ObjectiveTo investigate whether menaquinone-4 （MK-4） can exert a protective effect against carbon tetrachloride （CCl₄）-induced acute liver injury （ALI） in mice by alleviating ferroptosis. MethodsAfter adaptive feeding， adult male ICR mice， aged 8 weeks， were divided into Control group， MK-4 group， CCl₄ model group （6-hour， 12-hour， and 24-hour）， and MK-4+CCl₄ group （6-hour， 12-hour， and 24-hour）， with 6 mice in each group. The mice in the Control group were given intraperitoneal injection of an equal dose of corn oil； the mice in the MK-4 group were given intraperitoneal injection of 40 mg/kg MK-4 solution， followed by an equal dose of corn oil after 1 hour； the mice in the MK-4+CCl₄ group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 40 mg/kg MK-4 solution， and after 1 hour， the mice in this group and the CCl₄ model group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 0.3 mL/kg CCl₄ solution， with samples collected at 6， 12， and 24 hours. HE staining was used to observe the pathological changes of mouse liver； Prussian blue staining was used to observe iron accumulation in liver tissue； a biochemical analyzer was used to measure the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； related kits were used to measure the levels of tissue iron content and the oxidative stress indices malondialdehyde （MDA） and glutathione （GSH） in liver homogenate； RT-PCR was used to measure the expression levels of ferroptosis marker genes （acyl-CoA synthetase long-chain family member 4 ［ACSL4］， prostaglandin-endoperoxide synthase 2 ［PTGS2］， and glutathione peroxidase 4 ［GPX4］） and iron metabolism-related genes （hemojuvelin ［HJV］， transferrin receptor 1 ［TFR1］， and ferroportin ［FPN］）， and Western blot was used to measure the protein expression level of GPX4. 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. ResultsIn the aging study， compared with the Control group， the CCl₄ model group （6-hour， 12-hour， and 24-hour） had significant increases in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， and HE staining also showed that liver injury gradually aggravated over time. Meanwhile， compared with the CCl₄ model group （6-hour， 12-hour， and 24-hour）， the MK-4+CCl₄ （12-hour） group had significant reductions in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， with a reduction in the necrotic area of liver tissue， and therefore， 12-hour mouse tissue samples were used for detection in the following study. Compared with the Control group， the CCl₄ group had a significant increase in MDA and a significant reduction in GSH （both P<0.05）， and compared with the CCl₄ group， the MK-4+CCl₄ group had a significant reduction in MDA and a significant increase in GSH （both P<0.05）. Compared with the Control group， the CCl₄ group had significant increases in the key ferroptosis indices ASCL4 and PTGS2 and a significant reduction in GPX4 （all P<0.05）； compared with the CCl₄ group， the MK-4+CCl₄ group had significant reductions in the mRNA expression levels of ASCL4 and PTGS2 and a significant increase in the mRNA expression level of GPX4 （all P<0.05）. Western blotting showed that compared with the Control group， the CCl₄ group had a significant reduction in the protein expression level of GPX4 （P<0.05）， and compared with the CCl₄ group， the MK-4+CCl₄ group had a significant increase in the protein expression level of GPX4 （P<0.05）. Prussian blue staining showed that compared with the Control group， the CCl₄ group had a significant increase in iron accumulation； after MK-4 intervention， compared with the CCl₄ group， the MK-4+CCl₄ group had a significant reduction in iron accumulation. As for the measurement of iron metabolism genes in mouse liver， compared with the Control group， the CCl₄ group had a significant increase in iron content， significant reductions in the mRNA expression levels of FPN and HJV， and a significant increase in the mRNA expression level of TFR1 （all P<0.05）； after protection with MK-4， there was a significant reduction in iron content， significant increases in the mRNA expression levels of FPN and HJV， and a significant reduction in the mRNA expression level of TFR1 （all P<0.05）. ConclusionMK-4 intervention in advance can alleviate CCl₄-induced ALI in mice， possibly by inhibiting ferroptosis and improving the expression of iron metabolism-related genes in mouse liver.

Objective To investigate the mechanism of bis(2-ethylhexyl)phthalate(DEHP)in inducing cholestasis and liver injury in mice.Methods In the in vivo experiment,adult female ICR mice were randomly divided into control group(corn oil)and DEHP group(200 mg/kg/d),and a model of cholestasis was established by intragastric administration for 4 weeks.After blood and liver tissue samples were collected from all mice,a biochemical analyzer was used to measure the level of total bile acid(TBA)in serum and the liver,and a microplate reader was used to measure alkaline phosphatase(ALP)and gamma-glutamyl transpeptidase(GGT);HE staining was used to observe the pathological changes of the liver;RT-PCR was used to measure the mRNA expression levels of the inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in the liver;liquid chromatography/triple quadrupole mass spectrometry was used to measure the bile acid profile in the liver of mice.In the in vitro experiment,AML-12 mouse hepatocytes were cultured and treated with DEHP(250 μmol/L),DCA(125 μmol/L),and CDCA(125 μmol/L)for 24 hours,and RT-PCR was used to measure the mRNA expression levels of the inflammatory cytokines IL-1β,IL-6,and TNF-α.The independent-samples t test was used for comparison of continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the LSD-t test was used for further comparison between two groups.Results The in vivo experiment showed that compared with the control group,the DEHP group had significant increases in the serum levels of TBA,ALP,and GGT and the level of TBA in the liver(the t values are respectively-4.396,-5.109,-8.504,-3.792 and-7.974,all P<0.05,).Compared with the control group,the DEHP group had significant increases in cholic acid,chenodeoxycholic acid,taurocholic acid,deoxycholic acid,and ursodeoxycholic acid(the t values are respectively-2.802,-3.177,-2.633,-2.874 and-2.311,all P<0.05).HE staining of the liver showed that the mice in the DEHP group had enlargement of the portal area,bile duct deformation,inflammatory cell infiltration around the bile duct,and significant increases in the mRNA expression levels of the inflammatory factors IL-1β,IL-6,and TNF-α in the liver(the t values are respectively-2.539,-2.823 and-4.636,all P<0.05).The in vitro experiment showed that the actual difference in hepatocyte viability after 0-1 000 μmol/L DEHP treatment does not exceed 15%,but there were significant increases in the mRNA expression levels of the inflammatory cytokines IL-1β,IL-6,and TNF-α after treatment with DEHP at different concentrations of 125 μmol/L,250 μmol/L,and 500 μmol/L(all P<0.05).Compared with DEHP stimulation alone,the combined stimulation of CDCA and DEHP upregulates the cytokine in hepatocyte IL-1β mRNA levels(P<0.01);the combined stimulation of DCA and DEHP can significantly increase the cytokine in hepatocyte IL-1β and IL-6 mRNA levels(all P<0.01).Conclusion DEHP exposure can cause cholestasis and induce liver inflammation in mice,possibly by promoting the production of toxic bile acids and the secretion of inflammatory factors.

Objective To investigate the efficacy and safety of using the fourth arm in retroperitoneal robot-assisted partial nephrectomy(PN)for cT1b stage renal tumors.Methods Clinical data of 49 patients with cT1b stage renal tumors who underwent retroperitoneal robot-assisted PN performed by the same surgeon in our hospital during Jan.2022 and Dec.2023 were retrospectively analyzed.The patients were divided into two groups based on whether the fourth arm was used or not:application group(n=21)and non-application group(n=28).The basic information,operation time,warm ischemia time,intraoperative blood loss,postoperative complications and other data were compared between the two groups.Results All operations were successful,with no conversion to open surgery or radical nephrectomy.The application group had significantly shorter operation time[(128.76±31.58)min vs.(151.11±33.21)min,P=0.021],shorter warm ischemia time[(24.67±4.80)min vs.(27.61±3.54)min,P=0.017],and less intraoperative blood loss[(109.05±39.99)mL vs.(139.29±54.43)mL,P=0.037]compared with the non-application group.The increase of postoperative creatinine was(18.64±16.05)μmol/L in the application group and(20.30±13.49)μmol/L in the non-application group respectively.Complications occurred in 3 cases in the application group and 5 cases in the non-application group,with no significant difference(P＞0.05).Conclusion When we perform the retroperitoneal robot-assisted partial nephrectomy for cT1b stage renal tumors,using the fourth arm can shorten the operation time and warm ischemia time,and reduce the intraoperative blood loss,which should be applied more in clinic.

Objective:To explore the application and research progress of lasers in the treatment of kidney neoplasms through an integrated bibliometric and Meta-analysis study.Methods:On June 7th, 2024, an online search of the Web of Science Core Collection (WoSCC) and China National Knowledge Infrastructure (CNKI) databases for all relevant literature on lasers in kidney neoplasms was conducted. The retrieved results were subjected to a comprehensive bibliometric analysis. The high-quality studies were then screened to further describe the clinical characteristics of patients who underwent laser-assisted laparoscopic partial nephrectomy (LLPN). Subsequently, a Meta-analysis was performed using RevMan 5.4.1 software on further selected high-quality studies to compare the changes in renal function before and after LLPN treatment, and the differences in efficacy between LLPN and traditional laparoscopic partial nephrectomy (LPN).Results:Our study obtained a total of 549 publications on lasers in kidney neoplasms, including 513 in English and 36 in Chinese. Bibliometric analysis revealed an overall upward trend in the annual publications and citations in this field. China was found to be a leading contributor ranking second in total publications ( n=100, 18.2%). The primary application of laser treatment was in nephron-sparing surgery for kidney neoplasms, especially in LPN. We further screened 11 high-quality studies comprising 284 patients who underwent LLPN for kidney neoplasms. Comprehensive descriptive statistical analysis was performed on clinical characteristics of the 284 patients. All patients had T 1a stage tumors with a mean tumor length of 2.6 cm (range: 0.8-4.0 cm), all being local, solitary, and exophytic tumors. Further Meta-analysis indicated that there were no significant differences in renal function indicators including both serum creatinine levels ( MD=4.52, 95% CI-9.73-0.69, P = 0.09) and estimated glomerular filtration rate ( MD=3.05, 95% CI-1.03-7.13, P= 0.14) before and after LLPN. Additionally, compared to traditional LPN, LLPN showed significantly reduced operative time ( MD=-10.58, 95% CI= -13.11-8.06, P<0.001), but no significant differences in estimated blood loss ( MD= -27.09, 95% CI-67.38-13.21, P=0.19) and hospital stay ( MD=-1.59, 95% CI-3.42-0.25, P=0.09). Conclusions:The application of lasers in managing of kidney neoplasms is arousing increasing attention among urologists. LLPN offers several advantages, including precise cutting and effective hemostasis. This technique demonstrates considerable clinical value for patients with exophytic T 1a kidney neoplasms undergoing "zero-ischemia" nephron-sparing surgery.

Research on the pathogenesis of liver diseases has attracted great attention. Endoplasmic reticulum stress (ERS) is a self-protective mechanism of cells, but sustained and severe ERS can induce apoptosis, autophagy, and ferroptosis, among which ferroptosis has been a research hotspot in recent years. Ferroptosis is mainly characterized by the accumulation of iron-dependent lipid peroxides and plays a key role in the development and progression of liver diseases, but there are currently few studies on the involvement of ERS in ferroptosis in liver diseases. This article summarizes the research advances in ERS-related signaling pathways, the mechanism of ferroptosis, and the involvement of ERS in liver diseases, so as to provide more ideas for research on the treatment of liver diseases.

Objective : High performance liquid chromatography⁃mass spectrometry (LC⁃MS/MS) system was used to accurately determine 22 bile acids in serum , liver, amniotic fluid and placenta of pregnant mice , and a LC⁃MS/ MS method was established for efficient detection and analysis of bile acids in serum , liver, amniotic fluid and placenta of mice. Methods : Pregnant mice serum , liver, amniotic fluid and placenta samples were processed , with 0. 1% glacial acetic acid in 4 mmol/L ammonium acetate aqueous solution as mobile phase A and pure methanol as mobile phase B , the flow rate was 0. 4 ml/min , a gradient elution program was used to elute with Phenomenex Gemini 3 μm NX⁃C18 110A ( 100 mm × 2. 0 mm) chromatographic column elution , and mass spectrometry detection system used an electrospray ion source for negative ion multiple reaction monitoring. Results : The linear relationship of 22 bile acids in the quantitative range was good. The RSD of inter⁃day and intra⁃day precision at low , medium and high concentrations was 0. 5% - 7. 4% , the matrix effect was 88% - 110% , and the extraction recovery was 84% - 108% . Conclusion In this experiment , LC⁃MS/MS was established to detect 22 bile acids in serum , liver, amniotic fluid and placenta of pregnant mice. The method not only has high sensitivity and selectivity , but also can stably detect a large number of samples.

Objective : To investigate the protective effect of obeticholic acid (OCA) on di(2⁃ethylhexyl) phthalate (DEHP)Ⅳinduced cholestasis in mice. Methods : Animal experiment 1 : Female ICR mice were randomly divided into 3 groups: the control group, DEHP low⁃dose group [50 mg/(kg d)]and DEHP high⁃dose group [200 mg/ ( kg d)] . All mice were administered with DEHP by gavage for 18 days. Animal experiment 2: Female ICR mice were randomly divided into 4 groups: the control group, OCA group, DEHP model group[200 mg/(kg ·d)] and DEHP + OCA group. All mice were administered with DEHP by gavage for 18 days and the duration of OCA was 12 - 18 days. Serum and liver tissues of mice were collected. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid ( TBA) levels, liver TBA levels, protein expression of farnesoid X receptor (FXR) and mRNA levels of FXR and SHP were detected. HE staining was used to observe the pathological changes in liver tissues. Results : Experiment 1: Compared with the control group, the liver weight, liver coefficient and the TBA concentrations in serum and liver significantly increased only in DEHP[200 mg/(kg ·d)] group(P < 0. 01), indicating that the modeling was successful. Animal experiment 2: Compared with the DEHP model group, the liver weight and liver coefficient significantly decreased after OCA treatment, and the TBA concentrations in serum and liver both decreased (P < 0. 01) .Compared with the control group, the protein expression level and its mRNA level of FXR decreased after DEHP[200 mg/(kg ·d)]treatment; Compared with the DEHP model group, the protein expression of FXR and the mRNA levels of FXR and SHP significantly increased after OCA treatment(P < 0. 05) . Conclusion DEHP exposure can induce cholestatic liver injury in mice, and OCA posttreatment has a protective effect on DEHP⁃induced cholestasis in mice.

Objective:To investigate the current status of affective commitment and feedback-seeking behavior in junior nurses in three Class Ⅲ Grade A hospitals in Wenzhou and to explore the effect of affective commitment of junior nurses on feedback-seeking behavior.Methods:Methods Using the convenient sampling method, a total of 400 junior nurses in 3 ClassⅢ Grade A hospitals in Wenzhou in Zhejiang Province from October to December 2019 were selected as research objects. General data questionnaire, Affective Commitment Scale and Feedback-Seeking Behavior Scale were used to investigate the effect of affective commitment of junior nurses on feedback-seeking behavior. In this study, a total of 400 questionnaires were issued, and 372 valid questionnaires were collected, with an effective recovery rate of 93%.Results:The total score of Affective Commitment Scale for 372 junior nurses was (29.07±4.86) and that of Feedback-Seeking Behavior Scale was (40.47±6.47) . The results of univariate analysis showed that there were statistically significant differences in the feedback seeking behavior scores of junior nurses in terms of title, education background, department and employment mode ( P<0.05) . Pearson correlation analysis showed that the total score of Affective Commitment Scale for junior nurses was positively correlated with the total score of Feedback-Seeking Behavior Scale ( P<0.05) . Stratified regression analysis results showed that affective commitment had a predictive effect on feedback-seeking behavior of junior nurses ( P<0.05) . Conclusions:The affective commitment and feedback-seeking behavior of junior nurses are in the middle level and need to be further strengthened. Affective commitment positively affects feedback-seeking behavior, so nursing managers can improve the level of feedback-seeking behavior by strengthening the affective commitment level of junior nurses.

Objective To investigate the clinical feasibility and effectiveness of 3-D printing (3DP) combined with 3-D laparoscopic nephron-sparing surgery (LNSS) for partial endogenous renal cell carcinoma.Methods A retrospective analysis was made of the clinical data of 79 patients with partial endogenous renal cell carcinoma who were admitted to our department from July 2015 to October 2018.There were 46 males and 33 females.Their average age was (50.9 ± 7.9) years old,ranged from 33 to 68 years old.Tumor stages were T1aN0M0 in 53 cases and T1bN0M0 in 26 cases.The preoperative serum creatinine ranged from 40 to 107 μmol/L,with an average of (72.4 ± 14.2) μmol/L.The preoperative GFR ranged from 19 to 54 ml/min,with an average of (40.2 ± 6.2) ml/min.Thirty-four patients underwent 2-D laparoscopic nephron-sparing surgery (2DLNSS) based on preoperative enhanced CT scans.Forty-five patients underwent 3-D printing (3DP) based on three-dimensional reconstruction of renal CT scans.Seventeen patients underwent 2-D laparoscopic nephron-sparing surgery guided by 3-D printing model(3DP-2DLNSS),and 28 patients underwent 3-D laparoscopic nephron-sparing surgery guided by 3-D printing (3DP-3DLNSS).Serum creatinine levels ranged from 42 to 122 μmol/L with an average of (86.3 ± 14.8) μmol/L,and creatinine levels ranged from 8 to 66 μmol/L with an average of (19.1 ± 14.1) μmol/L.Six months after operation,the GFR of the kidney was 9-36 ml/min with an average of (21.4 ± 6.4)ml/min,and the fluctuation range was 6-40 ml/min with an average of (19.2 ± 8.8) ml/min.There was no statistical difference in the incidence of complications and pathological types after operation.Results There was no statistical difference in general data of preoperative patients.In intraoperative and post-operative statistics,the time of exploring renal artery was shorter than that of 2DLNSS (33.7 ± 7.5) min in 3DP-2DLNSS (28.3 ± 8.2,P =0.015) min and 3DP-3DLNSS (27.8 ± 6.5,P =0.002) min.In tumor detection time,3 DP-2DLNSS was shorter than 2DLNSS group (41.2 ± 6.6 vs.46.5 ± 6.9 min,P =0.012),and 3 DP-3DLNSS was shorter than 3DP-2DLNSS (35.4 ± 7.3 vs.41.2 ± 6.6 min,P =0.009).In warm ischemia time,3DP-2DLNSS min was shorter than 2DLNSS (23.5 ±9.7 vs.33.9 ±7.5 min P ＜0.001),and 3DP-3DLNSS was shorter than 3DP-2DLNSS (18.3 ± 4.6 vs.23.5 ± 9.7,P =0.023).In surgical time,3DP-2DLNSS (115.7 ± 23.0) min and 3DP-3DLNSS (103.3 ± 22.8) min were shorter than 2DLNSS (132.4 ± 28.9) min (P =0.031,P ＜ 0.001).In intraoperative bleeding volume,3 DP-3 DLNSS was less than 2DLNSS (117.9 ± 17.9 vs.130.6 ± 16.8,P =0.009) ml.Fasting for 1 to 4 days after operation,with an average of (1.7 ± 0.8) days.The indwelling catheterization ranged from 1 to 8 days after operation,with an average of (3.9 ± 1.3) days.Negative pressure drainage was removed 2-9 days after operation,with an average of (4.9 ± 1.4) days.And the hospitalization 5-11 days after operation,with an average of (7.3 ± 1.5) days.Conclusions Preoperative 3D printing combined with intraoperative 3D laparoscopic nephron sparing surgery for partial endogenous renal tumors is safe and effective,which is superior to the previous CT scan alone and intraoperative 2D laparoscopic treatment.

Objective To explore the efficacy and tolerance of adverse reactions of gene detection technique in guiding individualized targeted therapy for advanced metastatic renal cell carcinoma.Methods Retrospective analysis was performed on the clinical data of 62 patients with advanced metastatic renal cell carcinoma before and after receiving targeted drug treatment in our department from October 2015 to October 2017.Among the 62 patients,there were 36 males and 26 females,with an average age of (54 ± 13) years old.16 patients were treated with sunitinib,20 patients were treated with sorafenib and 26 patients were treated with pazopanib.A total of 28 patients (individualized group) were selected to receive targeted drug according to the results of gene detection,and 34 patients were treated with targeted drug empirically (empirical group).In individualized group,there were 17 males and 11 females with the average age of (51.3 ± 15.6) years old.20 patients accepted the operation.The distant metastasis included bone metastasis in 21 cases,lung metastasis in 7 cases,liver metastasis in 16 cases,epidermal metastasis in 4 cases and lymphatic metastasis in 14 cases.According to risk of MSKCC,the case number of low risk,moderate risk and high risk were 15,7,6,respectively.7 patients were treated with sunitinib,8 patients were treated with sorafenib and 13 patients were treated with pazopanib.In empirical group,there were 19 males and 15 females with the average age of (56.3 ± 10.1) years old.22 patients accepted the operation.The distant metastasis included bone metastasis in 20 cases,lung metastasis in 5 cases,liver metastasis in 13 cases,epidermal metastasis in 3 cases and lymphatic metastasis in 15 cases.According to risk of MSKCC,the case number of low risk,moderate risk and high risk were 20,g,6,respectively.9 patients were treated with sunitinib,12 patients were treated with sorafenib and 13 patients were treated with pazopanib.The baseline characteristics of the two groups of patients,including gender,age,whether operation was performed,site of metastasis,and risk of MSKCC,didn't show significant difference.Patients in both groups received the standard treatment regimen and the follow-up duration was 4-26 months to observe the efficacy,progression-free survival and tolerance to adverse reactions of the targeted therapy.Results After 12 months of treatment,15 patients in the individualized group was recorded objective remission.7 patients in the empirical group was recorded objective remission,as well.The tumor control efficacy of the individualized group was significantly better than that of the empirical group (46.4％ vs.20.6％,P =0.03).Meanwhile,the median progression-free survival time (15.2 months,3.7-24.2 months) in the individualized group was significantly longer than that in the empirical group (12.1 months,2.8-22.1 months) (P =0.009).Compared with the empirical group,the higher incidence of targeted treatment-related adverse reactions occurred in the individualized group,including thrombocytopenia (46.4％ vs.17.6％ P =0.014),leukopenia (46.4％ vs.17.6％ P =0.005),hypertension (71.4％ vs.44.1％,P =0.031) and hypothyroidism(60.7％ vs.29.4％,P=0.013).Conclusions Compared with the patients with empirical drugs,the application of gene detection technique to select individualized targeted drugs for the treatment of advanced metastatic renal cancer is obvious curatively effective,and to a certain extent extends the progression-free survival time of patients.