Search

Objective: To explore whether Bushen Huoxue Formula (BSHXF) improves the angiogenesis ability of transplanted endothelial progenitor cells (EPCs) in endplate and its potential mechanism in delaying intervertebral disc degeneration (IDD). Methods: BSHXF was analyzed via Ultra-High Performance Liquid Chromatography (UPLC). Rabbit axial compression lumbar IDD models were constructed and the effects of BSHXF, EPCs, and their combination in IDD were determined by MRI, histological evaluation, TUNEL, and immunofluorescence assays. Additionally, CCK-8 assay, flow cytometry, and tube formation assay were used to evaluate EPCs viability, proliferation, cell cycle and the angiogenesis ability of EPCs between groups. Results: BSHXF and transplanted EPCs both attenuate the process of IDD in the rabbit model assessed by MRI, HE staining and Masson staining. TUNEL-positive NP cells were significantly reduced in the BSHXF group, EPCs group, and EPC + BSHXF group compared to the model group (P

Objective: To establish a new animal model of intervertebral disc degeneration (IDD) by axial compression on lumbar spine of rabbits and to investigate the changes of microcirculation in bony endplates during the progress of IDD. Methods: 32 New Zealand white rabbits were equally divided into 4 groups as follows: Control group with no operation and compression, Sham operation group with apparatus placement only, 2-week compression group and 4-week compression group with the devices installed and compressed for their preset duration. All groups of rabbits underwent MRI, histological evaluation, disc height index measurement and Microfil contrast agent perfusions to examine the ratio of endplate microvascular channels. Results: The new animal model of IDD was successfully established after axial compression for 4 weeks. The MRI grades for the 4-week compression group was 4.63 ± 0.52 and significantly different to the sham operation group (P

Abstract Background This study was conducted to investigate the outcomes and complications of balloon kyphoplasty (KP) for the treatment of osteoporotic vertebral compression fracture (OVCF) in patients with rheumatoid arthritis (RA) and compare its radiological and clinical effects with OVCF patients without RA. Methods Ninety-eight patients in the RA group with 158 fractured vertebrae and 114 patients in the control group with 150 vertebrae were involved in this study. Changes in compression rate, local kyphotic angle, visual analog scale (VAS) and Oswestry disability index (ODI) scores, conditions of bone cement leakage, refracture of the operated vertebrae, and new adjacent vertebral fractures were examined after KP. In addition, patients in the RA group were divided into different groups according to the value of erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and whether they were glucocorticoid users or not to evaluate their influence on the outcomes of KP. Results KP procedure significantly improved the compression rate, local kyphotic angle, and VAS and ODI scores in both RA and control groups (p

The development of minimally invasive procedures and implant materials has improved the fixation strength of implants and is less traumatic in surgery. The purpose of this study was to propose a novel “double-point fixation” for calcaneal fractures and compare its biomechanical stability with the traditional “three-point fixation.” A three-dimensional finite element foot model with a Sanders type IIIAB calcaneal fracture was developed based on clinical images comprising bones, plantar fascia, ligaments, and encapsulated soft tissue. Double-point and three-point fixation resembled the surgical procedure with a volar distal radius plate and calcaneal locking plate, respectively. The stress distribution, fracture displacement, and change of the Böhler angle and Gissane’s angle were estimated by a walking simulation using the model, and the predictions between the double-point and three-point fixation were compared at heel-strike, midstance, and push-off instants. Double-point fixation demonstrated lower bone stress (103.3 vs. 199.4 MPa), but higher implant stress (1,084.0 vs. 577.9 MPa). The model displacement of double-point fixation was higher than that of three-point fixation (3.68 vs. 2.53 mm). The displacement of the posterior joint facet (0.127 vs. 0.150 mm) and the changes of the Böhler angle (0.9° vs. 1.4°) and Gissane’s angle (0.7° vs. 0.9°) in double-point fixation were comparably lower. Double-point fixation by volar distal radius plates demonstrated sufficient and favorable fixation stability and a lower risk of postoperative stress fracture, which may potentially serve as a new fixation modality for the treatment of displaced intra-articular calcaneal fractures.

In steel enterprises, the design of energy systems mainly depends on experience and lacks systematic optimization methods. Therefore, it is of great significance to propose an overall optimization design method for the energy system of steel enterprises. In this paper, a linear model is proposed to select the energy conversion equipment types and distribute energy sources with the aim of maximizing the economic benefits of an energy system. In the model, the choice of energy conversion technology and the distribution of energy source are considered comprehensively. For the S steel plant, the case analysis results show that under the condition of keeping the original energy conversion equipment unchanged and optimizing the distribution of energy source, the economic benefits of the energy system can be increased by 15.77 CNY/t steel, and under the conditions of optimizing the distribution schemes of the energy conversion equipment types and energy sources, the economic benefits of the energy system can be increased by 180.26 CNY/t steel. In addition, the effects of different energy conversion equipment configurations, different energy sources prices and different pollution cost standards on the steel plant energy economic benefits were analyzed.

Abstract Background The objective of this study was to examine and analyze differential methylation profiles in order to investigate the influence of hyper-methioninemia (HM) on the development of diabetic nephropathy (DN). Male Wistar rats, aged eight weeks and weighing 250–300 g, were randomly assigned into four groups: a control group (Healthy, n = 8), streptozocin-induced rats (STZ group, n = 8), HM + STZ group (n = 8), and the Tangshen Formula (TSF) treatment group (TSF group, n = 8). Blood glucose levels and other metabolic indicators were monitored before treatment and at four-week intervals until 12 weeks. Total DNA was extracted from the aforementioned groups, and DNA methylation landscapes were analyzed via reduced representative bisulfite sequencing. Results Both the STZ group and HM + STZ group exhibited increased blood glucose levels and urinary albumin/creatinine ratios in comparison with the control group. Notably, the HM + STZ group exhibited a markedly elevated urinary albumin/creatinine ratio (411.90 ± 88.86 mg/g) compared to the STZ group (238.41 ± 62.52 mg/g). TSF-treated rats demonstrated substantial reductions in both blood glucose levels and urinary albumin/creatinine ratios in comparison with the HM + STZ group. In-depth analysis of DNA methylation profiles revealed 797 genes with potential therapeutic effects related to TSF, among which approximately 2.3% had been previously reported as homologous genes. Conclusion While HM exacerbates DN through altered methylation patterns at specific CpG sites, TSF holds promise as a viable treatment for DN by restoring abnormal methylation levels. The identification of specific genes provides valuable insights into the underlying mechanisms of DN pathogenesis and offers potential therapeutic targets for further investigation.

To investigate the impact of electrode structure on Electrical Stimulation Therapy (EST) for chronic wound healing, this study designed three variants of flexible microelectrodes (FMs) with Ag-Cu coverings (ACCs), each exhibiting distinct geometrical configurations: hexagonal, cross-shaped, and serpentine. These were integrated with PPY/PDA/PANI (3/6) (full name: polypyrrole/polydopamine/polyaniline 3/6). Hydrogel dressing comprehensive animal studies, coupled with detailed electrical and mechanical modeling and simulations, were conducted to assess their performance. Results indicated that the serpentine-shaped FM outperformed its counterparts in terms of flexibility and safety, exhibiting minimal thermal effects and a reduced risk of burns. Notably, FMs with metal coverings under 3% demonstrated promising potential for optoelectronic self-powering capabilities. Additionally, simulation data highlighted the significant influence of hydrogel non-uniformity on the distribution of electrical properties across the skin surface, providing critical insights for optimizing EST protocols when employing hydrogel dressings.

Abstract Background The SARS-CoV-2 Omicron strain has multiple immune-escape mutations in the spike protein receptor-binding domain (RBD). Rapid detection of these mutations to identify Omicron and its lineages is essential for guiding public health strategies and patient treatments. We developed a two-tube, four-color assay employing asymmetric polymerase chain reaction (PCR)-based melting curve analysis to detect Omicron mutations and discriminate the BA.1, BA.2, BA.4/5, and BA.2.75 lineages. Methods The presented technique involves combinatory analysis of the detection of six fluorescent probes targeting the immune-escape mutations L452R, N460K, E484A, F486V, Q493R, Q498R, and Y505H within one amplicon in the spike RBD and probes targeting the ORF1ab and N genes. After protocol optimization, the analytical performance of the technique was evaluated using plasmid templates. Sensitivity was assessed based on the limit of detection (LOD), and reliability was assessed by calculating the intra- and inter-run precision of melting temperatures (Tms). Specificity was assessed using pseudotyped lentivirus of common human respiratory pathogens and human genomic DNA. The assay was used to analyze 40 SARS-CoV-2–positive clinical samples (including 36 BA.2 and 4 BA.4/5 samples) and pseudotyped lentiviruses of wild-type and BA.1 viral RNA control materials, as well as 20 SARS-CoV-2–negative clinical samples, and its accuracy was evaluated by comparing the results with those of sequencing. Results All genotypes were sensitively identified using the developed method with a LOD of 39.1 copies per reaction. The intra- and inter-run coefficients of variation for the Tms were ≤ 0.69% and ≤ 0.84%, with standard deviations ≤ 0.38 °C and ≤ 0.41 °C, respectively. Validation of the assay using known SARS-CoV-2–positive samples demonstrated its ability to correctly identify the targeted mutations and preliminarily characterize the Omicron lineages. Conclusion The developed assay can provide accurate, reliable, rapid, simple and low-cost detection of the immune-escape mutations located in the spike RBD to detect the Omicron variant and discriminate its lineages, and its use can be easily generalized in clinical laboratories with a fluorescent PCR platform.

Objective. A sensitive and specific multiplex fluorescence rapid detection method was established for simultaneous detection of SARS-CoV-2, influenza A virus, and influenza B virus in a self-made device within 30 min, with a minimum detection limit of 200 copies/mL. Methods. Based on the genome sequences of SARS-CoV-2, influenza A virus (FluA), and influenza B virus (FluB) with reference to the Chinese Center for Disease Control and Prevention and related literature, specific primers were designed, and a multiplex fluorescent PCR system was established. The simultaneous and rapid detection of SARS-CoV-2, FluA, and FluB was achieved by optimizing the concentrations of Taq DNA polymerase as well as primers, probes, and Mg2+. The minimum detection limits of the nucleic acid rapid detection system for SARS-CoV-2, FluA, and FluB were evaluated. Results. By optimizing the amplification system, the N enzyme with the best amplification performance was selected, and the optimal concentration of Mg2+ in the multiamplification system was 3 mmol/L; the final concentrations of SARS-CoV-2 NP probe and primer were 0.15 μmol/L and 0.2 μmol/L, respectively; the final concentrations of SARS-CoV-2 ORF probe and primer were both 0.15 μmol/L; the final concentrations of FluA probe and primer were 0.2 μmol/L and 0.3 μmol/L, respectively; the final concentrations of FluB probe and primer were 0.15 μmol/L and 0.25 μmol/L, respectively. Conclusion. A multiplex real-time quantitative fluorescence RT-PCR system for three respiratory viruses of SARS-CoV-2, FluA, and FluB was established with a high amplification efficiency and sensitivity reaching 200 copies/mL for all samples. Combined with the automated microfluidic nucleic acid detection system, the system can achieve rapid detection in 30 minutes.

IntroductionThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and influenza viruses can cause respiratory illnesses with similar clinical symptoms, making their differential diagnoses challenging. Additionally, in critically ill SARS-CoV-2–infected patients, co-infections with other respiratory pathogens can lead to severe cytokine storm and serious complications. Therefore, a method for simultaneous detection of SARS-CoV-2 and influenza A and B viruses will be clinically beneficial.MethodsWe designed an assay to detect five gene targets simultaneously via asymmetric PCR-mediated melting curve analysis in a single tube. We used specific probes that hybridize to corresponding single-stranded amplicons at low temperature and dissociate at high temperature, creating different detection peaks representing the targets. The entire reaction was conducted in a closed tube, which minimizes the risk of contamination. The limit of detection, specificity, precision, and accuracy were determined.ResultsThe assay exhibited a limit of detection of

Abstract Background Methylated SDC2 has been proved as a diagnostic marker for human colorectal cancer (CRC), noninvasive stool DNA-based methylation testing also emerges as a novel approach for detecting CRC. The aim of this study was to evaluate the clinical performance of stool DNA-based SDC2 methylation test by a new qPCR detection reagent for early detection of CRC. Methods A new qPCR detection reagent contained two differentially methylated regions in SDC2 CpG islands for the detection of CRC was used in this study. Performance of the SDC2 methylation detection reagent was evaluated by analyzing limit of detection, precision, and specificity. The effect of interfering substances on assay performance was also tested. 339 subjects (102 CRC patients, 50 patients with advanced adenomas, 39 patients with non-advanced adenomas, 18 colitis patients and 130 normal individuals) from the China-Japan Friendship Hospital were evaluated. Approximately 2.5 g of stool sample was collected from each participant. Stool DNA was extracted and bisulfite-converted, followed by qPCR assay, which contained two pairs of primers for the methylation detection of two fragments of the SDC2 gene (named SDC2-A and SDC2-B). The diagnostic value of this test in CRC was evaluated by calculating receiver operating characteristic (ROC) curve, and value of the area under the curve (AUC). Results The test kit was able to detect methylated SDC2 in stool DNA samples with concentrations as low as 90 copies/μL in 100% of replicates. The sensitivity for detecting CRC by methylated SDC2-A alone was 85.29% (95% CI 77.03–91.00%) with a specificity of 96.15% (95% CI 91.08–98.58%). The sensitivity by methylated SDC2-B alone was 83.33% (95% CI 74.82–89.42%) with a specificity of 97.69% (95% CI 93.14–99.51%). However, when methylated SDC2-A and methylated SDC2-B were combined, the sensitivity for CRC detection improved to 87.25% (95% CI 79.27–92.53%) with a specificity of 94.62% (95% CI 89.11–97.56%). Further, the detection reagent achieved ROC-AUC 0.874 (95% CI 0.822–0.927) for SDC2-A, 0.906 (95% CI 0.859–0.952) for SDC2-B, and 0.939 (95% CI 0.902–0.977) for SDC2-Combine A&B. Conclusions This study validated the capability of stool DNA-based SDC2 methylation test for early screening of CRC, and combined detection of two fragments of SDC2 gene could improve detection sensitivity.

Objectives. To establish and evaluate the analytical and clinical performance of the Flash20 SARS-CoV-2 nucleic acid rapid detection system free of RNA extraction. Methods. The limit of detection (LoD) was determined using a negative nasopharyngeal swab matrix spiked with different concentrations of SARS-CoV-2 virus; a total of 734,337 reference sequences of viral genomes from GenBank were used for the in-silico analysis to assess the inclusivity of the assay. The specificity of the system was evaluated by testing 27 medically relevant organisms. A total of 115 clinical specimens were collected and tested on the Flash20 SARS-CoV-2 detection system and with an FDA-approved comparator test to assess the clinical performance of the system. Results. The LoD of the Flash20 SARS-CoV-2 detection system is 250 copies/mL with a positive rate ≥90% (n = 20); alignments results showed that over 99% identity of the primer and probe of the Flash20 SARS-CoV-2 nucleic acid rapid detection system to the available SARS-CoV-2 sequences; the omicron samples tested 100% positive. None of the 27 organisms showed cross-reactivity with the Flash20 SARS-CoV-2 nucleic acid rapid detection system. Among all the 215 clinical samples, the Flash20 SARS-CoV-2 nucleic acid rapid detection system exhibits a high sensitivity of 99.24% (131/132) and 100% (83/83) specificity. Conclusion. The nucleic acid rapid detection system provides sensitive and accurate detection of SARS-CoV-2 free of RNA extraction. The high sensitivity and short time to results of approximately 35 minutes may impact earlier infection control and disease management.

BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.

Background. The differences in the antihypertensive treatment with angiotensin type II receptor blockers (ARBs) may be attributed to polymorphisms in genes involving drug-targeted receptor and drug metabolism. The present study aimed to investigate whether the antihypertensive effect of the ARB drug valsartan was associated with angiotensin II type 1 receptor (AGTR1) gene polymorphism (A1166 C) and cytochrome P450 enzyme 2C9 (CYP2C9) gene polymorphism (CYP2C9∗3). Methods. 281 patients with hypertension who received valsartan monotherapy in the past month were included in this retrospective study. Polymerase chain reaction-melting curve analysis was performed to genotype the AGTR1 and CYP2C9 gene polymorphisms. Based on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the time of visit, the patients were divided into well-controlled group (n = 144, SBP/DBP

Undoubtedly, opioid drugs have been the most popular treatment for refractory pain since found, such as morphine. However, tolerance to the analgesic effects caused by repeated use is inevitable, which greatly limits the clinical application of these drugs. Nowadays, it has become the focus of the world that further development of non-opioid-based treatment along with efficient strategies to circumvent opioid tolerance are urgently needed clinically. Fortunately, electro-acupuncture (EA) provides an alternative to pharmaceutic treatment, remaining its potential mechanisms unclear although. This study was aimed to observe the effects of EA on morphine-induced tolerance in mice and discover its underlying mechanism. Tail-flick assay and hot-plate test were conducted to assess the development of tolerance to morphine-induced analgesia effect. As a result of repeated administration scheme (10 mg/kg, twice per day, for 7 days), approximately a two-fold increase was observed in the effective dose of 50% (ED50) of morphine-induced antinociceptive effect. Interestingly, by EA treatment (2/100Hz, 0.5, 1.0, and 1.5 mA, 30 min/day for 7 days) at the acupoints Zusanli (ST36) and Sanyinjiao (SP6), morphine ED50 curves was remarkably leftward shifted on day 8. In addition, the RNA sequencing strategy was used to reveal the potential mechanisms. Due to the well described relevance of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), extracellular regulated protein kinases (ERK), and cAMP response element-binding (CREB) in brainstem (BS) to analgesia tolerance, the cAMP-PKA/ERK-CREB signaling was deeply concerned in this study. Based upon Enzyme-Linked Immunosorbent Assay, the up-regulation of the cAMP level was observed, whereas reversed with EA treatment. Similarly, western blot revealed the phosphorylation levels of PKA, ERK, and CREB were up-regulated in morphine tolerant mice, whereas the EA group showed a significantly reduced expression level instead. This study observed an attenuating effect of the EA at ST36 and SP6 on morphine tolerance in mice, and suggested several potential biological targets by RNA-seq, which include the cAMP-PKA/ERK-CREB signaling pathway, strongly supporting a useful treatment for combatting the opioid epidemic, and opioid-tolerant patients.

Abstract Aims/Introduction Blockade or reversal the progression of diabetic nephropathy is a clinical challenge. The aim of the present study was to examine whether recombinant human glucagon‐like peptide‐1 (rhGLP‐1) has an effect on alleviating urinary protein and urinary albumin levels in diabetic rats. Materials and Methods Streptozotocin‐induced diabetes rats were treated with rhGLP‐1 insulin and saline. Using immunostaining, hematoxylin–eosin, electron microscopy and periodic acid–Schiff staining to study the pathology of diabetic nephropathy, and we carried out quantitative reverse transcription polymerase chain reaction, western blot and immunohistochemistry to identify the differentially expressed proteins. The mechanism was studied through advanced glycation end‐products‐induced tubular epithelial cells. Results rhGLP‐1 inhibits protein kinase C (PKC)‐β, but increases protein kinase A (PKA), which reduces oxidative stress in glomeruli and in cultured glomerular microvascular endothelial cells. In tubules, rhGLP‐1 increased the expression of two key proteins related to re‐absorption – megalin and cubilin – which was accompanied by downregulation of PKC‐β and upregulation of PKA. On human proximal tubular epithelial cells, rhGLP‐1 enhanced the absorption of albumin, and this was blocked by a PKC activator or PKA inhibitor. Conclusions These findings suggest that rhGLP‐1 can reverse diabetic nephropathy by protecting both glomeruli and tubules by inhibiting PKC and activating PKA.

This study aimed to investigate the susceptibility of 8 polymorphisms in ApoB and PCSK9 genes to diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus. This is a case-control association study, including 575 DKD cases and 653 controls. Genotypes were determined using ligase detection reaction method, and data are analyzed using STATA software. The genotype distributions of rs1042034 and rs12720838 differed significantly between the two groups (P < 0.001 and P = 0.008, respectively). After adjusting for confounding factors, the mutations of rs1042034 and rs12720838 were associated with the significantly increased risk of DKD. For instance, carriers of rs1042034 T allele (CT and TT genotypes) were 1.07 times more likely to have DKD than carriers of rs1042034 CC genotype [odds ratio (OR) = 1.07, 95% confidence interval (CI): 1.03–1.10, P < 0.001]. Further, haplotype T-A-G-T in ApoB gene was overrepresented in cases (18.10%) compared with controls (12.76%) (PSimulated = 0.045), and haplotype T-A-G-T was associated with a 33% increased risk of DKD (OR = 1.33, 95% CI: 1.04, 1.70). In further haplotype-phenotype analysis, significant association was only noted for hypertension and omnibus haplotypes in ApoB gene (PSimulated = 0.001). Our findings indicate that ApoB gene is a candidate gene for DKD in Chinese patients with type 2 diabetes mellitus.

Background. Epoxide hydrolase 2 (EPHX2) gene coding for soluble epoxide hydrolase is a potential candidate in the pathogenesis of hypertension. Objectives. We aimed to assess the association of a missense mutation, R287Q, in EPHX2 gene with primary hypertension risk and examine its association with enzyme activity of soluble epoxide hydrolase. Methods. This study involved 782 patients with primary hypertension and 458 healthy controls. Genotyping was done using TaqMan technique. Activity of soluble epoxide hydrolase fusion proteins was evaluated by the conversion of 11,12-EET to corresponding 11,12-DHET using ELISA kit. Results. After taking carriers of R287Q variant GG genotype as a reference, those with GA genotype had a significantly reduced risk of hypertension (adjusted odds ratio: 0.72, 95% confidence interval: 0.56 to 0.93, P = 0.013). Five significant risk factors were identified, including age, body mass index, total cholesterol, homocysteine, and R287Q variant. These five risk factors for hypertension were represented in a nomogram, with a descent prediction accuracy (C-index: 0.833, P

Abstract Background Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Pancreas or islet transplantation has been reported to prevent the development of DN lesions and ameliorate or reverse existing glomerular lesions in animal models. Shortage of pancreas donor is a severe problem. Islets derived from stem cells may offer a potential solution to this problem. Objective To evaluate the effect of stem cell-derived islet transplantation on DN in a rat model of streptozotocin-induced DM. Methods Pancreatic progenitor cells were isolated from aborted fetuses of 8 weeks of gestation. And islets were prepared by suspension culture after a differentiation of progenitor cells in medium containing glucagon-like peptide-1 (Glp-1) and nicotinamide. Then islets were transplanted into the liver of diabetic rats via portal vein. Blood glucose, urinary volume, 24 h urinary protein and urinary albumin were measured once biweekly for 16 weeks. Graft survival was evaluated by monitoring human C-peptide level in rat sera and by immunohistochemical staining for human mitochondrial antigen and human C-peptide in liver tissue. The effect of progenitor-derived islets on filtration membrane was examined by electron microscopy and real-time polymerase chain reaction (PCR). Immunohistochemical staining, real-time PCR and western blot were employed for detecting fibronectin, protein kinase C beta (PKCβ), protein kinase A (PKA), inducible nitric oxide synthase (iNOS) and superoxide dismutase (SOD). Results Islet-like clusters derived from 8th gestational-week human fetal pancreatic progenitors survived in rat liver. And elevated serum level of human C-peptide was detected. Blood glucose, 24 h urinary protein and urinary albumin were lower in progenitor cell group than those in DN or insulin treatment group. Glomerular basement membrane thickness and fibronectin accumulation decreased significantly while podocytes improved morphologically in progenitor cell group. Furthermore, receptor of advanced glycation end products and PKCβ became down-regulated whereas PKA up-regulated by progenitor cell-derived islets. And iNOS rose while SOD declined. Conclusions DN may be reversed by transplantation of human fetal pancreatic progenitor cell-derived islets. And fetal pancreatic progenitor cells offer potential resources for cell replacement therapy.

The aim of this study was to investigate the relationship between EPHX2 rs751141 (R287Q polymorphism) and diabetic nephropathy (DN) in Chinese type 2 diabetes (T2D). This case-control study explored the association between EPHX2 rs751141 and DN in a total of 870 Chinese T2D patients (406 T2D patients with DN and 464 T2D patients without DN). DNA was extracted from peripheral leukocytes of the patients and rs751141 was genotyped. The A allele frequency of rs751141 was significantly lower in DN patients (20.94%) compared with non-DN controls (27.8%) (P=0.001), and the A allele of rs751141 was associated with a significantly lower risk of DN after adjustment for multiple covariates in the additive genetic model (OR = 0.68, 95% CI = 0.52–0.88, P=0.004). Significant association between rs751141 and homocysteine (Hcy) level on the risk of DN was observed, indicating that in patients with the highest Hcy levels, the A allele showed marked association with lower risk of DN in all three genetic models. In conclusion, the A allele of exonic polymorphism in EPHX2 rs751141 is negatively associated with the incidence of DN in the Chinese T2D population, which could be modulated by Hcy level status.

Diabetic nephropathy (DN) is one of the major chronic complications of diabetes. Genetic polymorphism of Apolipoprotein E (ApoE) has been proposed to participating in DN. The purpose of the study was to evaluate the relationship between ApoE genetic polymorphism and the presence of DN in Chinese type 2 diabetic patients. We studied 845 diabetic patients who were divided into DN group (n=429) and control group (n=416). ApoE genotype was determined by ApoE genotyping chip and the plasmatic biochemical characterization was performed on all subjects. There were differences (P

The aim of this study was to investigate the relationship between the combined effect of MTHFR C677T (rs1801133) and EPHX2 G860A (rs751141) polymorphism and ischemic stroke in Chinese T2DM patients. This case-control study included a total of 626 Chinese T2DM patients (236 T2DM patients with ischemic stroke and 390 T2DM patients without ischemic stroke). The rs1801133 and rs751141 were genotyped using real-time polymerase chain reaction. Statistical analysis was performed with SPSS 17.0. Results showed that the combined effect of MTHFR TT and EPHX2 GG or GA + AA genotype has a higher risk of ischemic stroke compared with the control group (combined effect of MTHFR CC and EPHX2 GA + AA genotypes; OR = 3.46 and OR = 3.42, resp.; P=.001 and P=.002, resp.). The A allele showed marked association with a lower risk of ischemic stroke in patients with the lowest Hcy levels under additive, recessive, and dominant genetic models (OR = 0.45, OR = 0.11, and OR = 0.44, resp.; P=.002, P=.035, and P=.008, resp.), which was not observed in medium or high Hcy level groups. In conclusion, the T allele of rs1801133 and the G allele of rs751141 may be risk factors of ischemic stroke in the Chinese T2DM population.