Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

Construction of Unique Spiro[dibenzo[a,f]azulene-6,2'-indenes] via Unprecedented Annulation of ortho-C-H Bond of Benzylidene Group.

The domino reaction of alkyl and aryl isocyanides with two molecules of 2-arylidene-1,3-indanediones in acetonitrile at 80 °C resulted in unique functionalized spiro[dibenzo[a,f]azulene-6,2'-indenes] in good yields, in which the two 2-arylidene-1,3-indanediones acted as different building blocks to construct the polycyclic system. More importantly, the unprecedented anticipation of the ortho-position of benzylidene group to form a novel dibenzo[a,f]azulene ring through a formal [5 + 2] cycloaddition process was first observed. On the other hand, DABCO-promoted reaction of the isocyanides with two molecules of 2-arylidene-1,3-indanediones in acetonitrile at 80 °C afforded functionalized spiro[cyclopenta[a]-indene-2,2'-indene] derivatives.

Ochratoxin A induces abnormal tryptophan metabolism in the intestine and liver to activate AMPK signaling pathway.

BACKGROUND: Ochratoxin A (OTA) is a mycotoxin widely present in raw food and feed materials and is mainly produced by Aspergillus ochraceus and Penicillium verrucosum. Our previous study showed that OTA principally induces liver inflammation by causing intestinal flora disorder, especially Bacteroides plebeius (B. plebeius) overgrowth. However, whether OTA or B. plebeius alteration leads to abnormal tryptophan-related metabolism in the intestine and liver is largely unknown. This study aimed to elucidate the metabolic changes in the intestine and liver induced by OTA and the tryptophan-related metabolic pathway in the liver. MATERIALS AND METHODS: A total of 30 healthy 1-day-old male Cherry Valley ducks were randomly divided into 2 groups. The control group was given 0.1 mol/L NaHCO3 solution, and the OTA group was given 235 µg/kg body weight OTA for 14 consecutive days. Tryptophan metabolites were determined by intestinal chyme metabolomics and liver tryptophan-targeted metabolomics. AMPK-related signaling pathway factors were analyzed by Western blotting and mRNA expression. RESULTS: Metabolomic analysis of the intestinal chyme showed that OTA treatment resulted in a decrease in intestinal nicotinuric acid levels, the downstream product of tryptophan metabolism, which were significantly negatively correlated with B. plebeius abundance. In contrast, OTA induced a significant increase in indole-3-acetamide levels, which were positively correlated with B. plebeius abundance. Simultaneously, OTA decreased the levels of ATP, NAD+ and dipeptidase in the liver. Liver tryptophan metabolomics analysis showed that OTA inhibited the kynurenine metabolic pathway and reduced the levels of kynurenine, anthranilic acid and nicotinic acid. Moreover, OTA increased the phosphorylation of AMPK protein and decreased the phosphorylation of mTOR protein. CONCLUSION: OTA decreased the level of nicotinuric acid in the intestinal tract, which was negatively correlated with B. plebeius abundance. The abnormal metabolism of tryptophan led to a deficiency of NAD+ and ATP in the liver, which in turn activated the AMPK signaling pathway. Our results provide new insights into the toxic mechanism of OTA, and tryptophan metabolism might be a target for prevention and treatment.

GO/iron series systems enhancing the pH shock resistance of anaerobic systems for sulfate-containing organic wastewater treatment.

In this study, the effect of pH shock during the treatment of sulfate-containing organic wastewater was investigated using an anaerobic fermentation system reinforced with graphene oxide (GO)/iron series systems. The results show that the anaerobic system with the GO/iron series systems exhibited enhanced resistance to pH shock. Among them, the GO/Fe0 system had the strongest resistance to pH shock, the systems of GO/Fe3O4 and GO/Fe2O3 followed close behind, while the blank system performed the worst. After pH shock, the CODCr removal rate, SO4 2- removal rate, and gas production of the GO/Fe0 group were significantly improved compared with those of the control group by 51.0%, 65.3%, and 34.6%, respectively, while the accumulation of propionic acid was the lowest. Further, detailed microbial characterization revealed that the introduction of the GO/iron series systems was beneficial to the formation of more stable anaerobic co-metabolic flora in the system, and the relative abundance of Geobacter, Clostridium, Desulfobulbus and Desulfovibrio increased after acidic and alkaline shock.

Effect of Etomidate vs Propofol for Total Intravenous Anesthesia on Major Postoperative Complications in Older Patients: A Randomized Clinical Trial.

Importance: Older patients may benefit from the hemodynamic stability of etomidate for general anesthesia. However, it remains uncertain whether the potential for adrenocortical suppression with etomidate may increase morbidity. Objective: To test the primary hypothesis that etomidate vs propofol for anesthesia does not increase in-hospital morbidity after abdominal surgery in older patients. Design, Setting, and Participants: This multicenter, parallel-group, noninferiority randomized clinical trial (Etomidate vs Propofol for In-hospital Complications [EPIC]) was conducted between August 15, 2017, and November 20, 2020, at 22 tertiary hospitals in China. Participants were aged 65 to 80 years and were scheduled for elective abdominal surgery. Patients and outcome assessors were blinded to group allocation. Data analysis followed a modified intention-to-treat principle. Interventions: Patients were randomized 1:1 to receive either etomidate or propofol for general anesthesia by target-controlled infusion. Main Outcomes and Measures: Primary outcome was a composite of major in-hospital postoperative complications (with a noninferiority margin of 3%). Secondary outcomes included intraoperative hemodynamic measurements; postoperative adrenocortical hormone levels; self-reported postoperative pain, nausea, and vomiting; and mortality at postoperative months 6 and 12. Results: A total of 1944 participants were randomized, of whom 1917 (98.6%) completed the trial. Patients were randomized to the etomidate group (n = 967; mean [SD] age, 70.3 [4.0] years; 578 men [59.8%]) or propofol group (n = 950; mean [SD] age, 70.6 [4.2] years; 533 men [56.1%]). The primary end point occurred in 90 of 967 patients (9.3%) in the etomidate group and 83 of 950 patients (8.7%) in the propofol group, which met the noninferiority criterion (risk difference [RD], 0.6%; 95% CI, -1.6% to 2.7%; P = .66). In the etomidate group, mean (SD) cortisol levels were lower at the end of surgery (4.8 [2.7] µg/dL vs 6.1 [3.4] µg/dL; P < .001), and mean (SD) aldosterone levels were lower at the end of surgery (0.13 [0.05] ng/dL vs 0.15 [0.07] ng/dL; P = .02) and on postoperative day 1 (0.14 [0.04] ng/dL vs 0.16 [0.06] ng/dL; P = .001) compared with the propofol group. No difference in mortality was observed between the etomidate and propofol groups at postoperative month 6 (2.2% vs 3.0%; RD, -0.8%; 95% CI, -2.2% to 0.7%) and 12 (3.3% vs 3.9%; RD, -0.6%; 95% CI, -2.3% to 1.0%). More patients had pneumonia in the etomidate group than in the propofol group (2.0% vs 0.3%; RD, 1.7%; 95% CI, 0.7% to 2.8%; P = .001). Results were consistent in the per-protocol population. Conclusions and Relevance: Results of this trial showed that, compared with propofol, etomidate anesthesia did not increase overall major in-hospital morbidity after abdominal surgery in older patients, although it induced transient adrenocortical suppression. Trial Registration: ClinicalTrials.gov Identifier: NCT02910206.

Persistent Purine Metabolic Abnormality Induces the Aggravation of Visceral Inflammation and Intestinal Microbiota Dysbiosis in Magang Goose.

Gout is a disease involving abnormal purine metabolism that is widespread in mammals and birds. Goose is especially susceptible for gout in early stage. However, a few studies investigated the ontogenetic pattern of goslings with purine metabolic abnormality. Our studies were conducted to investigate whether persistent purine metabolic abnormality would lead to aggravation of visceral inflammation and intestinal microbiota dysbiosis in goose. A total of 132 1-day-old Magang geese were randomly divided into six replicates and fed a high-calcium and protein meal-based diet from 1 to 28 days. The experiment lasted for 28 days. Liver and kidney damages were observed in 14- and 28-day-old Magang geese, and liver inflammation increased with increasing age. In 28-day-old Magang geese, serum CAT and liver GSH-Px activity were significantly reduced. Furthermore, jejunum intestinal barrier was impaired and the abundance of Bacteroides was significantly reduced at the genus level. Collectively, the high-calcium and high-protein (HCP) meal-based diet caused liver and kidney damage in 28-day-old Magang geese, leading to hyperuricemia and gout symptoms, and the intestinal barrier is impaired and the intestinal flora is disrupted.

Melatonin alleviates Ochratoxin A-induced liver inflammation involved intestinal microbiota homeostasis and microbiota-independent manner.

Melatonin (MEL) shows an anti-inflammatory effect and regulates intestinal microbiota communities in animals and humans; Ochratoxin A (OTA) induces liver inflammation through intestinal microbiota. However, it remains to know whether MEL alleviates the liver inflammation induced by OTA. In this study, MEL reversed various adverse effects induced by OTA. MEL recovered the swarming and motility of intestinal microbiota, decreased the accumulation of lipopolysaccharide (LPS), enhanced the tight junction proteins of jejunum and cecum segments; ultimately alleviated OTA-induced liver inflammation in ducks. However, it is worth noting that MEL still had positive effects on the OTA-exposed ducks after antibiotic treatment. These results suggest that both the maintenance of intestinal microbiota homeostasis and intestinal microbiota-independent manner involved the MEL anti-inflammatory function in OTA-induced liver inflammation. MEL represent a promising protective approach for OTA, even other mycotoxins.

Different effects of dexmedetomidine and midazolam on the expression of NR2B and GABAA-α1 following peripheral nerve injury in rats.

Neuropathic pain is a complex, chronic pain condition and the treatment is a major clinical challenge. Recent studies have shown that two FDA approved drugs dexmedetomidine (DEX) and midazolam (MZL), may be useful in treating neuropathic pain, but the mechanism is not fully dementated. Here, we investigated the effects and mechanisms of DEX and MZL treatment in the peripheral nerve injury model. Intramuscular injection with DEX and MZL attenuated the development of mechanical allodynia and thermal hyperalgesia in rats with chronic constriction injury (CCI). Concurrently, the expression of NMDA receptor subunit 2B (NR2B), GABA (A) receptor subunit alpha1 (GABAA-α1), and Sonic Hedgehog (SHH) displayed different temporal patterns in the thalamus and the ipsilateral dorsal horn of the spinal cord after CCI. Such that (1) NR2B expression was decreased on day 1 and 14, whereas GABAA-α1 expression was increased on day 1 in the thalamus, and NR2B expression was decreased on day 1, whereas GABAA-α1 expression was increased on day 1 and day 30 in the ipsilateral spinal cord dorsal horn after DEX treatment. (2) NR2B expression was increased on day 1, then decreased on day 14 and returned to baseline on day30, whereas GABAA-α1 expression was no significant changes on day 1, 14, 30 in the thalamus, and NR2B expression was decreased on day 14 and 30, whereas GABAA-α1 expression was no changes on day 1 and 14 but increased on day 30 after MZL treatment. Furthermore, the mechanical allodynia was significantly attenuated after PUR administration. Meanwhile the expression of NR2B was significantly decreased, and the expression of GABAA-α1 was significantly increased, in the thalamus and in the ipsilateral spinal cord dorsal horn when detected on postoperative day 1, 7, and 14. Our findings indicate that DEX and MZL have different mechanisms in CCI rats, suggesting different strategies could be considered in managing neuropathic pain in different individuals. © 2018 IUBMB Life, 70(2):143-152, 2018.

Macrophage migration inhibitory factor siRNA inhibits hepatic metastases of colorectal cancer cells.

The purpose of this study was to assess the anti-tumor effects of macrophage migration inhibitory factor (MIF) siRNA on colorectal cancer in a mouse xenograft model. MIF specific siRNA (MIF siRNA) or a nonspecific control siRNA was introduced to murine colorectal cancer CT-26 cells. Mouse xenograft models of colorectal cancer were established. MIF siRNA, control siRNA or water was injected twice a week intravenously for 4 weeks. MIF siRNA inhibited the proliferation and migration, while induced apoptosis of CT-26 cells in vitro. Injection of MIF siRNA resulted in a significant decrease of serum MIF and VEGF levels, and the weight and volume of cecum-grafted tumors in vivo. In contrast, the number of apoptotic cells and caspase-3 expression were increased by MIF siRNA in cecum graft tumor tissues. Moreover, the water and fodder consumption were significantly improved by MIF siRNA treatment. Importantly, MIF siRNA reduced the hepatic metastases from colorectal cancer. Our results suggest that siRNA targeting MIF is a promising agent for the treatment of hepatic metastasis of colorectal cancer cells.

Median effective effect-site concentration of sufentanil for wake-up test in adolescents undergoing surgery: a randomized trial.

BACKGROUND: To determine the median effective concentration of sufentanil as an analgesic during wake-up tests after sevoflurane anesthesia during surgery for adolescent idiopathic scoliosis (AIS). METHODS: This is a randomised controlled trial. Sixty patients aged 13-18 years scheduled for AIS surgery were randomized into six groups of 10 patients each to receive target effect-site concentrations of sufentanil of 0.19, 0.1809, 0.1723, 0.1641, 0.1563, and 0.1489 ng/ml (target concentration ratio, 1.05). Wake-up time was recorded. Median EC50 and 95% confidence interval (CI) for sufentanil target-controlled infusion (TCI) were determined using Kärber's method. The primary outcome was median EC50 for sufentanil TCI as an analgesic during the wake-up test after sevoflurane anesthesia during surgery for AIS. RESULTS: The EC50 and 95% CI of sufentanil TCI were 0.1682 ng/ml and 0.1641 ~ 0.1724 ng/ml, respectively. CONCLUSIONS: The EC50 of sufentanil TCI was 0.1682 ng/ml (95% CI: 0.1641 ~ 0.1724 ng/ml) during sevoflurane anesthesia in adolescents undergoing surgery for idiopathic scoliosis with intraoperative wake-up tests. TRIAL REGISTRATION: Clinicaltrials.gov identifier: ChiCTR-TTRCC-12002696.

Holmium laser endourethrotomy for the treatment of long-segment urethral strictures: a retrospective study of 190 patients.

PURPOSE: Long-segment urethral strictures (LSUS) are refractory to urethrotomy and urethroplasty. Holmium laser urethrotomy has shown favorable therapeutic outcomes in short-segment urethral stricture. We therefore evaluated the therapeutic effectiveness and safety of holmium laser endourethrotomy in the treatment of LSUS. MATERIALS AND METHODS: Holmium laser endourethrotomy was used to treat 190 consecutive male patients with LSUS. A urethrocystoscopic poking maneuver incorporating holmium laser ablation was used to eliminate the urethral strictures completely. Maximum flow rate (Qmax) on retrograde uroflowmetry, International Prostate Symptom Score (IPSS) and the Expanded Prostate Cancer Index Composite (EPIC) quality of life (QoL) index were assessed at baseline and at 1-, 3- and 6-months postoperatively. RESULTS: Holmium laser urethrotomy was successfully completed in all 190 patients. The mean operation time was 25 ± 17.8 min (range, 6-69 min). No significant intraoperative complications occurred, except that 23 patients (12.1%) experienced controllable scrotal and penile edema. None of these LSUS patients experienced recurrent strictures during a follow-up period of 6-36 months. From baseline to 6 months postoperatively, the mean Qmax increased significantly, from 1.4 ± 2.7 mL/sec to 19.7 ± 4.1 mL/sec (P < .001); mean IPSS decreased significantly, from 31.3 ± 7.2 points to 9.3 ± 3.1 points (P < .001); and mean QoL score showed significant improvement, from 5.7 ± 1.6 points to 1.8 ± 0.4 points (P < .001). CONCLUSION: Holmium laser endourethrotomy with the poking maneuver is a therapeutically effective and minimally invasive treatment for LSUS.

The selective binding character of a molecular imprinted particle for Bisphenol A from water.

A molecular imprinted particle for Bisphenol A (BPA-MIP) was successfully used for selective recognition of BPA in the water. The contaminants such as 3, 3', 5, 5'-Tetrabromobisphenol A (TBBPA), phenol and phenol red (PSP) were selected as the latent interferon to investigate the selectivity. The binding efficiencies of BPA-MIP for different phenols were explored at various initial concentrations in the single and mixed water. Various selective parameters such as Kd, K and K' of BPA-MIP for BPA were calculated. The influences of humic acid (HA) and common ions on the BPA binding were investigated. A physical model was proposed to illustrate the selective binding performance. The results showed that BPA-MIP possessed strong selectivity for BPA in competitive water, while the other similar phenols had the influence for BPA binding at the order of TBBPA > phenol > PSP. The HA and common ions indicated little effect on the BPA binding process onto BPA-MIP. It was found that the molecular geometry and the hydrogen bonding interactions between the hydroxyl and carboxyl played an important role in recognizing the target molecular in the binding process.

Draft Genome Sequence of Ralstonia solanacearum Race 4 Biovar 4 Strain SD54.

Ralstonia solanacearum is an important etiological agent that can cause serious bacterial wilt in a very wide range of potential host plants, including ginger. Here, we report the complete genome sequence of R. solanacearum SD54, a race 4 biovar 4 (R4B4) strain from a diseased ginger plant in China.

Effect of the intraoperative wake-up test in sevoflurane-sufentanil combined anesthesia during adolescent idiopathic scoliosis surgery: a randomized study.

STUDY OBJECTIVE: To investigate the effect of the intraoperative wake-up test on sevoflurane-sufentanil anesthesia for adolescent idiopathic scoliosis (AIS) surgery. DESIGN: Randomized, double-blind, parallel trial. SETTING: Operating room. PATIENTS: 30 ASA physical status 1 patients, aged 13 to 20 years, scheduled for AIS surgery. INTERVENTIONS: Patients were randomized to two groups: Group W patients received sevoflurane-sufentanil combined anesthesia and underwent the intraoperative wake-up test; Group NW received sevoflurane-sufentanil combined anesthesia without the wake-up test. Anesthesia was induced with an intravenous (IV) injection of midazolam, propofol, and sufentanil and maintained with sevoflurane inhalation, a target-controlled infusion (TCI) of sufentanil, and IV infusion of cisatracurium besylate. MEASUREMENTS: The primary outcome was postoperative delirium. Secondary outcomes were duration of surgery, duration of anesthesia, intraoperative blood loss and transfusion, exposure of drugs administered, time to eye opening, extubation, and consciousness. MAIN RESULTS: Postoperative delirium occurred in one patient from each group (P > 0.05). There were no significant differences between the two groups in duration of surgery (322 ± 65 min vs 336 ± 72 min), duration of anesthesia (356 ± 76 min vs 368 ± 81 min), intraoperative blood loss (1847 ± 423 mL vs 1901 ± 451 mL) and transfusion (1663 ± 398 mL vs 1649 ± 382 mL), average exposure of drugs (72 ± 13 mg vs 75 ± 15 mg for propofol, 116 ± 28 µg vs 109 ± 25 µg for sufentanil, and 22 ± 5 vs 23 ± 4 mg for cisatracurium), time to eye opening (4.7 ± 1.5 min vs 4.8 ± 1.4 min), extubation (7.5 ± 2.0 min vs 7.3 ± 2.2 min), and consciousness (8.9 ± 1.8 min vs 9.1 ± 2.1 min) (all P > 0.05). CONCLUSIONS: Sevoflurane-sufentanil combined anesthesia provides hemodynamic stability and rapid recovery from AIS surgery. There is no correlation between the intraoperative wake-up test and postoperative delirium after sevoflurane-sufentanil combined anesthesia.

[Report of 3162 cases of holmium laser enucleation of the prostate and review].

OBJECTIVE: To evaluate the safety, effectiveness, and outcomes of holmium laser enucleation of the prostate (HoLEP) for patients with symptomatic enlarged prostate after 11 years of experience. METHODS: The 3162 evaluable patients treated with holmium laser enucleation of the prostate at our institution between August 2001 and August 2011 were retrospectively analyzed. Study variables included International Prostate Symptom Score, quality of life, maximum urinary flow rate, and incidence of complications. RESULTS: HoLEP were performed successfully completed, not patients which occurs as electric cutting syndrome. The operation time was (60.8 ± 18.4) minutes; average resection of prostate quality was (45.4 ± 24.4) g. The hemoglobin reduce though surgery was (1.81 ± 0.93) g/L; percentage of red blood cell change was 1.24% ± 0.43%, and sodium blood drop was (1.14 ± 0.35) mmol/L. Postoperative patients of hospital stay (3.1 ± 1.1) days, average time of indwelling catheter time was (2.3 ± 0.8) days. Patients were followed up for 6-131 months time, an average of 32.4 months. Postoperative patients with international prostate symptom score progressive declined. The quality of life score was 2.2 ± 1.7, and it less than preoperative (5.7 ± 3.3, t = 2.447, P < 0.01). The time of follow-up droped further, and postoperative comparative differences have statistical significance (t = 2.179, 2.228, 2.306 and 2.365, P < 0.05). The maximum urinary flow rate also improved (P < 0.05). Postoperative complications included bladder neck contracture (4 cases), urinary tract infection (107 cases), urethral stricture (11 cases) and urinary incontinence (11 cases). The 11 patients reoperation. CONCLUSIONS: HoLEP treatment of benign prostatic hyperplasia could achieve the advantages of open surgery the same effect. It had fewer damage, faster recovery, fewer complications, and is a good treatment option.

Synthesis and properties of bisphenol A molecular imprinted particle for selective recognition of BPA from water.

Molecularly imprinted particle for bisphenol A (BPA-MIP) was prepared using the surface molecular imprinting technique with a sol-gel process on the surface of silica nanoparticles. The dosages of diethylenetriaminepentaacetic acid (DTPA) as a functional monomer and teraethyl orthosilicate (TEOS) as a cross-linker were optimized, respectively. The prepared BPA-MIP was characterized by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), Fourier transform infrared spectrometer (FTIR), thermogravimetric analysis (TGA), and a standard Brunauer-Emett-Teller (BET) analysis. Moreover, the proper binding and selective recognition ability were also investigated by a single batch binding experiment. The equilibrium data fitted well to the pseudo-second-order kinetic and the Langmuir model for BPA binding onto BPA-MIP, respectively. The saturate binding capacity of BPA-MIP was found to be 30.26 µmol g(-1), which was three times higher than that of BPA non-molecular imprinted particle (BPA-NIP). The satisfactory results demonstrated that the obtained BPA-MIP showed an appreciable binding specificity toward BPA than similar structural compounds in water phase. The BPA-MIP could serve as an efficient selective material for determining or removing BPA from water environment.

Motorcycle spoke injuries of the heel.

INTRODUCTION: The spoke injuries of the lower extremity seems never stop haunting the surgeons since its first report 62 years ago. A prospective study of motorcycle spoke injuries in the heel was undertaken to study the injury mechanism, the treatment protocols, and the outcomes. PATIENTS AND METHODS: From 2001 to 2010, 89 cases of motorcycle spoke injuries of the heel were examined. The various injury mechanisms were analysed. Flaps and other reconstruction surgeries were used to manage the involved extremity. RESULTS: The mechanisms of the motorcycle spoke injuries of the heel had some unique features. A grading system was developed for the injuries according to the tissues involved. The surgery protocols primarily consisted of flap transfers, Achilles tendon reconstruction, and calcaneus management. CONCLUSIONS: The eradication of the motorcycle spoke injuries is a difficult task, but the treatment outcomes have been greatly improved due to the advancement of surgical techniques.

Ser1369Ala variant in sulfonylurea receptor gene ABCC8 is associated with antidiabetic efficacy of gliclazide in Chinese type 2 diabetic patients.

OBJECTIVE: The purpose of this study was to investigate whether genetic variants could influence the antidiabetic efficacy of gliclazide in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 1,268 type 2 diabetic patients whose diabetes was diagnosed within the past 5 years and who had no recent hypoglycemic treatment were enrolled from 23 hospitals in China. All of the patients were treated with gliclazide for 8 weeks. Fasting and oral glucose tolerance test 2-h plasma glucose, fasting insulin, and A1C were measured at baseline and after 8 weeks of treatment. We used two independent cohorts to test the associations of 25 single nuclear polymorphisms in 11 candidate genes with the antidiabetic efficacy of gliclazide. A general linear regression model was used to test the association with adjustment for important covariates. RESULTS: After 8 weeks of gliclazide therapy, mean fasting plasma glucose (FPG) was reduced from 11.1 mmol/l at baseline to 7.7 mmol/l. In cohort 1, we genotyped all 25 SNPs (n = 661) and found that Ser1369Ala of the ABCC8 gene and rs5210 of the KCNJ11 gene were significantly associated with decreases in FPG (P = 0.002). We further genotyped Ser1369Ala in cohort 2 (n = 607) and confirmed the association identified in cohort 1. In the pooled analysis, compared with subjects with the Ser/Ser genotype, subjects with the Ala/Ala genotype had a 7.7% greater decrease in FPG (P < 0.001), an 11.9% greater decrease in 2-h plasma glucose (P = 0.003), and a 3.5% greater decrease in A1C (P = 0.06) after 8 weeks of treatment with gliclazide. CONCLUSIONS: In two independent cohorts of Chinese type 2 diabetic patients, we found consistent evidence that the Ser1369Ala variant in the ABCC8 gene can influence the antidiabetic efficacy of gliclazide.