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 investigate the effect of resveratrol(RSV)in the treatment of peri-implantitis in a murine model and its effect on nuclear factor kappa-B(NF-κB)signaling and mitogen-activated protein kinase(MAPKs)signal-ing.Methods This study has been reviewed and approved by the Ethics.After extracting the right maxillary molars of 40 C57BL/6 mice and allowing them to heal naturally for 8 weeks,implants were implanted at the site of the first molar.The mice were randomly divided into a control group,a mouse peri implantitis model group,a low-dose group of 20 mg/kg resveratrol(RSV-L),and a high-dose group of 40 mg/kg resveratrol(RSV-H).After 4 weeks of implant implantation,a silk thread ligation induced peri implantitis model was established in all mice except for the control group.The model group received intervention with physiological saline by gavage,while the drug group received intervention with resvera-trol by gavage for 6 consecutive weeks.After 6-week treatment,observe the swelling of the gums around the implant and measure the bone resorption around the mouse implant using micro CT.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of tumor necrosis factor alpha(TNF-α)and interleukin-6(IL-6)in gingival crevicular fluid.HE staining was used to observe the infiltration of inflammatory cells in the surrounding tissues of mouse implants.Pro-tein expression level and phosphorylation level of extracellular regulated protein kinases(ERK),p-ERK,c-Jun N-termi-nal kinase(JNK),p-JNK,p38 mitogen activated protein kinase(p38 MAPK),p-p38MAPK,nuclear factor kappa-B(NF-κB),p-NF-κB,nuclear factor-κB inhibitory protein(IκBα),p-IκBα in MAPKs/NF-κB signaling pathway were detected by Western blot(WB).Results Resveratrol group showed reduced tissue edema and decreased alveolar bone resorp-tion.Among them,the high-dose resveratrol group had lighter tissue edema and weaker bone resorption compared to the low-dose group.The micro CT results showed that significant changes in the bone level around the implant were observed in the model group mice at four sites:proximal,distal,buccal,and palatal.High dose resveratrol intervention reduced al-veolar bone resorption(P＜0.05);compared with the low-dose group,the high-dose group showed a decrease in palatal bone resorption(P＜0.05),while there was no significant difference in absorption between the mesial,distal,and buccal sides(P＞0.05).The ELISA results showed that compared with the model group,the levels of TNF-α and IL-6 in the gingival crevicular fluid of mice in the low-dose and high-dose resveratrol groups were lower(P＜0.05).The IL-6 in the gingival crevicular fluid of mice in the high-dose resveratrol group was lower than that in the low-dose group(P＜0.05).However,there was no significant difference in TNF-α levels between the two groups.HE staining showed a decrease in inflammatory cell infiltration in mice after treatment with resveratrol.The WB results showed that compared with the con-trol group,the expression levels of p-Erk,p-JNK,p-p38MAPK,p-IκA,and p-NF-κB phosphorylated proteins in the gingi-val tissue of the model group mice were significantly increased(P＜0.01).The resveratrol treatment group significantly inhibited the phosphorylation of p-Erk,p-JNK,p-p38MAPK,p-IκA,and p-NF-κB proteins.Compared with the low-dose group,the high-dose group inhibited the phosphorylation of MAPKs/NF-κB signaling pathway related proteins more sig-nificantly(P＜0.05).Conclusion Resveratrol protect ligature induced peri-implantitis murine model,which may be re-lated to its inhibition of phosphorylation of MAPKs/NF-κB pathway.

Purpose/Significance A prediction model is constructed based on real-world data to achieve prediction and early screening of type 2 diabetic microvascular complications.Method/Process Based on the real world data of Nanjing Drum Tower Hospital in the past 10 years,a particle swarm optimization based deep belief network(PSO-DBN)prediction model for microvascular complica-tions in type 2 diabetes mellitus is constructed by taking test results and medical record documents into consideration.Result/Conclusion The PSO-DBN model can predict diabetic microvascular complications,and the performance is better than that of random forest and sup-port vector machine(SVM)benchmark models,it provides references for the research of disease prediction model of real-world data.

Objective To analyze the risk factors of short-term re-obstruction after plastic stent placement by endoscopic retrograde cholangiopancreatography(ERCP)in patients with hilar malignant biliary obstruction.Methods A retrospective study was performed on clinical data of 93 patients with hilar malignant biliary obstruction who underwent ERCP biliary plastic stent placement from January 2015 to January 2024.Understanding the effects of general information,clinical characteristics,operative-related factors,and laboratory-related indicators on postoperative short-term re-obstruction.The dependent variable was whether biliary stent re-obstruction in short-term after operation,univariate and multivariate Logistic regression analysis were used to analyze the risk factors for the patients with hilar malignant biliary obstruction occurred re-obstruction in short-term after ERCP plastic stent placement.Results Among the 93 patients,49 patients had short-term recurrent biliary stent obstruction after plastic stent placement by ERCP and the recurrence rate was 52.7%.Univariate analysis showed that gender,types of malignant biliary strictures,preoperative cholangitis,no drainage before operation and endoscopic sphincterotomy(EST)during ERCP plastic stent placement,location of stent placement,fever within 24 h after ERCP plastic stent placement,the decrease less than 50%of total bilirubin(TBiL)at 2 weeks after operation,the decrease less than＜50%of γ-glutamyl transpeptidase(GGT)at 2 weeks after operation,GGT and alkaline phosphatase(ALP)by less than 50%at 2 weeks after operation were potential risk factors affecting for short-term re-obstruction after ERCP plastic stent placement in patients with hilar malignant biliary obstruction.Multivariate analysis showed that,no drainage before operation(O＾R=5.738,P=0.013),preoperative cholangitis(O＾R=5.347,P=0.025)and place stents on the left or on the right(O＾R=6.739,P=0.014;O＾R=9.719,P=0.005)were independent risk factors for short-term re-obstruction after ERCP plastic stent placement.Conclusion No drainage before operation,preoperative cholangitis,place stents on the left or on the right are independent risk factors for short-term re-obstruction after ERCP plastic stent placement in patients with hilar malignant biliary obstruction.Early identification of risk groups and timely intervention of risk factors in clinical practice are of great significance for the prevention of short-term re-obstruction after ERCP plastic stent placement in such patients.

Objective To investigate the clinical efficacy of different stents placement under endoscopic retrograde cholangiopancreatography(ERCP)in patients with malignant biliary obstruction(MBO)and the effect on patient survival time.Methods Clinical data of MBO patients treated with ERCP stent placement between January 2020 and March 2024 were collected,divided into recyclable stent group(33 cases),metal stent group(42 cases),and ordinary stent group(34 cases).Comparation of the three groups of preoperative and postoperative changes in liver function,complications of long-term cholangitis and pancreatitis,stent patency time,success rate of stent removal with a single clamping,survival time,monitoring follow-up situation.Results There was no statistically significant difference in the liver function of the three groups of patients before stent placement(P>0.05);One week after stent placement,the difference compared with preoperative between direct bilirubin(DBiL)and total bilirubin(TBiL)in the recyclable stent group and the metal stent group was significantly higher than that in the ordinary stent group,and the difference between the ordinary stent group and other two groups was statistically significant(P<0.05).The incidence of cholangitis in the recyclable stent group was the lowest,followed by the ordinary plastic biliary stent,and the metal biliary stent had the highest incidence of cholangitis,the incidence of cholangitis in the long term after stent placement was compared among the three groups of patients with a statistically significant difference(P<0.05).The incidence of postoperative pancreatitis in the three groups was not statistically significant(P>0.05).The success rate of stent removal with a single clamping was higher in the recyclable stent group than the ordinary stent group.Comparison of median stent patency time among the three groups,the difference was statistically significant(P<0.05).The metal stent group had the longest median patency time of 194.0 d,recyclable plastic stent had the second longest median patency time of 126.0 d,and ordinary plastic biliary stent had the shortest median patency time of 92.0 d.Median survival time among the three groups was statistically significant(P<0.05).The recyclable plastic biliary stent had the longest median survival time of 590.0 d,metal biliary stent had the second longest median survival time of 476.0 d,and ordinary plastic biliary stent had the shortest median survival time of 453.0 d.Conclusion Recyclable plastic biliary stent has a faster decrease in bilirubin index compared with the ordinary stent group after operation.And the recyclable plastic stent group has lower incidence of long-term cholangitis,higher success rate of one-time clamping of the stent,and more advantages in time to stent patency and survival time compared with ordinary plastic biliary stent,which is an effective choice of stenting modality for ERCP stent placement in patients with MBO.

Acute myocarditis(AM)may rapidly progress to fulminant myocarditis(FM),but lacks special clinical presentation.Multimodal echocardiography combined conventional transthoracic echocardiography,two-dimensional and three-dimensional speckle tracking imaging,myocardial contrast echocardiography and so on is helpful to detecting AM in early stage and assessing the severity,being of great value for clinical decision-making and prognostic evaluation.The research progresses of multimodal echocardiography in AM were reviewed in this article.

Objective:To explore the application of 3D visualisation technology combined with perforator flap transfer in reconstruction of soft tissue defects in traumatic hand and foot injury and explore the clinical outcomes.Methods:Between January 2021 and February 2023, a retrospective analysis was conducted in the Department of Emergency of the Affiliated Hospital of Jiangsu University and the Department of Sports Medical of Wuxi No. 9 People's Hospital, on the data of 12 patients (13 flaps) who received surgery of 3D visualisation technology combined with perforator flap transfer for soft tissue defects left by traumatic hand and foot injuries. The patients were 7 males and 5 females aged 45 [36.5, 55.8] years old. Nine patients had the defects in hand and 3 in foot, with 3 in the left and 9 in the right. The sizes of defects ranged from 8.0 cm×6.0 cm to 18.0 cm×17.0 cm. The time from injury to surgery was 13.5 [8.3, 20.8] days. Preoperative CTA scans of donor and recipient sites were performed, and the imaging data were processed for 3D image reconstruction and visualisation. A total of 13 flaps were designed and harvested, including 10 free anterolateral thigh perforator flaps (ALTPFs) and 3 pedicled perforator flaps of fibular artery containing fibular nerve nutrient vessel chains. The flap sizes ranged from 9.0 cm×6.0 cm to 20.0 cm×15.0 cm. Five of the donor sites were directly closed by suture and 8 by skin grafting. Monthly outpatient follow-ups were conducted for the first 3 months after surgery, and then the follow-up reviews were conducted through visits of outpatient clinic or reviewed via WeChat interviews. Information about the outcomes of the transferred flaps, complications and function recovery were recorded on all patients.Results:All 13 flaps were successfully harvested and transferred with the assistance of 3D visualisation technology. Preoperative location of perforator vessels was accurate and flap design was reasonable. The 3D visualisation provided an effective guidance for surgical manipulation. Twelve flaps survived completely after surgery. One flap that had partial necrosis healed after skin grafting. All patients were included in more than 6 months of postoperative follow-up, with a mean follow-up duration of 8.1 months±1.7 months. All flaps had good colour and texture. Four flaps that had swollen appearance received secondary thinning surgery with satisfactory outcomes. The recovery of 9 patients with hand injury was evaluated according to the Blood Circulation Elauation of Severed Finger Replantation Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association. At the final follow-up, the blood supply of flaps was excellent in 11 flaps and good in 2 flaps. Hand function was excellent in 2 hands, good in 4 hands and poor in 3 hands. Scores of American Orthopedic Foot and Ankle Societ(AOFAS) ankle-hindfoot was used for foot function evaluation and all 3 patients were in excellent. Of the postoperative complications, due to a haematoma beneath the flap, a local infection and a delayed fracture healing were occurred in 3 patients separately.Conclusion:The 3D visualisation technology assisted perforator flap transfer can achieve high-quality reconstruction of defects in hand and foot through precise preoperative flap design and simulated surgical incision, therefore it provides a better treatment outcomes for patients.

Cloud technology and the Internet of things ( IOT) technology can be used in building the patient-centered critical care medical information platform.The platform could inenable medical staff to efficiently obtain critical care medical information, and raise critical patients′ cure rates. The authors introduced the critical process of rapidly building and improving the urgent care medical information integration platform in a campus of the First Affiliated Hospital of Zhejiang University Medical School.The IOT platform could effectively interconnect a variety of critical care medical equipments, and features such functions as vital signs monitoring and life support, bedside treatment data retrieval, remote diagnosis and treatment, and cloud sharing. The platform featured the advantages of complete information integration, fast construction, and satisfactory system extensibility. It could improve the medical work efficiency, improve the effect of critical care, and reduce the frequency of contact with patients, hence providing references for rapidly establishing a vital care treatment platform for public health events.

Objective To investigate the relationship between the lifestyle actual-ideal self-discrepancy and the self-regulatory fatigue.Methods A sample of 434 healthy undergraduate students were recruited from September to October 2015.They were inquired the demographic information questionnaire,the lifestyle actual-ideal self-discrepancy of Chinese Adolescent Lifestyles Scale(CALS) and the Self-Regulatory Fatigue Scale (SRF-S).Results The scores of lifestyle actual-ideal self-discrepancy in study habits ranked the highest(1.00(0.60,1.40)),followed by physical exercise(0.86(0.43,1.29)),sleep status(0.80(0.40,1.00)),diet (0.75 (0.50,1.25)),recreational activities (0.63 (0.00,1.00)),coping style (0.50 (0.25,0.75)),interpersonal relationship (0.46(0.17,0.67)) and health habits(0.25(0.00,0.50)).Furthermore,the scores of actual-ideal self-discrepancy in interpersonal relationship,study habits,sleep,physical exercise,coping style and diet were positively correlated with the scores of self-regulatory fatigue (r=0.22,0.19,0.19,0.16,0.13,0.12,P＜0.05).There was no relationship between the scores of actual-ideal self-discrepancy and the scores of self-regulatory fatigue in health habits and recreational activities(r=0.31,0.04).Conclusion The actual-ideal self-discrepancy in interpersonal relationship,study habits,physical exercise,coping style,sleep and diet were positively correlated with the self-regulatory fatigue.The reduction in these lifestyle actual-ideal self-discrepancy may help college students ease their self-adjustment fatigue.

Objective To study the clinical application of the 2 flaps based on the proximal and distal perfo-rator from ulnar artery in the repair of defect of 2 fingers and evaluate the outcome of the procedures. Methods From January,2014 to January,2015, 8 cases with skin and soft tissue defects of 2 fingers were treated simultaneous-ly with the distal and proximal perforator flap of ulnar artery in ipsilateral limb. The area of the distal flaps ranged from 2.5 cm×4.5 cm to 4.0 cm×6.5 cm. The area of the proximal flaps ranged from 3.5 cm×4.5 cm to 4.5 cm×6.5 cm. The followed-up were performed at 3rd, 6th and 12th months post-operation. The patients' satisfaction of the appear-ance and function of repaired finger and working situation were investigated. The postoperatively pain prick , touch and temperature sensation of the flaps were examined. Total active range of motion (TAM) of the finger points were measured. Results All flaps survived. Two flaps got plastic surgery at 5 months post-operation. The pain , tempera-ture and light touch sensation were restored 12 months after the surgery. Five patients returned to work again 12 months after the operation. Conclusion The distal and proximal perforator flap has their own characteristics, can be used simultaneously to repair skin and soft tissue defects of the two fingers.