[Incidence of common gene mutations in early-onset colorectal cancer and the association with cancer survival: a meta-analysis].

Objective: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally; however, the molecular characteristics and prognosis of sporadic EOCRC are unclear. In this systematic review and meta-analysis, we aimed to investigate the incidence of gene mutations and their association with cancer survival in sporadic EOCRC, focusing on six common gene mutations (TP53, BRAF, KRAS, NRAS, PTEN, and APC). Methods: Ovid Embase and Ovid Medline electronic databases were searched for studies involving patients with sporadic EOCRC (i.e., diagnosed with colorectal cancer before the age of 50 years and with no evidence of hereditary syndromes predisposing to colorectal cancer). The included articles were evaluated using quality assessment tools. Meta-analysis was performed using random-effects and fixed-effects models. Cochran's Q statistic and the I2 index were used to assess heterogeneity. The incidence of the six common gene mutations listed above in sporadic EOCRC and their association with cancer survival were evaluated. Results: (1) Incidence of specific gene mutations in sporadic EOCRC. A total of 34 articles were included in this meta-analysis. The incidence of APC gene mutation was 36% (from 13 articles, 95%CI: 19%-55%, P=0.043); of KRAS gene mutation 30% (from 26 articles, 95%CI: 24%-35%, P=0.190); of BRAF gene mutation 7% (from 18 articles, 95%CI: 5%-11%, P=0.422); of NRAS gene mutation 4% (from five articles, 95%CI: 3%-5%, P=0.586); of PTEN gene mutation 6% (from six articles, 95%CI: 4%-10%, P=0.968); and of TP53 gene mutation 59% (from 13 articles, 95%CI: 49%-68%, P=0.164). (2) Association between gene mutations and survival in sporadic EOCRC. A total of six articles were included in this meta-analysis. Compared with wild-type BRAF, mutant BRAF was significantly associated with increased overall mortality risk in patients with EOCRC (pooled HR=2.85, 95%CI: 1.45-5.60, P=0.002). Subgroup analysis showed that the incidence of BRAF gene mutation was higher in Eastern than in Western countries, whereas the incidence of TP53, KRAS, NRAS, and APC gene mutations was lower. There was no significant difference in the incidence of PTEN gene mutation between different regions. Conclusion: Compared with colorectal cancer occurring in the general population, the incidence of APC and KRAS mutations is lower in EOCRC, whereas the incidence of TP53 mutation remains consistent. BRAF mutation is associated with increased overall mortality risk in patients with EOCRC.

[Epidemiological characteristics of early-onset colorectal cancer: a prospective cohort study from a single center].

Objective: To explore the differences in distribution of colorectal cancer-related risk factors between patients with early-onset colorectal cancer (EOCRC) and those with late-onset colorectal cancer (LOCRC) in a Chinese cohort, and to provide reference and guidance for the prevention, diagnosis, and treatment of EOCRC. Methods: Using data from the National Colorectal Cancer Cohort study cohort, 5377 patients with newly diagnosed colorectal cancer (CRC) attending the Department of Colorectal Surgery and Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2018 to February 2023 were included in the study cohort. Questionnaires capturing epidemiological features, including lifestyle and dietary habits, were administered. The patients were divided into two groups, the cut-off age being 50 years. Those aged ≥50 years were defined as having LOCRC and those aged <50 years as having EOCRC. Wilcoxon (continuous variates) or χ2 tests (categorical variates) were performed to compare differences in epidemiological features. Results: A total of 3799 people who had completed the questionnaire were included in this study, 491 of whom had EOCRC and 3308 LOCRC. The response rate to the questionnaire was 70.7%. The median ages of patients in the EOCRC and LOCRC groups were 43 and 66 years, respectively. There was a higher proportion of female patients (48.5% [253/491] vs. 35.8% [1184/3308], χ2=28.8, P<0.001) in the EOCRC than the LOCRC group. Patients with EOCRC and lower body mass index (medium 22.1 kg/m2 vs. 22.9 kg/m2, W=744 793, P=0.005) and lower proportion of abdominal obesity (87.2% [428/491] vs. 93.8% [3103/3308], χ2=38.3, P<0.001). Patients with EORC significantly less commonly reported a history of hypertension (5.9% [29/491] vs. 41.6% [1375/3308], χ2=231.8, P<0.001), diabetes (1.4% [7/491] vs. 14.4% [476/3308], χ2=63.6, P<0.001) and cardiovascular and cerebrovascular diseases (0.8% [4/491] vs. 7.3% [241/3308], χ2=28.6, P<0.001). However, the proportion of patients with a family history of CRC was significantly higher (P<0.05) in the EOCRC group (10.2% [50/491] vs. 6.9% [227/3 308], χ2=6.5, P=0.010]. In terms of lifestyle, patients with EOCRC had shorter sleep duration (median: 8.0 hours vs. 8.5 hours, W=578 989, P<0.001), and were less likely to participate in physical exercise (29.5% [145/491] vs. 38.7% [1281/3308] χ2=15.0, P<0.001) or engage in physical work (65.2% [320/491] vs. 74.1% [2450/3308], χ2=16.7, P<0.001). Meanwhile, in the EOCRC group a lower percentage of patients were smokers (29.3% [144/491] vs. 42.7% [1411/3308], χ2=46.9,P<0.001) and they smoked less (median 17.6 pack/year vs. 30.0 pack/year,W=55 850,P<0.001). Fewer patients in the EOCRC group habitually drank alcohol (21.0% [103/491] vs. 38.0% [1257/3308], χ2=57.5, P<0.001) or tea (17.5% [86/491] vs. 28.7% [948/3308], χ2=26.2, P<0.001) than in the LOCRC group. Compared with the LOCRC group, patients with EOCRC had a higher frequency of intake of fresh meat, fresh fruit, eggs, and dairy products and a lower frequency of intake of preserved meat and pickled vegetables; these differences are statistically significant (all P<0.05). There was no statistically significant difference in consumption of fresh vegetables or a high-sugar diet between the two groups (both P>0.05). Conclusions: This study highlights disparities in adverse lifestyle and dietary habits between patients in China with EOCRC versus LOCRC.

[Updates of colonoscopy surveillance guidelines after screening and polypectomy, and related research progress].

With the widespread application of colorectal cancer screening, the surveillance and management of the increasing number of screened population has become a pivotal aspect in preventing and controlling colorectal cancer. In recent years, researches have been conducted on the risk of colorectal cancer incidence and mortality in the population after screening. At the same time, various organizations in Europe and the United States have continuously updated colonoscopy surveillance after screening and polypectomy based on the latest research evidence. In this review, we summarized the current progress of studies on colorectal cancer risk in post-screening colorectal cancer populations and the key points of relevant guideline updates, in order to provide a reference for conducting relevant studies and formulating surveillance guidelines or consensus in China.

[From rural practice to national strategy for colorectal cancer screening in China--Mr. Zheng Shu who is a pioneer and practitioner].

Haining City and Jiashan County in Zhejiang Province are the first areas to carry out colorectal cancer screening in China, which started in the early 1970s and has been going on for more than 40 years. Meanwhile, Haining and Jiashan have also become the first batch of National Demonstration Bases for Early Diagnosis and Treatment of Colorectal Cancer. In the past 40 years, owing to Professor Zheng Shu who is brave and innovative, with an indomitable spirit, as well as the unremitting efforts and active exploration of all the team members, colorectal cancer screening which was unknown by the public and implemented with difficulties, has gradually been widely accepted and benefited the population. Today, remarkable achievements have been fulfilled in the colorectal cancer screening of Haining and Jiashan which has become the pioneer power in promoting the progress of colorectal cancer prevention and control in China and has certain influence both on China and the world. Meanwhile, a set of colorectal cancer screening strategies suitable for China has been explored and further promoted to be used nationwide, which is of great significance to the prevention and control of colorectal cancer in China. Looking forward to the future, the prevention and control of colorectal cancer in China is still difficult. We will continue to give full play to our existing advantages, not forget our original intention, move forward, explore innovation, and create greater glories!

Trichostatin A alleviates the process of breast carcinoma by downregulating LPAR5.

OBJECTIVE: To elucidate the role of histone deacetylase inhibitor Trichostatin A (TSA) in affecting metastasis of breast carcinoma, and its molecular mechanism. PATIENTS AND METHODS: LPAR5 levels in breast carcinoma tissues and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and its expression pattern was further verified in breast carcinoma cell lines. The relationship between LPAR5 and prognosis of breast carcinoma patients was analyzed. After TSA induction (100-400 nmol/L) for 6-48 h, the proliferative and migratory abilities of SKBR3 and MDA-MB-231 cells in overexpressing LPAR5 were examined by cell counting kit-8 (CCK-8), transwell and wound healing assay. By constructing a xenograft model in nude mice, the influences of TSA and LPAR5 on in vivo growth of breast carcinoma were examined. RESULTS: LPAR5 was upregulated in breast carcinoma samples. High level of LPAR5 predicted higher rates of lymphatic metastasis and distant metastasis, as well as lower overall survival and progression-free survival in breast carcinoma patients. LPAR5 level was dose-dependently downregulated in TSA-induced SKBR3 and MDA-MB-231 cells. In addition, TSA induction dose-dependently declined proliferative ability, and time-dependently attenuated migratory ability in breast carcinoma cells. In vivo overexpression of LPAR5 in nude mice reversed the inhibitory effect of TSA on breast carcinoma growth. CONCLUSIONS: TSA induction can suppress proliferative and migratory abilities in breast carcinoma by downregulating LPAR5.

Associations of TNF-α -308 G>A and TNF-ß 252 A>G with Physical Function and BNP-Rugao Longevity and Ageing Study.

OBJECTIVES: To explore the associations of TNF-α -308 G>A (rs1800629) and TNF-ß 252 A>G (rs909253) with physical function and plasma B-type natriuretic peptide (BNP). METHODS: Data of 1747 community-dwelling elders from the ageing arm of the Rugao Longevity and Ageing Study was used. Physical function was measured by handgrip strength, Timed Up and Go (TUG) test and 5-meter walking test (5MWT). RESULTS: AA genotype of the TNF-α -308 G>A was associated with higher mean time of TUG test and 5MWT (multivariable adjusted ß=5.75 and 5.70, respectively, p<0.05), compared with GG genotype. For the TNF-ß 252 A>G polymorphism, GG genotype was associated with higher mean time of TUG test and 5MWT (multivariable adjusted ß=1.55 and 0.83, respectively, p<0.05) and lower handgrip strength (multivariable adjusted ß=-0.69, p<0.05), compared with AA genotype. Further, GG was associated with greater odds of low handgrip strength (OR=1.47, 95% CI=1.06-2.04), low speed of TUG test (OR=1.87, 95% CI=1.20-2.01) and elevated BNP (OR=1.30, 95% CI=1.08-1.84). GG also interacted with elevated BNP to be associated with greater odds of low handgrip strength and 5MWT. CONCLUSIONS: TNF-ß 252 A>G was associated with physical function measurements, plasma BNP level, and odds of elevated BNP in an elderly population. TNF-ß 252 A>G also interacted with elevated BNP to be associated with greater odds of physical function measurements.

High calpain-1 expression predicts a poor clinical outcome and contributes to tumor progression in pancreatic cancer patients.

BACKGROUND: Pancreatic cancer (PC) is a highly aggressive and metastatic disease, with an elevated mortality rate. It is, therefore, crucial to assess factors affecting the prognosis of PC patients. Meanwhile, calpain-1 is associated with malignant tumor progression and metastasis. Thus, it is meaningful to evaluate the relationship between calpain-1 and PC. MATERIALS AND METHODS: Calpain-1 protein expression was assessed by immunohistochemistry in 96 pancreatic cancer samples and paired adjacent non-cancerous specimens. In addition, calpain-1 protein levels were assessed in six PC cell lines by western blot (WB). Next, PC cells were transfected with calpain-1 siRNA, and silencing was confirmed by WB. Finally, cell proliferation, colony formation, migration and invasion assays, and cell apoptosis analysis were performed to examine the effects of calpain-1 knockdown on proliferation, growth, apoptosis, migration, and invasion in PC cells. RESULTS: The results showed that calpain-1 was overexpressed in PC tissues and cells. Meanwhile, calpain-1 overexpression was associated with tumor site (P = 0.029), metastasis (P = 0.000), and TNM stage (P = 0.000), but showed no associations with histological grade (P = 0.396), age (P = 0.809), sex (P = 1.000), and lesion size (P = 0.679). The Kaplan-Meier method demonstrated that the low calpain-1 expression group had increased overall survival (OS) compared with patients expressing high calpain-1 levels (28.7 ± 4.1 vs. 17.0 ± 2.3 months) (P = 0.005). Besides, calpain-1 in PC cells was successfully silenced by liposome-mediated RNA interference, resulting in reduced cell growth, invasion, and metastasis in PC cells, with no effect on apoptosis. CONCLUSION: The above findings suggest that calpain-1 should be considered a potential biomarker for PC prognosis and therapy.

[National experts consensus on clinical diagnosis and treatment of inhalation injury (2018 version)].

Inhalation injury is caused by inhalation of heat, toxic or irritating gases which lead to respiratory and pulmonary parenchyma damage. At present, the clinical understanding about it is still limited and lack of effective diagnosis and treatment standard. Based on the experience of diagnosis and treatment of domestic inhalation injury, combined with reports of international researches, criteria (expert consensus) for inhalation injury were systematically discussed from pathological and pathophysiological changes, clinical diagnosis and evaluation, and clinical treatment, which provides reference for clinical diagnosis and treatment of patients inflicted with inhalation injury.

[National experts consensus on clinical diagnosis and treatment of inhalation injury (2018 version)].

Inhalation injury is caused by inhalation of heat, toxic or irritating gases which lead to respiratory and pulmonary parenchyma damage. At present, the clinical understanding about it is still limited and lack of effective diagnosis and treatment standard. Based on the experience of diagnosis and treatment of domestic inhalation injury, combined with reports of international researches, criteria (expert consensus) for inhalation injury were systematically discussed from pathological and pathophysiological changes, clinical diagnosis and evaluation, and clinical treatment, which provides reference for clinical diagnosis and treatment of patients inflicted with inhalation injury.

Association between dopamine D2 receptor gene polymorphisms and the risk of heroin dependence.

Heroin dependence is a chronic relapsing brain disease. Researchers have reported that the dopamine D2 receptor (DRD2) is involved in the development of opiate dependence. To identify markers that contribute to the genetic susceptibility to heroin addiction, we examined the potential association between heroin dependence and six polymorphisms of the DRD2 gene using the MassARRAY system. Three hundred and thirty-four patients with heroin dependence and 299 healthy controls participated in the research. Compared with the healthy controls, heroin-dependent patients had a significantly lower frequency of the AA genotype of rs6275 (P = 0.038), and a significantly higher frequency of the C allele of rs1125394 (P = 0.030). Statistically significant differences were observed in the genotypic and allelic frequencies of rs17115583 (P = 0.005 and P = 0.001, respectively) and rs1079597 (P = 0.03 and P = 0.02, respectively). Haplotype analysis revealed that the T-G-A (block 1) haplotype of the DRD2 gene conferred a protective effect (P = 0.020). These findings point to a role for DRD2 polymorphism in heroin dependence in the Chinese Han population, and may be informative for future genetic or neurobiological studies on heroin dependence.

The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis.

The aim of this study was to evaluate prospectively cytokine levels and disease activity in juvenile idiopathic arthritis (JIA) patients treated with and without tumour necrosis factor (TNF)-α inhibitors. TNF-α inhibitor-naive JIA subjects were followed prospectively for 6 months. Cytokine levels of TNF-α, interleukin (IL)-1ß, IL-6, IL-8, IL-10 and IL-17 were measured at baseline for JIA subjects and healthy controls (HCs). Cytokine levels were then measured at four time-points after initiation of TNF-α inhibition for anti-TNF-α-treated (anti-TNF) JIA subjects, and at two subsequent time-points for other JIA (non-TNF) subjects. JIA disease activity by Childhood Health Assessment Questionnaire (CHAQ) disability index/pain score and physician joint count/global assessment was recorded. Sixteen anti-TNF, 31 non-TNF and 16 HCs were analysed. Among JIA subjects, those with higher baseline disease activity (subsequent anti-TNFs) had higher baseline TNF-α, IL-6 and IL-8 than those with lower disease activity (non-TNFs) (P < 0·05). TNF-α and IL-10 increased, and IL-6 and IL-8 no longer remained significantly higher after TNF-α inhibitor initiation in anti-TNF subjects. Subgroup analysis of etanercept versus adalimumab-treated subjects showed that TNF-α and IL-17 increased significantly in etanercept but not adalimumab-treated subjects, despite clinical improvement in both groups of subjects. JIA subjects with increased disease activity at baseline had higher serum proinflammatory cytokines. TNF-α inhibition resulted in suppression of IL-6 and IL-8 in parallel with clinical improvement in all anti-TNF-treated subjects, but was also associated with elevated TNF-α and IL-17 in etanercept-treated subjects.

[Efficacy of interventional therapy on paravalvular leakage after mitral valve replacement].

OBJECTIVE: To evaluate the efficacy of transcatheter intervention of paravalvular leakage (PVL) after mitral valve replacement. METHODS: Present respective study included 15 patients (8 males and mean age (53.5±11.7) years) with mitral PVL who underwent interventional therapy in our hospital from April 2014 to May 2015. There were 9 cases with NYHA heart function Ⅲ, 6 cases with NYHA heart function Ⅳ. Left ventricular ejection fraction was (46.8±8.2)%, and mitral regurgitation volume was 12.0 (10.0, 15.0)ml before the intervention. Transcatheter intervention was carried out in the catheterization laboratory or the hybrid operation room with initial local anesthesia. By puncturing femoral artery and implantation of different congenital heart disease devices, the mitral PVL were occluded interventionally. To some complicated cases, the occluder was implanted by puncturing apex and atrial septum. Follow-up evaluation included peri-operational mortality, complications and postoperative residual shunt. RESULTS: The median time between transcatheter intervention and previous operation was 5.0 (0.6, 7.0) years. One patient did not tolerate the operation and occlude was not implanted in this patient. The success rate of transcatheter intervention was 93.3% (14/15). The average operation time was (126.7±56.4)min, and X ray exposure time was (21.0±10.0)min, and median hospitalization time was 7.0 (6.0, 10.0)d. The main post-operative complications included 1 case of hemoptysis, 1 case of acute renal failure, 1 case of hematuria and 4 cases of blood transfusion. The median follow-up time was 7.0 (4.0, 12.0) months. During the follow-up, there was no death and no serious complications. One month after the procedure, left ventricular ejection fraction significantly increased to(52.1±4.3)%, and median mitral regurgitation significantly reduced to 0.5 (0, 2.0)ml (all P<0.05). CONCLUSION: The interventional therapy for PVL after mitral valve replacement is safe and effective, and further studies are warranted to observe the long-term effect of this procedure.

Structure and polymorphism of novel X-chromosome short tandem repeat loci in a Chinese Han population.

Recently, 5 novel X-chromosome short tandem repeat (X-STR) loci with high degrees of polymorphism were examined. In this study, we investigated the genetic distribution of these loci in a Chinese Han population. The 5 X-STR loci were successfully examined by polyacrylamide gel electrophoresis in a total of 200 unrelated Shaanxi Han individuals (100 males and 100 females). Hardy-Weinberg equilibrium tests revealed no significant deviation from expected values (P > 0.05) for all 5 X-STR loci in the Shaanxi Han population.The loci were named DXS-p11.3, DXS-q12, DXS-q13.3, DXS-q22.1, and DXS-q25 and were found to contain 6, 8, 7, 7, and 5 alleles, respectively. In addition, 17, 21, 18, 19, and 11 genotypes, respectively, were detected in the female samples. The heterozygosities of the 5 X-STR loci were 0.75, 0.74, 0.74, 0.72, and 0.56, respectively. The polymorphic information contents of the 5 X-STR loci were 0.70, 0.69, 0.69, 0.68, and 0.51, respectively. The individual discrimination values of the 5 X-STR loci were 0.88, 0.86, 0.88, 0.87, and 0.74, respectively. Five new X-chromosome STR loci with high degrees of polymorphism were observed in our lab. The results of this study are important for forensic individual identification, paternity identification, and population genetics research.

Regulators of G-protein signaling 9 genetic variations in Chinese subjects with schizophrenia.

To identify single-nucleotide polymorphisms that contribute to the genetic susceptibility to schizophrenia, we examined the potential association between schizophrenia and 9 single nucleotide polymorphisms (rs1530351, rs4791230, rs2869577, rs8077696, rs8070231, rs2292592, rs9916525, rs1122079, and rs4790953) in the G-protein signaling 9 gene. The participants included 395 schizophrenia subjects and 400 healthy controls. The selected single nucleotide polymorphisms were genotyped using mass spectrometry techniques. The allelic or genotypic frequencies of the rs4791230 (promoter region) polymorphisms in subjects with schizophrenia were significantly different from those in healthy controls. The subjects with schizophrenia had a significantly higher frequency of the G allele (P = 0.030, odds ratio = 1.589, 95% confidence interval = 1.042-2.422) of rs4791230. Strong linkage disequilibrium was observed in 4 blocks (D' > 0.9). Significantly fewer T-A (rs1530351-rs4791230) haplotypes (P = 0.029) were found in subjects with schizophrenia. These findings suggest a role of G-protein signaling 9 polymorphisms in schizophrenia among Han Chinese and may be informative for future genetic or neurobiological studies on schizophrenia.

Association of the VRK2 gene rs3732136 polymorphism with schizophrenia in a Northwest Chinese Han population.

Previous studies have found that the vaccinia related kinase 2 gene (VRK2) polymorphism was associated with schizophrenia (SCZ) in the worldwide population. This association was further supported by VRK2 mRNA expression patterns and brain structure variations. Here, we analyzed four single nucleotide polymorphisms (SNPs) of the VRK2 gene in a total population of 893 samples, consisting of 360 patients with SCZ and 533 healthy controls of Han Chinese descent using the SNPscan method. Single SNP, haplotype, and gender-specific association analyses were performed. We found that rs3732136 was significantly associated with SCZ (P = 0.042; odds ratio = 1.25; 95% confidence interval = 1.01-1.55). Further genotype and haplotype association analyses suggested a similar pattern. Our data provide preliminary evidence that the VRK2 gene might play a major role in the development of SCZ in the Northwest Chinese Han population.

Characterization of a TIR-NBS-LRR gene associated with downy mildew resistance in grape.

Grapevine downy mildew, caused by Plasmopara viticola, is a devastating disease that results in considerable economic losses as well as environmental damage through the repeated application of fungicides. The nucleotide-binding site leucine-rich repeat gene family functions in plant immunoactivity against various pathogens and pests. In this study, the 5' and 3' ends of the resistance gene homology fragment RGA5 were obtained by rapid amplification of cDNA ends. The 4282-base pair full-length cDNA was obtained using gene-specific primers, and the corresponding 1335-amino acid protein sequence contained characteristic nucleotide-binding site leucine-rich repeat domains of plant resistance proteins, including the toll-interleukin receptor type region. Expression of RGA5 during P. viticola infection and abiotic stress was investigated using quantitative real-time polymerase chain reaction. The results showed that treatment with P. viticola and 4 abiotic stimuli (salicyclic acid, methyl-jasmonate, abscisic acid, H2O2) significantly induced RGA5 within 12 days of inoculation. Therefore, RGA5 may play a critical role in protecting grapevines against P. viticola via signaling pathways involving these molecules.

Single-nucleotide polymorphisms in dopamine receptor D1 are associated with heroin dependence but not impulsive behavior.

Previous studies suggested that dopamine receptors may be associated with drug dependence and impulsive behavior. In this study, we examined whether dopamine receptor D1 (DRD1) is associated with heroin dependence and the impulsive behavior in patients with heroin dependence. The participants included 367 patients with heroin dependence and 372 healthy controls from a Chinese Han population. We examined the potential association between heroin dependence and 8 single-nucleotide polymorphisms (rs686, rs4867798, rs1799914, rs4532, rs5326, rs265981, rs10078714, rs10078866) of DRD1, and the associations between single single-nucleotide polymorphism, haplotypes, and impulsive behavior. Compared with the healthy controls, heroin dependence patients showed a significantly lower frequency of GG homozygotes of rs5326 (P = 0.027), significantly lower frequency of the G allele of rs5326 (P = 0.007, odds ratio = 0.718, 95% confidence interval = 0.565-0.913), and higher frequency of the rs265981 G allele (P = 0.0002, odds ratio = 1.711, 95% confidence interval = 1.281-2.287). Furthermore, strong linkage disequilibrium was observed in 2 blocks (D' > 0.9). However, no association was observed between haplotypes and heroin dependence in the 2 blocks. This genetic behavior correlation study showed that the 2 single-nucleotide polymorphisms, rs5326 and rs265981, were not associated with the impulsive behavior in patients with heroin dependence. These findings indicate that DRD1 gene polymorphisms are related to heroin dependence in a Chinese Han population and may be informative for future genetic or biological studies on heroin dependence.

Dopamine receptor D1 but not D3 essential for morphine-induced conditioned responses.

Recent studies indicate the involvement of dopamine receptors D1 and D3 in the regulation of locomotor stimulant and conditioned responses to morphine in mice. Moreover, expression of brain-derived neurotrophic factor (BDNF) may be modulated by D1 and D3 receptor activities in the nucleus accumbens (NAc) and prefrontal cortex (PFC). However, the underlying interactions between D1 and D3 receptors and BDNF in the expression of behavioral responses controlled by drug-associated cues have not yet been fully elucidated. In this study, we used dopamine receptor mutant mice to explore the roles of the D1 and D3 receptors in locomotion and morphine-induced place preference; furthermore, we investigated the effects of morphine on BDNF expression in the NAc and PFC of the mouse brain. Our results show that D1 receptor but not D3 receptor mutant mice had decreased sensitivity to acute morphine-induced (10 mg/kg) locomotion (D1: 3814.82 ± 319.9 cm vs D3: 8089.64 ± 967.4 cm). Furthermore, D1 receptor mutant mice did not acquire morphine-conditioned place preference (D1: -18.3 ± 59.9, D3: 217.7 ± 64.1) and showed decreased BDNF expression in the NAc (D1: 0.33 ± 0.07 fold, D3: 2.21 ± 0.18 fold) and PFC (D1: 0.74 ± 0.15 fold, D3: 1.68 ± 0.22 fold) compared with wild-type and D3 receptor mutant mice. These findings suggest that the D1 receptor is necessary for the induction of cue-associated morphine seeking and modulates locomotor habituation processes in response to acute morphine. The dopamine receptor D1 but not the D3 is also critical for morphine-induced BDNF expression in the NAc and PFC.

Functional polymorphisms of the glutamate receptor N-methyl D-aspartate 2A gene are associated with heroin addiction.

Heroin dependence is a debilitating psychiatric disorder with a complex inheritance mechanism. Genetic polymorphisms in functional regions of the glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene, which encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor, may modulate the risk of heroin addiction. We investigated the potential association between 8 single nucleotide polymorphisms (SNPs) of the GRIN2A gene (SNPs rs3219790, rs1014531, rs8044472, rs8045712, rs9933624, rs9940680, rs1420040, and rs767749) and heroin addiction using the MassARRAY system and GeneScan. A total of 405 heroin-addicted patients and 397 healthy control subjects were recruited for this study. Statistically significant differences were observed for rs3219790 in the promoter region of the GRIN2A gene. The frequency of the (GT)26 repeats in the heroin addiction group was significantly higher than that in the control group [X(2) = 5.475, P = 0.019, odds ratio (OR) = 1.367, 95% confidence interval (CI) = 1.051-1.776]. Strong linkage disequilibrium was observed in block 1 (D' > 0.9). However, significant evidence of linkage disequilibrium was not observed between the 7 SNPs in our sample population. These data suggest that GRIN2A gene polymorphisms confer susceptibility to heroin addiction and support the hypothesis that dysfunction of GRIN2A is involved in the pathophysiological process of heroin addiction.

Significance of SODD expression in childhood acute lymphoblastic leukemia and its influence on chemotherapy.

This study explored the clinical significance of silencer of death domain (SODD) expression in childhood acute lymphoblastic leukemia (ALL) and its influence on chemotherapy as well as the effect of SODD expression on apoptosis of leukemic cells. The expression of SODD proteins in different ALL groups was determined by immunocytochemistry. The SODD RNAi-interfering plasmid was constructed and transferred to Jurkat cells, and the effects of SODD expression on cell proliferation and apoptosis were analyzed using the MTT and FCM methods. The expressions of SODD, Phospho-NF-κB-P65, Bcl-2, and Caspase 3 were detected by Western blot analysis. The expression of SODD proteins was significantly higher in the ALL groups than in the control group (P < 0.05). The positive expression rate of SODD was significantly higher in refractory/relapsed and clinical high-risk groups than in standard-risk, initial treatment, and complete remission groups (P < 0.05). Microtubule-targeting drugs such as vincristine and taxol can notably down-regulate SODD expression during apoptosis, whereas DNR, and Ara-c cannot. The sensitivity of Jurkat cells to chemotherapeutic drugs increased with down-regulated SODD expression induced by SODD-interfering plasmid transfection. The sensitivity of the cells transfected with SODD-cloning genes decreased. SODD expression was high in the ALL children. These findings indicated that SODD over-expression might be correlated with the clinical classification, curative effect, and prognosis of ALL cells. Microtubule-targeting drugs can specifically down-regulate SODD expression in leukemic cells, thereby increasing the sensitivity of leukemic cells to SODD-targeting chemotherapeutics. In contrast, increased SODD expression tends to reduce sensitivity.