This study aimed to elucidate the mechanism of action of metformin (MET) in inhibiting the malignant progression of hepatocellular carcinoma (HCC) by regulating the degradation of aldo-keto reductase family 1 member C3 (AKR1C3). The correlation between the sensitivity of different hepatocellular carcinoma cell lines to MET and their basal expression levels of AKR1C3 was firstly evaluated. MET was found to significantly reduce the level and accelerate the degradation rate of AKR1C3 protein by Western blot. The interaction between MET and AKR1C3 protein was confirmed by cellular thermal shift assay (CETSA). Proteasome inhibitor MG132 and the lysosomal inhibitor chloroquine (CQ) were used to screen the degradation pathway, and confirm, in combination with the HBSS starvation-induced autophagy model, that MET mediated the degradation of AKR1C3 through the autophagy lysosome pathway. Ubiquitylation assay showed that MET specifically enhanced the K63-linked polyubiquitylation modification of AKR1C3. Sequestosome 1 (SQSTM1/p62) knockdown, immunoprecipitation, and immunofluorescence co-localization analyses confirmed that the autophagy receptor p62 plays a key role in mediating MET-induced degradation of AKR1C3. The adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor compound C was used to demonstrate that the regulatory effect of MET on AKR1C3 is independent of the classical AMPK signaling pathway. The experimental results showed that metformin promoted the ubiquitination modification of AKR1C3 by targeting AKR1C3, enhanced the binding of AKR1C3 to autophagy receptor p62, then degraded the AKR1C3 protein through selective autophagy-like pathway, and ultimately inhibited the malignant phenotypes of hepatocellular carcinoma cells, which is a regulatory mechanism free of the classical AMPK activation pathway of metformin.

Objective:To compare the safety of radial artery puncture in elderly patients aged 75 years and older who are undergoing neurointerventional procedures.Methods:A single-center retrospective study was conducted, involving 350 elderly patients aged 75 years and older who received neurointerventional treatment at Beijing Tiantan Hospital, Capital Medical University, from June to December 2022.The participants were divided into two groups based on the puncture site: femoral artery puncture and radial artery puncture.The safety indicators compared between the two groups included puncture failure, changes in puncture site, general puncture complications(such as subcutaneous bleeding, puncture site hematoma, and vasospasm), severe puncture complications(including distal limb ischemia and pseudoaneurysm), and lower limb venous thrombosis.Multivariate Logistic regression analysis was conducted to evaluate the impact of different puncture methods on the occurrence of complications.Results:Among the 350 patients, 280 underwent femoral artery puncture, while 70 underwent radial artery puncture.There were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The proportions of patients using antiplatelet drugs prior to surgery, puncture failure rates, rates of change in puncture sites, and the incidence of severe complications-including distal limb ischemia and pseudoaneurysm-were not significantly different between the two groups( χ2=2.051, 0.075, 0.588, 3.175; P=0.152, 0.784, 0.443, 0.075).In the femoral artery puncture group, 20.4%(57 cases)of patients experienced general puncture complications(including subcutaneous bleeding, puncture site hematoma, and vasospasm), whereas only 8.6%(6 cases)in the radial artery puncture group experienced such complications, revealing a statistically significant difference between the two groups( χ2=5.720, P=0.022).Multivariate Logistic regression analysis indicated that, compared to femoral artery puncture, radial artery puncture was associated with a reduced risk of all complications( OR=0.272, 95% CI: 0.139-0.532, P<0.001), general puncture complications( OR=0.375, 95% CI: 0.153-0.919, P=0.032)and lower limb venous thrombosis( OR=0.219, 95% CI: 0.050-0.954, P=0.043). Conclusions:In elderly patients aged 75 years and older who are undergoing neurointerventional procedures, radial artery puncture is associated with a reduced incidence of general puncture complications and lower limb venous thrombosis when compared to femoral artery puncture, indicating a superior safety profile.

Objective:To construct a sensitive index system for nursing quality of patients with intracranial aneurysm rupture, so as to provide a basis for evaluating the nursing quality of patients with intracranial aneurysm rupture.Methods:Based on the "structure-process-outcome" quality structure model, a sensitive index system for nursing quality of patients with intracranial aneurysm rupture was preliminarily developed through literature analysis and semi-structured interviews. From December 2021 to March 2022, the Delphi method was used to conduct two rounds of consultation with 23 experts to establish a sensitive index system for nursing quality of patients with intracranial aneurysm rupture.Results:In the two rounds of consultation, the effective response rates of the questionnaires were all 100% (23/23), with expert authority coefficients of 0.78 and 0.75, and the Kendall's W of 0.170 and 0.101 respectively ( P<0.05). The final sensitive index system for nursing quality of patients with intracranial aneurysm rupture included 3 first-level indicators, 9 second-level indicators, and 39 third-level indicators. Conclusions:The sensitive index system for nursing quality of patients with intracranial aneurysm rupture is reliable and scientific, and can be used as a basis for evaluating the nursing quality of patients with intracranial aneurysm rupture.

[摘 要] 目的：探讨1,25-二羟维生素D3 [1,25(OH)2D3]对食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）细胞增殖、迁移和细胞周期的影响及其相关机制。方法：用不同浓度1,25(OH)2D3处理ESCC细胞TE-11、KYSE30、TE-1和KYSE510后，用CCK-8法检测细胞的增殖能力。再用浓度分别是0、0.1、0.15、0.2 μmol/L的1,25(OH)2D3处理TE-11和KYSE30细胞，划痕愈合实验、流式细胞术分别检测细胞的迁移能力和细胞周期分布情况，WB法检测细胞中cyclin D1、P27、ERK和p-ERK蛋白的表达水平。结果：1,25(OH)2D3显著抑制TE-11和KYSE30细胞的增殖能力，其抑制程度呈时间依赖性和浓度依赖性。0.1和0.2 μmol/L的1,25(OH)2D3处理48 h后，与空白对照组比较，TE-11和KYSE30细胞的迁移能力均显著降低（P<0.05或P<0.01），处于G0/G1期细胞显著增加（P<0.05或P<0.01），细胞中cyclin D1和p-ERK蛋白水平显著下调、P27蛋白水平明显上调（P<0.05或P<0.01）而ERK蛋白的表达无明显变化。结论：1,25(OH)2D3显著抑制ESCC细胞的增殖和迁移能力并阻滞细胞周期进程，其可能通过调控ERK信号通路而发挥作用。

Objective:To assess the influence of glimepiride on the plasma concentrations and antihypertensive effects of losartan and its active metabolite losartan carboxylic acid(E-3174) in the patients with type 2 diabetes mellitus and hypertension. Methods:Pragmatic randomized controlled trial was used in the clinical study. Forty-five patients were enrolled and randomized into glimepiride group and the control group. Losartan was used as the antihypertensive drug in the two groups. After two-week interference,the plasma concentrations of losartan and its active metabolite E-3174 were determined using an LC-MS/MS method and the reduction of hyperten-sion was measured. Results:The plasma trough concentrations of losartan in glimepiride group was not higher than those in the control group,and those of E-3174 in glimepiride group was not lower than those in the control group. Additionally,the reduction of hyperten-sion was similar in the two groups. Conclusion: Glimepiride does not influence the plasma concentrations and the antihypertensive effects of losartan and its active metabolite E-3174 in the patients with type 2 diabetes mellitus and hypertension, suggesting no drug-drug interactions between them. Owing to the small sample,large clinical trial should be performed to confirm the above conclusion.

Objective To explore the clinical characteristics of renal transplantation in patients with diabetes mellitus (DM)-induced end-stage nephropathy.Methods The clinical data of 408 cases who underwent renal transplantation in our center from 2009 to 2013 were retrospectively analyzed.The patients were divided into DM group (n =82) and non-DM group (n =326).The postoperative infection,delayed graft function (DGF),adverse events,and the survival rate of patients/kidneys were comparatively analyzed.Results The incidence of postoperative infection,DGF and adverse events was significantly higher in DM group than in non-DM group (23.2％ vs.15.6％,P =0.04;17.1％ vs.8.6 ％,P =0.04;13.4％ vs.8.3 ％,P =0.03).No significant difference was found in the 1-,2-,and 3-year survival rate of patients and kidneys between the two groups after operation (P＞ 0.05).Conclusion The incidence of postoperative infection,DGF and adverse events is higher in DM patients.The DM does not affect the survival rate of patients/kidneys through appropriate treatment.It is important to prevent complications in DM patients after renal transplantation.

_ Objective_ To analyze the relationship between the fasting plasma glucose ( FPG ) of pre-pregnancy women and occurrence of gestational diabetes mellitus( GDM) , and to explore the value of risk evaluation of GDM by lowerling cut-point for impaired fasting glucose ( IFG ) . Methods The general clinic check information before pregnancy, the plasma glucose levels during 24-28 weeks of pregnancy and pregnancy outcomes were collected prospectively in Weifang and Zhucheng Maternal and Child Health Hospital between February 2014 and November 2014. The FPG levels of the recruited women were lower than 6. 1 mmol/L. According to the criteria for GDM of Ministry of Health (MOH)of China in 2011, and based on the results of 75 g oral glucose tolerance test, pregnant women who underwent screening for GDM were recruited and separated into normal group and GDM group. Based on the FPG levels before pregnancy and according to the recommendation as American Diabetes Association ( ADA ) suggested in 2003, recruited women with normal FPG level according to World Health Organization ( WHO) criteria (1999)were divided into 5. 6-6. 1 mmol/L and<5. 6 mmol/L groups. Results Among the child-bearing age women with FPG<6. 1 mmol/L, the incidences of GDM and macrosomia were 19. 2% and 8. 2% respectively. In the group with FPG between 5. 6 and 6. 1 mmol/L, incidences of GDM and macrosomia were 34. 2% and 4. 7%respectively. While in the group with FPG<5. 6 mmol/L, incidences of GDM and macrosomia were 13. 2% and 15. 3% respectively. The risks of GDM and macrosomia were increased by 2. 6 times and 3. 3 times respectively in group with FPG between 5. 6 and 6. 1 mmol/L (34. 5%), compared with that in group with FPG<5. 6 mmol/L(P<0. 01). Age, FPG, and body mass index before pregnancy in GDM group were significantly higher than those in normal group. The receiver operating characteristic curves in predicting GDM showed that the optimum cut-points for age, FPG, and body mass index were 30 years old, 5. 55 mmol/L, and 23. 7 kg/m2 respectively. Conclusions The risk of GDM in childbearing aged women with FPG from 5. 55 to 6. 10 mmol/L was markedly increased. The optimum cut-point for FPG (5. 55 mmol/L) in predicting GDM was close to the low limit for IFG (5. 6 mmol/L) suggested by ADA in 2003. Decreasing the lower limit of IFG to 5. 6 mmol/L among women who checked before pregnancy and paying attention to those women with FPG from 5. 6 to 6. 1 mmol/L would have advantage to the evaluation and prevention of GDM.

Objective:To observe the effect of tuina manipulations on blood pressure and its variability in hypertension patients. Methods:Forty hypertension patients were randomized into an observation group and a medication group, 20 cases in each group. The observation group was intervened by tuina manipulations of kidney-tonifying blood-circulating and collaterals- unblocking in addition to regular medication, while the medication group was by the same medication. The 24-hour blood pressure monitoring was performed before intervention and after 3-month intervention. The blood pressure and its variability were observed and compared. Results:There were no significant differences in comparing the blood pressure and blood pressure variability between the two groups before intervention (P>0.05); after 3-month intervention, the blood pressure and its variability were significantly improved in both groups (P<0.05); the improvements in the observation group were more significant than those in the control group (P<0.05). Conclusion:Tuina manipulations of kidney-tonifying blood-circulating and collaterals-unblocking plus medication can produce a better effect than regular medication in promoting blood pressure and its variability, and this method is worth applying in clinic as it’s easy-to-operate and has no adverse effect.

Objective To evaluate the long-term effects and safety of diode laser in hair removal.Methods A retrospective study was conducted.In this study,350 patients with hypertrichosis were treated by an 800-nm diode laser with a pulse duration of 30 ms for various sessions.Two groups were divided based on the treatment sessions:group A receiving 6(≥4 for axillae)or more treatments,group B less than 6(＜4 for axillae)treatments.Patients were followed up for 8 months to 3 years(mean 22.5 months)by return visit or telephone.Evaluation of efficacy and side effects were performed.Results Follow-up and evaluation were completed in 235 patients,and a total of 375 sites treated.After 2-18 treatments,a total effective rate of 80.53%(302/375)was achieved.Significant higher effective rates were observed in group B compared with group A at all sites 86.84%(33/38)vs 35.00%(7/20)on the lips,68.42%(26/38)vs 30.77%(4/13)on the face and neck,92.00%(46/50)vs 55.56%(5/9)in lower extremities,86.96%(20/23)vs 50.00%(4/5)on the trunk.93.81%(91/97)vs 55.56%(5/9)at the axillae,92.16%(47/51)vs 73.68%(14/19)in the upper extremities(all P＜0.05),Side effects were noted in only 6 cases,including hyperpigmentation,itching,and development of follicular papules,blisters and white hair.Neither hypopigmentation nor scarring was observed.Conclusions Diode laser system is effective and safe for hair removal.The effect varies with lesional sites and treatment sessions.

Problems in managing implanted medical devices are analyzed,such as imperfectness of law,lack of management control and inadequate supervision.To solve these problems,countermeasures are proposed including completing related laws and rules,strengthening business training and setting user registration rules,etc.