Objective To investigate the effects of metformin(Met)on the proliferation of pancreatic cancer cells under different glucose concentration culture conditions,and to find the potential role of miR-139-5p in the process.Methods PANC-1 cells were treated with different concentrations of metformin(0/5/10/20 mmol/L)in 25 mmol/L(high-glucose group,HG)or 5 mmol/L(normal-glucose group,NG)glucose culture,cell proliferation,apoptosis,migration and cell cycle were detected after 48 h.The expression of miR-139-5p was quantitatively detected by RT-qPCR,and the miR-139-5p mimics were transfected into PANC-1 cells to clarify the role of miR-139-5p.Results Metformin inhibited the proliferation,promoted apoptosis,and induced S phase and G2/M phase arrest of PANC-1 cells under in high glucose and normal glucose culture conditions,and its anti-proliferation and pro-apoptosis effects were more significant in the normal glucose groups.The expression of miR-139-5p was up-regu-lated by metformin treatment in normal but not in high glucose culture.Further studies showed that miR-139-5p mimics inhibited of PANC-1 cells proliferation without metformin pre-incubation and enhanced the anti-prolifera-tion effect of 5 mmol/L metformin.The pro-apoptotic effect of 10 mmol/L metformin in normal glucose culture conditions.Conclusions In normal-glucose culture conditions,metformin can inhibit proliferation,induce apop-tosis and cell cycle arrest of PANC-1 cells more significantly than in higher-glucose culture,which may be partly related to the up-regulation of miR-139-5p.

ObjectiveTo systematically evaluate the efficacy and safety of omental wrapping technique for pancreaticojejunal anastomosis in preventing complications after pancreaticoduodenectomy. MethodsThis study was conducted according to the PRISMA guideline. English and Chinese databases including CNKI， Wanfang Data， VIP， CBM， the Cochrane Library， PubMed， Embase， and Web of Science were searched for clinical studies on omental wrapping technique for pancreaticojejunal anastomosis in preventing complications after pancreaticoduodenectomy published up to November 2022， and Stata 16 and Review Manager 5.4 were used to perform the meta-analysis. ResultsA total of 15 studies with 1 830 patients were included in this study. The meta-analysis showed that the omental wrapping group had a significantly lower overall incidence rate of postoperative pancreatic fistula （POPF） than the non-omental wrapping group （odds ratio ［OR］=0.30， 95% confidence interval ［CI］： 0.22‍ ‍—‍ ‍0.41， P<0.001）， and the subgroup analysis showed that the omental wrapping group had a significantly lower incidence rate of grade B/C POPF than the non-omental wrapping group （OR=0.29， 95%CI： 0.21‍ ‍—‍ ‍0.39， P<0.001）. Compared with the non-omental wrapping group， the omental wrapping group had significantly lower incidence rates of postoperative bile leakage （OR=0.30， 95%CI： 0.16‍ ‍—‍ ‍0.56， P<0.001）， postoperative hemorrhage （OR=0.35， 95%CI： 0.24‍ ‍—‍ ‍0.53， P<0.001）， delayed gastric emptying （OR=0.45， 95%CI： 0.31‍ ‍—‍ ‍0.64， P<0.001）， abdominal infection （OR=0.55， 95%CI： 0.40‍ ‍—‍ ‍0.75， P<0.001）， reoperation （OR=0.31， 95%CI： 0.18‍ ‍—‍ ‍0.54， P<0.001）， and death within 30 days after surgery （OR=0.42， 95%CI： 0.22‍ ‍—‍ ‍0.80， P=0.009）， a significantly earlier time to diet （mean difference ［MD］=-0.98， 95%CI： -1.84 to -0.11， P=0.03）， and a significantly shorter length of postoperative hospital stay （MD=-2.44， 95%CI： -4.10 to -0.77， P=0.004）. There were no significant differences between the two groups in the time of operation （MD=-13.68， 95%CI： -28.31 to -0.95， P=0.07） and intraoperative blood loss （MD=-17.26， 95%CI： -57.55 to -23.03， P=0.40）. ConclusionOmental wrapping can reduce the incidence rates of postoperative complications such as pancreatic fistula， bile leakage， postoperative hemorrhage， abdominal infection， and delayed gastric emptying， improve the prognosis of patients， and shorten the length of hospital stay， without increasing surgical difficulty or time of operation.

Objective To obtain the range of anatomical parameters of healthy knee joints in Chinese males and validate a statistical shape model(SSM)based on the geometric shape of a healthy knee to provide references for the design of knee SSM-based prostheses.Methods Computed tomography(CT)images of knee joints from 112 healthy males were acquired to build three-dimensional(3D)knee joint models.Each model was the target model separately,and the remaining models were used as the training set for principal component analysis(PCA).The obtained knee SSM was fitted to the target model to predict the SSM.The exact anatomical measurement points were marked on the sample and SSM prediction models,and 17 linear and 3 angular parameters were derived.The values of the anatomical parameters were statistically tested using an independent samples t-test and Mann-Whitney U-test,and the validity of the SSM in terms of geometric shape was demonstrated if the resulting P-values were all greater than 0.05.Results Qualitative and quantitative comparative analyses of anatomical parameters showed that the mean deviation of linear parameters was less than 6 mm,and that of angular parameters was less than 2.5°.The results of statistical tests showed P＞0.05 for all anatomical parameters,proving that the knee SSM prediction model was not statistically different from the true healthy model in terms of geometric shape.Conclusions This study derived a reference range of anatomical parameters for a healthy knee and demonstrated that the knee SSM model was consistent with the real healthy model in terms of shape.The results provide a reference for the design of knee SSM-based prostheses.

Objective To identify the relationship between physical activity,insulin resistance and cardiovascular risk in individuals with different glucose tolerance status and to provide evidence for exercise intervention in people with different glucose tolerance status.Methods A total of 691 patients with different glucose metabolism status were recruited as subjects of the research.Spearman correlation analysis was used to study the relationship between exercise frequency and insulin resistance,insulin sensitivity,neck circumference(NC)and neck circumference height ratio(NHtR)in the subjects with different glucose metabolism status,the relationship between NC and insu-lin resistance and insulin sensitivity in different glucose metabolism groups.Results 171(62.9%)Subjects with diabetes were intervened by exercised every day.Spearman correlation analysis showed the correlation between exer-cise frequency and tri-glyceride triglyceride-glucose index(TyG index)(r=-0.120,P＜0.05)and NC(r=-0.168,P＜0.05)were negatively correlated.In subjects with diabetes,NC was positively correlated with triglyc-erides(TG)(r=-0.100,P＜0.05),homeostasis model assessment of insulin resistance(HOMA-R)(r=-0.163,P＜0.05),total cholesterol/high-density lipoprotein(TC/HDL-C)(r=-0.214,P＜0.05)and TyG index(r=-0.156,P＜0.05).Conclusions Increased frequency of exercise is associated with reduced NC,improved insulin resistance,and cardiovascular risk factors in subjects of our team with newly diagnosed diabetes.Exercise has no significant effect on insulin resistance of subjects with normal glucose tolerance and pre-diabetes.

In recent years,the rapid advancement of biotechnology has shifted the focus of epigenetic research towards RNA modifications,which play pivotal roles across a diverse range of physiological and pathological processes,particularly in regulating the immune system.As a highly complex and precise regulatory network,the immune system involves the synergistic action of multiple im-mune cells to maintain the immune homeostasis.RNA epigenetic modification plays a crucial role in modulating the development and function of immune cells by influencing different metabolic processes of RNA.This review aims to provide a comprehensive overview of the functions and corresponding regulatory mechanisms of six RNA modifications:m6A,m1A,m5C,m7G,ac4C,and A-to-I editing in immune cells,and further explore their potential roles in complex diseases such as autoimmune diseases and tumors,in order to pro-vide new ideas and strategies for the prevention and treatment of immune-related diseases.

Mitochondrial diabetes mellitus (MDM) is a genetically heterogeneous disorder caused by mitochondrial DNA (mtDNA) or nuclear DNA mutations, characterized by multi-system involvement and diverse clinical phenotypes. We report a pediatric case presenting with growth retardation followed by subsequent development of diabetes mellitus. Systematic evaluation revealed concurrent bilateral sensorineural hearing loss, bilateral basal ganglia calcification, and electroencephalographic abnormalities. A post-exercise lactate test demonstrated significant elevation of serum lactate levels immediately after physical exertion. Genetic analysis identified a large-scale mitochondrial DNA deletion spanning from m.8649 to m.16084. This case report is complemented by a literature review focusing on the pathogenesis, genetic characteristics, and therapeutic approaches of mitochondrial diabetes, with particular emphasis on mitochondrial disorders exhibiting large-scale mtDNA deletions alongside diabetic manifestations. Our comprehensive analysis aims to enhance clinical understanding and inform diagnostic strategies for this complex disease entity.

Objective:To investigate the effect of liver cirrhosis complicated with thrombocytopenia on perioperative period.Methods:The retrospective and descriptive study was conducted. The clinical data of 75 cirrhosis patients complicated with thrombocytopenia who were admitted to the Fuyang City Second People's Hospital from July 2020 to February 2022 were collec-ted. There were 56 males and 19 females, aged (58±11)years. Observation indicators: (1) preoperative conditions; (2) intraoperative and postoperative conditions. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the one way ANOVA. Pairwise comparison was conducted using the LSD- t test. Count data were descri-bed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Results:(1) Preoperative conditions. Of 75 cirrhosis patients complicated with thrombocytopenia, there were significant differences in the preoperative Child-Pugh grading and platelet count between patients with mild, moderate, and severe thrombocytopenia ( P<0.05). Results of further analysis showed that compared with patients with mild thrombocytopenia, patients with moderate and severe thrombocytopenia had significantly lower preoperative platelet count ( P<0.05). Compared with patients with moderate thrombocytopenia, patients with severe thrombocytopenia had significantly lower preoperative platelet count ( P<0.05). (2) Intraoperative and postoperative conditions. Of 75 cirrhosis patients complicated with thrombocytopenia, there were significant differences in the surgical anesthesia methods, operation time, postoperative bleeding, duration of hospital stay between patients with mild, moderate, and severe thrombocytopenia ( P<0.05). Results of further analysis showed that compared with patients with mild or moderate thrombocytopenia, patients with severe thrombocytopenia had a higher proportion of general anesthesia during surgery ( P<0.05) and compared with patients with mild thrombocytopenia, patients with severe thrombocytopenia significantly increased operation time and duration of hospital stay ( P<0.05). Of the 6 patients with severe thrombocytopenia, 3 of 5 cases with intraoperative platelet transfusion and 1 case without intraoperative platelet transfusion experienced postoperative bleeding, respectively, showing no significant difference between them ( P>0.05). Four patients with postoperative bleeding were successfully stopped bleeding after treatment and there was no death in the 75 patients. Conclusions:Patients with severe thrombocytopenia have longer operation time and duration of hospital stay, and higher proportion of general anesthesia than those with mild or moderate thrombocytopenia. Perioperative platelet transfusion cannot reduce the risk of postoperative bleeding.

  Objective  By summarizing the clinical characteristics and follow-up outcomes of 5 patients with immune checkpoint inhibitor induced diabetes mellitus (ICI-DM) and reviewing the relevant literatures, the article aims at providing reference to clinicians in the diagnosis and treatment of the ICI-DM.  Methods  Clinical data of 5 patients with ICI-DM who were admitted to Peking Union Medical College Hospital from December 2018 to February 2023 and did retrospectively analyzed.  Results  Five patients with a mean age of (65±7)years received treatment by the programmed cell death 1 (PD-1) or its ligand inhibitor (PD-L1). The median time from the first immunotherapy to the discovery of elevated plasma glucose was 100 (43, 210)days, and the median cycle of immunotherapy was 7 (2.5, 10.5). The onset of the illness of all the 5 patients started with diabetic ketosis or ketoacidosis. At the onset, urine ketone bodies were positive, random plasma glucose was (36.36±15.89)mmol/L, glycosylated hemoglobin A1c (HbA1c)was (8.6%±0.66%), arterial blood pH was (7.28±0.16), and the median fasting C-peptide level was 0.09 (0.05, 0.32)μg/L. Five patients had an onset plasma glucose level of grade 3 or 4.Then, ICI treatment was discontinued in all patients and insulin therapy started. The daily dosage of insulin was (56±20)IU, supplemented with hypoglycemic drugs. After treatment, urine ketone body turned negative, pH value increased to normal range, and random plasma glucose decreased significantly (the median difference of random blood glucose before and after treatment was 21.30 mmol/L, P=0.043) showing that the treatment was effective. During the follow-up, all patients continued to use insulin. The PD-1 or PD-L1 inhibitors were restarted after hyperglycemia remission. The tumor condition was under control.  Conclusions  ICI-DM mainly occurs in patients who receive treatment with PD-1 or PD-L1 inhibitors usually with acute hyperglycemia whose laboratory tests indicate insulin secretion defects. Some patients had positive islet cell antibodies, glutamic acid decarboxylase antibodies and autoantibodies.Patients with positive autoantibodies needed early diagnosis and continuous insulin treatment. ICI treatment can be restarted after endocrinologists brought the blood glucose under control.

Objective:Both type 1 diabetes and type 2 diabetes are associated with abnormal bone metabolism, but they have different pathogenic mechanisms. Sclerostin(SOST), Dickkopf-related protein 1(DKK-1), and irisin are newly discovered factors involved in the regulation of bone metabolism. This study aims to compare the differences in serum levels of SOST, DKK-1, and irisin between patients with type 1 diabetes and type 2 diabetes.Methods:This cross-sectional study included 101 patients with type 1 diabetes who visited the Endocrinology Department of Peking Union Medical College Hospital from 2017 to 2019, as well as 55 patients with type 2 diabetes and 59 individuals with normal glucose tolerance who were confirmed through an oral glucose tolerance test as part of the Beijing Changping Community Type 2 Diabetes Management Program from 2014 to 2015. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of SOST, DKK-1, and irisin.Results:There were more female participants than male participants, with an average age of 49 years. The group with type 1 diabetes had a longer duration of illness( P<0.001) and higher HbA 1C levels( P<0.001) compared to the group with type 2 diabetes, and there was no statistical difference in age between the two groups. Both the type 1 diabetes and type 2 diabetes groups had lower levels of serum procollagen type 1 N-terminal propeptide(P1NP) compared to the control group [(8 579±400)pg/mL, (7 268±552)pg/mL vs(10 051±618)pg/mL, P=0.039, P=0.001]; But the β isomer of C-terminal cross-linking telopeptide of type 1 collagen(β-CTX) showed no statistical difference compared to the control group. Patients with type 1 diabetes and type 2 diabetes had higher SOST than controls [(129.7±6.8)pg/mL, (104.8±6.8)pg/mL vs(85.9±5.3)pg/mL, P<0.001, P=0.030], the differences between the type 1 diabetes group and the control group lost statistical significance after adjusting for factors such as fasting blood glucose and lipid levels. There was no significant difference in SOST between type 1 diabetes and type 2 diabetes groups. There was no significant difference in DKK-1 among three groups, but DKK-1 in type 1 diabetes group was lower or tended to be lower than that in type 2 diabetes group. Serum irisin in patients with type 1 diabetes was higher than that in controls and patients with type 2 diabetes[(16.6±0.7)ng/mL vs (9.6±0.6)ng/mL, (9.8±0.6)ng/mL, both P<0.001], but there was no significant difference in irisin level between type 2 diabetes and controls. Conclusions:Patients with both type 1 and type 2 diabetes showed inhibition of the bone formation marker P1NP, while the bone resorption marker β-CTX did not significantly change. SOST levels were elevated or showed an increasing trend in both type 1 and type 2 diabetes patients, which may be related to the inhibition of bone formation. Additionally, type 1 diabetes patients had increased levels of irisin, which may be involved in abnormal bone turnover.

Objective: To explore method for isolating and culturing human epidermal stem cells ( EPSCs) in vitro and isolating and purifying epidermal stem cell exsomes ( EPSCs-Exo) by optimizing the technical process． Method: Firstly，the improved separating enzyme was used to isolate the EPSCs derived from human skin tissue．Then，an improved serum-free culture medium and 10 specific factors were combined to construct optimized 2D culture medium which could stimulate the growth of EPSCs，promote the secretion of EPSCs-Exo，maintain the stemness and proliferation of EPSCs，and delay the differentiation and maturation of EPSCs． Further，the conditions of differential centrifugation was optimized，and then the human EPSCs-Exo was successfully extracted with high efficiency and high purity． Results: The human skin tissue was confirmed with the expressions of markers for epidermal cells． EPSCs were verified with high expression levels of integrin-α6，integrin-β1，P63 and CK19 by immunofluorescence staining and Western blot． The nanoparticle tracking analysis results showed the particles separated for EPSCs supernatant was saucepan with the detected diameter between 30 － 150 nm． The Western blot results showed the positive expression of membrane markers Tsg101，CD9 and CD63 and the negative expression of intracellular markers Calnexin and GAPDH． Conclusion The results show that the human-derived EPSCs have been successfully isolated and cultured in vitro，and the EPSCs-Exo have been successfully isolated and identified．