Simvastatin ameliorates synaptic plasticity impairment in chronic mild stress-induced depressed mice by modulating hippocampal NMDA receptor.

BACKGROUND: In our previous study, we showed simvastatin exerts an antidepressant effect and inhibits neuroinflammation. Given the role of synaptic impairment in depression development, we investigate the effect of simvastatin on synaptic plasticity in depression and the related mechanisms. METHODS: Electrophysiological analysis, Golgi staining, and transmission electron microscope were performed to analyze the effect of simvastatin on synaptic impairment in depression. In addition, the localization and reactivity of N-methyl-D-aspartate receptor (NMDAR) subunits and the downstream signaling were investigated to explore the mechanism of simvastatin's effect on synaptic plasticity. RESULTS: Simvastatin ameliorated the reduction of the magnitude of long-term potentiation (LTP) in Schaffer collateral-CA1, restored hippocampal dendritic spine density loss, improved the number of spine synapses, reversed the reduction in BrdU-positive cells in chronic mild stress (CMS)-induced depressed mice, and ameliorated NMDA-induced neurotoxicity in hippocampal neurons. Dysfunction of NMDAR activity in the hippocampus is associated with depression. Simvastatin treatment reversed the surface expression and phosphorylation changes of NMDAR subunits in NMDA-treated hippocampal neurons and depressed mice. In addition, simvastatin further increased the levels of mature BDNF, activating TrkB-Akt-mTOR signaling, which is critical for synaptic plasticity. CONCLUSIONS: These findings suggest that simvastatin can improve the dysfunction of NMDAR and ameliorate hippocampal synaptic plasticity impairment in depressed mice.

[Head and Face Protection of the Health Care Workers in the Operating Room of Peking Union Medical College Hospital during the Corona Virus Disease-19 Pandemic].

Objective To investigate the understanding of the head and face protection of the health care workers in operating room of Peking Union Medical College Hospital during the corona virus disease-19(COVID-19) pandemic.Methods The knowledge of head and face protection of health care workers in the operating room was evaluated based on the non-registered questionnaires for protection measures collected on-line.Results The survey was conducted in two phases.In the first phase(COVID-19 outbreak),153 questionnaires were collected.In the second phase(when Beijing lowered the emergency response to level 3 and normalized the epidemic prevention and control),101 questionnaires were collected.The results showed that 98% of health care workers had used any form of protective devices during the pandemic and anesthesiologists had the highest usage rate(93.0%)of ear-loop face mask with eye shield.During the pandemic,health care workers mainly used goggles(71.2%)for protection to diagnose and treat the patients with fever and ear-loop face mask with eye shield(56.2%)for protection to diagnose and treat the non-fever patients.In the first-and second-phase survey,43% and 68% of health care workers still used protection,and they mainly used face shield(50.0% and 56.5%)and ear-loop face mask with eye shield(56.1% and 68.1%).Conclusions During the pandemic,more than 90% of the health care workers in the operating room of Peking Union Medical College Hospital were aware of head and face protection.Different healthcare workers in the operating room had different choices of head and face protection,and more than 40% of them would still keep such protection during the normalized stage of pandemic prevention and control.

Compound LM9, a novel MyD88 inhibitor, efficiently mitigates inflammatory responses and fibrosis in obesity-induced cardiomyopathy.

Mechanisms of cardiomyopathy caused by obesity/hyperlipidemia are complicated. Obesity is usually associated with chronic low-grade inflammation and may lead to the onset and progression of myocardial fibrosis and remodeling. TLR4/MyD88 signaling pathway, as a key regulator of inflammation, plays an important role in the pathogenesis of obesity-induced cardiomyopathy. We previously demonstrated that LM9, a novel MyD88 inhibitor, attenuated inflammatory responses and fibrosis in obesity-induced cardiomyopathy by inhibiting the formation of TLR4/MyD88 complex. In this study, we investigated the protective effects of LM9 on obesity-induced cardiomyopathy in vitro and in vivo. We showed that LM9 (5, 10 µM) significantly attenuates palmitic acid (PA)-induced inflammation in mouse peritoneal macrophages, evidenced by decreased expression of proinflammatory genes including TNF-α, IL-6, IL-1ß, and ICAM-1. In cardiac-derived H9C2 cells, LM9 treatment suppressed PA-induced inflammation, lipid accumulation, and fibrotic responses. In addition, LM9 treatment also inhibited PA-activated TLR4/MyD88/NF-κB signaling pathway. We further revealed in HEK293 cells that LM9 treatment blocked the TLR4/MyD88 binding and MyD88 homodimer formation. In HFD-fed mice, administration of LM9 (5, 10 mg/kg, ig, every other days for 8 weeks) dose-dependently alleviated inflammation and fibrosis in heart tissues and decreased serum lipid concentration. In conclusion, this study demonstrates that MyD88 inhibitor LM9 exerts protective effects against obesity-induced cardiomyopathy, suggesting LM9 to be a promising therapeutic candidate drug for the obesity-related cardiac complications.

Remedial dosing recommendations for delayed or missed doses of lamotrigine in pediatric patients with epilepsy using Monte Carlo simulations.

OBJECTIVE: This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of lamotrigine (LTG) in children with epilepsy and established remedial dosing recommendations for nonadherent patients. METHODS: The Monte Carlo simulation based on a published LTG population PK model was used to assess the effect of different scenarios of nonadherence and the subsequently administered remedial regimens. The following three remedial approaches were investigated for each delayed dose: A) A partial dose was administered immediately, and the regular dose was administered at the next scheduled time. B) The delayed dose was administered immediately, followed by a partial dose at the next scheduled time. C) The delayed and partial doses were coadministered immediately, the next scheduled dose was skipped, and the regular dosing was resumed at the subsequent scheduled time. The most appropriate remedial regimen was that with the shortest deviation time from the individual therapeutic window. RESULTS: The effect of nonadherence on PK was dependent on the delay duration and daily dose, and the recommended remedial dose was related to the delay duration and concomitant antiepileptic drugs. Remedial dosing strategies A and B were almost equivalent, whereas C showed a larger PK deviation time. If one dose was missed, double doses were not recommended for the next scheduled time. CONCLUSIONS: Simulations provide quantitative insight into the remedial regimens for nonadherent patients, and clinicians should select the optimal regimen based on the status of patients.

[Adding Ondansetron in Morphine Intravenous Analgesia Pump for Prevention of Postoperative Nausea and Vomiting in Women].

Objective To evaluate the application of adding ondansetron in morphine intravenous analgesia pump for prevention of postoperative nausea and vomiting(PONV)in women. Methods Data of surgical female inpatients who received general anesthesia and postoperative intravenous analgesia with morphine in our center from January 1st,2013 to December 31st,2014 were retrospectively analyzed. Based on whether ondansetron was added,patients were divided into the observation group(n=834) and the control group(n=856). Outcome variables including morphine consumption,visual analogue scale(VAS) score,nausea score,and total times of vomiting within 48 hours after surgery were collected and compared. Results Age(t=0.432,P=0.665),morphine consumption during the first post-operative day(t=0.599,P=0.548) and during the second post-operative day(t=0.236,P=0.813),maximum VAS score of postoperative pain during movement during the first post-operative day [3(2,4) vs. 3(2,5);Z=1.850,P=0.064] and at rest during the second post-operative day [0(0,1) vs. 0(0,1);Z=1.511,P=0.131] were not significantly different between two groups. While the maximum VAS score of postoperative pain at rest during the first post-operative day [0(0,2) vs.0(0,2);Z=2.435,P=0.015] and during movement during the second post-operative day [3(1,3)vs.3(2,4);Z=3.445,P=0.001] were significantly different between two groups. The maximum score of postoperative nausea(χ2=9.810,P=0.020) and cumulative frequency of postoperative vomiting(Z=3.726,P=0.002)in the observation group were significantly lower than those in the control group during the first post-operative day;however,there was no significant difference during the second post-operative day(χ2=5.017,P=0.170;Z=0.000,P=1.000). Logistic regression analysis showed that adding ondansetron in morphine intravenous analgesia pump was an independent influencing factor of reduced postoperative nausea. The probability of nausea during the first post-operative day was 0.781 time(P=0.015)of that in the control group and 0.736 time(P=0.030)during the second post-operative day. Conclusion Adding ondansetron in morphine intravenous analgesia pump may reduce PONV in women.

[Retrospective Analysis of 16 Cases Receiving Cardiopulmonary Resuscitation in the Operating Room among 127 053 Anesthetics Undergoing Non-cardiac Surgeries].

Objective To identify the high-risk factors of cardiac arrest during non-cardiac surgery and to provide experience for the effective cardiopulmonary resuscitation (CPR). Method The baseline data,co-morbidities,causes of cardiac arrest,treatment responsees,and survivals of 16 patients undergoing CPR among 127 053 patients receiving non-cardiac surgeries in our center from January 2013 to December 2016 were retrospectively analyzed. Results The main causes of intraoperative CPR included the co-existing cardiovascular diseases,massive intraoperative blood loss/high-risk surgical procedures,and allergy-related factors. Nine patients survived after immediate CPR in the operating room,with a 30-day survival rate of 77.8%. Conclusions Intraoperative cardiac arrest is a rare but potentially catastrophic event during non-cardiac surgeries. The success rate of CPR decreases in elderly patients undergoing high-risk emergency surgeries,especially when massive blood loss occurs during the surgery.

A high-sensitivity electrochemical aptasensor of carcinoembryonic antigen based on graphene quantum dots-ionic liquid-nafion nanomatrix and DNAzyme-assisted signal amplification strategy.

In this work, we have developed an electrochemical aptasensor for high-sensitivity determination of carcinoembryonic antigen (CEA) based on lead ion (Pb2+)-dependent DNAzyme-assisted signal amplification and graphene quantum dot-ionic liquid-nafion (GQDs-IL-NF) composite film. We designed hairpin DNA containing CEA-specific aptamers and DNAzyme chains. In the presence of CEA, hairpin DNA recognized the target and performed a DNAzyme-assisted signal amplification reaction to yield a large number of single-stranded DNA. The GQDs-IL-NF composite film was immobilized on the glassy carbon electrode for the interaction with single-stranded DNA through noncovalent π-π stacking interaction. Therefore, the methylene blue-labeled substrate DNA (MB-substrate) was fixed on the electrode and exhibited an initial electrochemical signal. Under optimal conditions, the response current change was proportional to the concentration of CEA, demonstrating a wide linear range from 0.5fgmL-1 to 0.5ngmL-1, with a low detection limit of 0.34fgmL-1. Furthermore, the proposed aptasensor was successfully applied in determining CEA in serum samples, showing its superior prospects in clinical diagnosis.

Comparison of learning performance of 2 intubating laryngeal mask airways in novice: A randomized crossover manikin study.

BACKGROUND: Intubating laryngeal mask airways (LMAs) such as i-gel and Aura-i could serve as rescue devices in resuscitation and further ensure the airway by facilitating trachea intubation without ventilation interruption. But data regarding intubating LMAs in novice are limited and skill degeneration without regular training has not been evaluated. So we designed this prospective randomized crossover manikin study to compare the learning performance of 2 intubating LMAs (i-gel and Aura-i). METHODS: In total, 46 novice doctors participated in this study. After standardized training and finishing 3 consecutive successful intubations with both LMAs on manikin, each participant applied intubation with both LMAs in random order for initial evaluation. To evaluate skill retention, participants were reassessed 90 days later on the same manikin without retraining between times. Primary outcome was time to successful ventilation (TTV). RESULTS: The TTV for i-gel was significantly shorter than Aura-i (initial evaluation 11.8 ±â€Š2.9 seconds vs 22.4 ±â€Š5.2 seconds, 90-days reevaluation 14.9 ±â€Š3.6 seconds vs 28.9 ±â€Š10.0 seconds, initial evaluation, P = .001; second evaluation, P < .001); during re-evaluation, TTV taken for i-gel and Aura-i were both significantly longer (initial evaluation, P = .001; second evaluation, P < .001) and ease score of insertion both increased profoundly (i-gel P = .025; Aura-i P < .001). In both assessments, participants preferred i-gel as easier alternative (initial evaluation, P = .001; second evaluation, P < .001). There was no difference in successful intubation rate, first attempt success rate, bronchoscopy assessment, and insertion score for 2 LMAs. CONCLUSION: Compared with Aura-i, i-gel showed a faster and easier intubation by novice doctors in this manikin study; the skill retention of intubation performance after 3 months was acceptable for both intubating LMAs, but TTV prolonged significantly.

Endoscopic retrograde cholangiopancretography in modified double tracks anastomosis with anastomotic stenosis.

A 63-year-old man presented at our hospital with right upper abdomen pain and fever for 4 d. The patient's magnetic resonance cholangiopancreatography revealed dilated common bile duct and choledocholithiasis. In his past history, he received proximal gastrectomy and modified double tracks anastomosis. Endoscopic retrograde cholangiopancretography in modified double tracks anastomosis, especially accompanied with anastomotic stenosis, has been rarely reported. In the present case, the duodenoscope was successfully introduced over the guidewire and the stone taken out using a basket. The patient had good palliation of his symptoms after removal of the stone.

Low level of swiprosin-1/EFhd2 in vestibular nuclei of spontaneously hypersensitive motion sickness mice.

Susceptibility to motion sickness (MS) varies considerably among humans. However, the cause of such variation is unclear. Here, we used a classical genetic approach to obtain mouse strains highly sensitive and resistant to MS (SMS and RMS). Proteomics analysis revealed substantially lower swiprosin-1 expression in SMS mouse brains. Inducing MS via rotary stimulation decreased swiprosin-1 in the mouse brains. Swiprosin-1 knockout mice were much more sensitive to motion disturbance. Immunohistochemistry revealed strong swiprosin-1 expression in the vestibular nuclei (VN). Over-expressing swiprosin-1 in the VN of SMS mice decreased MS susceptibility. Down-regulating swiprosin-1 in the VN of RMS mice by RNAi increased MS susceptibility. Additional in vivo experiments revealed decreased swiprosin-1 expression by glutamate via the NMDA receptor. Glutamate increased neuronal excitability in SMS or swiprosin-1 knockout mice more prominently than in RMS or wild-type mice. These results indicate that swiprosin-1 in the VN is a critical determinant of the susceptibility to MS.

miR-24 suppression of POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) protects endothelial cell from diabetic damage.

The regulatory transcriptional factor PATZ1 is abnormally up-regulated in diabetic endothelial cells (ECs) where it acts as an anti-angiogenic factor via modulation of fatty acid-binding protein 4 (FABP4) signaling. The aim of the present work was to elucidate the upstream molecular events regulating PATZ1 expression in diabetic angiogenesis. The bioinformatics search for microRNAs (miRNAs) able to potentially target PATZ1 led to the identification of several miRNAs. Among them we focused on the miR-24 since the multiple targets of miR-24, which have so far been identified in beta cells, cardiomyocytes and macrophages, are all involved in diabetic complications. miR-24 expression was significantly impaired in the ECs isolated from diabetic hearts. Functionally, endothelial migration was profoundly inhibited by miR-24 suppression in Ctrl ECs, whereas miR-24 overexpression by mimics treatment effectively restored the migration rate in diabetic ECs. Mechanistically, miR-24 directly targeted the 3'untranslated region (3'UTR) of PATZ1, and miR-24 accumulation potentiated endothelial migration by reducing the mRNA stability of PATZ1. Together, these results suggest a novel mechanism regulating endothelial PATZ1 expression based on the down-regulation of miR-24 expression caused by hyperglycemia. Interfering with PATZ1 expression via miRNAs or miRNA mimics could potentially represent a new way to target endothelial PATZ1-dependent signaling of vascular dysfunction in diabetes.

Increased electrocatalyzed performance through hairpin oligonucleotide aptamer-functionalized gold nanorods labels and graphene-streptavidin nanomatrix: Highly selective and sensitive electrochemical biosensor of carcinoembryonic antigen.

We report a triplex signal amplification strategy for sensitive biosensing of cancer biomarker by taking advantage of hairpin-shaped oligonucleotide-functionalized gold nanorods (HO-GNRs), graphene and the avidin-biotin reation. The strategy expands electrochemical detection of carcinoembryonic antigen (CEA) by using an aptamer as biosensor's recognition element and HO-GNRs as signal enhancer. To construct this biosensor, the GNR was used as a carrier of horseradish peroxidase (HRP) and HO aptamer with a biotin at the 3'-end and a thiol at the 5'-end, which amplified the electrochemical response because of a large molar ratio of HRP to HO. In the presence of target CEA, the binding reactions of CEA with the loop portions of the HOs caused HOs' loop-stem structure opened and exposed the biotins, and then HRP-GNRs-HO conjugates were captured on graphene and streptavidin modified electrodes via the reaction between the exposed biotins and preimmobilized streptavidins. The accumulation of HRP effectively catalyzed the hydrogen peroxide-mediated oxidation of o-phenylenediamine to generate an electrochemical reduction current for CEA detection. Under optimal conditions, the electrochemical biosensor exhibited a wide dynamic range of 5pgmL(-1) and 50ngmL(-1) toward CEA standards with a low detection limit of 1.5pgmL(-1) (signal-to-noise ratio of 3). The proposed biosensor accurately detected CEA concentration in 8 human serum samples from patients with lung diseases, showing excellent correlations with standard chemiluminescence immunoassay. Furthermore, these results of target DNA detection made it abundantly clear that the proposed strategy can also be extended for detection of other relative biomarkers using different functional DNA structures, which shows great prospects in single-nucleotide polymorphisms analysis, biomedical sensing and application for accurate clinical diseases diagnostic.

Predictors for Massive Blood Loss During Posterior Correction of Congenital Scoliosis in Pre-school Children:A Retrospective Observation.

Objective To investigate the predictors for massive blood loss during posterior correction of congenital scoliosis in pre-school children. Methods Totally 124 children under six years of age,who received posterior correction of congenital scoliosis,were divided into two groups according to the ratio of intraoperative blood loss (BL) and estimated blood volume (EBV). Massive blood loss was defined as BL/EBV>0.15,and minor or moderate blood loss as BL/EBV≤0.15. All the records,including demographics,intraoperative fluids,pre- or postoperative laboratory parameters,and the length of hospital stay,were compared between these two groups. Results There were 57 children in the moderate or minor blood loss group and 67 children in the massive blood loss group. When compared with moderate or minor blood loss group,children in massive blood loss group had significantly lower body weight,shorter body height,longer anesthesia period,and more autologous or allogeneic transfusion (P<0.05). Binary Logistic regression analysis showed that body weight lower than 15 kg was the independent predictor for massive blood loss (OR=0.435,95% CI=0.197-0.962). Conclusions The incidence of massive blood loss is about 54% in children under six years of age who have received posterior correction of congenital scoliosis. The body weight of lower than 15 kg is an independent predictor for massive blood loss during the surgery.

Two-year follow-up for 45 patients with achalasia who underwent peroral endoscopic myotomy.

OBJECTIVES: Achalasia is an oesophageal disorder characterized by abnormalities of peristalsis and impaired swallowing-induced relaxation. The therapeutic approach at present remains palliative. Peroral endoscopic myotomy (POEM) is thought to be less invasive and to maintain the function of the lower oesophageal sphincter postoperatively. However, the effects of POEM still need to be evaluated and understood. METHODS: We analysed the outcome for 45 achalasia patients who underwent POEM in our centre, described the details of surgery and evaluated the effects by 4 s integrated relaxation pressure (4s-IRP). All patients were followed up for at least 2 years and were assessed by the dysphagia score, the Eckardt score, oesophageal manometry and the gastro-oesophageal reflux disease (GERD) Q-questionnaire. According to the new Chicago classification of oesophageal motility using high-resolution manometry, the patients were diagnosed and classified into types I, II and III. RESULTS: The average age of the patients was 46.32 ± 19.04 years (range 26-72 years), and the ratio of women to men was 1.81. All patients were suffering from dysphagia; more than half of them experienced regurgitation. The data revealed that POEM considerably reduced the 4s-IRP, dysphagia score and Eckardt score postoperatively (all P < 0.05). The patients with type III achalasia had higher values of 4s-IRP than the others (type I, P = 0.025; type II, P = 0.022) before treatment and at 3 months after treatment (type I, P = 0.028; type II, P = 0.047). In type I patients, GERD symptoms were more likely to appear at 24 months after POEM than in type II and III patients (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: Peroral endoscopic myotomy provides definite relief of symptoms in these patients with achalasia and offers them long-term therapeutic benefit. Considering the risks of surgery, we believe that POEM is a better choice than surgery for achalasia patients and carries lower risk. However, our study is a preliminary exploration; therefore, larger-scale studies are needed for further research on POEM.

Evaluation of risk factors for arytenoid dislocation after endotracheal intubation: a retrospective case-control study.

OBJECTIVE: To investigate the risk factors for postoperative arytenoid dislocation. METHODS: From September 2003 to August 2013, the records of 16 patients with a history of postoperative arytenoid dislocation were reviewed. Patients matched in terms of date and type of procedures were chosen as the controls (n=16). Recorded data for all patients were demographics, smoking status, alcoholic status, preoperative physical status, airway evaluation, intubation procedures, preoperative laboratory test results, anesthetic consumption and intensive care unit stay. For arytenoid dislocation cases, we further analyzed the incidences of the left and right arytenoid dislocation, and the outcomes of surgical repair and conservative treatment. Categorical variables were presented as frequencies and percentages, and were compared using the chi-squared test. Continuous variables were expressed as means±SD and compared using the Student's unpaired t-test. To determine the predictors of arytenoid dislocation, a logistic regression model was used for multivariate analysis. RESULTS: Sixteen patients with postoperative arytenoid dislocation were enrolled, with a median age of 52 years. Most postoperative arytenoid dislocation patients (15/16, 93.75%) received surgical repair, except one patient who recovered after conservative treatment. None of the postoperative arytenoid dislocation patients were smokers. Red blood cell (P=0.044) and hemoglobin (P=0.031) levels were significantly lower among arytenoid dislocation cases compared with the controls. CONCLUSIONS: Non-smoking and anemic patients may be susceptible to postoperative arytenoid dislocation. However, neither of them was independent risk factor for postoperative arytenoid dislocation.

Effect of low-frequency rTMS on aphasia in stroke patients: a meta-analysis of randomized controlled trials.

BACKGROUND: Small clinical trials have reported that low-frequency repetitive transcranial magnetic stimulation (rTMS) might improve language recovery in patients with aphasia after stroke. However, no systematic reviews or meta-analyses studies have investigated the effect of rTMS on aphasia. The objective of this study was to perform a meta-analysis of studies that explored the effects of low-frequency rTMS on aphasia in stroke patients. METHODS: We searched PubMed, CENTRAL, Embase, CINAHL, ScienceDirect, and Journals@Ovid for randomized controlled trials published between January 1965 and October 2013 using the keywords "aphasia OR language disorders OR anomia OR linguistic disorders AND repetitive transcranial magnetic stimulation OR rTMS". We used fixed- and random-effects models to estimate the standardized mean difference (SMD) and a 95% CI for the language outcomes. RESULTS: Seven eligible studies involving 160 stroke patients were identified in this meta-analysis. A significant effect size of 1.26 was found for the language outcome severity of impairment (95% CI = 0.80 to 1.71) without heterogeneity (I2 = 0%, P = 0.44). Further analyses demonstrated prominent effects for the naming subtest (SMD = 0.52, 95% CI = 0.18 to 0.87), repetition (SMD = 0.54, 95% CI = 0.16 to 0.92), writing (SMD = 0.70, 95% CI = 0.19 to 1.22), and comprehension (the Token test: SMD = 0.58, 95% CI = 0.07 to 1.09) without heterogeneity (I2 = 0%). The SMD of AAT and BDAE comprehension subtests was 0.32 (95% CI = -0.08 to 0.72) with moderate heterogeneity (I2 = 32%,P = 0.22). The effect size did not change significantly even when any one trial was eliminated. None of the patients from the 7 included articles reported adverse effects from rTMS. CONCLUSIONS: Low-frequency rTMS with a 90% resting motor threshold that targets the triangular part of the right inferior frontal gyrus (IFG) has a positive effect on language recovery in patients with aphasia following stroke. Further well-designed studies with larger populations are required to ascertain the long-term effects of rTMS in aphasia treatment.

Genetic polymorphism of 15 Y chromosomal STR loci and haplotypes of Henan Han population.

We studied and established a DNA database of 15 Y-STRs (DYS438, DYS446, DYS391, DYS390, DYS458, DYS534, DYS426, DYS626, DYS504, DYS505, DYS576, DYS532, DYS594, DYS522, DYS540) in a population sample of 102 unrelated, healthy, male individuals of Henan Han population. Allelic frequencies and statistical parameters of Han population were calculated. Totally 90 alleles were observed, with the corresponding allelic frequencies ranging from 0.0098 to 0.9020. 102 haplotypes were found in the studied group, the haplotype diversity for 15 Y-STR loci was 1. The results of present study were valuable for human identification and paternity tests routine forensic applications in the region.

Genetic variations of human CYP2D6 in the Chinese Han population.

AIM: The purpose of this study was to determine the genetic polymorphisms of the CYP2D6 gene and to elucidate the allele distribution pattern in the Chinese Han population. MATERIALS & METHODS: We used PCR and bidirectional sequencing methods to analyze all nine exons of the CYP2D6 gene in 2129 unrelated, healthy Chinese Han subjects from two geographical locations in China: the northern and southern regions. RESULTS: In total, 165 mutated sites were detected in 2129 participants, of which 67 sites were reported for the first time. Among these novel mutation sites, 22 were nonsynonymous and 12 were named as novel alleles (*87-*93, *94A, *94B and *95-*98) by the Human CYP Allele Nomenclature Committee. In addition, 29 previously reported alleles and 84 genotypes were also detected in 1954 volunteers. Functional prediction of novel variants revealed that eight variants might have a deleterious effect on CYP2D6. Linkage disequilibrium analysis and tagSNP selection were performed separately. By using these methods, distinct differences were found between the two regions. CONCLUSION: This study provides the most comprehensive data concerning CYP2D6 polymorphisms in the Chinese Han population to date and increases the number of known alleles; these findings may greatly contribute to the development of personalized medicine for the Chinese Han population.