole,the coupling coordination degree model and fuzzy set qualitative comparative analysis were used to analyze the coordinated development status and influence mechanism of their service capacity and county economic level.Results:High-level county economic structure is a necessary condition to promote coupling and coordinated development.Among the six configuration paths that affect the improvement of coupling and coordination degree,the core conditions are stable county economic foundation and sufficient health human resources or(and)health financial resources.The overall solution consistency is 0.996(≥0.8),and the coverage is 0.780(≥0.5).The model has strong explanatory power.Conclusion:Multi-factor internal and external cooperation to promote the coordinated development of the service capacity of the compact medical community and the county economy should focus on the county economic foundation and structure,further improve the income of the compact medical community and pay attention to the optimization and expansion of the talent team.

Objective:To explore the leading role and influence path of the coordinated development of the tight medical community service capacity and the high level of county economy,so as to provide a basis for its deepening reform and long-term development.Methods:Taking 39 pilot compact medical communities in Guangxi in 2022 as research samples,from the perspective of set and whole,the coupling coordination degree model and fuzzy set qualitative comparative analysis were used to analyze the coordinated development status and influence mechanism of their service capacity and county economic level.Results:High-level county economic structure is a necessary condition to promote coupling and coordinated development.Among the six configuration paths that affect the improvement of coupling and coordination degree,the core conditions are stable county economic foundation and sufficient health human resources or(and)health financial resources.The overall solution consistency is 0.996(≥0.8),and the coverage is 0.780(≥0.5).The model has strong explanatory power.Conclusion:Multi-factor internal and external cooperation to promote the coordinated development of the service capacity of the compact medical community and the county economy should focus on the county economic foundation and structure,further improve the income of the compact medical community and pay attention to the optimization and expansion of the talent team.

Objective:To explore the leading role and influence path of the coordinated development of the tight medical community service capacity and the high level of county economy,so as to provide a basis for its deepening reform and long-term development.Methods:Taking 39 pilot compact medical communities in Guangxi in 2022 as research samples,from the perspective of set and whole,the coupling coordination degree model and fuzzy set qualitative comparative analysis were used to analyze the coordinated development status and influence mechanism of their service capacity and county economic level.Results:High-level county economic structure is a necessary condition to promote coupling and coordinated development.Among the six configuration paths that affect the improvement of coupling and coordination degree,the core conditions are stable county economic foundation and sufficient health human resources or(and)health financial resources.The overall solution consistency is 0.996(≥0.8),and the coverage is 0.780(≥0.5).The model has strong explanatory power.Conclusion:Multi-factor internal and external cooperation to promote the coordinated development of the service capacity of the compact medical community and the county economy should focus on the county economic foundation and structure,further improve the income of the compact medical community and pay attention to the optimization and expansion of the talent team.