Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety, low cost, and outstanding hypoglycemic effect clinically. The mechanisms underlying these benefits are complex and still not fully understood. Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin, leading to reduced ATP production and activation of AMP-activated protein kinase (AMPK). Meanwhile, many novel targets of metformin have been gradually discovered. In recent years, multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes. Herein, we summarized the benefits of metformin in four types of diseases, including metabolic associated diseases, cancer, aging and age-related diseases, neurological disorders. We comprehensively discussed the pharmacokinetic properties and the mechanisms of action, treatment strategies, the clinical application, the potential risk of metformin in various diseases. This review provides a brief summary of the benefits and concerns of metformin, aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research. Although there have been countless studies of metformin, longitudinal research in each field is still much warranted.
Humans ; Metformin/pharmacokinetics* ; Diabetes Mellitus, Type 2/metabolism* ; Hypoglycemic Agents/pharmacology* ; AMP-Activated Protein Kinases/metabolism* ; Aging

Objective:To analyze the usage intention and key issues of medical staff to use telemedicine, for improving telemedicine service system in China.Methods:From October to November 2019, medical workers of both the inviting party and invited party who experienced telemedicine in seven provinces of Fujian, Hainan, Henan, Hunan, Guizhou, Sichuan and Qinghai were selected for an online questionnaire survey. Areas covered included their usage intention, satisfaction and cognitive appraisal of telemedicine. Descriptive statistical analysis and non-parametric test were used to discuss the intention of further use, satisfaction and challenges of medical workers in various provinces and regions.Results:1 084 valid questionnaires were recovered. The data found the overall satisfaction was 98.62%, and the proportion of their intention of further use was 98.25%, and those from the eastern and western provinces presented higher intention of usage. The top challenges as reflected by these medical workers were named as follows: timeliness of consultation progress and information feedback; long latency time; low Internet speed, poor and interrupted Internet signal; inadequate system equipments and inconvenient operation; difficulties in remote physical checkup and overall understanding of patient conditions; as well as substandard, incomplete and poor medical records.Conclusions:These medical workers are satisfied with the telemedicine services and willing to continue to use telemedicine.For those existing problems, it is suggested to strengthen the infrastructure and optimize the process of telemedicine services, so as to encourage them in greater use of telemedicine.

Objective:To analyze the actual and expected incentives and key issues of telemedicine providers in China and to provide important references for optimizing telemedicine incentive policies.Methods:The sample data came from a questionnaire survey of 1 084 providers in 7 provinces of Fujian, Hainan, Henan, Hunan, Guizhou, Sichuan and Qinghai in October and November 2019 and a semi-structured interview data at 6 hospitals in Henan province in January 2020. Descriptive analysis was used to sort such data into text data for classified summation.Results:The greatest gaps were found between actual incentives and expected ones in expense subsidies, title promotion and excellence awards, with such gaps as high as 18.65, 28.26, 29.28 percentages among providers of junior, deputy senior and senior academic titles respectively. Hospitals fall short in providing adequate incentives for telemedicine providers, not to mention lack of differentiation and diversification in personnel incentives, and poor implementation of incentive policies.Conclusions:It is suggested to strengthen incentive demand analysis, break the homogenization bottleneck of incentive policies, and consolidate internal publicity and implementation of incentive policies.

Dendritic cell-based cancer vaccines (DC vaccines) have been proved efficient and safe in immunotherapy of various cancers, including melanoma, ovarian and prostate cancer. However, the clinical responses were not always satisfied. Here we proposed a novel strategy to prepare DC vaccines. In the present study, a fusion protein SNU containing a secretin-penetratin (SecPen) peptide, NY-ESO-1 and ubiquitin was designed and expressed. To establish the DC vaccine (DC-SNU), the mouse bone marrow-derived DCs (BMDCs) were isolated, pulsed with SNU and maturated with cytokine cocktail. Then peripheral blood mononuclear cells (PBMCs) from C57BL/6 mice inoculated intraperitoneally with DC-SNU were separated and cocultured with MC38/MC38

Objective To retrospectively investigate the value of contrast enhanced ultrasound ( CEUS) in breast cancer biopsy . Methods A total of 49 consecutive patients with biopsy confirmed breast cancer were retrospectively analyzed . All patients underwent CEUS and biopsies were thus performed targeting both the high perfusion and low/non‐perfusion regions on CEUS . T he diagnostic performance and core cancer involvement of the biopsy cores taken from the high perfusion regions were compared with those from the low/non‐perfusion . Results A total of 53 breast cancer lesions were biopsy confirmed in 49 patients .CEUS revealed homogeneous enhancement in 8 lesions ( 15 .1% ) ,and heterogeneous enhancement in 45 lesions ( 84 .9% ) . T he diagnostic accuracy rate for biopsy cores taken from the high perfusion regions was significantly higher than that from the low/non‐perfusion regions ( 98 .5% vs 72 .9% , P ＜0 .01) . T he core cancer involvement was also higher in high perfusion lesions ( 55% vs 30% , P ＜0 .01) . Conclusions CEUS can differentiate the active area and necrotic fibrosis area of breast tumors by displaying the microvessels ,thus contributing to the selection of biopsy sites .

Objective: To retrospectively investigate the value of contrast enhanced ultrasound (CEUS) in breast cancer biopsy. Methods: A total of 49 consecutive patients with biopsy confirmed breast cancer were retrospectively analyzed. All patients underwent CEUS and biopsies were thus performed targeting both the high perfusion and low/non-perfusion regions on CEUS. The diagnostic performance and core cancer involvement of the biopsy cores taken from the high perfusion regions were compared with those from the low/non-perfusion. Results: A total of 53 breast cancer lesions were biopsy confirmed in 49 patients.CEUS revealed homogeneous enhancement in 8 lesions (15.1%), and heterogeneous enhancement in 45 lesions (84.9%). The diagnostic accuracy rate for biopsy cores taken from the high perfusion regions was significantly higher than that from the low/non-perfusion regions (98.5% vs 72.9%, P<0.01). The core cancer involvement was also higher in high perfusion lesions (55% vs 30%, P<0.01). Conclusions CEUS can differentiate the active area and necrotic fibrosis area of breast tumors by displaying the microvessels, thus contributing to the selection of biopsy sites.

Objective To retrospectively evaluate the influence of prostate volume on prostate cancer detection using elastography targeted transperineal biopsy. Methods A total of 573 consecutive patients suspicious for prostate cancer were enrolled in this study. Patients underwent combined elastography-targeted biopsy and 10 core-systematic transperineal biopsy.In correlation with prostate biopsy pathology, the sensitivity of elastography-targeted biopsy and systematic biopsy were compared among four subgroups with different prostate volume.Results The overall prostate cancer detection rate was 42.9% (246/573). The increase in cancer detection rate by elastography-targeted biopsies was 9.1% (52/573).In patients with prostate volume of ≤30 ml,30-50 ml,50 -80 ml and >80 ml,the sensitivity of elastography targeted biopsy were 91.1% (72/79),81.3% (87/107),70.5% (31/44) and 50.0% (8/16),respectively ( P =0.000).The sensitivity of systematic biopsy were 77.2% (61/79),77.6% (83/107),86.4% (38/44) and 75.0% (12/16),respectively,in comparison among these four groups ( P = 0.601). For patients with prostate volume ≤30 ml,the sensitivity of elastography targeted biopsy was significantly higher than that of systematic biopsy (P= 0.028). Conclusions Prostate cancer detection rate can be improved by elastography targeted biopsy. Prostate volume is correlated with the accuracy of elastography. The sensitivity of elastography targeted biopsy is higher in patients with a smaller prostate gland.

Objective To assess transrectal contrast enhanced ultrasound (CEUS ) targeted biopsy (TB) for detection prostate cancer (PCa) by comparing with systematic biopsy (SB) .Methods 151 consecutive patients scheduled for prostate biopsy were enrolled in this prospective study with a mean age of 68 8.± 8 0. (47-86) and prostate specific antigen (11 5.± 6 9.)μg/L (0 3.-39 8.μg/L) .CEUS was performed by a single experienced radiologist who was blinded to all clinical data with the Sequoia 512 ultrasonography system equipped with EV8C4 endfire probe .Hypoperfusion lesions ,hyperperfusion lesions and lesions with rapid wash‐in or wash‐out were suspicious for malignant ,and these lesions were sampled with 2-4 cores in addition with 10‐core SB .Results The overall PCa detection rate was 40 4.% (61/151) .Of 61 PCa patients , 11 (18 0.% ) had positive cores in TB ,18 (23 0.% ) had positive cores in SB and 36 (59 0.% ) had positive cores in both biopsy protocols .The PCa detection rate of TB and SB was 33 1.% and 31 1.% respectively (P=0 7.12) .A total of 1 755 cores were sampled including 1 510 SB cores and 245 TB cores .The positive rate for TB was significantly higher than SB (52 2.% vs 11 5.% ,P =0.000) .Of 61 PCa patients ,18 had low‐grade cancer (Gleason score<7) and 43 had high‐grade cancer (Gleason score≥7) .The sensitivity for high‐grade PCa was 86 0.% with TB ,which was significantly higher than low‐grade cancer (55 6.% ,P =0.018) . Conclusions The PCa detection rate of CEUS‐TB was equal with SB ,whereas the positive rate by core of CEUS‐TB was significant higher than SB .Furthermore ,CEUS‐TB was more sensitive in detection of high grade prostate cancer .

Objective To determine whether cadence contrast pulse sequencing (CPS) harmonic ultrasonography can be used to predict aggressiveness of peripheral zone prostate cancer.Methods CPS harmonic ultrasonography was performed in 62 biopsy-proved prostate cancer patients.Time intensity curves were reconstructed for biopsy-proved or radical prostatectomy histopathology proved prostate cancer lesions.The characteristics of the curves were described using hemodynamic parameters including arrival time (AT),time-to peak (TTP) and peak intensity (PI).The differences of hemodynamic parameters between different Gleason score and pathologic stage were analyzed.Results Prostate biopsy revealed 156 peripheral zone prostate cancer lesions among 62 patients,including 40 low grade lesions and 116 high grade lesions.In comparison with low-grade lesions,the contrast agents arrived and distributed earlier in highgrade lesions (P =0.005,0.023).In addition to lower AT and TTP,high-grade tumors had higher PI than low-grade tumors (P =0.008).Among 21 patients underwent radical prostatectomy,histopathology documented 14 low grade tumors and 17 high grade tumors,significant differences of hemodynamic parameters were found between these two groups (P ＜0.05).Furthermore,prostate cancer lesions with extra capsular extension also had high PI than those confined in the gland (P =0.000).Conclusions Contrast-enhanced ultrasound and hemodynamic parameters might be helpful in predicting aggressiveness of prostate cancer.

Objective To determine the utility of elastography guided biopsies in men undergoing transrectal ultrasound-guided transperineal prostate biopsies.Methods A total of 108 consecutive patients suspicious for prostate cancer due to elevated serum prostate specific antigen level or abnormal digital rectal examination were enrolled in this prospective study.All patients underwent combined elastography-targeted and 10 core-systematic transperineal biopsy.The impact of elastography-targeted biopsies on the prostate cancer detection rate was analyzed in comparison with prostate biopsy pathology.Results The overall prostate cancer detection rate was 49.1％ (53/108).The prostate cancer detection rate of systematic biopsy was 35.2％(38/108).The increase in cancer detection rate by elastography-targeted biopsies was 13.9％(15/108,P =0.039).A total of 1296 cores were sampled among 108 patients,including 1080 systematic biopsy cores and 216 targeted biopsy cores.The positive rate of targeted biopsy was significantly higher than systematic biopsy (50.9％ vs 14.1％,P ＜0.0001).Conclusions Prostate cancer detection rate could be significantly improved by elastography targeted transperineal biopsy.