Tanshinone IIA suppresses ferroptosis to attenuate renal podocyte injury in diabetic nephropathy through the embryonic lethal abnormal visual-like protein 1 and acyl-coenzyme A synthetase long-chain family member 4 signaling pathway.

AIMS/INTRODUCTION: Tanshinone IIA (TIIA) is one of the main components of the root of the red-rooted Salvia miltiorrhiza Bunge. However, the molecular mechanisms underlying TIIA-mediated protective effects in diabetic nephropathy (DN) are still unclear. MATERIALS AND METHODS: High glucose (HG)-induced mouse podocyte cell line (MPC5) cells were used as the in vitro model of DN and treated with TIIA. Cell viability, proliferation and apoptosis were detected using 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide, 5-ethynyl-2'-deoxyuridine and flow cytometry assays. The protein levels were assessed using western blot assay. The levels of inflammatory factors were deleted by enzyme-linked immunoassay. Fe+ level, reactive oxygen species, malondialdehyde and glutathione products were detected using special assay kits. After ENCORI prediction, the interaction between embryonic lethal abnormal visual-like protein 1 (ELAVL1) and acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) was verified using co-immunoprecipitation assay and dual-luciferase reporter assays. ACSL4 messenger ribonucleic acid expression was measured using real-time quantitative polymerase chain reaction. RESULTS: TIIA repressed HG-induced MPC5 cell apoptosis, inflammatory response and ferroptosis. ACSL4 upregulation relieved the repression of TIIA on HG-mediated MPC5 cell injury and ferroptosis. ELAVL1 is bound with ACSL4 to positively regulate the stability of ACSL4 messenger ribonucleic acid. TIIA hindered HG-triggered MPC5 cell injury and ferroptosis by regulating the ELAVL1-ACSL4 pathway. TIIA blocked DN progression in in vivo research. CONCLUSION: TIIA treatment restrained HG-caused MPC5 cell injury and ferroptosis partly through targeting the ELAVL1-ACSL4 axis, providing a promising therapeutic target for DN treatment.

Left ventricular strain changes at high altitude in rats: a cardiac magnetic resonance tissue tracking imaging study.

BACKGROUND: Long-term exposure to a high altitude environment with low pressure and low oxygen could cause abnormalities in the structure and function of the heart. Myocardial strain is a sensitive indicator for assessing myocardial dysfunction, monitoring myocardial strain is of great significance for the early diagnosis and treatment of high altitude heart-related diseases. This study applies cardiac magnetic resonance tissue tracking technology (CMR-TT) to evaluate the changes in left ventricular myocardial function and structure in rats in high altitude environment. METHODS: 6-week-old male rats were randomized into plateau hypoxia rats (plateau group, n = 21) as the experimental group and plain rats (plain group, n = 10) as the control group. plateau group rats were transported from Chengdu (altitude: 360 m), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (altitude: 3850 m), Yushu, China, and then fed for 12 weeks there, while plain group rats were fed in Chengdu(altitude: 360 m), China. Using 7.0 T cardiac magnetic resonance (CMR) to evaluate the left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), as well as myocardial strain parameters including the peak global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). The rats were euthanized and a myocardial biopsy was obtained after the magnetic resonance imaging scan. RESULTS: The plateau rats showed more lower left ventricular GLS and GRS (P < 0.05) than the plain rats. However, there was no statistically significant difference in left ventricular EDV, ESV, SV, EF and GCS compared to the plain rats (P > 0.05). CONCLUSIONS: After 12 weeks of exposure to high altitude low-pressure hypoxia environment, the left ventricular global strain was partially decreased and myocardium is damaged, while the whole heart ejection fraction was still preserved, the myocardial strain was more sensitive than the ejection fraction in monitoring cardiac function.

Bacteroides ovatus accelerates metformin-induced vitamin B12 deficiency in type 2 diabetes patients by accumulating cobalamin.

Vitamin B12 (VB12) deficiency, which may lead to hematologic and neurologic symptoms, has been associated with metformin use, but the underlying mechanism is unclear. Here we report the B. ovatus as an effective VB12 catcher which was enriched in the type 2 diabetes patients suffered from VB12 deficiency after 3 to 6 months of metformin treatment. Colonization of B. ovatus increased the plasma levels of methylmalonic acid and homocysteine in high-fat diet (HFD)-fed mice treated with metformin, and compromised the efficacy of metformin against the HFD-induced metabolic disorders. Mechanistically, metformin increased the intracellular accumulation of VB12 in B. ovatus via btuB upregulation and promoted ATP production for energy-dependent translocation of VB12 transporters at the inner membrane, leading to an enhanced colonization of B. ovatus to compete for VB12 with hosts and subsequently an aggravated VB12 deficiency in the host. Our findings illustrate a previously unappreciated mechanism of metformin leads to host VB12 deficiency by acting directly on gut bacteria to increase their VB12 uptake and consumption, and suggest that inter-host-microbe competition for nutrients may broadly impact human health and drug safety.

[GLIS family zinc finger protein 2 (GLIS2) negatively regulates the Wnt/ß-catenin pathway to inhibit the osteogenic differentiation of human bone marrow mesenchymal stem cells].

Objective To investigate how the human GLIS family zinc finger protein 2 (GLIS2) regulate the Wnt/ß-catenin pathway and its influence on the differentiation of human bone marrow mesenchymal stem cells (BMMSCs). Methods Human BMMSCs were randomly divided into blank group, osteogenic induction group, GLIS2 gene overexpression (ad-GLIS2) group, ad-GLIS2 negative control group, gene knockdown (si-GLIS2) group, and si-GLIS2 negative control (si-NC) group. The expression of GLIS2 mRNA in each group was detected by reverse transcription-PCR to determine the transfection status; alkaline phosphatase (ALP) activity was detected by phenyl-p-nitrophenyl phosphate (PNPP), and calcified nodule formation was tested by alizarin red staining to determine its osteogenic properties; the activation of intracellular Wnt/ß-catenin pathway was detected by T cell factor/lymphoid enhancer factor (TCF/LEF) reporter kit; the expression of GLIS2, Runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osterix was detected by Western blot analysis. The interaction between GLIS2 and ß-catenin was verified by GST-pulldown. Results Compared with the blank group, the ALP activity and calcified nodule formation of BMMSCs in the osteogenic induction group increased, and the Wnt/ß-catenin pathway activity and the expression of osteogenic differentiation-related proteins increased, the osteogenic ability increased, while the expression of GLIS2 decreased. Up-regulating the expression of GLIS2 could inhibit the osteogenic differentiation of BMMSCs, while suppress the activity of the Wnt/ß-catenin pathway and the expression of osteogenic differentiation-related proteins on the contrary. Down-regulating the expression of GLIS2 could promote the osteogenic differentiation of BMMSCs, and improve the activity of the Wnt/ß-catenin pathway and the expression of osteogenic differentiation-related proteins. There was an interaction between ß-catenin and GLIS2. Conclusion GLIS2 may negatively regulate the activation of Wnt/ß-catenin pathway and affect the osteogenic differentiation of BMMSCs.

7.0T cardiac magnetic resonance imaging of right ventricular function in rats with high-altitude deacclimatization.

Background: High-altitude deacclimatization syndrome (HADAS) is a severe public health issue. The study of the changes in right ventricular function caused by high-altitude deacclimatization (HADA) is of great significance for the prevention and treatment of HADAS. Methods: Six-week-old, male Sprague Dawley (SD) rats were randomly divided into the plain, plateau and the HADA group. Rats in the plateau and plain group were exposed to altitudes of 3,850 and 360 m, respectively, for 12 weeks. Rats in HADA group were exposed to the plateau altitude of 3,850 m for 12 weeks and subsequently transported to the plain altitude of 360 m for 4 weeks. Right ventricular ejection fraction (RVEF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and myocardial strain parameters, including the global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS), were evaluated by 7.0T cardiac magnetic resonance (CMR). The levels of red blood cell (RBC), hemoglobin (HGB), and hematocrit (HCT) in the blood were measured, and hematoxylin-eosin (HE) staining was used to observe the pathological changes in the myocardium. Results: In rats in the plateau group, the right ventricular fibrous space was slightly widened, and partial focal steatosis were observed. However, in the HADA group, only a few focal steatoses were found. Rats in the plateau group had elevated levels of RBC, HGB and HCT, increased right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV) and right ventricular stroke volume (RVSV), and decreased right ventricular global longitudinal strain (RVGLS), right ventricular global circumferential strain (RVGCS), and right ventricular global radial strain (RVGRS) compared to rats in the plain group (P<0.001). The RVEDV, RVGCS, and RVGRS in the HADA group basically returned to the plain state. Interestingly, the RVESV in the HADA group was higher, while the RVSV, RVEF, and RVGLS were lower than those in the other two groups. Conclusions: After 12 weeks of exposure to high-altitude environment, there were some pathological changes and the whole contractile strain of the right ventricle was observed. Some pathological changes in the myocardial tissue and stroma recovered after returning to the plain for 4 weeks. However, the right ventricular systolic function and strain did not recover completely.

An ecological remediation model combining optimal substrate amelioration and native hyperaccumulator colonization in non-ferrous metal tailings pond.

The vegetation deterioration and pollution expansion from non-ferrous metal tailings pond have been found in many countries leading to water soil erosion and human health risk. Conventional ecological remediation technologies of mine tailings such as capping were costly and elusive. This study provided an economic and effective model as an alternative by substrate amelioration and vegetation restoration. A field experiment was carried out on a silver tailings pond in southwest China. Tailings substrate was ameliorated by adding organic matter (decomposed chicken manure, DCM), structural conditioner (polyacrylamide, PAM), water-retaining agent (acrylic acid-bentonite water-retaining agent, AAB), and heavy metal immobilizer (biofuel ash, BFA), which were optimized by laboratory experiment. Native heavy metal hyperaccumulator, Bidens pilosa, was colonized. Vegetation coverage and plant height of Bidens pilosa reached about 80% and over 30 cm respectively after 3 months, and the turbidity of tailings leaching solution decreased by 60%. The practice showed that the proportion of available heavy metals in tailings substrate was significantly lower than that in the soil surrounding mining area. Immobilization didn't have stabilization effect on Cd, Zn, and Pb, and As was only 0.002%, phytoremediation had stabilization effect of Cd, Zn, As, and Pb were 2.5-3.5%, 1-2%, 0.25-0.5%, and 0.25-0.75%. Phytoremediation was more effective significantly in controlling heavy metal pollution risk of tailings than immobilization. These results provided a new ecological remediation OSA-NHC model, meaning a combination of optimal substrate amelioration and native hyperaccumulator colonization, which could achieve vegetation restoration and augment heavy metal pollution control in non-ferrous metal tailings pond.

Effects of Capsaicin on the Hypoglycemic Regulation of Metformin and Gut Microbiota Profiles in Type 2 Diabetic Rats.

Dietary capsaicin (CAP), the main irritant component in pepper, can reduce the incidence of diabetes, while metformin (MET) is a first-line oral hypoglycemic drug. The purpose of this study was to investigate whether CAP on the hypoglycemic effect of MET is pertinent to gut microbiota. The glucose and insulin tolerance of diabetic rats were monitored. The glycolipid metabolism was analyzed by detecting blood biochemical parameters. Liver pathological changes were observed by Hematoxylin eosin (HE) staining. The inflammatory cytokines and intestinal tight junction proteins were detected by RT-qPCR and Western blot. 16S rRNA sequencing was employed to analyze gut microbiota profiles. The results showed that CAP and MET co-treatment could significantly reduce fasting blood glucose, improve glucose tolerance, lessen liver injury and inflammatory infiltration, down-regulate inflammatory cytokines and up-regulate intestinal tight junction proteins in diabetic rats by comparing it with MET monotherapy. Moreover, CAP and MET co-treatment altered gut microbiota profiles by regulating microbials' abundances such as Akkermansia. In conclusion, CAP showed the significant hypoglycemic effect of MET and remodulated gut microbiota profiles in diabetic rats.

Application of 7.0 T ultra-high-field MRI in evaluating the structure and function of the right ventricle of the heart in rats under a chronic hypoxic environment at high altitude.

BACKGROUND: Long-term exposure to a high-altitude environment with low pressure and low oxygen can cause abnormalities in the structure and function of the heart, in particular the right ventricle. Monitoring the structure and function of the right ventricle is therefore essential for early diagnosis and prognosis of high-altitude heart-related diseases. In this study, 7.0 T MRI is used to detect cardiac structure and function indicators of rats in natural plateau and plain environments. METHODS: Rats in two groups were raised in different environments from 6 weeks of age for a period of 12 weeks. At 18 weeks of age both groups underwent 7.0 T cardiac magnetic resonance (CMR) scanning. Professional cardiac post-processing software was used to analyze right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), right ventricular stroke volume (RVSV), right ventricular ejection fraction (RVEF), Right ventricular end-diastolic myocardial mass (RV Myo mass, diast), Right ventricular end-systolic myocardial mass (RV Myo mass, syst), tricuspid valve end-diastolic caliber (TVD), tricuspid valve end-systolic caliber (TVS), right ventricular end-systolic long-axis (RVESL) and right ventricular end-diastolic long-axis (RVEDL). Prior to the CMR scan, blood was collected from the two groups of rats for evaluation of blood indicators. After the scan, the rats were sacrificed and the myocardial tissue morphology observed under a light microscope. RESULTS: In the group of rats subject to chronic hypoxia at high altitude for 12 weeks (the plateau group), red blood cell (RBC) count, hemoglobin (HGB) and hematocrit (HCT) increased (P<0.05); RVEDV, RVESV, RVSV, RV Myo mass (diast), RV Myo mass (syst), TVS, RVESL, and RVEDL also increased (P<0.05). Observation of the right ventricle of rats in the plateau group using a light microscope mainly showed a slightly widened myocardial space, myocardial cell turbidity, vacuolar degeneration, myocardial interstitial edema, vascular congestion and a small amount of inflammatory cell infiltration. CONCLUSIONS: The importance of ultra-high-field MRI for monitoring the early stages of rat heart injury has been demonstrated by studying the changes in the structure and function of the right ventricle of rats subject to chronic hypoxia at high altitude over a period of 12 weeks.

circRPS28 (hsa_circ_0049055) is a novel contributor for papillary thyroid carcinoma by regulating cell growth and motility via functioning as ceRNA for miR-345-5p to regulate frizzled family receptor 8 (FZD8).

Circular RNA 40S ribosomal protein S28 (circRPS28; hsa_circ_0049055) is upregulated in papillary thyroid carcinoma (PTC) patients. However, its role remained uncovered in the progression of PTC. Above all, expression of circRPS28 was determined in PTC samples by real-time quantitative PCR and circRPS28 was highly expressed in tumor tissues and cells. Besides, circRPS28 was predominantly distributed in the cytoplasm. Functional experiments were launched using colony formation assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2-deoxyuridine (EdU) assay, transwell assays, scratch wound assay, and flow cytometry. As a result, blocking circRPS28 restrained PTC cell viability, EdU positive cell rate, colony formation number, wounding healing rate, and numbers of migration and invasion cells, accompanied with apoptosis rate promotion. These effects paralleled with low B-cell lymphoma (Bcl)-2 level and high Bcl-2-associated X protein (Bax), matrix metalloproteinase-2 (MMP2), and MMP9 levels, as analyzed by western blotting. Overexpressing microRNA (miR)-345-5p exerted similar roles to circRPS28 silencing. Notably, dual-luciferase reporter assay and RNA immunoprecipitation confirmed the target relationship between circRPS28 and miR-345-5p, miR-345-5p and frizzled family receptor 8 (FZD8). Downregulating miR-345-5p abrogated effects of circRPS28 blockage in PTC cells, and restoring FZD8 counteracted miR-345-5p roles, either. Furthermore, xenograft tumor model was established in mice, and exhausting circRPS28 delayed the growth of PTC cells in vivo by regulating miR-345-5p and FZD8. In conclusion, we demonstrated that blocking circRPS28 and/or promoting miR-345-5p suppressed PTC cell growth and motility via regulating FZD8. This study might suggest a novel circRPS28/miR-345-5p/FZD8 competing endogenous RNA pathway in PTC.

Anti-diabetic Role of Adropin in Streptozotocin Induced Diabetic Rats via Alteration of PI3K/Akt and Insulin Signaling Pathway.

Diabetes mellitus (DM) is a hyperglycemia-related multifactorial condition with an elevated risk of microvascular and microvascular complications associated with this disease. The current experimental study was to examine the antidiabetic activity of streptozotocin (STZ)-induced adropin against diabetic rats by altering the PI3K/Akt and insulin signaling pathways. STZ (60 mg/kg) was used for the induction of DM and rats were divided into different groups and received the adropin (20, 40 and 80 mg/kg) and glibenclamide (10 mg/kg) till 28 days. Body weight, plasma insulin, blood glucose and food intake were estimated, respectively. Biochemical enzymes, carbohydrate enzymes, lipid parameters, AMPK and insulin signalling pathway parameters were estimated. GLUT4 and PPARγ expression were also estimated. Oral administration of adropin significantly (p < 0.001) increased the glycogen, glucose-6-phosphatase dehydrogenase, insulin, hexokinase and belittled the blood glucose level, fructose 1-6-biphosphatase, glucose-6-phosphatase at dose dependent manner. Adropin significantly (p < 0.001) reduced the level of triglyceride, cholesterol, low density lipoprotein, very low density lipoprotein and increased the level of high density lipoprotein at dose dependent manner. Adropin significantly (p < 0.001) activated the Akt, IRS-2, IRS-1, IR, p-AKT and PI3k, which are the key modulator molecules of PI3K/Akt, AMPK and insulin signalling pathway in DM rats. The current experimental study confirms the anti-diabetic effect of adropin on DM rats induced by AMPK and insulin signalling pathway against STZ.

Added value of circulating miRNA expression profiling to sonographic TI-RADS classification in the diagnosis of thyroid nodules.

Potential use of sonographic TI-RADS classification combined with circulating miRNA expression profiling in the diagnosis of thyroid nodules was explored. Retrospective analysis was performed on clinical data of 121 patients with thyroid nodules. The biopsy specimens of patients obtained through ultrasound-guided aspiration and blood specimens were evaluated in Zhengzhou Central Hospital Affiliated to Zhengzhou University from June 2018 to June 2019. In addition, the blood specimen test results of 121 healthy volunteers (control group) who underwent physical examination were retrospectively analyzed. Results of sonographic TI-RADS classification and circulating miRNA expression profiling were compared with the pathological results. Of the 212 nodules, 2 fell into TI-RADS category 2 and were diagnosed as benign. Malignant nodules accounted for 4.35, 37.14, 84.78, 93.33 and 96.77% of those nodules that fell into TI-RADS categories 3, 4a, 4b, 4c and 5, respectively. Of the 121 patients, 92.55% had with nodular goiter, 3.31% had inflammatory nodules, 2.48% toxic nodular goiter, 0.83% thyroid cysts and 0.83% thyroid tumors. A nodule that fell into a higher TI-RADS classification category had a higher risk of malignancy. The expression levels of miRNA146b, miRNA187, miRNA375, miRNA-222-3p and miRNA-151a-5p were higher, while the level of miRNA138 was lower, in patients with either benign or malignant thyroid nodules compaed to those in the control group. The expression levels of miRNA146b, miRNA187, miRNA375, miRNA-222-3p and miRNA-151a-5p were higher, while the level of miRNA138 was lower, in patients with malignant thyroid nodules than those in patients with benign thyroid nodule (P<0.05). The AUC of the combined diagnostic method was 0.973, which was significantly different from the AUCs of the individual diagnostic method (P<0.05). In conclusion, sonographic TI-RADS classification combined with circulating miRNA expression profiling can improve the diagnosis of thyroid nodules.

Chemical weathering and CO2 consumption rates of rocks in the Bishuiyan subterranean basin of Guangxi, China.

To investigate the influence of chemical weathering on CO2 consumption, an analysis was performed of water chemistry by applying water chemistry equilibria methods in the Bishuiyan subterranean basin, SW China. The average value of total ion concentrations (TZ+) was 1,854.97 µEq/L, which was significantly higher than the global average value (TZ+ = 1,250 µEq/L). Ca2+ and HCO3- were the main ionic constituents in the waters. SO42- and NO3- concentrations were relatively higher than other anion concentrations, and Cl- concentrations were consistently the lowest. Dissolved load balance models result showed that carbonate weathering, silicate weathering, and atmospheric input were the primary ionic contributors, wherein the effects of carbonate weathering > silicate weathering > atmospheric input for the whole catchment, with the exception of Taiping, where silicate weathering was prominent over carbonate weathering. In addition, these analyses indicated that the erosion via rock weathering was also affected by atmospherically derived CO2 and allogenic acids. The estimated yield by quantitative calculation for the carbonate weathering rate was 59.7 t/(km2 year), which was 4.40 times higher than that of silicate weathering rate. Further, the carbonate and silicate weathering components of the carbon sink accounted for 71.2% and 28.8%, respectively, of the total basin rock weathering carbon sink.

Silencing of SPARC represses heterotopic ossification via inhibition of the MAPK signaling pathway.

Heterotopic ossification (HO), the pathologic formation of extraskeletal bone, can be disabling and lethal. However, the underlying molecular mechanisms were largely unknown. The present study aimed to clarify the involvement of secreted protein acidic and rich in cysteine (SPARC) and the underlying mechanism in rat model of HO. The mechanistic investigation on roles of SPARC in HO was examined through gain- and loss-of-function approaches of SPARC, with alkaline-phosphatase (ALP) activity, mineralized nodules, and osteocalcin (OCN) content measured. To further confirm the regulatory role of SPARC, levels of mitogen-activated protein kinase (MAPK) signaling pathways-related proteins (extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), p38, nuclear factor κ-B (NF-κB), and IkB kinase ß (IKKß)) were determined. Bone marrow mesenchymal stem cells were treated with pathway inhibitor to investigate the relationship among SPARC, MAPK signaling pathway, and HO. The results suggested that SPARC expression was up-regulated in Achilles tendon tissues of HO rats. Silencing of SPARC could decrease phosphorylation of ERK, JNK, p38, NF-κB, and IKKß. Additionally, silencing of SPARC or inhibition of MAPK signaling pathway could reduce the ALP activity, the number of mineralized nodules, and OCN content, thus impeding HO. To sum up, our study identifies the inhibitory role of SPARC gene silencing in HO via the MAPK signaling pathway, suggesting SPARC presents a potential target for HO therapy.

Paeonol prevents IL-1ß-induced inflammatory response and degradation of type II collagen in human primary chondrocytes.

Osteoarthritis (OA) is a common joint disease for which a safe and reliable treatment has yet to be developed. Here, we demonstrated the potential benefit of treatment with paeonol, a derivative of Paeonia suffruticosa, in the treatment and prevention of OA. Chondrogenic cell line ATDC5 cells were cultured with IL-1ß and the effects of paeonol were assessed through qRT-PCR, western blot analysis, MTT, ELISA, and NF-κB luciferase reporter gene assay. Our findings demonstrate a novel ability of paeonol to inhibit numerous factors of OA, including expressions of IL-6, TNF-α, NOX2, PTGS2, NUCB2/nesfatin-1, ICAM-1, VCAM-1, MMP-3/13, degradation of type II collagen, and NF-κB activation through the rescue of IκBα. Additionally, we assessed the effects of paeonol on cell viability to confirm its safety. These findings implicate a valuable potential role of paeonol in the treatment and prevention of OA.

Effect of AMP-activated protein kinase subunit alpha 2 (PRKAA2) genetic polymorphisms on susceptibility to type 2 diabetes mellitus and diabetic nephropathy in a Chinese population.

BACKGROUND: It is well known that AMP-activated protein kinase (AMPK) is a key factor affecting the development of type 2 diabetes mellitus (T2DM). The single nucleotide polymorphism (SNP) rs2746342 in the AMPK alpha 2 subunit gene (PRKAA2) has been found to be associated with susceptibility to T2DM in the Chinese Han population. The present study further investigates the association of PRKAA2 genotypes with susceptibility to T2DM and its complication, diabetic nephropathy. METHODS: The PRKAA2 genotypes of 406 T2DM patients and 214 controls from the Chinese Han population were determined with regard to SNPs rs10789038, rs2796498 and rs2746342. The association between these SNPs and susceptibility to T2DM and diabetic nephropathy was evaluated. The clinical characteristics differed significantly between T2DM patients and controls. RESULTS: After adjustment for age, sex and body mass index, there was an obvious relationship between T2DM and both rs10789038 (odds ratio [OR] 1.634; P = 0.015) and rs2796498 (OR 0.656; P = 0.030), but not rs2746342. There was haplotype association of PRKAA2 rs10789038-rs2796498-rs2746342 with T2DM susceptibility. In addition, rs2796498 was found to be related to the susceptibility to diabetic nephropathy. CONCLUSIONS: Polymorphisms in rs10789038 and rs2796498 are associated with the susceptibility to T2DM, and rs2796498 may be related to diabetic nephropathy.

STK11 rs2075604 Polymorphism Is Associated with Metformin Efficacy in Chinese Type 2 Diabetes Mellitus.

Metformin is a classical oral antidiabetic drug, often recommended to be the first-choice treatment of type 2 diabetes mellitus (T2DM). Based on the previous research on STK11 and diabetes, we aimed to investigate the distributive characteristic of STK11 rs2075604 polymorphism and the potential influence of STK11 rs2075604 polymorphism on metformin efficacy among Chinese T2DM patients. There was no significant difference between T2DM patients (G = 64.8%, T = 35.2%) and healthy subjects (G = 62.7%, T = 37.2%) in STK11 rs2075604 genotype and allele frequencies. After 12 weeks of treatment, 62 patients were defined as the responders and 32 patients as nonresponders according to the decrease of HbA1c level. And the GT + TT genotype in STK11 rs2075604 can decrease HbA1c level more significantly than the GG genotype. Furthermore, the allele frequency of T in the STK11 rs2075604 was higher in the responders than the nonresponders (43.55% versus 26.56%). The T allele in the STK11 rs2075604 had a 2.133 times great chance of responding to metformin treatment. In conclusion, this study suggested that the STK11 rs2075604 genetic polymorphism was significantly associated with metformin efficacy in Chinese T2DM patients and the carriers of the T allele may gain a better therapeutic metformin efficacy compared with the G allele. This trial is registered with clinical study registration number NCT03155087.

[Alterations of brain network efficiency in patients with post-concussion syndrome].

OBJECTIVE: To discuss the alterations of brain network efficiency in patients with post-concussion syndrome. METHODS: A total of 23 patients from Anhui Provincial Hospital in the period from 2013/6 to 2014/3 who have had the concussion for 3 months were enrolled and 23 volunteers paired in sex, age and education were also enrolled as healthy controls. Comparisons of selective attention of both groups were conducted using Stroop Word-Color Test. The data of resting-state functional magnetic resonance imaging (fMRI) in both groups were collected and the data were dealt with Network Construction which is a part of GRETNA software to obtain the Matrix of brain network. Network analysis was used to obtain Global and Nodal efficiency, then independent t-test was used for statistical analyses of the value of Global and Nodal efficiency. RESULTS: The difference in Global efficiency of two groups in every threshold value had no statistical significance. Compared with healthy controls, the Nodal efficiencies in patients with post-concussion syndrome were significantly different in the brain regions as below: left orbital middle frontal gyrus, left posterior cingulate, left lingual, left thalamus, left superior temporal gyrus, right anterior cingulate, right posterior cingulate, right supramarginalgyrus. CONCLUSIONS: Compared with healthy controls, there is no significant changes of Globe efficiency in patients with post-concussion syndrome, and the brain function deficits in these patients may be caused by changes of Nodal efficiency in their brain network.

[Functional connectivity of amygdala in refractory epilepsy:a resting-state functional study of magnetic resonance imaging].

OBJECTIVE: To explore the functions of amygdala functional connectivity in the pathogenesis of refractory epilepsy with resting-state functional magnetic resonance imaging (RS-fMRI). METHODS: A total of 19 patients with refractory epilepsy were recruited from August 2013 to June 2014. And 19 healthy persons were selected as the controls.No obvious epileptogenic lesions of intracranial structures were found on multi-modal neuroimaging.Ictal and interictal epileptic activities on long-term video electroencephalogram (EEG) showed spine spread spike and wave in bilateral cerebral hemispheres. All fMRI data were preprocessed after RS-fMRI scanning. Then left and right amygdalas were selected as regions of interest (ROIs) for calculating the linear correlation between amygdala and whole brain. As relative to the control group, the changes of brain areas in functional connectivity were examined for the intractable epilepsy group. RESULTS: Compared with the controls, left amygdala in refractory epilepsy group showed increased functional connectivity with bilateral fusiform gyrus, bilateral calcarine gyrus and right lingual, on the contrary decreased functional connectivity with bilateral cuneus, bilateral precuneus, bilateral caudatas and left thalamus.However, right amygdala demonstrated increased functional connectivity with bilateral calcarine gyrus and bilateral linguals, but decreased functional connectivity with bilateral caudatas and left putamen (P < 0.05). CONCLUSION: Altered functional connectivity of amygdala reflects its dysfunction in refractory epilepsy patients. It suggested that amygdala is an important component of "epileptic network" participating in the occurrence and development of refractory epilepsy.

[Response Mechanism of Trace Metals in the Bishuiyan Subterranean River to the Rainfall and Their Source Analysis].

High-frequency sampling was conducted at the outlet of Guangxi Bishuiyan karst subterranean river using an automatic sampler during the rainfall events. The hydrochemical drymanic variation characteristics of trace metals (Cu, Pb, Zn, Cd) at the outlet of Guangxi Bishuiyan karst subterranean river were analyzed, and the sources of the trace metals in the subterranean river as well as their response to rainfall were explored. The results showed that the rainfall provoked a sharp decrease in the major elements (Ca²âº, Mg²âº, HCO3⁻, etc.) due to dilution and precipitation, while it also caused an increase in the concentrations of dissolved metals including Al, Mn, Cu, Zn and Cd, due to water-rock reaction, sediment remobilization, and soil erosion. The water-rock reaction was more sensitive to rainfall than the others, while the sediment remobilization and soil erosion took the main responsibility for the chemical change of the heavy metals. The curves of the heavy metal concentrations presented multiple peaks, of which the maximum was reached at 9 hours later after the largest precipitation. Different metal sources and the double-inlet structure of the subterranean river were supposed to be the reasons for the formation of multiple peaks. During the monitoring period, the average speed of the solute in the river reached about 0.47 km · h⁻¹, indicating fast migration of the pollutants. Therefore, monitoring the chemical dynamics of the karst subterranean river, mastering the sources and migration characteristics of trace metal components have great significance for the subterranean river environment pollution treatment.

Spatial variations of dimethylsulfide and dimethylsulfoniopropionate in the surface microlayer and in the subsurface waters of the South China Sea during springtime.

Spatial variations in dimethylsulfide (DMS) and dimethylsulfoniopropionate (DMSP) were surveyed in the surface microlayer and in the subsurface waters of the low productivity South China Sea in May 2005. Overall, average subsurface water concentrations of DMS and DMSP of dissolved (DMSPd) and particulate (DMSPp) fractions were 1.74 (1.00-2.50), 3.92 (2.21-6.54) and 6.06 (3.40-8.68) nM, respectively. No enrichment in DMS and DMSPp was observed in the microlayer. In contrast, the microlayer showed a DMSPd enrichment, with an average enrichment factor (EF, defined as the ratio of the microlayer concentration to subsurface water concentration) of 1.40. In the study area, none of the sulfur components were correlated with chlorophyll a. An important finding in this study was that DMS, DMSP and chlorophyll a concentrations in the surface microlayer were respectively correlated with those in the subsurface water, suggesting a close linkage between these two water bodies. The ratios of DMS:Chl-a and DMSPp:Chl-a showed a gradually increasing trend from North to South. This might be due to changes in the proportion of DMSP producers in the phytoplankton community with the increased surface seawater temperature. A clear diurnal variation in the DMS and DMSP concentrations was observed at an anchor station with the highest concentrations appearing during the day and the lowest concentrations during the night. The higher DMS and DMSP concentrations during daytime might be attributed to the light-induced increase in both algal synthesis and exudation of DMSP and biological production of DMS. The mean flux of DMS from the investigated area to the atmosphere was estimated to be 2.06 micromo lm(-2)d(-1). This low DMS emission flux, together with the low DMS surface concentrations was attributed to the low productivity in this sea.