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 re-port is complemented by a literature review focusing on the pathogenesis,genetic characteristics,and therapeu-tic 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 explore inhibitory effect of Tianzhi granule on neuroinflammation in vascular dementia(VD)rats.Methods:Sixty rats were randomly divided into Sham group,VD group,TZG-L group and TZG-H group,with 15 rats in each group.Bilateral common carotid artery occlusion was used to construct VD rats model,Sham group was not ligated.Rats in TZG-L group and TZG-H group were gavaged with Tianzhi granule 5 g/kg,20 g/kg every day,while rats in Sham group and VD group were gavaged with same amount of normal saline for 8 weeks.Y-maze test was used to detect cognitive ability of rats;Nissl staining and FJC staining were used to assess neuronal damage;TUNEL staining was used to detect neuronal apoptosis;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 protein levels in temporal cortex tissue.PC12 cells was divided into Control group,Glutamate group,TZG-L group and TZG-H group.Glutamate(20 μmol/L)was used to construct neuron injury model.TZG-L group and TZG-H group were added with Tianzhi granule 1 mg/ml,4 mg/ml.Neurons in each group were incubated for 48 h.CCK8 method and TUNEL staining were used to detect activity and apoptosis of neurons;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,Nrf2,HO-1 protein levels in cells.Results:Compared with Sham group,cognitive ability of rats in VD group were decreased,TUNEL positive neurons ratio was increased,Bcl-2 level was decreased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 levels were increased(all P<0.05).Compared with VD group,cognitive ability of rats in TZG-L group and TZG-H group were increased,TUNEL positive neurons ratio was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO levels were decreased(all P<0.05).Morphology of neurons in control group were normal;compared with control group,neurons in Glutamate group were swollen,activity of neurons was decreased,apoptosis rate was increased,Bcl-2 level was decreased,Bax,Caspase-3,Nrf2,HO-1 levels were increased(all P<0.05);compared with Glutamate group,cell damage in TZG-L group and TZG-H group were reduced,activity of neurons was increased and apoptosis rate was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3 levels were decreased(all P<0.05).Conclusion:Tianzhi granule can inhibit neuronal apoptosis and expression of NLRP3 inflammasome in VD rats,inhibit activa-tion of microglia/astrocytes and neutrophil infiltration,improve neuroinflammation of VD,which may play a role by activating Nrf2/HO-1 signaling pathway in neurons.

Objective:To explore inhibitory effect of Tianzhi granule on neuroinflammation in vascular dementia(VD)rats.Methods:Sixty rats were randomly divided into Sham group,VD group,TZG-L group and TZG-H group,with 15 rats in each group.Bilateral common carotid artery occlusion was used to construct VD rats model,Sham group was not ligated.Rats in TZG-L group and TZG-H group were gavaged with Tianzhi granule 5 g/kg,20 g/kg every day,while rats in Sham group and VD group were gavaged with same amount of normal saline for 8 weeks.Y-maze test was used to detect cognitive ability of rats;Nissl staining and FJC staining were used to assess neuronal damage;TUNEL staining was used to detect neuronal apoptosis;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 protein levels in temporal cortex tissue.PC12 cells was divided into Control group,Glutamate group,TZG-L group and TZG-H group.Glutamate(20 μmol/L)was used to construct neuron injury model.TZG-L group and TZG-H group were added with Tianzhi granule 1 mg/ml,4 mg/ml.Neurons in each group were incubated for 48 h.CCK8 method and TUNEL staining were used to detect activity and apoptosis of neurons;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,Nrf2,HO-1 protein levels in cells.Results:Compared with Sham group,cognitive ability of rats in VD group were decreased,TUNEL positive neurons ratio was increased,Bcl-2 level was decreased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 levels were increased(all P<0.05).Compared with VD group,cognitive ability of rats in TZG-L group and TZG-H group were increased,TUNEL positive neurons ratio was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO levels were decreased(all P<0.05).Morphology of neurons in control group were normal;compared with control group,neurons in Glutamate group were swollen,activity of neurons was decreased,apoptosis rate was increased,Bcl-2 level was decreased,Bax,Caspase-3,Nrf2,HO-1 levels were increased(all P<0.05);compared with Glutamate group,cell damage in TZG-L group and TZG-H group were reduced,activity of neurons was increased and apoptosis rate was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3 levels were decreased(all P<0.05).Conclusion:Tianzhi granule can inhibit neuronal apoptosis and expression of NLRP3 inflammasome in VD rats,inhibit activa-tion of microglia/astrocytes and neutrophil infiltration,improve neuroinflammation of VD,which may play a role by activating Nrf2/HO-1 signaling pathway in neurons.

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.

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.

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 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 .