Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

The anti-neoplastic effects of metformin modulate the acquired phenotype of fbroblast cells in the breast cancer-normal fbroblast co-culture system

Intracellular communications between breast cancer and fibroblast cells were reported to be involved in cancer proliferation,growth,and therapy resitance.The hallmarks of cancer fibroblast interactions,consisting of caveolin 1(Cav1)and mono-carboxylate ransporter 4(MCT4)(metabolic coupling markers),along with IL-6,TGFB,and lactate secretion,are considered robust biomarkers predicting recurrence and metastasis.In order to promote a novel phenotype in normal fibroblasts,we predicted that breast cancer cells could be able to cause loss of Cavl and increase of MCT4,as well as elevate IL 6 and TGF in nearby nomal fibroblasts.We created a co culture model using breast cancer(4T1)and normal fibroblast(NIH3T3)cell lines cultured under specific experimental conditions in order to directly test our theory.Moreover,we show that long-term co-culture of breast cancer cells and normal fibroblasts promotes loss of Cavl and gain of MCT4 in adjacent fibroblasts and increase lactate secretion.These results were validated using the monoculture of each group separately as a control.In this system,we show that me tformin inhibits IL-6 and TGFB secretion and re expresses Cavl in both cells.However,MCT4 and lactate stayed high after treatment with metformin.In conclusion,our work shows that co-culture with breast cancer cells may cause signifcant alterations in the phenotype and secretion of normal fibroblasts.Metformin,however,may change this state and affect fibroblasts'acquired phenotypes.Moreover,mitochondrial inhibition by metformin after 8 days of treatment,signi ficantly hinders tumor growth in mouse model of breast cancer.

Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Metformin alleviates spinal cord injury by inhibiting nerve cell ferroptosis through upregulation of heme oxygenase-1 expression

Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.

Promising use of metformin in treating neurological disorders:biomarker-guided therapies

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

赛沃替尼治疗MET基因突变非小细胞肺癌的药物浓度与疗效和不良反应的关系

目的:探讨药物浓度与疗效和不良反应之间的关系,了解赛沃替尼治疗MET14外显子跳跃突变晚期非小细胞肺癌患者的疗效和安全性。方法:回顾性分析2018年4月至2019年9月北京大学肿瘤医院收治的携带MET14外显子跳跃突变,并且接受赛沃替尼治疗的16例局部晚期或转移性非小细胞肺癌患者的临床资料及其血浆药物浓度,评估赛沃替尼治疗的疗效和安全性,分析药物浓度与疗效及不良反应的相关性。随访患者的无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS),采用Kaplan-Meier法计算中位PFS和OS。结果:16例患者中男性9例(56.3%),年龄范围51~84岁。肺癌病理类型包括:腺癌11例,肉瘤样癌5例,鳞癌1例。赛沃替尼的客观缓解率为50.0%(8/16),疾病控制率达到87.5%(14/16)。评效达到部分缓解患者和未达到者相比,赛沃替尼的药物谷浓度分别为77.2 ng/mL和146.7 ng/mL(P=0.06)。治疗中出现过2级以上不良反应的患者和仅出现过1级不良反应者,其药物谷浓度分别为116.5 ng/mL和93.2 ng/mL(P=0.59)。所有患者的中位PFS为8.5个月,中位OS为14.1个月。结论:赛沃替尼治疗MET基因突变非小细胞肺癌的效果较好,不良反应可耐受。常规用药剂量下,赛沃替尼的血浆药物谷浓度与疗效可能存在一定负相关,但药物浓度与不良反应的程度无明显相关性。

Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endothelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

GNSS/MET观测的台风“烟花”对上海地区PWV的影响

利用上海5个GNSS/MET站2021-07-21~08-08的观测数据,使用GAMIT软件反演大气可降水量(PWV),研究台风“烟花”期间上海地区PWV与降雨量之间的关系及PWV的空间分布特征。结果表明,GNSS PWV与探空PWV之间相关系数大于0.9。降水生成前,PWV经历了3次波动性上升过程,降水生成时间比台风登陆时间早约60 h;降水持续期间,PWV剧烈变化时会造成降水量急升或急降;降水结束后,PWV逐渐下降至40 mm以下。台风登陆前,PWV基本在75 mm以上,PWV大于80 mm的区域主要分布于上海南部和中部;台风登陆后,PWV在80 mm以上,高值区可达90 mm;台风远离后,PWV下降至85 mm以下。PWV高值区向西北方向的扩大、推移与台风路径基本吻合。

免疫联合化疗逆转MET D1228E合并EGFR L858R介导的MET 14外显子跳跃突变肺腺癌耐药

1例间质-上皮细胞转化因子(MET)14外显子跳跃突变的Ⅳ期肺腺癌患者服用MET酪氨酸激酶抑制剂(TKI)赛沃替尼8.5个月后疾病进展(PD),耐药基因检测提示出现新的MET 19外显子D1228E及表皮生长因子受体(EGFR)21外显子L858R错义突变。遂将治疗方案改为EGFR-TKI奥希替尼联合克唑替尼治疗,23天后临床症状加重,复查CT提示PD。经多学科诊疗(MDT)讨论,将三线治疗方案改为以铂类为基础的化疗联合免疫治疗,期间最佳疗效评价为部分缓解(PR),无进展生存期为6.4个月。目前,对于MET-TKIs耐药后新发二次突变合并EGFR突变的患者尚无标准治疗方案,本案例为此类患者提供了一种可供参考的后续治疗方案。

Comparison of efficacy of metformin and D-chiro-inositol on clinical biomarkers in patients with polycystic ovarian syndrome:an open label study

Objective:Polycystic ovary syndrome(Pcos)is a pathophysiological disorder affecting reproductive and metabolic indices in females.The present study was designed to compare the efficacy of metformin and D-chiroinositol in PcoS patients.Methods:In a tertiary care hospital in North India,prospective observational research was undertaken on 1o0 patients with PCOS,which was diagnosed based on European Society of Human Reproduction and Embryology Guidelines and ultrasound of lower abdomen.The study involves various clinical characteristics into consideration for the determination of statistical significance(P<0.05)in PCOS patients.Student's t-test along with the association between PCOS and patients taking metformin and D-chiro-inositol,as well as their impact on various biochemical parameters,were investigated finally using Pearson Correlation Analysis.Results:This study comprises 50 patients taking metformin and 50 patients taking D-chiro-inositol in women suffering from PCOS.Body mass index(BMI)and waist-to-hip ratio(WHR)were statistically significant(P<0.05)within the groups of both metformin and D-chiro-inositol.Biochemical parameters such as luteinizing hormone(LH),follicle stimulating hormone(FSH),anti-mullerian hormone(AMH)and glycated hemoglobin(HbA1c)were found to be statistically significant(P<0.05)in both groups.LH,FSH and AMH(14.40±0.52;14.28±0.53;1.99±0.10)were comparatively lower in patients taking D-chiro-inositol as compared to metformin group(14.17±0.42;19.88±1.01;2.61±0.04).HbA1c(3.71±0.08)with P<0.05 was found to be decreased more in metformin group as compared to patients taking D-chiro-inositol(4.90±0.09).A positive correlation was found between HbAlc and LH in metformin,&HbAlc and FSH in D-chiro-inositol groups,respectively.Conclusion:The results indicate that D-chiro-inositol shows better results in reducing clinical variables involved in causing PCOS as compared to metformin whereas metformin has better glycemic control in PCOS patients.

c-MET在非小细胞肺癌中的研究现状

非小细胞肺癌(NSCLC)是一种异质性疾病,可由许多基因突变驱动发生。间质–上皮细胞转化因子(MET)是继表皮生长因子受体(EGFR)、间变性淋巴瘤激酶(ALK)等之后的又一热门研究靶点。MET异常已被证实在多种致癌中,促进肿瘤侵袭、血管生成和转移。c-MET不仅是独立的肺癌驱动因子,也是介导其他驱动基因靶向治疗耐药的副驱动因子。目前,针对c-Met通路的治疗策略主要包括单克隆抗体和靶向MET基因的小分子TKIs。作者对MET改变的NSCLC的研究现状及治疗进展进行综述。

Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway

Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of angiogenesis during the regeneration process,we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells,thereby promoting microvascular regeneration in aged mice after spinal cord injury.In this study,we established young and aged mouse models of contusive spinal cord injury using a modified Allen method.We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord.Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro.Furthermore,intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord,thereby improving neurological function.The role of metformin was reversed by compound C,an adenosine monophosphate-activated protein kinase inhibitor,both in vivo and in vitro,suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury.These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway,thereby improving the neurological function of aged mice after spinal cord injury.

Relaxin-encapsulated polymeric metformin nanoparticles remodel tumor immune microenvironment by reducing CAFs for efficient triple-negative breast cancer immunotherapy

Cancer-associated fibroblasts(CAFs)are one of the most abundant stromal cells in the tumor microenvironment which mediate desmoplastic response and are the primary driver for an immunosuppressive microenvironment,leading to the failure of triple-negative breast cancer(TNBC)immunotherapy.Therefore,depleting CAFs may enhance the effect of immunotherapy(such as PD-L1 antibody).Relaxin(RLN)has been demonstrated to significantly improve transforming growth factor-β(TGF-β)induced CAFs activation and tumor immunosuppressive microenvironment.However,the short half-life and systemic vasodilation of RLN limit its in vivo efficacy.Here,plasmid encoding relaxin(pRLN)to locally express RLN was delivered with a new positively charged polymer named polymeric metformin(PolyMet),which could increase gene transfer efficiency significantly and have low toxicity that have been certified by our lab before.In order to improve the stability of pRLN in vivo,this complex was further formed lipid poly-γ-glutamic acid(PGA)/PolyMetpRLN nanoparticle(LPPR).The particle size of LPPR was 205.5±2.9 nm,and the zeta potential was+55.4±1.6 mV.LPPR displayed excellent tumor penetrating efficacy and weaken proliferation of CAFs in 4T1luc/CAFs tumor spheres in vitro.In vivo,it could reverse aberrantly activated CAFs by decreasing the expression of profibrogenic cytokine and remove the physical barrier to reshape the tumor stromal microenvironment,which enabled a 2.2-fold increase in cytotoxic T cell infiltration within the tumor and a decrease in immunosuppressive cells infiltration.Thus,LPPR was observed retarded tumor growth by itself in the 4T1 tumor bearing-mouse,and the reshaped immune microenvironment further led to facilitate antitumor effect when it combined with PD-L1 antibody(aPD-L1).Altogether,this study presented a novel therapeutic approach against tumor stroma using LPPR to achieve a combination regimen with immune checkpoint blockade therapy against the desmoplastic TNBC model.

基于转录组测序探究C-MET表达在非小细胞肺癌中的免疫调控机制

目的通过转录组测序技术分析C-MET表达在非小细胞肺癌中的免疫调控机制。方法使用siRNA分子干扰技术将C-MET高表达肺腺癌细胞株(H1993)、肺鳞癌细胞株(EBC-1)的C-MET表达沉默,利用转录组测序技术检测C-MET沉默前后细胞差异表达的基因(DEGs),通过生物信息学分析挖掘出C-MET可能参与调控的免疫微环境信号通路及相关基因。最后使用人免疫细胞与H1993、EBC-1共培养技术验证C-MET对免疫因子(INF-γ、INF-β、CXCL-10)的影响。结果通过转录组测序技术共检测到505个DEGs,其中H1993的C-MET调控前后表达差异组的表达差异基因共有38个,上调的差异表达基因有24个,下调的差异表达基因有14个。EBC-1的C-MET调控前后表达差异组的表达差异基因共有467个,上调的差异表达基因有347个,下调的差异表达基因121个。差异基因的KEGG分析表明,C-MET表达可能通过白细胞介素(IL-17)信号通路、白细胞分化、细胞因子受体活性、细胞周期、细胞因子-细胞因子受体相互作用参与免疫细胞调节因子的调控。使用肺癌细胞与人免疫细胞共同培养技术验证C-MET对免疫因子分泌的影响,Rt-qPCR检测结果提示:与C-MET高表达组共培养的PBMC中干扰素(INF-γ)的m RNA转录水平是低表达组的77倍、CXCL-10的mRNA转录水平是低表达组的1.6倍,INF-β的mRNA转录水平是低表达组的2倍。结论C-MET表达可能通过IL-17信号通路、白细胞分化、细胞因子受体活性通路参与肿瘤周围免疫微环境调控。

Diarrhea and Acute Renal Injury Culminating in Metformin-Induced Lactic Acidosis

Background: Metformin (M) is an effective first-line hypoglycemic agent in obese type 2 diabetes mellitus due to its low cost and safety profile. The Case: A 66-year-man presented with shock due to lactic acidosis induced by M-supersaturation subsequent to acute renal failure following infective diarrhea. The drug has been used, by this patient, for >10 years without complication. Physical examination, laboratory tests, radiological investigations and blood cultures did not show evidence of new cardiac, hepatic and septic insult. Despite discontinuation of M and 2-days of aggressive hydration, bicarbonate infusions and pressors;toxic levels of the drug persisted and shock-state culminated in severe and oliguric renal failure with serum urea and creatinine up to 50 mmol/L and 1270 umol/L, respectively. Hence, continuous venovenous hemodiafiltration (CVVHDF) was used, for 16-hours, to remove the drug, correct his acidosis and support his severe renal complications. Hours after the procedure;drug level, lactic acidosis and its associated shock improved followed by gradual renal recovery. The patient was discharged after 6 days and serum creatinine reached his base line (180 umol/L) 2 weeks later. The drug was not recommended for his future use. Conclusion: M-induced lactic acidosis, should be considered in assessment of shock in M-treated patients and management of unstable patients indicates early-use of CVVHDF.

Myo-inositol versus metformin effects on clinical features, endocrine and metabolic profiles in infertile women with polycystic ovary syndrome: A randomized controlled trial

Objective:To compare the effectiveness of inositol and metformin on the clinical characteristics,and endocrine and metabolic profiles of infertile polycystic ovarian syndrome(PCOS)women from Vietnam.Methods:From June 2018 to August 2022,a randomized trial was undertaken at the Hue Center for Endocrinology and Reproduction on infertile women aged 18 to 40 years with polycystic ovarian syndrome.The clinical,endocrine,and metabolic features of these individuals were assessed before and after 3 months of treatment with 2 g of inositol or 1700 mg of metformin per day.Natural pregnancy rates,adverse effects,and tolerance of inositol were recorded.Results:The study included 171 infertile PCOS women who were eligible to participate and took part in the baseline assessment,of whom 132 women participated in data analysis after 3 months.After metformin treatment,42.1%of women with oligomenorrhea experienced regular menstruation.Metformin significantly lowered body mass index(BMI),waist circumference and testosterone levels,but had no effect on other clinical characteristics,endocrine profiles,or metabolic profiles.29.2%Of women reported experiencing side effects.21%Of them attained pregnancy,which resulted in 17.1%of live births.In the inositol group,the rate of regular cycle increased by 18.2%and the total testosterone concentration significantly decreased.In overweight/obese women with PCOS,inositol significantly decreased weight,BMI,waist and hip circumferences(P<0.05).100%Of women tolerated inositol and continued treatment.18.9%Of them became pregnant,leading to 17%of live births.Conclusions:Metformin and inositol can improve weight and waist circumference in overweight/obese infertile women with PCOS.Metformin is associated with a higher rate of regular menstruation,whereas inositol is associated with a lower rate of adverse effects.The spontaneous conception,clinical pregnancy,and live birth rates between two groups are comparable.

Prognostic role of metformin in diabetes mellitus type 2 patients with hepatocellular carcinoma:A systematic review and meta-analysis

BACKGROUND Hepatocellular carcinoma(HCC)is among the commonest malignancies associated with significant cancer-related death.The identification of chemopreventive agents following HCC treatments with the potential to lower the risk of HCC adverse course is intriguing.Metformin,a first-line agent used in the treatment of type 2 diabetes mellitus(T2DM),has been associated with inhibition of HCC growth.AIM To determine whether metformin can prevent adverse events(i.e.,death,tumor progression,and recurrence)after any HCC treatment in T2DM patients.METHODS A systematic review of the published literature was undertaken focused on the role of metformin on outcomes in patients with T2DM and HCC receiving any tumor therapy.A search of the PubMed and Cochrane Central Register of Controlled Trials Databases was conducted.RESULTS A total of 13 studies(n=14886 patients)were included in this review.With regard to the risk of death,a decreased risk was reported in cases receiving metformin,although this decrease was not statistically significant[odds ratio(OR)=0.89,P=0.42].When only patients treated with curative strategies were considered,a more marked correlation between metformin and favorable cases was reported(OR=0.70,P=0.068).When analyzing palliative treatment,there was no statistical significance in terms of the correlation between metformin and favorable cases(OR=0.74,P=0.66).As for the risks of progressive disease and recurrence,no obvious correlation between metformin use and reduced risk was reported.When sub-analyses were performed for patients from different regions,the results for patients from Eastern countries showed a tendency for decreased risk of death in T2DM cases receiving metformin(OR=0.69,P=0.17),but the same was not seen in patients from Western countries(OR=1.19,P=0.31).CONCLUSION Metformin failed to show a marked impact in preventing adverse effects after HCC treatment.A trend was reported in T2DM cases receiving curative therapies in relation to the risk of death,especially in patients from Eastern regions.Great heterogeneity was reported among the different studies.Further large studies are required to definitively clarify the real impact of metformin as a chemopreventive agent for HCC.

Effects of Cisplatin and Metformin on Proliferation of Nasopharyngeal Carcinoma SUNE-1 Cells

[Objectives]This study was conducted to investigate the effects of different concentrations of cisplatin and metformin on the growth and proliferation of nasopharyngeal carcinoma SUNE-1 cells.[Methods]The concentrations of cisplatin were set as 2.5,5.0,10.0,25.0,40.0μg/mL,and those of metformin were set as 0.625,1.25,2.5,5,10,and 20 mmol/L.After 48 h of intervention in nasopharyngeal carcinoma SUNE-1 cells,the proliferation inhibitory rate and the median inhibitory concentration(IC_(50))of SUNE-1 cells were measured by the CCK-8 method.[Results]It was found that different concentrations of cisplatin and metformin all had an inhibitory effect on the proliferation of SUNE-1 cells,and the inhibitory effect became more significant with the increase of concentration.The IC_(50)values of cisplatin and metformin were 43.57μg/mL and 6.855 mmol/L,respectively.[Conclusions]Cisplatin and metformin inhibited the proliferation of SUNE-1 cells in a concentration-dependent manner,providing a theoretical guidance for the clinical treatment of nasopharyngeal carcinoma.

斜刺动痛穴结合MET运动针法治疗Ⅰ~Ⅲ级膝骨关节炎的临床研究

目的 针对Ⅰ~Ⅲ级膝骨关节炎患者接受斜刺动痛穴结合MET运动针法治疗的临床效果展开分析与探讨。方法 选择2021年1月—2023年3月本院收治的60例膝骨关节炎患者为研究对象,按就诊顺序编号,并通过随机数字表法划分为治疗组(30例)、对照组(30例)。两组基础治疗方案相同,治疗组配合斜刺动痛穴结合MET运动针法治疗,对照组配合电针疗法治疗,针对两组治疗效果展开对照分析。结果 治疗前,两组骨关节指数对比差异无统计学意义(P>0.05);治疗后,治疗组各骨关节指数均低于对照组(P<0.05)。治疗组临床总疗效、关节积液总疗效、滑膜厚度总疗效、生活质量评分均高于对照组(P<0.05)。结论 使用斜刺动痛穴结合MET运动针法的治疗方案,有助于将Ⅰ~Ⅲ级膝骨关节炎患者临床疗效显著提升,并改善其生活质量,患者各项临床指标优化效果良好,值得普及。

METS-IR与心血管疾病研究进展

随着生活水平提高,心血管疾病发病率及病死率逐年上升,已成为重要的公共卫生问题。胰岛素抵抗状态与心血管疾病发生及发展中的病理生理过程密切相关。深入研究二者之间的内在联系对于心血管疾病的早期预防、治疗和随访至关重要。传统的胰岛素抵抗检测方法操作繁琐、耗时,价格昂贵,不适合在医院开展,更无法在大规模人群中推广。胰岛素抵抗代谢评分(METS-IR)是一个新型的胰岛素抵抗预测指标,其反映胰岛素抵抗具有高效及简便的特点,并且METS-IR升高与心血管疾病发生及不良心血管预后具有正相关性。基于此,本文就METS-IR对常见心血管疾病的诊断及临床应用价值进行综述。