OBJECTIVE To investigate the effects of total flavonoids from Carthamus tinctorius L. （TFCTL） on hepatic stellate cell （HSC） activation based on the microRNA （miRNA）-204/NUAK family SNF1-like kinase 1 （NUAK1）/Hippo signaling axis， thereby elucidating the potential mechanism underlying their antifibrotic effects. METHODS The HSC-T6 cells were divided into control group， model group， TFCTL low-concentration group （20 μg/mL）， TFCTL medium-concentration group （40 μg/mL）， and TFCTL high-concentration group （60 μg/mL）. Except for control group， the remaining groups were treated with 5 ng/mL of transforming growth factor-β to induce the activation of hepatic stellate cells， followed by the addition of corresponding drug solutions/culture medium and incubation for 24 hours. Cell apoptosis was assessed， the expression levels of α-smooth muscle actin （α-SMA）， type Ⅰ collagen （Collagen Ⅰ） and proteins associated with the Hippo/Yes-associated protein （YAP） pathway [YAP， large tumor suppressor kinase 1 （LATS1）， and mammalian STE20-like kinase 1 （MST1）] were detected. Additionally， cell transfection was used to investigate the activity of the miRNA-204/NUAK1/Hippo signaling axis at both the genetic and protein levels. RESULTS After intervention with TFCTL， the apoptosis rate of HSC-T6 cells and the protein expressions of MST1 （except for the TFCTL high-concentration group） and LATS1 were significantly increased （P＜0.05）， while the protein expressions of α-SMA， CollagenⅠ， and YAP （except for the TFCTL medium-concentration group） were significantly decreased （P＜0.05）. Further results from cell transfection experiments revealed that after transfection with miRNA-204 mimics， the mRNA it’s protein expressions of α-SMA， CollagenⅠ， NUAK1， and YAP in HSC-T6 cells were significantly decreased （P＜0.05）， while the mRNA and protein expressions of LATS1 and the mRNA expression of MST1 were significantly increased （P＜0.05）. Conversely， the results were opposite following transfection with miRNA-204 inhibitors. CONCLUSIONS TFCTL can exert anti-hepatic fibrosis effects by up-regulating the expression of miRNA-204， thereby down- regulating the expressions of NUAK1， inactivating the Hippo/YAP pathway， which in turn suppresses the activation of HSC and promotes their apoptosis.

Medical technology proficiency is a key indicator of a municipal-level hospital′s core competitiveness. To continuously enhance its medical capabilities, a tertiary prefecture-level hospital in Zhejiang province launched the " 100 high-tech projects" in 2010, designating it as a priority technical development program. The hospital established a hospital-level knowledge management team in 2020 to build a knowledge management system for high-tech projects. This system fostered a virtuous cycle of synergistic advancement in medical technology innovation, knowledge management, and talent development by extracting both explicit and tacit knowledge from the hospital′s high-tech projects, absorbing tacit knowledge from benchmark hospitals′ relevant technologies, and establishing a knowledge-sharing platform. From January 2021 to October 2024, the hospital secured approval for 9 national and provincial-level clinical key specialties, established 7 municipal key technological innovation teams, and enrolled 46 provincial/municipal-level talents. A the same time, talent attrition remained low. The implementation of the knowledge management system to empower high-tech development had achieved phased results. This practice could provide references for other hospitals to enhance their medical technology capabilities.

AIM:To elucidate the pharmacody-namic and network pharmacological mechanisms of total flavonoids of Carthamus tinctorius L.,to ex-plore their key targets and related pathways,and to clarify their mechanism of action against hepatic fibrosis.METHODS:The total flavonoids of Cartha-mus tinctorius L.were determined by LC-MS/MS and analysed for their compositions;the active in-gredients were screened by TCMSP database,SWISS ADME database and literature search;the targets related to total flavonoids of Carthamus tinctorius L.were screened by Swiss Target Predic-tion database;and the targets related to hepatic fi-brosis were screened by GeneCards database;the anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained by taking the intersection of Venny.2.1.0;the protein interac-tions were analysed by STRING database;the visu-alization analysis was carried out by Cytoscape soft-ware;the GO function and KEGG pathway analysis was carried out by Metascape platform;and molec-ular docking was verified by using AutoDock soft-ware for the core targets and active ingredients.The mechanism of anti-hepatic fibrosis of total fla-vonoids of Carthamus tinctorius L.was verified by animal model and in vitro cell experiments.RE-SULTS:A total of 41 flavonoid components were identified in Carthamus tinctorius L.Through the network pharmacological analysis,149 anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained,including 23 core tar-gets.The GO enrichment analyses involved a total of three aspects,namely,biological process(BP),cellular component(CC),and molecular function(MF).KEGG enrichment results showed that PI3K/Akt and MAPK are pathways involved in the devel-opment of hepatic fibrosis.Molecular docking veri-fied that the active ingredients Quercetin,Acacetin and Glabridin were tightly bound to Akt1 and HI-FIA,respectively.In animal model experiments,it was observed by HE and Masson staining that fibro-plasia was reduced,collagen deposition was re-duced,inflammatory cell infiltration was reduced,and fibrotic liver tissues were improved in total fla-vonoids of Carthamus tinctorius L.administration group.In isolated cell experiments:Western blot-ting results suggested that total flavonoids of Car-thamus tinctorius L.could decrease the hepatic fi-brosis marker factor α-SMA,Collagen1(P＜0.01)and PI3K,Akt protein expression(P＜0.01).CONCLU-SION:Total flavonoids of Carthamus tinctorius L.ex-erted anti-hepatic fibrosis effects through multi-components,multi-targets and multi-pathways,and their mechanism of action may be achieved by regulating the PI3K/Akt signalling pathway.

AIM:To elucidate the pharmacody-namic and network pharmacological mechanisms of total flavonoids of Carthamus tinctorius L.,to ex-plore their key targets and related pathways,and to clarify their mechanism of action against hepatic fibrosis.METHODS:The total flavonoids of Cartha-mus tinctorius L.were determined by LC-MS/MS and analysed for their compositions;the active in-gredients were screened by TCMSP database,SWISS ADME database and literature search;the targets related to total flavonoids of Carthamus tinctorius L.were screened by Swiss Target Predic-tion database;and the targets related to hepatic fi-brosis were screened by GeneCards database;the anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained by taking the intersection of Venny.2.1.0;the protein interac-tions were analysed by STRING database;the visu-alization analysis was carried out by Cytoscape soft-ware;the GO function and KEGG pathway analysis was carried out by Metascape platform;and molec-ular docking was verified by using AutoDock soft-ware for the core targets and active ingredients.The mechanism of anti-hepatic fibrosis of total fla-vonoids of Carthamus tinctorius L.was verified by animal model and in vitro cell experiments.RE-SULTS:A total of 41 flavonoid components were identified in Carthamus tinctorius L.Through the network pharmacological analysis,149 anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained,including 23 core tar-gets.The GO enrichment analyses involved a total of three aspects,namely,biological process(BP),cellular component(CC),and molecular function(MF).KEGG enrichment results showed that PI3K/Akt and MAPK are pathways involved in the devel-opment of hepatic fibrosis.Molecular docking veri-fied that the active ingredients Quercetin,Acacetin and Glabridin were tightly bound to Akt1 and HI-FIA,respectively.In animal model experiments,it was observed by HE and Masson staining that fibro-plasia was reduced,collagen deposition was re-duced,inflammatory cell infiltration was reduced,and fibrotic liver tissues were improved in total fla-vonoids of Carthamus tinctorius L.administration group.In isolated cell experiments:Western blot-ting results suggested that total flavonoids of Car-thamus tinctorius L.could decrease the hepatic fi-brosis marker factor α-SMA,Collagen1(P＜0.01)and PI3K,Akt protein expression(P＜0.01).CONCLU-SION:Total flavonoids of Carthamus tinctorius L.ex-erted anti-hepatic fibrosis effects through multi-components,multi-targets and multi-pathways,and their mechanism of action may be achieved by regulating the PI3K/Akt signalling pathway.

Medical technology proficiency is a key indicator of a municipal-level hospital′s core competitiveness. To continuously enhance its medical capabilities, a tertiary prefecture-level hospital in Zhejiang province launched the " 100 high-tech projects" in 2010, designating it as a priority technical development program. The hospital established a hospital-level knowledge management team in 2020 to build a knowledge management system for high-tech projects. This system fostered a virtuous cycle of synergistic advancement in medical technology innovation, knowledge management, and talent development by extracting both explicit and tacit knowledge from the hospital′s high-tech projects, absorbing tacit knowledge from benchmark hospitals′ relevant technologies, and establishing a knowledge-sharing platform. From January 2021 to October 2024, the hospital secured approval for 9 national and provincial-level clinical key specialties, established 7 municipal key technological innovation teams, and enrolled 46 provincial/municipal-level talents. A the same time, talent attrition remained low. The implementation of the knowledge management system to empower high-tech development had achieved phased results. This practice could provide references for other hospitals to enhance their medical technology capabilities.

Objective:To evaluate the prognostic value of sepsis-induced coagulopathy (SIC) in patients with sepsis.Methods:From January 2019 to December 2021, patients with sepsis admitted to the Intensive Care Unit of our hospital were retrospectively classified into the SIC group and non-SIC group according to SIC diagnostic criteria. The baseline clinical data, severity score, total length of hospital stay, length of ICU stay and 28-day survival were compared between the two groups. Kaplan-Meier was used to compare the 28-day survival of patients with sepsis between the two groups. Cox proportional hazard regression model was employed to analyze the risk factors of prognosis in patients with sepsis.Results:Totally 274 patients with sepsis were included in the analysis, including 139 patients in the SIC group and 135 patients in the non-SIC group. The two groups were compared in the perspectives of the Platelet count (PLT), prothrombin time (PT) , procalcitonin (PCT), D dimer, hematocrit, red blood cell distribution width, hemoglobin, acute kidney injury (AKI), the use of continuous renal replacement treatment (CRRT), the use of vasoactive drugs, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHEⅡ) score were compared between the two groups and the difference were statistically different (all P<0.05). Kaplan-Meier analysis showed that the 28-day mortality rate in the SIC group was significantly higher than that in the non-SIC group (32.4% vs. 14.1%, P<0.05). COX proportional hazard model showed that SIC score ( HR= 2.17, 95% CI: 1.15-3.91, P<0.05), APACHEⅡ score ( HR= 1.13, 95% CI: 1.09-1.17, P<0.05) and the use of vasoactive drugs ( HR=3.66, 95% CI: 1.53-8.75, P<0.05) were independent influencing factors for 28-day death in patients with sepsis. Conclusions:Patients with sepsis and SIC have more severe disease and increased mortality risk. SIC score exhibits good clinical value in predicting the prognosis of patients with sepsis.

The thyroid function test is universally used for the evaluation of thyroid function. However, there are factors other than endocrine diseases, such as special physiological conditions, interference in laboratory measurement, or disorders in other systems that should be taken into consideration. When encountering thyroid function test results that are not in line with clinical manifestation, a comprehensive evaluation is essential for a correct and timely diagnosis. We presented a case of a significant rise in serum total triiodothyronine(TT 3) secondary to multiple myeloma. Through case studies and literature review, we intended to provide clinicians with experience for better interpretation of abnormal thyroid function test results.

Objectives: To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer. Methods: The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ² test, survival analysis was carried by Kaplan-Meier and Log-rank test. Results: Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ²=288.60,P<0.01),N stage(χ²=68.10, P<0.01), vascular invasion(χ²=128.70, P<0.01)and neural invasion(χ²=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ²=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05). Conclusion With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.

Objective: To discuss the rationality of stage pT3 in the AJCC 8^th TNM criteria of gallbladder carcinoma. Methods: A retrospective study was performed to analyze the clinical and pathological data of 88 patients with pT3 gallbladder carcinoma admitted to Department of Second Biliary Surgery of Eastern Hepatobiliary Surgery Hospital, affiliated to Naval Medical University from May 2013 to September 2018.pT3 stage tumors were divided into two groups: (1) pT3a stage: tumors had penetrated serosa but not directly invaded liver and/or an adjacent organ or structure; (2) pT3b stage: tumor penetrating serosa and directly invaded liver and/or an adjacent organ or structure. There were 45 patients with pT3a stage, including 15 males and 30 females, aged 36 to 80 years, with a median age of 59 years; 43 patients with pT3b, including 24 males and 19 females, aged 41 to 78 years old, median aged 63 years old.Patients with pT3a and pT3b were further divided into two groups respectively: radical resection group and extended radical resection group according to surgical radicalization. Independent sample t-test was used for comparison between two groups with normal distribution measurement data. Wilcoxon rank sum test was used between groups of non-normally distributed measurement data.The comparison of the count data was performed by χ² test or Fisher exact probability method. Survival analysis was performed using Kaplan-Meier method, and survival rate was compared using Log-rank test. Results: (1)Serum total bilirubin(15.6(90.3)mmol/L), albumin(40.2(4.8)mmol/L), and CA19-9(132.90(455.78)U/ml) levels in pT3b patients were higher than that in pT3a patients(10.2(6.8)mmol/L, 41.8(4.9)mmol/L, 14.35(36.27)U/ml), respectively(Z=-3.816, -1.966, -3.739, all P<0.05),postoperative complication rate in pT3b patients(24.4%) was higher than that in pT3a patients(8.9%)(P<0.05),postoperative hospital stay(12(7)days) and overall hospital stay((26±17)days) of pT3b patients were longer than that of pT3a patients((10±5) days and (19±7)days) (P<0.05). (2) The 1-, 3-, 5-year survival rates of pT3b and pT3a patients were 53%,22%,22% and 69%, 46%,38%,and the median survival time was 13 months and 26 months, respectively. The difference in survival rates between the two groups was statistically significant(χ²=5.117, P=0.024). (3)The 1-, 3-year survival rates of extended radical resection group(n=19) and radical resection group(n=24) in the pT3b stage were 73%, 36% and 28%, 7%, respectively.The survival time was 20 months and 9 months,respectively,and the difference in survival rates between the two groups was statistically significant(χ²=4.976, P=0.026). Conclusions pT3 gallbladder carcinoma could be further subdivided into pT3a stage and pT3b stage based on the TNM criteria of AJCC 8^th gallbladder carcinoma. Extended radical resection for pT3b gallbladder carcinoma should be further considered after comprehensive assessment of the patient′s basic condition and surgical tolerance.

Objective To discuss the rationality of stage pT3 in the AJCC 8th TNM criteria of gallbladder carcinoma. Methods A retrospective study was performed to analyze the clinical and pathological data of 88 patients with pT3 gallbladder carcinoma admitted to Department of Second Biliary Surgery of Eastern Hepatobiliary Surgery Hospital, affiliated to Naval Medical University from May 2013 to September 2018.pT3 stage tumors were divided into two groups: (1) pT3a stage:tumors had penetrated serosa but not directly invaded liver and/or an adjacent organ or structure;(2) pT3b stage:tumor penetrating serosa and directly invaded liver and/or an adjacent organ or structure. There were 45 patients with pT3a stage, including 15 males and 30 females,aged 36 to 80 years,with a median age of 59 years;43 patients with pT3b, including 24 males and 19 females,aged 41 to 78 years old,median aged 63 years old.Patients with pT3a and pT3b were further divided into two groups respectively: radical resection group and extended radical resection group according to surgical radicalization. Independent sample t?test was used for comparison between two groups with normal distribution measurement data. Wilcoxon rank sum test was used between groups of non?normally distributed measurement data.The comparison of the count data was performed by χ2 test or Fisher exact probability method. Survival analysis was performed using Kaplan?Meier method, and survival rate was compared using Log?rank test.Results (1)Serum total bilirubin(15.6(90.3)mmol/L), albumin(40.2(4.8)mmol/L), and CA19?9(132.90(455.78)U/ml) levels in pT3b patients were higher than that in pT3a patients(10.2(6.8)mmol/L, 41.8(4.9)mmol/L, 14.35(36.27)U/ml), respectively(Z=-3.816,-1.966,-3.739, all P<0.05),postoperative complication rate in pT3b patients(24.4%) was higher than that in pT3a patients(8.9%)(P<0.05),postoperative hospital stay(12(7)days) and overall hospital stay((26±17)days) of pT3b patients were longer than that of pT3a patients((10±5) days and (19±7)days)(P<0.05).(2) The 1?,3?, 5?year survival rates of pT3b and pT3a patients were 53%,22%,22% and 69%, 46%,38%,and the median survival time was 13 months and 26 months, respectively. The difference in survival rates between the two groups was statistically significant(χ2=5.117, P=0.024). (3)The 1?, 3?year survival rates of extended radical resection group(n=19) and radical resection group(n=24) in the pT3b stage were 73%, 36% and 28%, 7%, respectively.The survival time was 20 months and 9 months,respectively,and the difference in survival rates between the two groups was statistically significant(χ2=4.976, P=0.026). Conclusions pT3 gallbladder carcinoma could be further subdivided into pT3a stage and pT3b stage based on the TNM criteria of AJCC 8th gallbladder carcinoma. Extended radical resection for pT3b gallbladder carcinoma should be further considered after comprehensive assessment of the patient′s basic condition and surgical tolerance.