A New δ-Globin Gene Variant: Hb A2-Yulin [δ46(CD5)Gly→Arg,HBD: C.139G > A].

We report a new δ-chain hemoglobin (Hb) variant observed in a 5-year-old female living in Yulin, Guangxi, China. Capillary electrophoresis revealed splitting of the Hb A2 peak into two fractions (Hb A2 and Hb A2 variant), and the Hb A2 variant was also detected by high-performance liquid chromatography. However, it could not be detected using matrix-assisted laser desorption lonization-time of flight mass spectrometry. CD41-42 (-TCTT) heterozygosity was observed on the HBB gene by PCR and reverse dot-blot hybridization. Sanger sequencing showed a new transition (G > A) at codon 46 of the HBD gene, resulting in glycine changing to arginine. Based on the patient's place of residence, the new variant was named Hb A2-Yulin [δ46(CD5)Gly→Arg,HBD:c.139G > A].

Hb Hebei [α20 (B1) His→Leu; HBA2:C.62A > T]: A Novel Hemoglobin Variant Found during Measurement of Glycated Hemoglobin.

We report a novel hemoglobin (Hb) variant found in a 34-year-old Chinese male during a routine measurement of glycated hemoglobin. The variant resulted in a P3 peak of 27.5% of the total Hb on high performance liquid chromatography (HPLC) with a glycated hemoglobin mode. However, no abnormal Hb peaks were observed in capillary electrophoresis (CE) with 3.1% Hb A2 and 96.9% Hb A. The amino acid substitution was determined by Sanger sequencing as α20 (B1) His→Leu; the corresponding DNA mutation was identified as CAC > CTC at the first position of codon 20 of the α-chain. This is the first description of the mutation, and we have named it Hb Hebei for the region of origin of the proband.

Misdiagnosis of ß-Thalassemia Major Due to Chinese Gγ+(Aγδß)0-Thalassemia Combined with ß0-Thalassemia.

δß-thalassemia is a rare type of thalassemia characterized by increased Hb F levels, including mainly Chinese Gγ(Aγδß)0-thalassemia, Yunnanese Gγ(Aγδß)0-thalassemia, Cantonese Gγ(Aγδß)0-thalassemia in China. Due to the low rate of δß-thalassemia carriers, there are few reports of δß-thalassemia combined with ß-thalassemia causing ß-thalassemia major. Herein, we described the combination of Chinese Gγ(Aγδß)0-thalassemia and ß-thalassemia leading to ß-thalassemia major in a Chinese patient. Hemoglobin analysis was performed by capillary electrophoresis (CE). Routine genetic analysis was carried out by gap-polymerase chain reaction (Gap-PCR) and PCR and reverse dot blot (PCR-RDB). Multiple ligation-dependent probe amplification (MLPA) was used to detect the large deletion, and Gap-PCR confirmed the deletion. A CE result showed an elevated Hb F level of 98.7% and 11.7% in the proband and her mother, but the proband was diagnosed with ßCD17M/ßCD17M using routine genetic analysis. However, her father was heterozygous for CD17 in ß-globin, and her mother was detected as SEA heterozygous. The further analysis presented that the proband had actually missed the diagnosis of Chinese Gγ(Aγδß)0-thalassemia by MLPA and PCR-RDB. Finally, the genotype of the proband was corrected from ßCD17M/ßCD17M to ßCD17M/ßGγ(Aγδß)0. This is the first report of Chinese Gγ(Aγδß)0-thalassemia combined with ß-thalassemia resulting in ß-thalassemia major in China. Screening for δß-thalassemia by Hb analysis could be an effective method.

Hb Huadu [α124(H7)Ser→Thr (TCC>ACC), HBA2: c.373T>A]: A Novel Variant of the α-Globin Gene.

Here, we report a novel α chain hemoglobin (Hb) variant found during routine thalassemia screening. This Hb variant can be detected by capillary electrophoresis (CE) but cannot be recognized by high performance liquid chromatography (HPLC). Sanger sequencing revealed a heterozygous missense substitution at nucleotide 373 on the HBA2 gene, which results in the replacement of serine by threonine at codon 124 [α124(H7)Ser→Thr (TCC>ACC), HBA2: c.373T>A]. It is the first report of this variant, named Hb Huadu for the birthplace of the proband. In addition, the proband coinherited the heterozygous codons 41/42 (-TTCT) (HBB: c126_129delCTTT) on the ß-globin gene.

The Combined Analysis of Transcriptome and Antioxidant Enzymes Revealed the Mechanism of EBL and ZnO NPs Enhancing Styrax tonkinensis Seed Abiotic Stress Resistance.

As global climate change worsens, trees will have difficulties adapting to abiotic pressures, particularly in the field, where environmental characteristics are difficult to control. A prospective commercial and ornamental tree species, Styrax tonkinensis, has its seed oil output and quality reduced as a result, which lowers the economic benefits. This necessitates growers to implement efficient strategies to increase the seeds of woody biofuel species' tolerance to abiotic stress. Numerous studies have shown that ZnO nanoparticles (NPs), a new material, and BRs assist plants to increase their resilience to abiotic stress and subsequently adapt to it. However, there have not been many investigations into S. tonkinensis seed resistance. In this study, we examined the changes in antioxidant enzyme activities and transcriptomic results of S. tonkinensis seeds throughout the seed development period to investigate the effects of 24-epibrassinolide (EBL), one of the BRs, and ZnO NPs treatments alone or together on the stress resistance of S. tonkinensis seeds. On 70, 100, and 130 days after flowering (DAF), spraying EBL or ZnO NPs increased the activity of antioxidant enzymes (POD, SOD, and CAT) in S. tonkinensis seeds. Moreover, when the EBL and ZnO NPs were sprayed together, the activities of antioxidant enzymes were the strongest, which suggests that the positive effects of the two can be superimposed. On 70 and 100 DAF, the EBL and ZnO NPs treatments improved seed stress resistance, mostly through complex plant hormone crosstalk signaling, which includes IAA, JA, BR, and ABA signaling. Additionally, ABA played an essential role in hormone crosstalk, while, on 130 DAF, due to the physiological characteristics of seeds themselves in the late stage of maturity, the improvement in seed stress resistance by EBL and ZnO NPs was related to protein synthesis, especially late embryogenesis-abundant protein (LEA), and other nutrient storage in seeds. Spraying EBL and ZnO NPs during the seed growth of S. tonkinensis could significantly increase seed stress resistance. Our findings provide fresh perspectives on how cultural practices can increase abiotic stress tolerance in woody seedlings.

Association of ATM and BMI-1 genetic variation with breast cancer risk in Han Chinese.

We tested the hypothesis that genetic variation in ATM and BMI-1 genes can alter the risk of breast cancer through genotyping 6 variants among 524 breast cancer cases and 518 cancer-free controls of Han nationality. This was an observational, hospital-based, case-control association study. Analyses of single variant, linkage, haplotype, interaction and nomogram were performed. Risk was expressed as odds ratio (OR) and 95% confidence interval (CI). All studied variants were in the Hardy-Weinberg equilibrium and were not linked. The mutant allele frequencies of rs1890637, rs3092856 and rs1801516 in ATM gene were significantly higher in cases than in controls (P = .005, <.001 and .001, respectively). Two variants, rs1042059 and rs201024480, in BMI-1 gene were low penetrant, with no detectable significance. After adjustment, rs189037 and rs1801516 were significantly associated with breast cancer under the additive model (OR: 1.37 and 1.52, 95% CI: 1.10-1.71 and 1.14-2.04, P: .005 and .005, respectively). In haplotype analysis, haplotypes A-C-G-G (in order of rs189037, rs3092856, rs1801516 and rs373759) and A-C-A-A in ATM gene were significantly associated with 1.98-fold and 6.04-fold increased risk of breast cancer (95% CI: 1.36-2.90 and 1.65-22.08, respectively). Nomogram analysis estimated that the cumulative proportion of 3 significant variants in ATM gene was about 12.5%. Our findings collectively indicated that ATM gene was a candidate gene in susceptibility to breast cancer in Han Chinese.

Analysis of Renal Artery Stenosis in Patients with Heart Failure: A RASHEF Study.

BACKGROUND: Previous data are controversial about the association of renal artery stenosis (RAS) with clinical outcome in patients with heart failure. Definition of RAS in previous studies might not be appropriate. By definition of RAS with renal duplex sonography, we investigated the association of RAS with clinical outcome in patients with heart failure. METHODS: In this retrospective study, we identified 164 patients with heart failure (New York Heart Association classification ≥II; left ventricular ejection fraction <50%) who had received renal duplex sonography during hospital stay. RAS was defined as renal-aortic ratio ≥3.5 or a peak systolic velocity ≥200 cm/s (or both), or occlusion of the renal artery. Categorical data of patients were compared using the Chi-square test or Fisher's exact test. Cox proportional hazards regression modeling technique was used to investigate the prognostic significance of possible predictors. RESULTS: Finally, 143 patients were enrolled. Median follow-up time was 32 months (1-53 months). Twenty-two patients were diagnosed as RAS by renal duplex sonography, including 13 unilateral RAS (3 left RAS, 10 right RAS) and 9 bilateral RAS. There were more all-cause mortality and cardiovascular death in patients with RAS than patients without RAS. By multivariate analysis, RAS was a significant predictor for all-cause death and cardiovascular death (hazard ratio [HR] = 4.155, 95% confidence interval [CI]: 1.546-11.164, P = 0.005; and HR = 3.483, 95% CI: 1.200-10.104, P = 0.022, respectively). As for composite endpoint events, including death, nonfatal myocardial infarction, ischemic stroke or intracranial hemorrhage, rehospitalization for cardiac failure, and renal replacement therapy, only angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker was significant predictor. RAS was not a significant predictor for composite endpoint events. CONCLUSIONS: Our data suggested that RAS is associated with a poorer clinical outcome in patients with heart failure.

Genetically-reduced serum ACE activity might be a causal risk factor for obstructive sleep apnea syndrome: A meta-analysis.

We meta-analytically summarized the associations of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with ACE activity and obstructive sleep apnea syndrome (OSAS) to see whether ACE activity is causally associated with OSAS. Literature search and data abstraction were done in duplicate. Sixteen articles including 2060 OSAS patients and 1878 controls were summarized. Overall, no significance was observed for the association of I/D polymorphism with OSAS, whereas carriers of II genotype (weighted mean difference or WMD, 95% confidence interval or CI, P: -11.976, -17.168 to -6.783, <0.001) or I allele (-9.842, -14.766 to -4.918, <0.001) had a lower level of serum ACE activity compared with DD genotype carriers, respectively. In subgroup analyses, carriers of II genotype were 3.806 times more likely to develop OSAS (95% CI, P: 1.865 to 7.765, <0.001) in OSAS patients with hypertension, without heterogeneity. Mendelian randomization analysis indicated there was 37.4% (95% CI: 1.115 to 3.142) and 32.4% (1.106 to 2.845) increased risk of OSAS by a reduction of 1 U/L in ACE activity for the II genotype and I allele carriers versus DD genotype carriers, respectively. There was no observable publication bias. Collectively, genetically-reduced serum ACE activity might be a causal risk factor for OSAS.

[Determination of Nucleosides and Nucleobases in Natural, Cultured and Tissue Culture Anoectochilus roxburghii Using LC-MS].

OBJECTIVE: To establish a method for simultaneous determination of nucleosides and nucleobases in natural, cultured and tissue culture Anoectochilus roxburghii by high performance liquid chromatography-electrospray ionization/ion trap mass spectrometry (HPLC-ESI/MS). METHODS: The separation was performed on a Welch Ultimate XB-C18 column (250 mm x 4.6 mm,5 µm). 20 mmol/L ammonium acetate solution and methanol were adopted as the mobile phase with gradient elution. The flow rate was 1.0 mL/min. The injection volume was 20 µL. The column temperature and UV wavelength were set at 30 degrees C and 260 nm, respectively. RESULTS: Cytosine, uracil, cytidine, uridine, hypoxanthine, adenine, inosine, guanosine,fl-thymidine and adenosine were identified in natural, cultured and tissue culture Anoectochilus roxburghii. The total content of nucleosides and nucleotides in Anoectochilus roxburghii were 1.6639, 1.8568 and 2.2013 mg/g,respectively. CONCLUSION: The contents of nucleosides and nucleobases in herb are affected by its growth pattern. The total content of nucleosides and nucleotides was tissue culture herb > cultured herb > natural herb. This investigation would provide the theoretic basis for quality standards and applications of Anoectochilus roxburghii in clinical research.

rAd-p53 enhances the sensitivity of human gastric cancer cells to chemotherapy.

AIM: To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy. METHODS: Three gastric cancer cell lines with distinct levels of differentiation were treated with various doses of rAd-p53 alone, oxaliplatin (OXA) alone, or a combination of both. Cell growth was assessed with an 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide assay and the expression levels of p53, Bax and Bcl-2 were determined by immunohistochemistry. The presence of apoptosis and the expression of caspase-3 were determined using flow cytometry. RESULTS: Treatment with rAd-p53 or OXA alone inhibited gastric cancer cell growth in a time- and dose-dependent manner; moreover, significant synergistic effects were observed when these treatments were combined. Immunohistochemical analysis demonstrated that treatment with rAd-p53 alone, OXA alone or combined treatment led to decreased Bcl-2 expression and increased Bax expression in gastric cancer cells. Furthermore, flow cytometry showed that rAd-p53 alone, OXA alone or combination treatment induced apoptosis of gastric cancer cells, which was accompanied by increased expression of caspase-3. CONCLUSION: rAd-p53 enhances the sensitivity of gastric cancer cells to chemotherapy by promoting apoptosis. Thus, our results suggest that p53 gene therapy combined with chemotherapy represents a novel avenue for gastric cancer treatment.

Effect of transcutaneous electrical acupoint stimulation on nausea and vomiting induced by patient controlled intravenous analgesia with tramadol.

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on nausea and vomiting (N&V) induced by patient controlled intravenous analgesia (PCIA) with Tramadol. METHODS: Sixty patients who were ready to receive scheduled operation for tumor in the head-neck region and post-operation PCIA, aged 39-65 years, with the physique grades I-II of ASA, were randomized into two groups, A and B, 30 in each group. The pre-operation medication, induction of analgesia and continuous anesthesia used in the two groups were the same. TEAS on bilateral Hegu (LI4) and Neiguan (PC6) points was intermittently applied to the patients in group A starting from 30 min before analgesia induction to 24 h after operation, and the incidence and score of nausea and vomiting, antiemetic used, visual analogue scores (VAS), and PCIA pressing times in 4 time segments (0-4, 4-8, 8-12 and 12-24 h after the operation was finished) were determined. The same management was applied to patients in Group B, with sham TEAS for control. RESULTS: The incidence and degree of N&V, as well as the number of patients who needed remedial antiemetic in Group A were less than those in Group B. The VAS score and PCIA pressing time were lower in Group A than those in Group B in the corresponding time segments respectively. CONCLUSION: TEAS could prevent N&V induced by PCIA with Tramadol.