Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson's disease through Mfn2-cGAS signaling.

BACKGROUND: Senescent astrocytes play crucial roles in age-associated neurodegenerative diseases, including Parkinson's disease (PD). Metformin, a drug widely used for treating diabetes, exerts longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. METHODS: Long culture-induced replicative senescence model and 1-methyl-4-phenylpyridinium/α-synuclein aggregate-induced premature senescence model, and a mouse model of PD were used to investigate the effect of metformin on astrocyte senescence in vivo and in vitro. Immunofluorescence staining and flow cytometric analyses were performed to evaluate the mitochondrial function. We stereotactically injected AAV carrying GFAP-promoter-cGAS-shRNA to mouse substantia nigra pars compacta regions to specifically reduce astrocytic cGAS expression to clarify the potential molecular mechanism by which metformin inhibited the astrocyte senescence in PD. RESULTS: We showed that metformin inhibited the astrocyte senescence in vitro and in PD mice. Mechanistically, metformin normalized mitochondrial function to reduce mitochondrial DNA release through mitofusin 2 (Mfn2), leading to inactivation of cGAS-STING, which delayed astrocyte senescence and prevented neurodegeneration. Mfn2 overexpression in astrocytes reversed the inhibitory role of metformin in cGAS-STING activation and astrocyte senescence. More importantly, metformin ameliorated dopamine neuron injury and behavioral deficits in mice by reducing the accumulation of senescent astrocytes via inhibition of astrocytic cGAS activation. Deletion of astrocytic cGAS abolished the suppressive effects of metformin on astrocyte senescence and neurodegeneration. CONCLUSIONS: This work reveals that metformin delays astrocyte senescence via inhibiting astrocytic Mfn2-cGAS activation and suggest that metformin is a promising therapeutic agent for age-associated neurodegenerative diseases.

Serum stromal cell-derived factor-1 levels are associated with diabetic kidney disease in type 2 diabetic patients.

The present study was designed to explore whether serum stromal cell-derived factor-1 (SDF-1) levels were associated with diabetic kidney disease (DKD). Serum SDF-1 levels were measured by sandwich ELISA. Patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g for 3 months were identified as having DKD. Among the recruited type 2 diabetic patients, 18.71% (n = 32) were found to have DKD, and the serum SDF-1 levels of these patients were higher than those of patients without DKD (p < 0.05). Serum SDF-1 levels were positively correlated with cystatin C levels, the UACR and DKD incidence (r = 0.330, 0.183 and 0.186, respectively, p < 0.05) and inversely related to eGFR (r = -0.368, p < 0.001). After adjusting for other clinical covariates by multivariate logistic regression analyses, serum SDF-1 levels were found to be an independent contributor to DKD, and the odds ratio (95% confidence interval) was 1.438 (1.041-1.986). Furthermore, receiver operating characteristic analysis revealed that the optimal SDF-1 cutoff value for indicating DKD was 5.609 ng/mL (its corresponding sensitivity was 82.00%, and specificity was 46.90%). Our results demonstrated that serum SDF-1 levels were closely associated with DKD and could be considered a potent indicator for DKD in patients with T2D.

Association of high circulating testosterone with increased glycaemic variability in type 2 diabetes: A cross-sectional study in China.

BACKGROUND: Testosterone affects insulin resistance, but the effect of testosterone treatment on type 2 diabetes (T2D) remains controversial. We aimed to investigate the association between circulating total testosterone (TT) and glycaemic variability using continuous glucose monitoring (CGM) in patients with T2D. METHODS: A total of 248 men with T2D were enrolled in the study. Clinical characteristics and plasma for glycated haemoglobin (HbA1c) and C-peptide assessment were collected. TT was measured using a chemiluminescent immunometric assay. All patients were subjected to a 3-day CGM before making adjustments for hypoglycaemic therapy. RESULTS: TT positively correlated with the standard deviation of mean blood glucose (SDBG) (P < 0.05), especially in older patients. Linear regression analysis showed that SDBG was associated with HbA1c (ß = 0.354, P < 0.001) and TT (ß = 0.164, P = 0.008) after adjusting for age, duration of diabetes, body mass index, fasting/postprandial C-peptide, and use of different hypoglycaemic drugs. The cut-off value of TT for predicting glycaemic variability was 14.76 mmol/L according to receiver operating characteristic (ROC) analysis. SDBG, the coefficient of variation, the incremental area under the curve of glucose (AUC) > 10 mmol/L, and AUC night were increased in the group with TT > 14.76 nmol/L (P < 0.01 for all variables). Body mass index and fasting/postprandial C-peptide were lower in the group with TT > 14.76 nmol/L than in the group with TT ≤ 14.76 nmol/L (P < 0.05). CONCLUSIONS: Circulating TT levels should be assessed in patients with T2D in addition to HbA1c for predicting glycaemic variability. More frequent blood glucose monitoring or CGM is suggested for patients with T2D and high testosterone levels. CLINICAL TRIALS REGISTRATION: NCT03519529, ClinicalTrials.gov.

Comparative Study on Three Pretreatment Methods for Atomic Absorptive Spectrophotometry Determination of Metal Elements in Lycium Barbarum.

A simple, fast and accurate method was explored to determine the mineralelements in Lycium barbaru.Three different pretreatment methods, including dry ashing method, HNO3-H2O2 and HNO3-HClO4 wet digestion, method were employed for digestion of the samples of Lycium barbaru. The concentrations of Na，K，Ca，Mg，Fe，Cu，Zn，Ni，Pb and Cd were determined by using atomic absorption spectrometry. The experimental results showed that the recovery rates of dry ashing method, HNO3-H2O2 and HNO3-HClO4 wet digestion method were in the ranges from 89.88% to 102.15%, 92.34% to 103.21% and 94.52% to 102.10% respectively; the relative standard deviation (RSD) of dry ashing method, HNO3-H2O2 and HNO3-HClO4 wet digestion method were lower than 3.037%, 2.751% and 2.496% separately. The RSD and recovery of three pretreatment methods were all satisfied with the analysis requirements. But compared with dry ashing method and HNO3-H2O2 wet digestion method, the recovery of HNO3-HClO4 wet digestion method was better, and the precision was higher. Besides, compared with three pretreatment methods, the average value of Na, K, Ca, Fe and Cd had statistical difference (p<0.05), and HNO3-HClO4 wet digestion method was significantly higher than others.In addition, HNO3-HClO4 wet digestion method taken a shorter time and less consumption of reagents. Therefore, HNO3-HClO4 wet digestion method can be used as the preferably pretreatment method for the determination of the contents of metal elements by atomic absorption spectrophotometry method.

PGE1 improves diabetic peripheral neuropathy in patients with type 2 diabetes.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes. We aim to investigate the efficacy of Prostaglandin E1 (PGE1) treatment in addition to intensive insulin therapy on DPN in patients with type 2 diabetes. METHODS: Seventy-seven patients with DPN received daily intravenous injection of Prostaglandin E1 (PGE1) in lipid microspheres (Lipo-PGE1) for 10days as an additional therapy to standard glucose control therapy (PGE1 group). Another 42 patients with DPN receiving only standard glucose control therapy (intensive insulin therapy) acted as a control group. Michigan neuropathy screening instrument (MNSI) score, neurophysiology examination, transcutaneous oxygen sensory threshold, and ankle-brachial index (ABI) were measured to evaluate the efficacy of PGE1 treatment as compared with control group. RESULTS: Standard glucose control therapy decreased plasma glucose to a similar level in both PGE1 and control groups. Compare to control group, PGE1 group displayed improvement in several nerve electrophysiological indexes. MNSI score was significantly improved in patients who received PGE1 treatment compared with the control group (p<0.001) after 10days of PGE1 treatment. Similarly, nerve conduction velocity and foot sensory thresholds (p<0.05 for all) also significantly improved compared with the control group after 10days of PGE1 treatment. However, only intensive insulin therapy did not improve any neural function. CONCLUSIONS: Lipo-PGE1 can effectively improve neural function of patients with DPN.

Thymosin ß4 attenuates early diabetic nephropathy in a mouse model of type 2 diabetes mellitus.

The chronic inflammatory processes and endothelial dysfunction play important roles in the development of diabetic nephropathy (DN); the study aims to evaluate the effect of thymosin ß4 (Tß4), which has apparent anti-inflammatory properties and is capable of improving endothelial dysfunction, in early DN in a mouse model of type 2 diabetes mellitus. KK Cg-Ay/J (KK) mice, aged 12-14 weeks, were divided into the following groups: KK control group that was treated with saline; KK Tß4 group that was treated with Tß4 100 ng/10 g of intraperitoneal injection once a day. Nondiabetic age-matched C57BL mice were used as additional normal control and also treated with Tß4. The urinary albumin/creatinine ratio (ACR), plasma urea nitrogen and creatinine, body weight, fasting blood glucose and 2-hour blood glucose during oral glucose tolerance testing, blood hemoglobin A1c, cholesterol, and triglyceride were determined at baseline time and 12 weeks after Tß4 treatment for phenotypic characterizations. The KK Tß4 group had reduced the mean fasting blood glucose, 2-hour blood glucose during oral glucose tolerance testing, hemoglobin A1c, and triglyceride levels compared with that in the KK control group (P < 0.05). Tß4 treatment markedly reduced ACR (KK Tß4 = 328.54 ± 46.14 mg/g vs. KK control = 540.34 ± 50.31 mg/g, P < 0.05). Tß4 also significantly ameliorated renal pathological changes of KK Tß4 mice as compared with that in KK control mice. Tß4 treatment did not affect glucose homeostasis and urinary ACR and glomeruli of C57BL mice. These data in a novel mouse model of DN suggest that Tß4 may ameliorate renal damage. This peptide may be a novel potential alternative agent for treatment of DN.

Individualized intensive insulin therapy of diabetes: Not only the goal, but also the time.

Intensive insulin therapy has been extensively used to control blood glucose levels because of its ability to reduce the risk of chronic complications of diabetes. According to current guidelines, intensive glycemic control requires individualized glucose goals rather than as low as possible. During intensive therapy, rapid blood glucose reduction can aggravate microvascular and macrovascular complications, and prolonged overuse of insulin can lead to treatment-induced neuropathy and retinopathy, hypoglycemia, obesity, lipodystrophy, and insulin antibody syndrome. Therefore, we need to develop individualized hypoglycemic plans for patients with diabetes, including the time required for blood glucose normalization and the duration of intensive insulin therapy, which deserves further study.

The complete chloroplast genome sequence of Lilium saccatum S. Yun Liang (Liliaceae, Lilieae) and its phylogenetic analysis.

Lilium saccatum is a species of ornamental plant found in southeastern Xizang, China. In the present study, the complete chloroplast (cp) genome of L. saccatum was sequenced using next-generation sequencing (NGS). The de novo assembled cp genome was 151,839 bp in length, including a pair of inverted repeat regions (IRs; 26,421 bp), a small single-copy region (SSC; 17,528 bp), and a large single-copy region (LSC; 81,469 bp). The cp genome encodes 113 unique genes, including 79 protein-coding genes (PCGs), 30 tRNA genes, and four rRNA genes. The total GC content of the cp genome was 37.0%. Phylogenetic analysis of 24 cp genomes revealed that L. saccatum was closely related to L. souliei. This study could provide fundamental information for the phylogenomics and utilization of Lilium.

Single-Cell RNA Sequencing Analysis of Steroidogenesis and Spermatogenesis Impairment in the Testis of db/db Mice.

Objective: The mechanism of steroidogenesis and spermatogenesis impairment in men with type 2 diabetes remains unclear. We aimed to explore the local changes of steroidogenesis and spermatogenesis in the testis of db/db mice. Research Design and Methods. We performed single-cell RNA sequencing analysis in the testis of db/db and C57BL/6J mice. The differentially expressed genes were then confirmed by real-time PCR. The histopathological characteristics of testis in db/db mice and C57BL/6J control were also performed. Results: The 20-week-old db/db mice had significantly higher blood glucose and body weight (both p < 0.001). The serum testosterone levels (4.4 ± 0.8 vs. 9.8 ± 0.7 ng/ml, p=0.001) and weight of the testis (0.16 ± 0.01 vs. 0.24 ± 0.01 g, p < 0.001) were significantly lower in db/db mice than that in C57BL/6J controls. db/db mice had a lower cross-sectional area of seminiferous tubules and thickness of the cell layer (both p < 0.05). The numbers of Sertoli cells and Leydig cells decreased in db/db mice (both p < 0.01). Single-cell RNA sequencing analysis showed that compared with the control group, the percentage of spermatogonia was significantly higher in the db/db mouse (p < 0.001), while the proportions of spermatocytes, round and elongating spermatids, and sperms were all lower in the db/db mouse (p all < 0.001). The most differentially expressed genes were found in round spermatids (n = 86), which were not found in spermatogonia, spermatocyte, and sperm. Igfbp5 was the most significantly decreased gene in Leydig cells of the db/db mouse, while the expression of Cd74, H2-Aa, and H2-Eb1 was elevated. Ccl7 and Ptgds were the most significantly increased and decreased genes in Sertoli cells of the db/db mouse. Conclusions: The present study indicates spermiogenesis and steroidogenesis defects in db/db mice. The mechanism of steroidogenesis impairment in the testis of db/db mice deserves further investigation.

Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes.

BACKGROUND: Insulin antibodies (IAs) affect blood glucose control in patients receiving insulin therapy. AIM: To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional, retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy. All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array. RESULTS: A total of 1863 patients were enrolled. There were 902 (48.4%) patients who had positive IAs (IA level > 5%), with a mean IA level of 11.06% (10.39%-11.72%). IA levels were positively correlated with high fasting blood glucose (odds ratio = 1.069, P < 0.001). The proportion of positive IAs was lowest in patients using glargine only (31.9%) and highest in patients using human insulin only (70.3%), P < 0.001. The IA levels in patients using sulfonylureas/glinides (8.3%), metformin (9.6%), and dipeptidyl peptidase-4 inhibitors (8.2%) were all lower than in patients without these drugs (all P < 0.05). CONCLUSION: Nearly half of patients on insulin therapy have positive IA antibodies, and IA antibody levels are associated with blood glucose control. Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

[Analysis of Heavy Metal Sources in Farmland Soil of Sewage Irrigation and Industrial Complex Area Based on APCS-MLR and PMF].

The contents of eight heavy metals （Cr, Ni, Cu, Zn, Cd, Pb, As, and Hg） were determined based on the surface soil samples of sewage irrigation and industrial complex in Kaifeng City. The absolute factor analysis-multiple linear regression （APCS-MLR） model and positive matrix factorization （PMF） model were used to analyze the sources and contribution rates of heavy metals in soil combined with correlation analysis and systematic cluster analysis. The results showed that： ① The average values of ω（Cr）, ω（Ni）, ω（Cu）, ω（Zn）, ω（Cd）, ω（Pb）, ω（As）, and ω（Hg） in the study area were 52.19, 25.00, 42.03, 323.53, 1.79, 53.45, 9.43, and 0.20 mg·kg-1, respectively, and Cr, Ni, and As are lower than the background values of tidal soil. Cu, Zn, Cd, Pb, and Hg are higher than the background values of the tidal soil. ② There were four sources of the eight heavy metals： natural sources, agricultural sewage irrigation sources, industrial atmospheric sedimentation sources, and transportation sources. Cr and Ni were mainly from natural sources； Cu, Zn, Cd, and Pb were mainly from agricultural sewage irrigation and transportation sources； As was mainly from natural sources and agricultural sewage irrigation； and Hg was mainly from industrial atmospheric sedimentation. ③ The APCS-MLR and PMF source analysis results indicated that industrial and agricultural activities were the main sources of heavy metals in the soil of the study area. The average contribution rates of APCS-MLR in the nine sampling areas of the research area were 76.01% （natural sources and agricultural sewage irrigation sources）, 22.71% （industrial atmospheric sedimentation sources and transportation sources）, and 1.28% （unknown sources）. The average contribution rates of PMF were 59.66% （natural sources and agricultural sewage irrigation sources） and 40.34% （industrial atmospheric sedimentation sources and transportation sources）. The source analysis results of the LZ, XZ, NLT, PT, YLZ, and BC models were basically consistent, and WL was better in the APCS-MLR model, whereas SG and QT were better in the PMF model. The research results can provide a scientific basis for the prevention and control of soil heavy metal pollution and environmental remediation.

[Source Apportionment and Health Risk Assessment of Heavy Metals in Dust Around Bus Stops in Kaifeng City Based on APCS-MLR Model].

In order to reveal the influence of urban transportation systems on the quality of urban ecological environment, this study selected surface dust from bus stops, which is strongly disturbed by transportation, as the research object. The contents of eight heavy metals (V, Cr, Co, Ni, Cu, Zn, Cd, and Pb) in the dust were determined through inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectroscopy (ICP-ASE). The spatial distribution characteristics and pollution levels of the eight heavy metals in the dust were analyzed using the geo-accumulation index method. A combined qualitative (correlation analysis and principal component analysis) and quantitative (absolute principal component scores-multiple linear regression model (APCS-MLR)) method was used to explore the sources of heavy metals in surface dust near bus stops. The spatial distribution characteristics of heavy metals from different sources were elucidated using the Kriging interpolation method. The health risk assessment model proposed by the United States Environmental Protection Agency was used to evaluate the human health risks. The results showed that the average values of ω(V), ω(Cr), ω(Co), ω(Ni), ω(Cu), ω(Zn), ω(Cd), ω(Pb), and ω(As) in the bus stop surface dust were 68.36, 59.73, 5.81, 19.34, 40.10, 208.32, 1.01, and 49.46 mg·kg-1, respectively. The concentrations of heavy metals (Cd, Zn, Pb, Cu, and Cr) in the dust were all higher than the background values in the surrounding dust, exceeding them by 3.37, 2.70, 2.01, 1.95, and 1.28 times, respectively. The order of the geo-accumulation index for the eight heavy metals was Cd > Zn > Pb > Cu > Cr > V > Ni > Co, with Cd, Zn, Cu, and Pb in the dust indicating mild pollution levels and the others showing no pollution. The source analysis results showed that Cr, Co, and Ni were natural sources, whereas Cu, Zn, Pb, and Cd were traffic sources, and V was derived from a combination of industrial and natural sources. The APCS-MLR results indicated that the average contribution rates of the four sources were as follows:natural source (34.17 %), traffic source (29.84 %), industrial-natural mixed source (14.64 %), and unknown source (21.35 %). The spatial distribution map of the contribution rate of the traffic source was consistent with the trends of traffic volume and bus route density distribution. According to the health risk assessment, the cancer risk and non-cancer risk for children were both higher than those for adults. Cr was the main non-cancer factor, and Cd was the main cancer-causing factor. Natural and traffic sources contributed the most to non-cancer risk and cancer risk, respectively.

[The association between vitamin D deficiency and diabetic nephropathy in type 2 diabetic patients].

OBJECTIVE: To evaluate the association between vitamin D deficiency and diabetic nephropathy in type 2 diabetic patients. METHODS: A total of 594 patients with type 2 diabetes were enrolled from the inpatients of the Nanjing Medical University Affiliated Nanjing Hospital. Fasting serum lipid profile, 25-hydroxycalciferol vitamin D and urinary albumin excretion rate were investigated. The relationship between nephropathy and vitamin D deficiency ( < 20 µg/L) or insufficiency (20-<30 µg/L) was analyzed. RESULTS: Nephropathy was found in 177 subjects (29.8%) with albuminuria in 141 and proteinuria in 36 subjects. Vitamin D deficiency was found in 180 subjects and insufficiency in 157 subjects. The proportion of vitamin D deficiency was higher in the individuals with nephropathy than those without nephropathy (36.2% vs 27.8%, P < 0.05). The urinary albumin excretion rate was significantly higher in the patients with vitamin D deficiency than those with normal vitamin D concentration [(123.0 ± 299.2) mg/24h vs (47.6 ± 97.1) mg/24h, P < 0.01]. The prevalence of nephropathy was higher in the patients with vitamin D deficiency than those with normal vitamin D concentration (35.6% vs 26.1%, P < 0.05), while the prevalence of proteinuria was higher in patients with vitamin D deficiency (12.2% vs 3.1%, P < 0.01). Logistic regression analysis demonstrated that vitamin D deficiency was associated with nephropathy (OR 1.57, 95%CI 1.04-2.37), even after the adjustment for age, gender, hypertension, dyslipidemia, smoking status, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (OR 1.78, 95%CI 1.12-2.81). The Vitamin D concentration was significantly negatively correlated with urinary albumin excretion rate (r = -1.783, P < 0.001). CONCLUSIONS: Type 2 diabetic patients have a high prevalence of vitamin D deficiency. Vitamin D deficiency is independently associated with diabetic nephropathy.

[Pollution Characteristics and Source Analysis of Heavy Metals in Soils in Yellow River Cultural Park Based on APCS-MLR and PMF Receptor Model].

With open spaces and good ecological environments, urban parks have become the first choice for the leisure and entertainment of many people. Therefore, the quality of park soil environments has gradually attracted the extensive attention of scholars. In this study, we take the Yellow River Cultural Park, a typical human disturbance area in the lower reaches of the Yellow River, as the research area to discuss the characteristics and sources of heavy metal pollution in the soil. Thirty-three soil surface samples were collected from the Yellow River Cultural Park, and the contents of seven heavy metals (Cr, Ni, Cu, Zn, Cd, Pb, and As) were determined using an inductively coupled plasma emission spectrometer (ICP-AES) and an inductively coupled plasma mass spectrometer (ICP-MS). The geo-accumulation index and geo-statistics method were used. Meanwhile, the absolute factor analysis-multiple linear regression (APCS-MLR) receptor model and positive matrix factorization (PMF) analysis model were employed to reveal the sources of soil heavy metals. The results showed that the average contents of heavy metals (Cd, Zn, Cu, Pb, and As) in the surface soil of the study area were 4.62, 1.78, 1.41, 1.08, and 1.03 times higher than the background values of soil elements in the tidal soil area of the lower reaches of the Yellow River, respectively. Except for Zn, the contents of other elements were lower than the corresponding values of soil elements in different regions along the Yellow River Basin. Among the seven heavy metal elements, the coefficients of variation of Cd and As were greater than 50%, showing obvious spatial variability. The decreasing trend of the accumulation index of the seven elements was Cd>Zn>Cu>Ni>Pb>As=Cr, and the element Cd belonged to the middle pollution category, which was obviously accumulated in the surface soil. The spatial distribution of heavy metals in the soil differed:the high contents of Cr, Cu, and Ni were distributed in the southwest and northeast, and the high-value areas of Cd and Pb were consistent with the areas of human activity intensity. The high-value areas of Zn and As were located in the center of lacustrine sediments. The combined results of the APCS-MLR and PMF models suggested that the first pollution source of soil heavy metal elements in the Yellow River Cultural Park could have been a natural source, the second pollution source may have been a transportation source, and the third source of pollution was judged as a mixed source. Human activities such as transportation sources and mixed sources were the main sources of heavy metal soil pollution, and Cr, Cu, and Ni were affected by natural factors. The contribution rates of APCS-MLR were 46.67%, 24.11%, 16.12%, and 13.10%, respectively, and the contribution rates of PMF were 35.50%, 35.48%, and 29.02%, respectively. This research can provide a basis for improving the ecological environment quality of the park and improving the health level of the population and can also provide support for the ecological environment risk management and comprehensive management along the Yellow River.

Low Total Testosterone Levels in Men with Newly Diagnosed Early-Onset Type 2 Diabetes: A Cross-Sectional Study in China.

Objective: There is a bidirectional interaction between circulating testosterone and blood glucose levels. We aim to investigate the testosterone levels in men with early-onset type 2 diabetes (T2DM). Methods: A total of 153 drug naive men with T2DM were enrolled in the study. Early- (n = 63) and late-onset (n = 90) T2DM was classified according to age 40 years old. Clinical characteristics and plasma for biochemical criterions were collected. Gonadal hormones were measured using chemiluminescent immunometric assay. The concentrations of 3ß- and 17ß-HSD were determined using ELISA. Results: Compared with men with late-onset T2DM, those with early-onset T2DM had lower serum total testosterone (TT), sex hormone-binding globulin (SHBG), and FSH, but higher dehydroepiandrosterone sulfate (DHEA-S) level (p < 0.05). The mediating effect analysis showed that the decreased TT levels in patients with early-onset T2DM were associated with the higher HbA1c, BMI, and triglyceride in these patients (both p < 0.05). The early-onset of T2DM directly correlated with increased DHEA-S (both p < 0.01). The 3ß-HSD concentration in the early-onset T2DM group was lower than that in the late-onset T2DM group (11.07 ± 3.05 vs. 12.40 ± 2.72 pg/mL, p = 0.048) and was positively correlated with fasting C-peptide, while negatively correlated with HbA1c and fasting glucagon (p all < 0.05). Conclusions: Patients with early-onset T2DM showed inhibition of conversion from DHEA to testosterone, which may attribute to the low level of 3ß-HSD and high blood glucose in these patients.

[Soil Heavy Metal Contamination, Sources, and Health Risk of Typical Drinking Water Sources in the Suspended Reach of the Lower Yellow River].

With the implementation of ecological protection and a high-quality development strategy in the Yellow River Basin, the environmental conditions around the Yellow River have attracted wide attention from scholars. In this study, the soil of drinking water sources(Heichi and Liuchi) in the typical suspended reach of the lower reaches of the Yellow River was selected as the research object. The geo-accumulation index and pollution load index were used to analyze the pollution characteristics of seven heavy metals(Cr, Ni, Cu, Zn, Cd, Pb, and As), and correlation analysis, principal component analysis, and absolute factor score-multiple linear regression(APCS-MLR) were employed to reveal the sources of soil heavy metals from both qualitative and quantitative perspectives. The health risk assessment model recommended by the United States Environmental Protection Agency(USEPA) was used to analyze the impact of soil heavy metals on human health, and the contribution rate of pollution sources to health risks was analyzed by combining the APCS-MLR model. The results showed that the average values of ω(Cr), ω(Ni), ω(Cu), ω(Zn), ω(Cd), ω(Pb), and ω(As) in the soil around the water source were 60.27, 30.00, 35.14, 77.75, 0.38, 21.74, and 9.70 mg·kg-1, respectively. Except for As, the contents of Cr, Ni, Cu, Zn, Cd, and Pb were higher than the background values of soil elements in the fluvo-aquic soil area of the lower Yellow River, whereas the contents of Cu and Zn in the soil around Liuchi were significantly higher than those in Heichi. Both the geo-accumulation index and the single-factor index showed that the black pond and the willow pond were slightly polluted by heavy metals, and Cd was the main pollution factor. The pollution load index model showed that the number of non-polluted and mildly polluted samples in the study area accounted for 5% and 95% of the total samples, respectively, indicating that the study area was at a mild pollution level. The source apportionment showed that Cr, Ni, Cu, and As were mainly affected by parent materials. The analysis results of the APCS-MLR model showed that the soil pollutants in the study area were mainly from natural sources, traffic sources, agricultural sources, and unknown sources, and their contribution rates were 42.95%, 23.39%, 16.95%, and 16.71%, respectively. The health risk assessment showed that As was the main non-carcinogenic factor, and Ni was the main carcinogenic factor. The non-carcinogenic risk of heavy metals to adults and children was negligible, and there was a tolerable carcinogenic risk to the human body. For both adults and children, the non-carcinogenic and carcinogenic risk contribution rates of the four pollution sources were:natural sources>unknown sources>traffic sources>agricultural sources, among which natural sources contributed the most to non-carcinogenic and carcinogenic risks. Therefore, it is of great significance to study the characteristics, sources, and effects of soil pollution on human health around the water source area of the suspended reach of the lower reaches of the Yellow River, which is of great significance for the protection of water sources and provides theoretical support for the high-quality development of the ecological environment along the Yellow River.

[Changes in the physical growth of children aged 3 to 6 years in urban areas of Lanzhou from 2001 to 2010].

OBJECTIVE: To study changes in the physical growth of preschool children aged 3 to 6 yeas in urban areas of Lanzhou from 2001 to 2010. METHODS: Stratified, randomized, cluster sampling was used to collect physical examination data on children from 35 private and public kindergartens located in different urban areas of Lanzhou in 2001, 2006, and 2010. Changes in physical growth were analyzed using body height, body weight and body mass index (BMI) as main indices. Growth retardation, underweight, overweight, emaciation and obesity were screened out using height for age (HAZ), weight for age (WAZ), and weight for height (WHZ) and changes from 2001 to 2010 were analyzed. RESULTS: Body height, body weight and BMI increased from 2001 to 2010 in children at different ages (P<0.05). Body height and weight increased with age, while BMI decreased with age. Mean values of HAZ, WAZ, and WHZ increased over time, showing that prevalence rates of underweight, growth retardation, and emaciation decreased from 2001 to 2010 while those of overweight and obesity increased. CONCLUSIONS: Changes in the physical growth of preschool children in urban areas of Lanzhou from 2001 to 2010 were obvious, with increases in body height and body weight. However, problems such as overweight and obesity emerged. In response, while malnutrition is being solved, attention should be paid to over-nutrition that has an adverse effect on physical growth.

Response of blood glucose and GLP-1 to different food temperature in normal subject and patients with type 2 diabetes.

BACKGROUND: Eating behavior is a major factor in type 2 diabetes. We investigated the different responses of glucose-regulating hormones to cold and hot glucose solutions in normal subjects and patients with type 2 diabetes. METHODS: In this crossover, self-controlled study, normal subjects (N = 19) and patients with type 2 diabetes (N = 22) were recruited and randomly assigned to a hot (50 °C) or a cold (8 °C) oral glucose-tolerance test (OGTT). The subsequent day, they were switched to the OGTT at the other temperature. Blood glucose, insulin, GIP, glucagon-like peptide-1 (GLP-1), and cortisol were measured at 0, 5, 10, 30, 60, and 120 min during each OGTT. After the hot OGTT, all subjects ingested hot (>42 °C) food and water for that day, and ingested food and water at room temperature (≤24 °C) for the day after cold OGTT. All participants had continuous glucose monitoring (CGM) throughout the study. RESULTS: Compared to cold OGTT, blood glucose was significantly higher with hot OGTT in both groups (both P < 0.05). However, insulin and GLP-1 levels were significantly higher in hot OGTT in normal subjects only (both P < 0.05). The GIP and cortisol responses did not differ with temperature in both groups. CGM showed that normal subjects had significantly higher 24-h mean glucose (MBG) (6.11 ± 0.13 vs. 5.84 ± 0.11 mmol/L, P = 0.021), and standard deviation of MBG with hot meals (0.59 ± 0.06 vs. 0.48 ± 0.05 mmol/L, P = 0.043), T2DM patients had higher MBG only (8.46 ± 0.38 vs. 8.88 ± 0.39 mmol/L, P = 0.022). CONCLUSIONS: Food temperature is an important factor in glucose absorption and GLP-1 response. These food temperatures elicited differences are lost in type 2 diabetes.

Short-time intensive insulin therapy upregulates 3 beta- and 17 beta-hydroxysteroid dehydrogenase levels in men with newly diagnosed T2DM.

Objective: Our previous study has found that short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes mellitus (T2DM) increased serum testosterone levels, but the underlying mechanisms remain unclear. Design and methods: In this self-controlled study, 43 men with newly diagnosed drug naïve T2DM, aged 18-60 years, with HbA1c >9.0% were treated with continuous subcutaneous insulin infusion (CSII) to normalize blood glucose within one week. Venous blood specimens were collected for measuring of serum total testosterone, dehydroepiandrosterone sulfate (DHEA-S), 3ß- and 17ß-hydroxysteroid dehydrogenase (3ß- and 17ß-HSD) concentrations before and after insulin therapy. Results: Testosterone increased from 13.0 (11.3, 14.6) nmol/L to 15.7 (13.9, 17.5) nmol/L after intensive insulin therapy (p<0.001), while the levels of DHEA-S decreased significantly after treatment (from 6.5 (5.7, 7.3) µmol/L to 6.0 (5.3, 6.7) µmol/L, p=0.001). The ratio of testosterone/DHEA-S increased significantly (2.4 (2.0, 2.8) vs. 3.1 (2.6, 3.7) nmol/µmol, p<0.001). After blood glucose normalization with the short-term CSII therapy, 3ß-HSD increased from 11.0 (9.5, 12.5) pg/mL to 14.6 (13.5, 15.7) pg/mL, p=0.001, and 17ß-HSD increased from 20.7 (16.3, 25.2) pg/mL to 28.2 (23.8, 32.5) pg/mL, p=0.009. Conclusions: Blood glucose normalization via short-term intensive insulin therapy increases plasma total testosterone levels in men with newly diagnosed type 2 diabetes, associated with a decreased level of DHEA-S, probably because of the enhanced conversion from DHEA to testosterone catalyzed by 3ß-HSD and 17ß-HSD.

Effects of Pacemaker Implantation on Sudden Cardiac Death Rate and Quality of Life in Atrial Fibrillation Patients With Ventricular Pauses.

Ventricular arrest is a rare arrhythmic disease in the clinic; 35% to 55% of cases are associated with atrial fibrillation (AF). It is well known that ventricular arrest for ≥3 seconds can lead to brain symptoms such as dizziness and even syncope, but it is not clear whether ventricular pauses (≥3 seconds) with AF will lead to sudden cardiac death. If the implantation of a pacemaker can improve the quality of life of patients with permanent AF with ventricular arrest and whether it has a long-term protective effect on sudden cardiac death. To this end, we conducted a prospective follow-up observation study, which was conducted through telephone interviews and clinical hospital observation to obtain information on the quality of life, survival rate, and other details. The results show that for patients with permanent AF with ventricular arrest, pacemaker implantation cannot reduce sudden cardiac death, cardiovascular events, and stroke nor can it improve the cumulative survival rate. Fortunately, the implantation of pacemakers can improve the quality of life of patients.