Objective To exploring the correlation between serum miR-195 and metabolic associated fatty liver disease(MAFLD)in type 2 diabetes mellitus(T2DM)patients.Methods A total of 79 patients with T2DM who were treated in the Endocrinology Department of Gansu Provincial People's Hospital were enrolled in this study from October 2022 to August 2023.They were divided into simple T2DM(n=37)and MAFLD group(MAFLD,n=42)according to whether they were complicated with MAFLD.Meanwhile,34 healthy individuals who underwent physical examinations were selected as the normal control(NC)group.Results Compared with the NC group,FPG,HbA1c and HOMA-IR increased,while HDL-C decreased in T2DM and MAFLD group(P<0.05).The TG and hs-CRP levels were higher in MAFLD group than in NC and T2DM group(P<0.05).The serum miR-195 expression decreased sequentially(P<0.05),while FAS increased sequentially in NC,T2DM,and MAFLD group(P<0.05).Spearman correlation analysis showed that miR-195 was negatively correlated with FPG,HOMA-IR,hs-CRP,and FAS(P<0.05).Multiple linear regression analysis showed that HOMA-IR and FAS were the influencing factors for serum miR-195.Conclusions Down-regulation of serum miR-195 expression in patients with T2DM combined with MAFLD may be by glucose and lipid metabolism,IR and inflammatory response.

A 53-year woman and her 18-year daughter presenting with bone pain, bone fractures, bone deformities and short stature were admitted to Gansu Provincial People′s Hospital in March 2021. Laboratory tests showed low blood phosphorus, low renal phosphorus threshold, normal or low blood calcium, and normal or increased PTH. The high-throughput sequencing indicated heterozygous mutations of the PHEX gene (Phosphate-regulating gene with Homology to Endopeptidases on the X chromosome) in two patients, which was not detected in other family members; finally the diagnosis of X-linked dominant hypophosphatemic rickets/osteomalacia(XLH)was confirmed for these two patients. Treated with neutral phosphorus solution and Rocaltrol, bone pain was relieved completely in the younger patient, but not for her mother due to long disease course and severe complications. Because of the large heterogeneity of the disease there are high missed diagnosis and misdiagnosis rates for XLH. In this paper a pedigree of XLH is reported with literature review.

Objective:To observe the effect of high glucose downregulated microRNA(miR)-99a on hepatic sinus dysfunction and metformin intervention, and to explore the pathogenesis of diabetes-induced fatty liver and possible mechanism of metformin.Methods:The cultured human liver sinusoidal endothelial cells were randomly divided into normal control group, high glucose model group, miR-99a overexpression group, miR-99a overexpression negative control group, insulin-like growth factor 1 receptor(IGF-1R) inhibitor group, mammalian target of rapamycin(mTOR) inhibitor group, and metformin treatment group. The mRNA expressions of miR-99a were detected with realtime quantitative PCR(RT-qPCR), and the expression levels and distribution of IGF-1R, phosphorylated(p-)mTOR and vitronectin(VN) were detected by Western blotting and immunofluorescence. The ultrastructure of human liver sinusoidal endothelial cells was observed using scanning electron microscope.Results:Compared with normal control group, the mRNA expression of miR-99a was downregulated( P=0.008), while the protein expressions of IGF-1R, mTOR, and VN were significantly increased, and the diameter and number of fenestrae decreased significantly in high glucose model group. Compared with high glucose model group, after the treatment with metformin, the mRNA expression of miR-99a was upregulated, while the protein expressions of IGF-1R, mTOR, and VN were significantly decreased( P=0.001, P=0.016, P=0.005, respectively), the number of fenestras increased and the diameter became larger in miR-99a overexpression group, IGF-1R inhibitor group, mTOR inhibitor group, and metformin treatment group. After overexpression of miR-99a, the protein expressions of IGF-1R, p-mTOR, and VN were significantly reduced( P=0.007, P=0.013, P=0.003, respectively); After administration of IGF-1R inhibitors, the expressions of p-mTOR and VN significantly decreased( P=0.006, P=0.009, respectively), following treatment with the mTOR inhibitor, the expression of VN was significantly reduced( P=0.008), while the expression of IGF-1R remained unchanged( P=0.553). Conclusions:Downregulating of miR-99a with high glucose induced hepatic sinus dysfunction, which may be related to the regulation of IGF-1R/mTOR pathway. Metformin increased the expression of miR-99a, thereby inhibiting high glucose-induced hepatic sinusoidal dysfunction.

Objective:To investigate the risk factors of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients in plain-sand areas and loess hilly areas of Gansu province.Methods:A total of 1 599 T2DM patients who participated in chronic disease and risk factors monitoring and basic public health service management were selected by multi-stage stratified random sampling method in the sandy plain areas and loess hilly areas of Gansu province. Questionnaire survey, physical measurement and laboratory tests were performed. Multivariate binary logistic model was used to analyze the influencing factors.Results:The prevalence of DKD was 22.1% (174/787) among T2DM patients in the sandy plain areas and 19.1%(155/812) in the loess hilly area, respectively. Hypertension ( OR=3.022), hyperuricemia ( OR=2.114) and HbA1c≥7%( OR=2.231) were the risk factors for DKD in the plain-sand areas, and the risk of DKD increased with age. In the loess hilly areas, female sex ( OR=0.379) was the protective factor for DKD; while duration of disease≥10 years ( OR=2.476), hyperuricemia ( OR=1.907), HbA1c≥7% ( OR=1.927) were the risk factors for DKD; and the risk of DKD increased with the increase of age, and decreased with the increase of per capita monthly income. Conclusions:The prevalence of DKD and its influencing factors are different between sandy plain areas and loess hilly areas in Gansu province. The prevention and treatment of hypertension should be given more attention in sandy plain areas. In addition, the screening of DKD should be conducted among T2DM patients, particularly for those with old age, hyperuricemia and HbA1c≥7% in both areas of the province.

To characterize the clinical and molecular features of a patient with maturity-onset diabetes of the young 11(MODY11) and literature review. The patient was a 30-year-old female with hyperglycemia for 2 years. Failure to thrivea, primary amenorrhea, intellectual impairment, and severe hyperlipidemia were present at the same time. A novel mutations of the B lymphocyte kinase gene(BLK) c. 1025C>T(p.A342V) was found in the patient. Literature review revealed that there were more than ten mutation sites in BLK-MODY11. Some of them had hyperglycemia, over weight or systemic lupus erythematosus. To date, the clinical characteristics of the patient, such as growth retardation, primary amenorrhea, and intellectual impairment have not been reported in MODY11. Our clinical report further expands the clinical presentations and variabilities of MODY11.

Objective To investigate the correlation of serum uric acid (SUA) level with the prevalence of metabolic syndrome (MS). Methods A random, multi-stage cross-sectional study was performed in 2364 resuden, aged from 20 to 74, in Lanzhou, Gansu province.The resudents were divided into groups according to the level of SUA or 4 components of MS. The relationship between SUA and MS was analyzed. Results The overall morbidity of MS was 20.13 % in Lanzhou , and the morbidity of MS was higher in female than that in male (23.22% vs. 17.37%, P < 0.05);The prevalences of MS was higher in the hyperuricemia (HUA) people than that in the healthy people (32.40 % vs. 17.70 %,P < 0.05); With the increase of SUA level, the morbidity rates of MS and its components increased;The risk of MS showed a gradual increase with the SUA level, the risk of MS(odds ratio,95%CI)in sex-specific quartiles of SUA was 2.33(1.45 ~ 3.71),2.33(1.45 ~3.71),2.44(1.53 ~ 3.89)in male;and 1.58(0.97~2.56),2.54(1.60 ~ 4.00),5.29(3.41 ~ 8.22)in female. The more the components of MS , the higher the SUA level was found for both the male and the female subjects , with the higher rate of HUA morbidity(P < 0.05). Conclusion There is a significant association between SUA level and MS, as well as the MS components. Comprehensive prevention and control should be taken for the reduction of the risk factors, and much attention should be paid to monitor the SUA level.

Objective To investigate the regulation of parathyroid hormone(1-34) on mRNA expression of osteoclast inhibitory lectin (OCIL) gene in UMR106 osteoblastic-like cells and involved signaling pathway.Methods Rat UMR106 osteoblastic-like cells were cultured and treated with various concentration of PTH(1-34) and specific agonists or inhibitors of PKA,PKC,Ca2+/calmodulin-dependent protein kinase (CaMK) and mitogen-activated protein kinase (MAPK) signal pathways for indicated time intervals.Then the cells were gathered at indicated time points and total RNA were extracted.OCIL mRNA expression was analyzed using real-time PCR technique.Results PTH(1-34) stimulated OCIL mRNA expression in a time-and dose-dependentmanner.A dose of 10 nmol/L PTH(1-34) started to induce OCIL mRNA from 6 h,with a highest increase of about 2.8-fold vs.control group (without PTH treatment) at 24 h.The up-regulation of OCIL mRNA began and reached maximum later than RANKL induction and OPG suppression effected by PTH(1-34).Protein Kinase A (PKA) signaling activators forskolin(FSK) and dibutyryl cAMP (db-cAMP),as well as calcium ionophore A23187 all up-regulated OCIL mRNA with the maximal induction of about 4.2-fold,4.5-fold and 5.1-fold.Protein Kinase C (PKC) activator phorbol-12-myristate-13-acetate(PMA) reduced OCIL mRNA expression at the early stage(2-6 h),with the highest down-regulation of 50％ at 6 h.However,the inhibitory effect on OCIL mRNA turned into slightly stimulatory effect later (24 h).PKA inhibitor KT5720,calmodulin antagonist W-7,CaMK Ⅱ inhibitor KN-62 and mitogen-activated protein kinase (MAPK) inhibitor PD98059 all blocked PTH(1-34)-induced OCIL mRNA expression by the maximal reduction of 56％,61％,63％ and 50％ respectively.There also exist cross-talks between different signal pathways.MAPK inhibitor PD98059 blocked the expression of OCIL mRNA which was stimulated by PKA activators FSK or db-cAMP,with the reduction of 98％ and 63％ respectively,while the OCIL mRNA expression stimulated by A23187 remained unaffected.Conclusion PTH(1-34) increased OCIL mRNA expression in vitro through cAMP/PKA,Ca2+/CaMK and MAPK signaling pathways.

The recombinant adenovirus Toll like receptor 4 (TLR4) shRNA vector (pGSadeno-TLR4) was constructed and transfected into human aortic vascular smooth muscle cells (HA-VSMC).After HA-VSMC were treated with palmitate or different signaling pathway inhibitors,the mRNA and protein levels of interleukin-6 (IL-6)and NF-κB activity were tested with real-time PCR and ELISA,respectively.The results showed that palmitate increased mRNA and protein levels of IL-6 in HA-VSMC in a dose-dependent manner.The expression of IL-6 mRNA reached peak after treatment with 400 μmol/L of palmitate for 6 h,being 10.43 fold of control (P＜0.01).Treatment with 400 pmol/L of palmitate for 24 h maximally upregulated the protein level of IL-6,which was 2.18 fold of control (P＜0.01).NF-κB inhibitor parthenolide markedly inhibited palmitate-stimulated increased in IL-6 mRNA level by 65％ and protein level by 59％ (both P＜0.01).Protein kinase C (PKC) inhibitor chlerythrine suppressed palmitateinduced IL-6 mRNA expression by 24％ and IL-6 protein level by 28％.By contrast,extracellular signal-regulated protein kinase inhibitor PD98059 and phosphatidylinositol 3-kinase inhibitor wortmannin had no effect on the induction of IL-6 by palmitate.Blockade of TLR4 with pGSadeno-TLR4 significantly suppressed palmitate-induced IL-6 mRNA expression by 72％ and IL-6 protein expression by 75％ (both P＜0.01),along with decrease of NF-κB p65 activity decreased by 62％.These results suggest that TLR4/NF-κB and PKC pathways mediate palmitate-induced IL-6 expression in HA-VSMC.

To investigate the regulation of osteoclast inhibitory lectin (OCIL) mRNA expression by prostaglandin E2 ( PGE2 ) in rat osteoblastic cells and the involved signaling pathways. Rat primary osteoblasts and UMR106 osteoblast-like cells were cultured and treated with various doses of PGE2 or regulators of different signaling pathways for different periods of time, the cells were then harvested at indicated dates. Total RNA were isolated and OCIL mRNA expression were studied by real-time PCR. PGE2, Forskolin, db-cAMP, and A23187 increased OCIL mRNA by 2. 38 fold,4. 2 fold,4. 5 fold, and 5. 1 fold ( all P＜0. 01 ) respectively, while PMA downregulated OCIL mRNA expression by 50% ( P＜0. 01 ). KT-5720, verapamil, W7, and PD98059 downregulated PGE2 induced OCIL mRNA expression by 56%, 40%, 65%, and 60%, respectively( all P＜0. 0l ). While chelerythrine enhanced PGE2 induced OCIL mRNA expression by 30% ( P＜0. 05 ). PGE2 up-regulated the expression of OCIL in rat osteoblastic cells via PKA, MAPK, and Ca2+/Calmodulin signaling pathways.

Objective To investigate the effects of the traditional herb-epimedium on the expression of interleukin-6 (IL-6) mRNA in bone of ovariectomized rat. Methods Forty female rats were randomly allocated into 4 groups, 10 in each: ovariectomized (OVX) group, sham operation group, OVX followed by epimedium (group 3)or nilestriol (group 4) for 3 months respectively. All rats were then sacrificed,and total RNA were directly isolated from their right tibia. Interleukin-6 mRNA expression was detected by relative semiquantitative reverse transcription-polymerase chain reaction technique. Lumbar bone mineral density (BMD) was measured by dual-energy X ray absorptiometry before sacrifice. Results The BMD of epimedium group was significantly higher than that in the OVX group ( P