Metformin is recognized for its dual action in lowering blood glucose levels and enhancing insulin sensitivity, positioning it as the primary oral drug for managing type 2 diabetes mellitus (T2DM). Despite its ability to cross the placenta and expose the fetus, extensive clinical application has not revealed significant adverse effects. Metformin finds widespread application during pregnancy in conditions such as obesity, polycystic ovary syndrome, T2DM, and gestational diabetes mellitus. This article aims to establish an evidence-based perspective on the impact of metformin administered during pregnancy on maternal and fetal outcomes, as well as the long-term health of offspring. Generally deemed safe and effective, metformin is viewed as a means to control hyperglycemia and manage gestational weight gain without conspicuous adverse effects on maternal and fetal pregnancy outcomes. However, metformin alone may not suffice for achieving glycemic control, necessitating the addition of insulin. Besides, the long-term offspring risks of metformin exposure are controversial, long-term follow-up study is urgent to bring certainty into this field. Thus, tight control over indications for metformin use during pregnancy is crucial to ensure optimal maternal and fetal health outcomes. Although not suggested as a first-line agent for glycemic control in pregnancy, it may be considered as an adjunctive option in cases of severe insulin resistance or in low-resource areas where access to insulin is challenging.

Objective To observe the correlations of pontine biological indicators on fetal brain median sagittal MRI with gestational week.Methods Data of head MRI of 226 normal fetuses without obvious abnormalities of central nervous system(normal group)and 17 fetuses with abnormalities(abnormal group)at gestational age of 23 to 38 weeks were retrospectively analyzed.Pontine biological indicators based on median sagittal MRI were obtained,including pons anteroposterior diameter(PAD),total pons area(TPA),pontine basal anteroposterior length(AP),pontine basal cranio-caudal length(CC),basis pontis area(BPA)and pontine angle of midbrain(MAP).According to the gestational week,the fetuses of normal group were divided into 8 subgroups.The distributing ranges of pontine biological indicators at different gestational weeks were analyzed,and the correlations of pontine biological indicators with gestational week in normal group were explored,and the developmental status of fetal pons in abnormal group were assessed.Results In normal group,PAD,TPA,AP,CC and BPA all showed linear positive correlation(r=0.887,0.914,0.787,0.866,0.865,all P＜0.001),while MAP was not significantly correlated with gestational week(P＞0.05).Among 17 fetuses in abnormal group,abnormal PAD or TPA was found each in 8 fetuses,abnormal AP was observed in 14,abnormal CC was noticed in 3 and abnormal BPA was found in 11 fetuses.Conclusion Fetal pontine biological indicators such as PAD,TPA,AP,CC and BPA on median sagittal MRI were positively correlated with gestational week,hence being able to be used for evaluating fetal pontine development.

Malignant insulinoma is a kind of rare and challenging neuroendocrine tumor. It is often accompanied by distant metastasis, among which liver metastasis is most common, and the prognosis is often non-promising. In this paper, we report a case of multiple liver metastases from malignant insulinoma. The patient, a 70-year-old male, was admitted to the hospital due to "episodic consciousness disorder for more than four months." Blood glucose monitoring revealed recurrent hypoglycemia in the early morning, after meals, and at night. Pancreatic perfusion CT and dynamic enhanced MRI of the liver revealed a mass in the uncinate process of the pancreatic head and multiple liver metastases. Percutaneous liver biopsy confirmed the diagnosis of insulinoma. After multidisciplinary discussions, hepatic artery embolization and radiofrequency ablation were performed in stages, in combination with everolimus treatment. Thereafter, the enhanced CT demonstrated that some liver metastases shrank. The patient had regular meals, and the blood sugar gradually increased and remained normal thereafter. This article discusses this case's clinical characteristics and multidisciplinary collaborative diagnosis and treatment, aiming to provide experience for the comprehensive clinical diagnosis and treatment of malignant insulinoma patients.

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 predictive value of non-invasive parameters in assessing detrusor function in patients with benign prostatic hyperplasia (BPH). 【Methods】 Clinical data of 384 BPH patients to undergo surgery were enrolled and retrospectively analyzed. The patients’ age and medical history time (MHT) were recorded. The free urinary flow rate was measured and maximum flow rate (Qmax) was recorded. Post-void residual (PVR) and voiding volume (VV) were measured with Bladder Scan, and bladder voiding efficiency (BVE) was calculated. Parameters including detrusor pressure (Pdet@Qmax) and Watts factor (WFmax) were collected in invasive urodynamic examination. Patients were grouped as detrusor underactivity (DU) group and non detrusor underactivity (NDU) group according to the results of WFmax, and the factors influencing detrusor function were analyzed with Logistic regression. The optimal cut-off values were confirmed with receiver operating characteristic (ROC) curve. 【Results】 Significant differences were observed in patients’ age, MHT, Qmax, PVR, BVE, Pdet@Qmax between the DU and NDU groups. Logistic regression showed that the overall prediction accuracy was higher when MHT, Qmax and BVE were included. The model prediction formula was Y=6.020-0.451XMHT+0.554XQmax-0.074XBVE. ROC curve showed when age ≥70.5 years and MHT≥ 7.5 years, there was a greater possibility of DU. When Qmax ≥5.7 mL/s and BVE ≥75.5%, the contractile function of detrusor was normal. Model prediction formula Y≥0.72 showed that detrusor contractility was normal. 【Conclusion】 Age, MHT, Qmax and BVE have certain predictive value for assessing detrusor function in BPH patients.

Objective To investigate the effect of IGF1R β subunit mutants sb-IGF1R and ma-IGF1R on the biological behavior of osteosarcoma 143B cells. Methods We designed and constructed sb-IGF1R and ma-IGF1R fragments. They were cloned into adenovirus AdEasy shuttle plasmid, to obtain Ad-sbIGF1R and Ad-maIGF1R. We observed the proliferation, migration and apoptosis of the osteosarcoma cells transfected with Ad-sbIGF1R, Ad-maIGF1R and Ad-IGF1R. The Ad-sbIGF1R, Ad-maIGF1R and Ad-GFP nude mouse models were constructed to evaluate the tumor growth in vitro. Results By plasmid PCR, IGF-1R β subunit mutant was overexpressed in osteosarcoma cells. Ad-sbIGF1R and Ad-maIGF1R significantly inhibited the proliferation and migration of osteosarcoma cells, and promoted cell apoptosis, and inhibited tumor growth in subcutaneous tumor-bearing nude mouse models. Conclusion IGF1R β subunit mutants inhibit the proliferation and migration of osteosarcoma cells and induce cell apoptosis.

Objective:To produce 161Tb from enriched 160Gd 2O 3 isotope-enriched target material and realize domestic production of the novel medical isotope 161Tb. Methods:The 160Gd 2O 3 isotope-enriched target material was irradiated with neutrons by the China Mianyang Research Reactor (CMRR). The no-carrier-added 161Tb product was obtained after the processes of target broken, sample dissolution, separation and purification with lanthanide (LN) resin and solution replacement with diglycolamide (DGA) column. Various key indicators such as γ spectral purity, metal impurity content, specific activity, radiochemical purity, and radioactive concentration were used to conduct the quality inspection and the control of 161Tb products. Results:161TbCl 3 of 33.4 GBq was obtained in a single time with the radioactive concentration of 16.8 GBq/ml, nuclear purity more than 99.9%, and radiochemical purity of 99.2%. Metal impurity content was met the established standards, with the specific activity of 6.02×10 17 Bq/mol. The radiochemical purities of 161Tb labeling with 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) after 0 and 72 h were 100% and 95.8% respectively. Conclusion:The preparation of no-carrier-added 161Tb by using LN resin has the advantages of high separation performance and high sample loading, which has great significance in the field of medical isotope preparation and lays a good nuclide guarantee for the research and development of domestic 161Tb-labeled drugs.

OBJECTIVE To isolate and ide ntify the chemical constituents of the root of Ardisia virens and preliminarily evaluate the in vitro anti-inflammatory activity of the compounds. METHODS The ethyl acetate extraction part from 70％ ethanol extract of the root of A. virens were separated and purified by silica gel column chromatography ，ODS column chromatography ， etc. The structures of the compounds were identified according to physical and chemical properties and spectral data. The inflammation model of RAW 264.7 cells was induced by lipopolysaccharide ，and anti-inflammatory activity of the compound was investigated by MTT assay. RESULTS A total of 11 compounds were isolated from the ethyl acetate extraction part ，and were identified as cyclamiretin A （1），α-spinasterol （2），（3S，5R，6S，7E）-3，5，6-trihydroxy-7-megastigmen-9-one （3）， （+）-angelicoidenol（4），octadeca-dienoic acid- 2，3-dihydroxypropyl ester （5），α-linolenic acid （6），glycerol monooleate （7），5， 5′-（4，7-hexadecadlene-1，16-diyl）bisresorcinol（8），1-（3，5-dihydroxyphenyl）heptan-1-one（9），5-heptylresorcinol and （10） 5-n-nonylresorcinol（11）. The in vitro anti-inflammatory results showed that 80，40，20，10，5 μg/mL of compounds 2，8，9 and 10 could reduce the cell survival rate in different degrees. CONCLUSIONS Compounds 1-11 are isolated from this plant for the first time，and compound 8 is a new natural product. Compound 2，8，9 and 10 show certain anti-inflammatory activity in vitro .

Aim To investigate the effects of dalbinol on proliferation and apoptosis of human colon cancer HCT1 16 cells and its mechanisms.Methods Anti-proliferative effect of dalbinol was evaluated by MTT assay.The morphological changes of apoptosis were observed by Hoechst33342 staining.Apoptotic rate and ROS generation were analyzed by flow cytometry.The related proteins of Wnt/β-catenin pathway and the ap-optosis-associated proteins expression were measured by Western blot.Results The growth of HCT1 16 treated with dalbinol was inhibited in a dose and time dependent manner with IC50 (4.8 ±0.53 ),(2.5 ± 0.43)and (0.6 ±0.22)μmol·L-1 at 24,48 and 72 h,respectively.Typical morphological changes of ap-optosis such as cell shrinkage,karyopyknosis and nu-clear condensation were observed by Hoechst33342 staining.Meanwhile,the apoptotic rate and intracellu-lar ROS generation of dalbinol were both increased dose-dependently. Western blot results showed that dalbinol could activate the expression of cleaved Caspase-3 and cleaved PARP by decreasing anti-apop-totic protein levels such as Bcl-2 and Mcl-1 and in-creasing pro-apoptotic protein levels such as Bax and Bim,which induced further apoptosis.Moreover,dal-binol can reduce the protein expression of the total and nuclear β-catenin,but not cytoplasmic β-catenin by suppressing the protein expression of Dvl-2 and GSK-3β(pS9 ),as well as its target proteins c-Myc and Sur-vivin.Conclusion dalbinol can induce apoptosis in colon cancer HCT1 16 cells by upregulating the intra-cellular ROS generation and suppressing Dvl/GSK-3β/β-catenin pathway.

Objective To investigate the diagnosis value of spleen stiffness measurement by transient elastography (FibroScan, FS) for esophageal-gastric varices (EV) in patients with HBV-related liver cirrhosis receiving anti-viral treatment. Method Total of 41 patients from Jan 2014 to Dec 2014 diagnosed with HBV-related liver cirrhosis receiving anti-viral treatment were enrolled. All patients were evaluated for spleen and liver stiffness measurement by FS and checked by gastroscopy for diagnosis of EV. Using gastroscopy as the gold standard, the area under receiver operating characteristic curve (AUROC) were used to evaluate the value of the spleen stiffness and liver stiffness in diagnosis of EV and its degree. Results The spleen and liver FS values in patients were (40.64 ± 25.45) kPa and (20.76 ± 13.21) kPa respectively, and they showed a positive correlation (r = 0.402, P < 0.001). The spleen FS values in patients without EV were significantly lower than those in patients with mild EV and moderate-severe EV (all P < 0.05). Furthermore, they showed significantly lower in patients with mild EV than those in patients with moderate-severe EV too (P < 0.05). The AUROC of spleen FS in patients with EV was 0.863, with sensitivity of 79.4% and specificity of 83.2%. Moreover, the AUROC of spleen FS in patients with moderate-severe EV was 0.924, with sensitivity of 87.9% and specificity of 91.3%. Both of them were much higher than those of liver FS. Conclusion Spleen FS may act as a non-invasive marker to predict EV and its degree in patients with HBV-related liver cirrhosis receiving anti-viral treatment.