Upregulation of Myeloid Zinc Finger 1 in Dorsal Root Ganglion via Regulating Matrix Metalloproteinase-2/9 and Voltage-gated Potassium 1.2 Expression Contributes to Complete Freund's Adjuvant-induced Inflammatory Pain.

Myeloid zinc finger 1 (MZF1) belongs to the Kruppel family of zinc-finger transcription factors. Recent studies have demonstrated that in dorsal root ganglion (DRG) neurons, MZF1 is involved in the development and maintenance of neuropathic pain. However, the role of MZF1 in inflammatory pain still remains unknown. In the present study, the mechanism of MZF1 in chronic inflammatory pain was investigated in rats received an intraplantar injection of complete Freund's adjuvant (CFA). Subsequently, a series of assays including Western blotting, qRT-PCR, immunohistochemistry, and chromatin immunoprecipitation (ChIP) were performed. We found that CFA led to MZF1 upregulation in ipsilateral L4/5 DRGs. Pre- and post-microinjection of MZF1 siRNA into the ipsi-L5 DRG blocked the development of CFA-induced chronic inflammatory pain and alleviated the mechanical allodynia and thermal hyperalgesia in the maintenance phase. CFA also increased MMP-2/9 and Nav1.8 expression but reduced voltage-gated potassium 1.2 (Kv1.2) and Cav1.2 expression in L4/L5 DRGs. Microinjection of MZF1 siRNA into DRG diminished the CFA-induced changes in MMP-2/9 and Kv1.2 expression. However, the expressions of Nav1.8 and Cav1.2 were not changed by the treatment. Double immunofluorescence staining showed that MMP-2/9 and Kv1.2 were co-localized with MZF1 in DRGs. The ChIP-PCR results revealed that MZF1 binds directly to the promoter region of MMP-2/9 gene. Together, the above results imply that upregulation of MZF1 in DRGs might contribute to the development and maintenance of CFA-induced chronic inflammatory pain by regulating MMP-2/9 and Kv1.2 expression. Targeting DRG-localized MZF1 might be a promising therapeutic strategy for the treatment of chronic inflammatory pain in the clinic.

Efficacy of Internet-delivered cognitive-behavioral therapy for the management of chronic pain in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Pediatric chronic pain is relatively common in the world. Although cognitive behavior therapy (CBT) has been shown to be efficacious in children and adolescents, it is generally recognized that availability and accessibility of CBT are limited. While Internet-delivered cognitive-behavioral therapy (ICBT) performs better in these areas. OBJECTIVES: This systematic review aims to evaluate the clinical effects of ICBT for chronic pain in youth when compared with the control treatments. METHODS: We searched electronic databases to identify randomized controlled trials that compared ICBT with the control therapy for pediatric chronic pain. The primary outcomes were 95% confidence intervals and mean difference or standardized mean difference in change of pain intensity and activity limitations. RESULTS: Four trials met the inclusion criteria with a total of 404 participants of whom 208 received ICBT. Compared with pretreatment, children reported significant, medium to large benefits on pain intensity, activity limitations, and parental protective behaviors after receiving ICBT immediately. Significant small to medium effects were found for outcomes of depressive symptoms, anxiety, and sleep quality from baseline to post-treatment in the ICBT group. But most measures of ICBT did not show statistically significant superiority to those of the control conditions, except parental protective behaviors. Generally children and their parents were highly acceptable and satisfied with ICBT. CONCLUSION: ICBT for physical and psychological conditions in youth with chronic pain is a full potential therapy; it can be successful on clinically effects and socioeconomic benefits. However, only limited data supported the conclusion, we require further methodologically robust trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017069811.

Effect of Pregnane X Receptor*1B genetic polymorphisms on postoperative analgesia with fentanyl in Chinese patients undergoing gynecological surgery.

BACKGROUND: The purpose of the study was to investigate the effects of the pregnane X receptor (PXR)*1B polymorphisms on CYP3A4 enzyme activity and postoperative fentanyl consumption in Chinese patients undergoing gynecological surgery. METHODS: A total of 287 females of Han ethnicity, aged 20 to 50 years old, ASA I or II, scheduled to abdominal total hysterectomy or myomectomy under general anesthesia were enrolled. The analgesic model used was fentanyl consumption via patient-controlled intravenous analgesia (PCIA) in the post-operative period. Additionally, pain was assessed using a visual analog score (VAS). Pain scores, occurrence of adverse reactions and consumption of fentanyl were recorded during the 24 h postoperative period. The enzyme activity of CYP3A4 was evaluated by measuring the plasma ratio of 1'-hydroxymidazolam to midazolam 1 h after intravenous administration of 0.1 mg/kg midazolam. PXR genotyping was performed by direct DNA sequencing and the PXR * 1B haplotype was analyzed via PHASE V.2.1 software. RESULTS: The polymorphism frequency of PXR11156A > C/11193 T > C and 8055C > T were 49.6 and 49.3%, and the rate of PXR * 1B haplotype was 48.8% in our study. None of the pain scores, consumption of fentanyl 24 h post-operatively or enzyme activity of CYP3A4, showed differences among different genotypes. CONCLUSIONS: PXR11156A > C, PXR11193T > C, PXR8055C > T or the PXR * 1B haplotype do not appear to be important factors contributing to CYP3A4 activity and interindividual variations in postoperative fentanyl consumption in Han female patients undergoing gynecological surgery. TRIAL REGISTRATION: The DNA samples were obtained since 2007 to 2010 year in our hospital, there was no registration at that time. So this section is not applicable to our research.

Effect of ABCB1 rs12720464 and rs1055302 polymorphisms in Chinese patients on the time course of action of rocuronium administered as a single dose.

OBJECTIVE: To determine whether ABCB1 gene polymorphisms affect the time course of action of rocuronium in Chinese patients. METHODS: This study included 105 unrelated Chinese patients undergoing general anesthesia with propofol, fentanyl, and rocuronium. Neuromuscular monitoring was performed with calibrated acceleromyography. Patients were allowed to recover spontaneously from the neuromuscular block. The time interval between the first maximum depression of the train of four (TOF) and spontaneous recovery TOF ratio of 0.25/0.7/0.8/0.9 was recorded. The Sequenom MassArray® single-nucleotide polymorphism (SNP) detection technology was used to detect the genotypes of the ABCB1 rs12720464, rs1055302. Demographic and non-genetic clinical data were also collected. RESULTS: In the present study, the mean time to spontaneous recovery of TOF ratio 0.8/0.9 in ABCB1 rs12720464 GG genotype was longer compared to that observed in ABCB1 rs12720464 AG genotype (56.77 ± 14.23 minutes vs. 49.50 ± 10.49 minutes, and 62.58 ± 18.16 minutes vs. 53.20 ± 12.56 minutes, respectively, p < 0.05). Further, the time to spontaneous recovery of TOF 0.7/0.8/0.9 in ABCB1 rs1055302 GG genotype was longer than that in ABCB1 rs1055302 AG genotype (52.00 ± 12.10 minutes vs. 44.83 ± 7.38 minutes, 55.96 ± 13.92 minutes vs. 46.83 ± 7.67 minutes, 61.66 ± 17.70 minutes vs. 49.50 ± 8.44 minutes, respectively, p < 0.05). CONCLUSION: In Chinese patients who were administered a single dose of rocuronium, the genetic variants ABCB1 rs12720464, and rs1055302 contribute to the individual< variability of time course of action.

CYP3A4 * 1G Genetic Polymorphism Influences Metabolism of Fentanyl in Human Liver Microsomes in Chinese Patients.

PURPOSE: This study aimed to investigate whether CYP3A4*1G genetic polymorphism influences the metabolism of fentanyl in human liver microsomes in Chinese patients. METHODS: The human liver microsomes were obtained from 88 hepatobiliary surgery patients who accepted liver resection surgery in this study. A normal liver sample (confirmed by the Department of Pathology) was taken from the outer edge of the resected tissue. The metabolism of fentanyl in human liver microsomes was studied. The concentration of fentanyl was measured by high performance liquid chromatography. The CYP3A4*1G variant allele was genotyped using the PCR restriction fragment length polymorphism method. RESULTS: The frequency of the CYP3A4*1G variant allele was 0.188 in the 88 Chinese patients who had received hepatobiliary surgery. The metabolic rate of fentanyl in patients homozygous for the *1G/*1G variant (0.85 ± 0.37) was significantly lower than that in patients bearing the wild-type allele *1/*1 (1.89 ± 0.58) or in patients heterozygous for the *1/*1G variant (1.82 ± 0.65; p < 0.05). There were no gender-related differences in the metabolic rate of fentanyl (p > 0.05) nor was there any correlation between age and metabolic rate of fentanyl (p > 0.05). Results from different hepatobiliary diseases showed no significant difference in the metabolic rate of fentanyl (p > 0.05). The difference of CYP3A4 mRNA among different CYP3A4*1G variant alleles was significant (p < 0.05). There was positive correlation between CYP3A4 mRNA and metabolic rate of fentanyl (p < 0.01). CONCLUSIONS: CYP3A4*1G genetic polymorphism decreases the metabolism of fentanyl. There is a positive correlation between CYP3A4 mRNA level and metabolism of fentanyl.

Genetic characterization of echovirus 6 isolated from meningitis and encephalitis cases in Shandong Province, China / 病毒学报

To analyze the genetic characteristics of echovirus 6 (E6) isolated from meningitis and encephalitis cases in Shandong Province, China, we collected cerebrospinal fluid samples from meningitis and encephalitis cases in Shandong Province from 2007 to 2012 for virus isolation. Viral RNAs were extracted from positive isolates, and complete VP1 coding regions were amplified by RT-PCR and sequenced. Homology comparison and phylogenetic analysis were performed. Six isolates were identified as E6 by microneutralization assay and molecular typing. The homology analysis showed that the six isolates had 78. 6%-99. 8% nucleotide and 95. 5%-100. 0% amino acid identities with each other, as well as 76. 9%-78. 4% nucleotide and 92. 3%-95. 1% amino acid identities with the prototype strain (D' Amori). The phylogenetic analysis based on the integrated VP1 sequences indicated that all Shandong E6 isolates could be separated into four clusters, designated as A, B, C, and D. The six E6 isolates belonged to clusters A, B, and D. Our study reveals high genetic differences between Shandong E6 isolates and suggests different transmission lineages of E6 co-circulated in Shandong Province.

Temporal fluctuation and genetic characterization of echovirus 11 isolates upon surveillance of environmental sewage in Shandong Province, China / 病毒学报

We wished to analyze the genetic characterization of echovirus 11 (Echo11) from samples of environmental sewage in Shandong Province (China). The VP1 coding region was typed as the strains were amplified. Phylogenetic analyses on the VP1 sequences from these isolates, strains isolated from AFP cases in the period 1994-2010 and others published in GenBank were conducted. From 2011 to 2012, 94 Echo11 strains were isolated from samples of environmental sewage in Jinan and Linyi City in Shandong Province. Numbers of Echo11 were seasonal and reached peaks in the summer and autumn in both cities; A- mong these isolates, nucleotide (nt) identities were 89.5%-100.0% whereas amino acid (aa) identities were 95.4%-100.0%. The nt and aa identities were 76.6%-79.7% and 90.4%-92.5% between those strains and the prototype (Gregory) strain of Echo11, respectively. All isolates from Shandong Province were the A genotype and the strains evolved very rapidly, which suggested that several transmission chains was co-circulating. We described the temporal fluctuation and genetic characterization of Echo11 isolates from surveillance of environmental sewage in Shandong Province, thereby providing important information for exploring the dynamic change and genetic variation of circulating human enteroviruses in this Province in China.

Seroprevalence of the newer enterovirus types A71, A90 and B87 in healthy individuals in Shandong Province, China / 病毒学报

This study aimed to investigate antibody levels of the newer human enteroviruses (EV) A71, A90, and B87 in the population of Shandong Province, and provide a scientific basis for the development of prevention and control measures. In this study, serum specimens were collected from 400 individuals living in Yantai city, Shandong Province in 2010. EV-A71, A90, and B87 antibodies were detected using neutralization tests, and the results were analyzed by statistical methods. It was found that the positive neutralizing antibody rates of EV-A71, A90 and B87 in the population were 46.0%, 8.8%, and 47.0%, respectively. Their geometric mean titers (GMT) were 1 : 5.20, 1 : 1.49, and 1 : 4.02, respectively. Positive antibody rates for EV-A71 and EV-B87 were lowest in the 1-yr and 7-mo age groups, respectively. Positive rates increased gradually with age, and become consistent in the population aged >5 years. Positive antibody rates of EV-A90 were consistent across all age groups. Maternal antibody levels of EV-A71 declined rapidly after birth, and the increase in seroprevalence among 3-7 years old children implied that most EV-A71 infections occurred in preschool and early elementary school children. High positive antibody rates of EV-B87 in healthy individuals, especially children, implied that there may be an immune barrier within the general population. The population monitoring of EV-A90 should be strengthened, as its positive antibody rate is low.

Preliminary analysis on the prevalence and causes of breakthrough hepatitis B virus infection among children in Shandong province, China / 中华预防医学杂志

<p><b>OBJECTIVE</b>To know the prevalence and probable causes of breakthrough hepatitis B virus (HBV) infection among children born after the introduction of universal infant hepatitis B vaccination in Shandong province, China.</p><p><b>METHODS</b>The subjects of this study were selected from the provincial hepatitis B serosurvey conducted in 2006, who were born between 1992 and 2005 (aged 1-15 years) and were confirmed to have completed three or more doses of hepatitis B vaccine. Finally 3527 subjects were involved in this study and were investigated using a unified question are. Blood samples were collected from them to detect hepatitis B surface antigen (HBsAg), antibody against HBsAg (Anti-HBs) and antibody against hepatitis B core antigen (Anti-HBc). The parents of children positive for HBsAg were followed up. Blood samples were collected from their parents to detect for HBsAg. The rate and correlative factors of breakthrough HBV infection were gotten by single-factor and multiple-factor analysis.</p><p><b>RESULTS</b>For the 3527 subjects, the overall prevalence rates of breakthrough HBV infection were 3.15% (111/3527), which decreased while birth year grew (χ(2)(Trend) = 44.83, P < 0.01) , the rate of subjects born in 1992 was the highest (9.9%, 16/161) , subjects born in 2000 was the least (0.8%, 2/258) , the rate of the self-report positive HBsAg status of mother, father and the other family members (15.22%, 7/46;34.09%, 15/44;17.65%, 6/34) were higher than the negative (2.99%, 104/3481, 2.76%, 96/3483, 3.01%, 105/3493) (χ(2) values were 22.28, 13.97, 23.68, respectively, all P values were < 0.01) , timely first dose of hepatitis B vaccine (5.37%, 41/763) was higher than the subjects that not in time (2.53%, 70/2764) (χ(2) = 15.596, P < 0.01) . The overall prevalence rates of breakthrough chronic HBV infection was 1.08% (38/3527), which decreased while birth year grew (χ(2)(Trend) = 9.96, P < 0.05) , the rate of subjects born in 1992 was the most (3.1%, 5/161) , subjects born in 1997 was the least (0.4%, 1/261) , the rate of the self-report positive HBsAg status of mother, father and the other family members (13.04%, 6/46;29.55%, 13/44;17.65%, 6/34) were higher than the negative (0.92%, 32/3481;0.72%, 25/3483;0.92%, 32/3493) (χ(2) values were 62.62, 338.80, 88.44, respectively, all P values were < 0.05) , timely first dose of hepatitis B vaccine (1.83%, 14/763) was lower than the subjects that not in time (0.87%, 24/2764) (χ(2) = 5.16, P = 0.02) . Multiple factors analysis showed that compared to the negative, the self-report positive HBsAg status of father, mother increased the risk of breakthrough HBV infection,OR (95%CI) values were 3.73 (1.09-12.75) and 26.76 (11.86-60.37) , respectively (all P values were < 0.05) , compared with eastern cities, the risk of western cities were the highest (OR (95%CI) = 6.00 (2.50-14.40) , P < 0.05) the risk of children born in 1992-2001 was higher than those born in 2002 ( (OR (95%CI) = 1.91 (1.10-3.32) , P < 0.05) . Compared to the negative, the self-report positive HBsAg status of father, mother and the other family members increased the risk of breakthrough chronic HBV infection,OR (95%CI) values were 7.51 (1.44-39.17) , 99.99 (34.29-291.62) , 8.94 (1.81-44.10) , respectively (all P values were < 0.05) , compared with eastern cities, the risk of western rural areas were the highest (OR (95%CI) = 12.51 (2.78-56.25) , P < 0.05) , sharing tooth brush with the others increased the risk (OR (95%CI) = 8.67 (1.14-66.14) , P < 0.05) . Among HBsAg-positive children, those with HBsAg positive mother and father accounted for 12/23 and 6/19, respectively.</p><p><b>CONCLUSION</b>The prevalence of breakthrough HBV infection and breakthrough chronic HBV infection among children was low in Shandong province. Mother to infant transmission might be the main reason for the infection while the role of the horizontal transmission within the family shouldn't be ignored.</p>

Economic burden and related factors on inpatients with HBV-related diseases in Shandong province / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the economic burden of patients with acute and chronic hepatitis B, cirrhosis and liver cancer caused by hepatitis B virus (HBV).</p><p><b>METHODS</b>Cluster sampling was used on cases consecutively collected during the study period. Questionnaire survey was conducted and information on the expenses during hospitalization was collected from the hospital records and through interviewing those patients.</p><p><b>RESULTS</b>Yearly costs related to patients with acute hepatitis B, severe hepatitis B, chronic hepatitis B, cirrhosis, hepatocellular carcinoma were 66.7, 138.1, 127.4, 151.7 and 377.2 thousand Yuan, respectively.</p><p><b>RESULTS</b>from multiple linear regression model showed that the type of medical insurance scheme, annual days of hospitalization, classifications of HBV-related diseases and personal income were major influencing factors on the cost.</p><p><b>CONCLUSION</b>HBV infection caused considerable burden to families and the society, indicating that HBV infection control programs would bring huge potential benefits. The reform of insurance scheme should be administrated to promote social fairness.</p>

Isolation and characterization of a human enterovirus 74 isolated in Shandong Province, China / 病毒学报

Human Enterovirus HEV 74 is a new member of species Human enterovirus B (HEV-B). To understand its evolution and restructuring characteristics, we report the complete genome sequence of a HEV74 strain 05293/SD/CHN/2005(abbreviated as 05293) isolated from an acute flaccid paralysis (AFP) case in Shangdong Province, China, 2005. Analysis of the complete genomic sequence of 05293 showed that its genome was collinear with that of previously described 2 HEV74 strains, except for insertions and deletions at the 5'NTR and the 3 NTR regions. The complete genome sequence of strain 05293 displayed 80. 8% nucleotide and 96% amino acid identity to the prototype strain USA/CA75-10213, and 80. 6% and 95. 9% to another isolated strain Rikaze-136. The P1, P2 and P3 coding regions of strain 05293 displayed 81. 5%, 80. 0%, 79. 7% nucleotide and 95. 9%, 96. 0%, 96.2% amino acid identity to the prototype strain USA/CA75-10213, and 81. 9%, 78. 8%, 79. 5% and 95. 9%, 96. 1%, 95. 7% to strain Rikaze-136, respectively. The phylogenetic tree and Simplot analysis on 05293 and HEV-B genome sequences were performed, and the result indicated frequent recombination within HEV-B.

Analysis of the spatial and temporal characteristics of measles patients younger than 1 year old in Shandong province / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the spatial and temporal characteristics of measles patients younger than 1 year old in Shandong province.</p><p><b>METHODS</b>A total of 5309 cases of measles, whose patients were younger than 1 year old in Shandong province between year 1999 and 2008 were collected. The epidemic features of measles were described, and the annual infant incidence was calculated. Software ArcGIS9.3 was applied to draw the spatial map of the disease, and the software GeoDa0.95i-beta was adopted to analyze the spatial autocorrelation.</p><p><b>RESULTS</b>The incidence among infants younger than 1 year old reported in Shandong province rose from 23.45/100 000 (206 cases) in 1999 to 269.60/100 000 (2791 cases) in 2008.5309 cases covered all month-aged infants under 1 year old, except 12 months old. Most patients (3494 cases) aged between 6 - 9 months old; especially the infants around 8 months old, accounting for 20.7% (1100/5309). The epidemic peak was between March and May, accounting for 45.5% (2414/5309). The spatial and temporal distribution features showed an up and down temporal trend and an increase from east to west in spatial trend. The global Moran's I values of measles incidence among infants in Shandong province were 0.346, 0.150, 0.396, 0.213, 0.477, 0.354 and 0.331 in year 1999, 2001 - 2002, 2005 - 2008 (P < 0.01) and 0.076 in year 2004 (P < 0.05). The local spatial autocorrelation analysis showed that southwest and northwest districts of Shandong were highly clustered districts of measles.</p><p><b>CONCLUSION</b>In Shandong, the measles incidence among infants younger than 1 year old rose obviously; especially the infants aged between 6-9 months age. The epidemic peak was between March and May. A positive spatial correlation was found, the disease showed a distinct regional distribution feature, and a cluster district was found.</p>

Identification and genetic characterization of coxsackieviruses A2, 6, 8 and 12 isolated in Shandong Province / 病毒学报

In previous study, molecular typing method was performed to identify human enteroviruses (HEVs) isolates collected from acute flaccid paralysis (AFP) cases from 1989 to 2011 and hand, foot and mouth disease (HFMD) patients, and 8 HEV-A serotypes were identified. In order to explore the genotypes and molecular evolution characteristics of HEV-A in Shandong province, viral RNA of the remaining isolates was extracted and entire VP1 coding region was amplified, sequenced and identified with HEV-A primers. Another 7 HEV-A Shandong isolates were obtained, and identified as Coxsackievirus A (CVA) 2, 6, 8 and 12 by molecular typing method. Homologous comparison showed that the nucleotide acid identities of Shandong strains ranged from 80.8% to 85.0% with prototype strains. Phylogenetic analysis based on VP1 sequences indicated that CVA8 and CVA12 strains were genetically related with domestic strains. However, CVA2 and CVA6 strains were distinct from both domestic and foreign strains. In addition, multiple transmission chains of CVA2 and CVA6 existed within Shandong province. So far, a total of 12 HEV-A serotypes were identified in Shandong province. This study enriched the distribution of serotypes and genetic evolution characteristics of HEV-A isolates in Shandong, and revealed different transmission chains of CVA2, 6, 8, 12 serotypes co-circulated in Shandong province or in China.

Identification and molecular characterization of human enteroviruses type 74, 80, and 87 isolated in Shandong Province, China / 病毒学报

An increasing number of new types of human enteroviruses (HEV) have been identified with the application of molecular typing method based on VP1 sequence analysis. In this study, the non-polio enteroviruses (NPEV) isolated from acute flaccid paralysis (AFP) cases in Shandong Province, China were typed via molecular typing method, and 1 EV74, 3 EV80 and 1 EV87 strains were identified. Homologous comparison revealed EV74, EV80 and EV87 Shandong strains had 81.4%, 76.4%-81.7%, and 80.3% VP1 identities with prototype strains. Phylogenetic analysis suggested a remote genetic distance with other strains. This is the first report of EV74 and EV87 in mainland China, and the low isolation rate in AFP surveillance suggested these three serotypes has not been the predominant viruses in China.

Influence of CYP3A5*3 polymorphism and interaction between CYP3A5*3 and CYP3A4*1G polymorphisms on post-operative fentanyl analgesia in Chinese patients undergoing gynaecological surgery.

BACKGROUND AND OBJECTIVE: Fentanyl is metabolised by cytochrome P450 (CYP) 3A4 and CYP3A5. Our previous work demonstrated that the CYP3A4*1G polymorphism significantly affects the post-operative fentanyl analgesic effect in Chinese women undergoing gynaecological surgery. However, whether CYP3A5*3, a frequent single nucleotide polymorphism of CYP3A5 in Chinese people, affects the post-operative analgesic effect of fentanyl is unclear. In this study, we assessed the influence of the CYP3A5*3 polymorphism and the interaction of the CYP3A5*3 and CYP3A4*1G polymorphisms on post-operative fentanyl analgesia in Chinese women undergoing gynaecological surgery. METHODS: We enrolled 203 women scheduled for abdominal total hysterectomy or myomectomy under general anaesthesia. Intravenous fentanyl patient-controlled analgesia was provided post-operatively for adequate analgesia. Pain scores and fentanyl consumption were recorded 24 h post-operatively. Midazolam was used as a probe drug, and CYP3A activity was measured by plasma ratio of 1'-hydroxymidazolam to midazolam 1 h after intravenous administration of 0.1 mg kg-1 midazolam. Blood samples were genotyped for the CYP3A5*3 polymorphism. RESULTS: The frequency of the CYP3A5*3 allele was 72.4% in 203 patients. CYP3A activity did not differ among CYP3A5*3 genotypes. Fentanyl consumption 24 h post-operatively was lower with CYP3A5*1/*3 and CYP3A5*3/*3 polymorphisms than with CYP3A5*1/*1, but the differences were not statistically significant. However, combined with CYP3A4*1G polymorphism, post-operative fentanyl consumption at 24 h was significantly lower for the CYP3A5*1/*3 or CYP3A5*3/*3 group than the CYP3A5*1/*1 group. CONCLUSION: CYP3A5*3 is not the main genetic factor contributing to interindividual variation in the post-operative analgesic effect of fentanyl in Chinese women undergoing gynaecological surgery; an interaction between CYP3A5*3 and CYP3A4*1G polymorphisms can significantly influence the post-operative effect.

Genetic characterization of poliovirus isolates from environmental sewage surveillance in Shandong, 2010 / 病毒学报

To investigate the genetic characteristics of poliovirus isolates from environmental sewage surveillance in Shandong province, we collected sewage samples in Jinan and Linyi City. Serotyping and VP1/ 3D sequencing were performed on polioviruses isolated from the concentrated sewage samples, and VP1 mutation and recombination were analyzed. Thirty-two of sewage samples were collected, and polioviruses were detected in 10 of the samples with a positive rate of 31.3%. Eighteen Sabin strains were isolated including three type 1, nine type 2, and six type 3 polioviruses, and the number of nucleotide substitutions in VP1 coding region varied from 0 to 4. Recombination was found in three Sabin 2 and four Sabin 3 polioviruses. Analysis of neurovirulence sites of VP1 revealed that one Sabin 1 vaccine strain had a nucleotide change of A to G at nt 2749, one Sabin 2 strain had a nucleotide change of A to G at nt 2908, three Sabin 2 strains had a nucleotide change of U to C at nt 2909, and all six Sabin 3 strains had a nucleotide change of C to U at nt 2493. Poliovirus vaccine strains could be isolated from environmental sewage with a high rate of gene recombination and back mutation of neuvirulence-associated sites. None of wild-type poliovirus or vaccine-derived poliovirus was detected.

Study on the genetic characterization and molecular epidemiology of echovirus 11 strains isolated in Shandong province, China / 中华流行病学杂志

Objective To analyze the evolution and genetic characterization of echovirus 11 (Echo11 ) from the acute flaccid paralysis (AFP) cases in Shandong province. Methods Isolation of Enterovirus was performed from stool samples of AFP cases from 1994 to 2009. All positive strains were sero-typed by neutralization test. Entire VP1 coding region from 27 strains typed as Echo 11 was amplified by reverse transcription-polymerase chain reaction(RT-PCR), and subsequently phylogenetic analyse on VP1 sequences from these strains and others published in GenBank were conducted. Results From 1994 to 2009, altogether 915 non-polio enterovirus (NPEV) strains were isolated with 79(8.6% ) isolates serotyped as Echo11. There were 876 nucleotides (nt) in the complete VP1 genes, encoding 292 amino acids (aa). The nt identities were 76.4%-100.0% among those Echo11 Shandong strains with the aa identities as 91.4% -100.0%. The nt and aa identities were 77.7%-80.7% and 90.7%-94.8% between Shandong strains and prototype strains, respectively.Conclusion All Echo11 strains could be divided into four genotypes. Shandong strains that forming three (A1, A2 and C1) new sub-genotypes, with every sub-genotype had several brands.Sub-genotype A1 appeared to be the lately circulating one.

CYP3A4*1G genetic polymorphism influences CYP3A activity and response to fentanyl in Chinese gynecologic patients.

PURPOSE: To investigate whether the CYP3A4*1G genetic polymorphism contributes to the variability in CYP3A activity and response to fentanyl. METHODS: One hundred and forty-three gynecologic patients who were scheduled to undergo abdominal total hysterectomy or myomectomy with general anesthesia were enrolled in this study. Intravenous fentanyl patient-controlled analgesia was provided postoperatively for satisfactory analgesia. The degrees of pain at rest during PCA treatment were assessed with visual analog scale. The fentanyl consumption and occurrence of any adverse effects were recorded in the first 24 h postoperatively. CYP3A activity was measured by plasma 1'-hydroxymidazolam-to-midazolam ratio 1 h after intravenous administration of 0.1 mg/kg midazolam. CYP3A4*1G variant allele was genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The frequency of the CYP3A4*1G variant allele was 0.269 in 143 Chinese gynecologic patients. The activity of CYP3A4 in patients homozygous for the *1G/*1G variant (0.34 +/- 0.15) was significantly lower than that in patients bearing the wild-type allele (*1/*1) (0.46 +/- 0.14) or in patients heterozygous for the *1/*1G variant (0.46 +/- 0.12) (P < 0.05). The patients with the CYP3A4*1G/*1G genotype needed less fentanyl (227.8 +/- 55.2 microg) to achieve pain control than patients carrying the CYP3A4*1/*1 (381.6 +/- 163.6 microg) and CYP3A4*1/*1G (371.9 +/- 180.1 microg) genotypes (P < 0.05) during the first 24 h postoperatively. There was no significant difference in incidence of adverse events among the different genotype groups (P > 0.05). CONCLUSIONS: CYP3A4*1G genetic polymorphism decreases CYP3A activity and fentanyl consumption for postoperative pain control.

Identification and phylogenic analysis of Coxsackie-virus B5 during an outbreak of aseptic meningitis in Shandong / 中华流行病学杂志

Objective To identify the pathogen that caused an outbreak of aseptic meningitis in Shandong province in 2005. Phylogenic analysis was carried out on Coxsackie-virus B5 (CVB5) which was isolated during this outbreak. Methods 78 stool and 58 cerebrospinal fluids (CSF) specimens were collected from some inpatients during this outbreak. Virus isolation and reverse transcription-polymerase chain reaction (RT-PCR) was then performed. Phylo-genetic trees based on entire and partial VP1 sequences were constructed among CVB5 isolates and others published in GenBank. Results The isolation rates of stool and CSF specimens were 38.5% (30/78) and 48.3% (28/58) respectively. Among the results of serotype identification and molecular typing of 58 positive isolates, 54 were identified as CVB5, 2 as ECHO24, 1 as CVB3 and 1 as CVA9. Results from viral investigation showed that CVB5 was the main pathogen causing this outbreak. Data from homological comparisons indicated that Shandong strains had the highest nucleotide acid identity with the Zhejiang/ 12/02 strain (97.5%-97.8%), and lower identity (78.3%-78.6%) with the prototype strain (Faulkner strain). Phylogenic tree in VP1 region showed that CVB5 could be separated into four genotypes. Isolates of this outbreak belonged to genotype D. Conclusion CVB5 was the major etiological agent correlated with this outbreak. The shift of predominant genotype might serve as one of the causes that associated with the outbreaks of aseptic meningitis.

The analysis of "a" dominant mutation of hepatitis B virus in community-based population of Shandong Province, China / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To determine the rate and type of "a" dominant mutation of hepatitis B virus (HBV) in community-based population of Shandong province and the possible effect of hepatitis B vaccination upon "a" dominant mutation.</p><p><b>METHODS</b>The anticipants aged 1-59 years were selected by multi-stage random sampling from the general population of Shandong province. Hepatitis B vaccination status was obtained by inquisition (for those over 15 years old) or immunization record (for those under 14 years old). The blood samples were collected and detected for HBsAg by ELISA. HBV DNA was extracted from the sera with positive HBsAg and S gene was amplified by nested-PCR. The PCR produce was sequenced and compared with the standard sequence.</p><p><b>RESULTS</b>Overall, 7601 anticipants were investigated. HBV DNA was successfully amplified and sequenced in 102 of 239 samples with positive HBsAg. 14.70% sera samples mutated in HBV "a" determinant region and 13 mutation types were detected. There were no statistically differences in the mutation rate by age groups (born before or after national universal infant hepatitis B vaccination) and hepatitis B vaccination status.</p><p><b>CONCLUSION</b>The "a" determinant mutation seemed to be uncommon in community-based population of Shandong province and the mutation sites were relatively scattered. Hepatitis B vaccination has no effect on "a" dominant mutation of hepatitis B virus.</p>