[Influential factors of non-motor symptoms prognosis in Parkinson's disease patients undergoing deep brain stimulation].

Objective: To investigate the effects of electrode activated contact location, volume of tissue activated (VTA) and age on non-motor symptoms, such as emotional symptoms and cognitive function, in Parkinson's disease (PD) patients with deep brain stimulation (DBS). Methods: PD patients who underwent DBS of subthalamic nucleus (STN) at the Department of Functional Neurosurgery of Beijing Tiantan Hospital from September 1, 2020 to August 31, 2022 were retrospectively enrolled. The International Parkinson and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination Scales (MMSE) were used at the preoperative, 1-month and 12-month postoperative time points. In this study, patients were divided into middle-aged (age<60 years,n=39) and elderly (age≥60 years,n=62) groups to investigate the effect of age factor on the clinical outcome of surgery. Lead-DBS software was used to convert the patients' electrode reconstruction results into Montreal standard space, and the patients were divided into sensorimotor(n=43) and combined groups(n=53) according to the distribution of activation contact locations in the subzones of the STN. In addition, the patients were divided into a cognitive improvement group(n=57)and a cognitive deterioration group(n=44) based on the results of MoCA at 12 months. The positional information of the electrode activation contacts was collected and the VTA was calculated to analyze the effects on electrode activation electroshock location and activated tissue volume on patients' non-motor symptoms. Results: A total of 101 patients with PD were enrolled, including 46 males and 55 females, aged (62.6±8.4) years. Middle-aged patients had significantly higher MoCA scores, delayed recall scores, attention scores, and naming scores than older patients at 12 months postoperatively (all P<0.05). At 12-month follow-up, the improvement rate of MoCA score, HAMA score and HAMD score were -1.77%±20.36%, 39.65%±42.91% and 36.23%±45.45% respectively in sensorimotor group. At 12-month follow-up, the improvement rate of MoCA score, HAMA score and HAMD score was 11.69%±22.24%, 16.62%±68.10% and 2.30%±95.04% respectively in the combined group, and the difference between the two groups was statistically significant (MoCA: P=0.002; HAMA: P=0.040; HAMD: P=0.033) The distribution of VTA in the sensory motor area and marginal area of the left hemisphere STN in patients with improved cognitive function was significantly smaller than that in the deterioration group [(60.53±52.04)mm³vs (84.55±61.00)mm³, P=0.035; (41.81±33.36)mm³vs (59.05±45.46)mm³, P=0.030]. Conclusion: The effect of STN-DBS on emotional symptoms and cognitive function in PD patients is influenced by various factors and is closely related to the patient's age, electrode activation contact location and VTA.

Optimising diffusion-weighted imaging of the thyroid gland using dedicated surface coil.

AIM: To assess the feasibility of applying field-of-view (FOV) optimised and constrained undistorted single-shot (FOCUS) diffusion-weighted imaging (DWI) in the thyroid gland by comparing its image quality with conventional DWI (C-DWI) qualitatively and quantitatively using a dedicated surface coil exclusively designed for the thyroid gland at 3 T magnetic resonance imaging (MRI). MATERIALS AND METHODS: In this prospective study, 32 healthy volunteers who had undergone 3 T the thyroid gland MRI with FOCUS-DWI and C-DWI were enrolled. Two independent reviewers assessed the overall image quality, artefacts, sharpness, and geometric distortion based on a five-point Likert scale. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) were quantified for both sequences. Interobserver agreement, qualitative scores, and quantitative parameters were compared between two sequences. RESULTS: Agreement between the two readers was good for FOCUS-DWI (κ = 0.714-0.778) and moderate to good for C-DWI (κ = 0.525-0.672) in qualitative image quality assessment. Qualitatively, image quality (overall image quality, artefacts, sharpness, and geometric distortion) was significantly better in FOCUS-DWI than that in the C-DWI (all p<0.05); however, quantitatively, FOCUS-DWI had significantly lower SNRs (p<0.001) and CNRs (p=0.012) compared with C-DWI. The ADC value on FOCUS-DWI was significantly higher than that on C-DWI (p<0.001). CONCLUSION: FOCUS-DWI depicted the thyroid gland with significantly better image quality qualitatively and less ghost artefacts, but had significantly lower SNR and CNR quantitatively, compared with C-DWI, suggesting that both DWI sequences have advantages and could be chosen for different purposes.

[Clinical analysis of 34 cases of acute fatty liver of pregnancy].

Objective: To analyze the characteristics, diagnosis and prognosis of acute fatty liver of pregnancy (AFLP), and to guide the management of AFLP patients. Methods: The clinical data of 34 AFLP patients admitted to Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 2009 to December 2019 were retrospectively analyzed. The general situation, diagnostic characteristics, treatment and maternal and neonatal prognosis of the AFLP patients were collected and analyzed. Results: The incidence of AFLP in our hospital was 0.022% (34/152 383). The age of onset was (30.6±4.9) years old, and the gestational age was (35.3±2.4) weeks. Most of the first symptom was gastrointestinal symptoms of unknown cause in the third trimester of pregnancy (53%, 18/34), accompanied by different degrees of elevated liver enzymes. Cesarean section was performed in 97% (33/34) of patients for termination of pregnancy. Only one pregnant woman was diagnosed prenatal and delivered vaginally, and the prognosis of both mother and infant was good. Five cases were transferred to intensive care unit, including 2 cases of acute renal failure, 1 case of gastrointestinal bleeding and 2 cases of disseminated intravascular coagulation. There was no maternal death. Severe asphyxia occurred in 2 neonates. Conclusions: Attention should be paid to the digestive tract symptoms during the third trimester of pregnancy and the diversity of clinical manifestations of AFLP for early detection. Once AFLP is diagnosed, pregnancy should be terminated as soon as possible to improve maternal and infant outcomes.

[Effect of induced labor on delivery outcome of pregnant women undergoing vaginal trial of labor after cesarean section].

Objective: To explore the effect of induced labor on delivery outcome of pregnant women undergoing vaginal trial of labor after cesarean section. Methods: Totally, 173 pregnant women undergoing vaginal trial of labor after cesarean from April 1st, 2016 to October 31st, 2017 were involved. According to whether or not induced labor, pregnant women were divided into induced labor group (n=47) and natural labor group (n=126). The two groups of the general situation, the situation of delivery and delivery outcome were compared. Further more, the induced labor group were divided into cesarean section patients (n=20) and vaginal delivery patients (n=27) based on pregnancy outcomes, induction situation and delivery situation were analyzed. Results: (1) The gestational weeks was 39.2±1.1 in induced labor group, 38.7±1.0 in natural labor group. The 1-minute Apgar score was 9.98±0.15 in induced labor group, and 9.87±0.60 in natural labor group. The neonatal weight was (3 497±426) g in induced labor group, and (3 288±350) g in natural labor group. The thickness of lower uterine segment at 36-39 weeks of pregnancy was (2.4±0.6) mm in induced labor group, (2.1±0.6) mm in natural labor group. There were obviously differences in the gestational week, the 1-minute Apgar score, the neonatal weight and the thickness of lower uterine segment at 36-39 weeks of pregnancy between the two groups (all P<0.05). There were no significant differences in 5-minute Apgar score, the interval between previous cesarean delivery, postpartum hemorrhage, fetal distress, and intrauterine infection, secondary uterine inertia, placental abruption and uterine ruption between the two groups (all P>0.05). (2) In induced labor group, the cervical score of cesarean section patients was 3.8±1.7, while the cervical score of vaginal delivery patients was 5.2±1.7. The induced labor days of cesarean section patients was (1.6±0.9) days, while the induced labor days of vaginal delivery patients was (1.2±0.4) days. There were obviously differences in the cervical score and the induced labor days among the two subgroup patients (all P<0.05). There were no significiant differences in Apgar score, neonatal weight, the thickness of lower uterine segment at 36-39 gestational weeks and the interval times of previous cesarean delivery between the two subgroup patients (P>0.05). Conclusion: Induction of labor does not reduce neonatal Apgar score, and does not increase the incidence of postpartum complications, and eliminats the increase of cesarean section rate caused by increased gestational weeks and fetal enlargement, and increases the vaginal delivery rate of pregnant women undergoing vaginal trail of labor after cesarean section.

Chronic Obstructive Pulmonary Disease Risk and Smoking Cessation Changes Induced by CHRNA5-A3 and CHRNB3-A6 Variation in a Chinese Male Population.

Most studies in the field of CHRNA5-A3 and CHRNB3-A6 have only focused on lung cancer risk; however, the associations with chronic obstructive pulmonary disease (COPD) risk and smoking cessation is less understood, particularly in the Chinese male population. In this study, samples from 823 male patients with COPD (non smokers: 416; still smoking: 407) and 435 smoking male healthy control subjects were performed with DNA extraction and single nucleotide polymorphism (SNP) genotyping. We studied three SNPS in two genes, namely rs667282 and rs3743073 in CHRNA5-A3 and rs4950 in CHRNB3-A6, and their distributions in the three groups are not statistically different (p >0.05). We grouped COPD patients according to whether they had successfully quit smoking, the CT genotype of rs667282 demonstrated association with an increased rate of successful smoking cessation compared with the TT genotype [adjusted odds ratio (OR) = 0.54, 95% confidence interval (95% CI) = 0.37-0.7, p <0.001); rs4950 AG genotypes were distinctly associated with increased rates of successful smoking cessation (adjusted OR = 0.55, 95% CI = 0.40-0.76, p <0.001). The effect is significant under the assumption of an over dominant mode of inheritance (adjusted OR = 0.58, 95% CI = 0.43 to 0.79, p <0.001). No significant difference in rs3743073 was found (p >0.05). Our findings confirmed the hypothesis that CHRNA5-A3 and CHRNB3-A6 variation are not associated with the risk of COPD. We found CHRNA5-A3 and CHRNB3-A6 were significantly associated with successful smoking cessation in smoking COPD patients.

[A 3.0 T MRI study on the alterations of the volume and morphology of fifteen subcortical nucleus in patients with early post-stroke depression].

Objective: To investigate the alterations of the volumes and 3D shapes of fifteen subcortical nucleus in patients with post-stroke depression (PSD) and to explore the pathogenesis regularity and mechanism of early PSD. Methods: From 2015 to 2017, a total of 28 patients with PSD and 18 stroke patients without depression (PSND), 13 patients with depression (De) and 11 cases of healthy volunteers (NC) were enrolled to perform 3.0 T high resolution MRI.Computer automatic segmentation and vertex analysis were used to segment and measure the volume of bilateral nucleus accumbens, caudate nucleus, putamen, globus pallidus, thalamus, hippocampus, mygdale and brainstem. Results: The volume of bilateral nucleus accumbens and bilateral thalamus, left pallidum were different among groups with statistical difference (P<0.05). The nucleus volume of the PSD group was (415±128) mm(3) (L-Nac)/(303±90) mm(3) (R-Nac), (7 590±867) mm(3) (L-Th)/(7 459±905) mm(3) (R-Th), (1 675±328) mm(3) (L-Pa), which was smaller than that of PSND group (433±100) mm(3) /(307±88) mm(3), (7 999±961) mm(3) /(7 753± 955) mm(3), (1 790±286) mm(3) and other groups.The nuclei with significantly statistical differences between inter-group were found in following: between PSD group and NC group, right accumbens and bilateral thalamus (P<0.01); between PSD group and De group, right accumbens and right thalamus (P<0.001), left accumbens, left pallidum and left thalamus (P<0.01); between PSND group and NC group, right accumbens (P<0.05); between PSND group and De group, right accumbens (P<0.001), left accumbens and right thalamus (P<0.05). Significant differences in morphology changes of nuclei (P<0.05) by F test mainly located on the top and tail of right accumbens, the anterior and middle body of right caudate nucleus, the most part of bilateral thalamus, the ventromedial body of bilateral hippocampus, the anterior and body of left caudate nucleus, especially in left thalamus. Conclusion: PSD has abnormal volume and morphological structure of subcortical nuclei, which supports the role of subcortical structures changes in the pathophysiology and pathogenesis of early PSD.

Association between ADAM metallopeptidase domain 33 gene polymorphism and risk of childhood asthma: a meta-analysis.

This study aimed to investigate the association between ADAM metallopeptidase domain 33 (ADAM33) gene polymorphisms and the risk of childhood asthma. The relevant studies about the relationship between ADAM33 gene polymorphisms and childhood asthma were searched from electronic databases and the deadline of retrieval was May 2016. The single nucleotide polymorphisms (SNPs) of ADAM33 (rs511898, rs2280092, rs3918396, rs528557, rs2853209, rs44707, rs2280091 and rs2280089) were analyzed based on several models including the allele, codominant, recessive and dominant models. The results showed that the ADAM33 rs2280091 polymorphism in all four genetic models was associated with an increased risk of childhood asthma. Positive associations were also found between the polymorphisms rs2280090, rs2787094, rs44707 and rs528557 and childhood asthma in some genetic models. This meta-analysis suggested that ADAM33 polymorphisms rs2280091, rs2280090, rs2787094, rs44707 and rs528557 were significantly associated with a high risk of childhood asthma.

Nickel oxide nanoparticles induced pulmonary fibrosis via TGF- ß1 activation in rats.

Nano nickel oxide (NiO), widely used in industry, has recently been discovered to have pulmonary toxicity. However, no subchronic exposure studies about nano NiO-induced pulmonary fibrosis have been reported. The objective of this study was to investigate pulmonary fibrosis induced by nano NiO and its potential mechanism in rats. Male Wistar rats ( n = 40, 200-240 g) were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg/kg), and micro NiO group (0.024 mg/kg). All rats were killed to collect lung tissue after intratracheal instillation of NiO particles twice a week for 6 weeks. To identify pulmonary fibrosis, Masson trichrome staining, hydroxyproline content, and collagen protein expression were performed. The results showed widespread lung fibrotic injury in histological examination and increased content of hydroxyproline, collagen types I and III in rat lung tissue exposed to nano NiO. To explore the potential pulmonary fibrosis mechanism, transforming growth factor beta 1 (TGF- ß1) content was measured by enzyme-linked immunosorbent assay, and the messenger RNA expression of key indicators was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The TGF- ß1 content was increased in nano NiO exposure groups, as well as the upregulated gene expression of TGF- ß1, Smad2, Smad4, matrix metalloproteinase, and tissue inhibitor of metalloproteinase. The findings indicated that nano NiO could induce pulmonary fibrosis, which may be related to TGF- ß1 activation.

[Effect of magnesium sulfate on MMP-9 and AQP-9 protein in placenta of patients with hypertensive disorders complicating pregnancy].

OBJECTIVE: To investigate the protein content and protein expression of MMP-9 and AQP-9 in the placenta of patients with hypertensive disorders complicating pregnancy.And to investigate the mechanism of magnesium sulfate in the treatment of hypertensive disorders complicating pregnancy. METHODS: The patients with hypertensive disorders complicating pregnancy were divided into treatment group (n=51) and untreated group (n=45), and 20 cases of normal pregnant women were selected as the control group. The three groups were taken from the placenta after delivery. ELISA and immunohistochemistry method were used to detect the protein content and protein expression of AQP-9 and MMP-9 in placenta of each group. RESULTS: The protein contents and protein expression of MMP-9 in placenta tissues of treatment group were 5.89±0.52 and 125.2±0.5; AQP-9's were 4.3±0.5 and 110±4. The protein contents and protein expression of MMP-9 in placenta tissues of untreated group were 1.85±0.26 and 148.6±5.2; AQP-9's were 9.4±0.8 and 92±3. The protein contents and protein expression of MMP-9 in placenta tissues of control group were 6.13±0.84 and 120.7±4.4; AQP-9's were 4.1±0.7 and 114±3. Compared with the control group, the protein contents and protein expression of MMP-9 in placenta tissues of untreated group were significantly decreased, and that of AQP-9 was significantly increased, both with the statistically significant difference (P<0.01). The protein contents and protein expression of MMP-9 protein in placenta tissues of the treatment group were slightly lower, AQP-9 was intensity increased (both P>0.05). CONCLUSION: Magnesium sulfate can increase the level of MMP-9 protein and down regulate the protein level of AQP-9, which may be one of the effective mechanisms of the treatment of hypertensive disorders complicating pregnancy.

Anxiety-like behavior and dysregulation of miR-34a in triple transgenic mice of Alzheimer's disease.

OBJECTIVE: MicroRNAs (miRNAs) play an important role in the development of the brain and also implicated in the pathogenesis of neurological diseases such as Alzheimer's disease (AD). Recent studies implied that dysregulation of miRNAs is involved in neuropsychiatric disorders such as anxiety disorder in AD. MATERIALS AND METHODS: In this study, behavioral experiments such as open field test, elevated plus maze test and light-dark box test were performed to evaluate anxiety-like behaviors in a triple transgenic mouse model of AD (3xTg-AD mice), and Q-PCR was used to measure the change of miR-34a expression. RESULTS: Behavioral tests revealed anxiety-like behaviors in 3xTg-AD mice. Q-PCR assay showed significantly elevated expression of miR-34a in the hippocampus of 3xTg-AD mice compared with the age- and gender-matched wild-type mice. Western-blot analysis showed that the expression of metabotropic glutamate receptor 7 (GRM7) but not fibroblast growth factor-2 (FGF2), two anxiety disorder-related target genes of miR-34a, was significantly decreased in hippocampus of 3xTg-AD mice compared with the wild-type mice. CONCLUSIONS: We concluded that anxiety-like behavior occurred in 3xTg-AD mice with an involvement of miR-34a/GRM7.

[Indications and pregnancy outcomes of intrapartum cesarean section after the new partogram applied].

OBJECTIVE: To study the changes of intrapartum cesarean rate, cesarean indications and pregnancy outcomes after the new partogram applied. METHODS: Totally 3 290 pregnant women trying to vaginal delivery which were managed according to the new partogram in Beijing Obstetrics and Gynecology Hospital, Capital Medical University from August to October in 2014(new partogram group)were involved; 2 987 pregnancy women trying to vaginal delivery from May to July in 2014 which were managed according to the old partogram(old partogram group)were involved as control. The intrapartum cesarean rate, cesarean indications and the pregnancy outcomes between the two groups were analyzed. RESULTS: The rate of intrapartum cesarean delivery was 8.50%(254/2 987)in old partogram group, and was significantly higher than that in new partogram group(6.2%, 204/3 290; P<0.01). Cesarean indications in old partogram group included 18 labor protraction(7.1%, 18/254), 82 labor arrest(32.3%, 82/254), 44 relative cephalopelvic disproportion(17.3%, 44/254), 80 fetal distress(31.5%, 80/254), 23 intrauterine infection(9.1%, 23/254)and 7 cesarean delivery on maternal request(CDMR; 2.8%, 7/254). Cesarean indications in new partogram group included 33 labor arrest(16.2%, 33/204), 71 relative cephalopelvic disproportion(34.8%, 71/204), 73 fetal distress(35.8%, 73/204)and 22 intrauterine infection(10.8%, 22/204), 5 CDMR(2.5%, 5/204). There were no significant differences in incidence of asphyxia neonatorum and puerperal morbidity(P> 0.05), but the incidence of postpartum hemorrhage in new partogram group was higher than the old partogram group[6.9%(14/204)versus 1.6%(4/254), P<0.05]. CONCLUSION: After the new partogram applied, the rate of intrapartum cesarean delivery is significantly decreased, but the incidence of postpartum hemorrhage is increased.

[Mode of delivery and perinatal outcomes in women with premature rupture of membranes at term].

OBJECTIVE: Comparative study of delivery mode and perinatal outcomes in women with premature rupture of membranes at term compared to those with intact membranes. METHODS: A cross sectional survey of all deliveries in 39 hospitals in 3 geographic regions of mainland China from January 1 to December 31, 2011 was carried out to investigate the demographic data and delivery outcomes. RESULTS: In our analysis of 103 124 pregnancies, 14 073(13.6%) were complicated by premature rupture of membranes. Compared to those with intact membrane, the risks of postpartum hemorrhage, maternal complications and neonatal complications were increased significantly for women with premature rupture of membranes at term, especially the prevalence of neonatal respiratory distress syndrome(NRDS) and meconium aspiration syndrome. The risk of low Apgar (<7) at 1 minute was decreased for women with premature rupture of membranes at term. CONCLUSION: The adverse perinatal outcomes are slightly higher in women with term premature rupture of membranes than those with intact membrane.

Cloning and sequence analysis of the LOC339524 gene in Sprague-Dawley rats.

We cloned the LOC339524 gene in Sprague-Dawley (SD) rats and analyzed the structure and function of the protein encoded by it. Based on the known human LOC339524 gene sequences, the full-length coding sequence of the LOC339524 gene in SD rats was cloned and amplified by the polymerase chain reaction using the complementary DNA of SD rats as a template. Bioinformatics analysis showed that the length of the cloned LOC339524 gene (GenBank accession No. KM224520) was 831 bp and it encoded a deduced protein of 276 amino acids. Sequence analysis revealed that the coded protein was identical to that produced in humans and its functional domain was located in the 138-236 amino acid fragments, a proline-rich region. Our results suggest that the encoded protein may be a significant regulator of the inflammatory response and may provide sufficient information to justify an in-depth investigation of the role of the LOC339524 gene.

Neutrophil extracellular trap formation is associated with autophagy-related signalling in ANCA-associated vasculitis.

Increasing evidence indicates that aberrant neutrophil extracellular trap (NET) formation could contribute to the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Recent research has provided evidence that a novel type of ANCA autoantibody, anti-lysosomal membrane protein-2 (LAMP-2) antibody, may have a pathogenic role in AAV. We have shown previously that anti-LAMP-2 antibody-stimulated NET formation contains autoantigens and anti-microbial peptides. The current study sought to determine whether LAMP-2, as a novel antigen of ANCA, was present on NETs in AAV patients, the influence of the anti-LAMP-2 antibody on the neutrophil apoptosis rate and the role of autophagy in anti-LAMP-2 antibody-induced NET formation. NET formation was assessed using immunofluorescence microscopy, scanning electron microscopy or live cell imaging. The neutrophil apoptosis rate was analysed using fluorescence activated cell sorting (FACS). Autophagy was detected using LC3B accumulation and transmission electron microscopy. The results showed that enhanced NET formation, which contains LAMP-2, was observed in kidney biopsies and neutrophils from AAV patients. The apoptosis rate decreased significantly in human neutrophils stimulated with anti-LAMP-2 antibody, and this effect was attenuated by the inhibitors of autophagy 3-methyladenine (3MA) and 2-morpholin-4-yl-8-phenylchromen-4-one (LY294002). The anti-LAMP-2 antibody-stimulated NET formation was unaffected by benzyloxycarbonyl-Val- Ala-Asp (OMe)-fluoromethylketone (zVAD-fmk) and necrostatin-1 (Nec-1), which are inhibitors of apoptosis and necrosis, respectively, but was inhibited by 3MA and LY294002. Moreover, the proportion of LC3BI that was converted to LC3BII increased significantly (P=0.0057), and massive vacuolizations that exhibited characteristics typical of autophagy were detected in neutrophils stimulated with anti-LAMP-2 antibody. Our results provide further evidence that autophagy is involved in ANCA-induced NET formation in human neutrophils.

Common polymorphisms in the HIF-1α gene confer susceptibility to digestive cancer: a meta-analysis.

Recent evidence suggests that common functional polymorphisms in the hypoxia inducible factor-1α (HIF-1α) gene may play an important role in the development and progression of digestive cancer, but individually published results are inconclusive. Our meta-analysis is aimed to derive a more precise estimation of the relationships between HIF-1α gene polymorphisms and digestive cancer risk. An extensive literature search for relevant studies was conducted on Pubmed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratios (OR) with 95% confidence interval (CI) were calculated. Eight case-control studies were included with a total of 1276 digestive cancer patients and 3392 healthy controls. Our meta-analysis revealed that the A variant of HIF-1α G1790A polymorphism might be associated with increased risk of colorectal, esophageal, gastric, and liver cancers, especially among Asian populations. However, no statistically significant associations were found between HIF-1α C1772T polymorphism and susceptibility to digestive cancer. No publication bias was detected in this meta-analysis. The current meta-analysis suggests that the HIF-1α G1790A polymorphism may increase the risk of colorectal, esophageal, gastric, and liver cancers, especially among Asian populations.

Melatonin reduced volume of cerebral infarct induced by photothrombosis in wild-type mice, not in Cyclooxygenase-1 gene knockout mice.

Cyclooxygenase (COX) is crucial in inflammation and plays important role in cerebral ischemia. Antiinflammatory effects of melatonin have been verified in previous studies. In this study, cerebral blood flow (CBF) was monitored during operation, infarct volume (IFV) was determined with 5-triphenyltetrazolium chloride (TTC) staining and MR image, and neurological functions were evaluated with turn in an alley and fall pole test in both COX1-gene knockout and wide-type mice with or without melatonin administration 3 days after photothrombosis. CBF reduction, IFV and neurological deficits were not significantly different in COX-1 wild-type and COX-1 knockout mice. Melatonin (15 mg/kg) intraperitoneal injection decreased the CBF reduction, IFV and the latency to turn in an alley in COX-1 wide-type mice, whereas the neuroprotective effect of melatonin was attenuated in COX-1 knockout mice. We concluded that melatonin reduced susceptibility to photothrombotic stroke. COX-1 gene knockout does not alter the susceptibility to cerebral ischemia caused by photothrombosis. COX-1 plays an important role in the pathway of the protection of melatonin.

Effect of tetramethyl pyrazine on L-type calcium channel in rat ventricular myocytes.

To elucidate possible ionic mechanisms of antimyocardial ischemia and antiarrythmia of tetramethyl pyrazine (TP), we studied L-type Ca2+ currents (I(Ca.L)) in adult rat ventricular myocytes using the whole-cell patch-clamp technique. The results showed: (i) under physiological conditions, 0.25 mmol/L TP decreased amplitude of I(Ca.L) to 60.6% and this inhibition was increased with increasing concentration of TP. ID50 was 0.20 mmol/L. (ii) The Ca2+-antagonistic effect of TP was voltage-dependent. A marked negative shift of the steady-state inactivation curve was observed with long (10 s) conditioning prepulses, but not with short (350 ms) ones. (iii) The time course of inhibition during TP treatment was increased with an increase in drug concentration, and recovery from TP-induced inactivation of I(Ca.L) was slower than in control cases. (iv) Tonic block and use-dependent block with TP treatment, which was induced by increasing the frequency of stimulation, occurred. We suggest that TP inhibits the I(Ca.L) mainly by binding to inactivated Ca2+ channels. The high affinity of TP for the inactivated state of I(Ca.L) may play an important role in developing therapies for pathological conditions.

[LC/MS research on the isomers of special melanoma antigen-encoding gene-2 epitope peptide induced by solvent].

To study the influence of different solvent systems on the isomers of melanoma antigen-encoding gene-2(MAGE-2) epitope peptide synthesized by Marrifield's solid synthesis method, MAGE-2(171-179) epitope peptides were pre-treated using ethanol and methanol systems respectively, and then analysed by RP-HPLC/MS, with dimethyl-sulphoxide (DMSO) as control solvent. Results demonstrated that 100% ethanol and 100% methanol solvents could induce the production of isomers of MAGE-2, while 100% DMSO, 50% ethanol and 50% methanol could not. These isomeric peptides could be reversed greatly if treated with trifluoroacetic acid (TFA). The results also showed that the analysis would be distorted and the yield of peptides would decrease dramatically if the peptides were pre-treated with high concentrations of ethanol and methanol before RP-HPLC analysis and preparation. Thus it is suggested that it might be better to decrease the concentration of organic phase in the solvent system for the resolvable hydrophobic peptides, acidified ethanol and methanol might also be better for the highly hydrophobic peptides, and DMSO would be a good solvent for hydrophobic peptides analysis provided that it would not influence the resolving power of chromatography.