[The prediction value of combined serum levels of TMAO and TML for poor prognosis in patients with heart failure].

Objective: To evaluate the predictive value of combined serum levels of trimethylamine N-oxide (TMAO) and trimethyllysine (TML) for poor prognosis in patients with heart failure. Methods: This single-center prospective cohort study included hospitalized patients with heart failure and complete baseline data from the Department of Cardiology at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2017 to December 2020. Patients were categorized into four groups based on median serum levels of TMAO and TML after admission: TMAO low level TML low level group (TMAO<9.7 µmol/L, TML<0.73 µmol/L), TMAO low level TML high level group (TMAO<9.7 µmol/L, TML≥0.73 µmol/L), TMAO high level TML low level group (TMAO≥9.7 µmol/L, TML<0.73 µmol/L) and TMAO high level TML high level group (TMAO≥9.7 µmol/L, TML≥0.73 µmol/L). The primary endpoint was a composite endpoint of cardiovascular death and readmission for heart failure. Multiple factor Cox regression analysis was conducted to evaluate the correlation between serum TMAO and TML levels and poor prognosis in patients with heart failure. Results: A total of 471 patients with heart failure were included, with an mean age of (62.5±12.0) years and a median follow-up time of 1.61 (1.06, 2.90) years. Multivariate Cox regression analysis showed that after adjusting for age, gender, and traditional risk factors, the TMAO high level TML high level group had a higher incidence of primary endpoint events compared to the TMAO low level TML low level group (HR=1.71, 95%CI 1.05-2.77, P=0.03). Conclusion: Elevated serum levels of both TMAO and TML can effectively predict the occurrence of long-term adverse events in patients with heart failure.

[Research progress in N6-methyladenosine modification in the field of stomatology].

N6-methyladenosine (m6A) is the most abundant and widely distributed internal RNA modification in eukaryotic cells, and it is involved in the regulation of gene expression and biological processes in many cells. In recent years, studies on the role of m6A modification in oral cavity have emerged gradually. Existing researches show that m6A-related proteins are involved in the regulation of oral squamous cell carcinoma and its resistance to therapy. Methyltransferase-like 3 regulates apoptosis and autophagy of chondrocytes in inflammation, the angiogenesis and osteogenesis during distraction osteogenesis of endothelial progenitor cells, inflammatory response of dental pulp cells, the differentiation and osteogenesis of dental pulp stem cells, the development of tooth roots and the differentiation of bone marrow mesenchymal stem cells and so on. Moreover, m6A modification may also be related to the occurrence and development of periodontitis, oral ulcers and oral submucosal fibrosis. These studies have provided new ideas for the pathogenesis of various oral diseases and the diagnosis and treatment of oral bone tissue repair and regeneration. This paper reviews the recent research progress on the role of m6A modification in the field of stomatology and summarize the current research status of m6A in the field of stomatology, in order to provide reference for the further research of m6A function and mechanism in the field of stomatology.

[A prospective study on association between sleep duration and the risk of chronic obstructive pulmonary disease in adults in Suzhou].

Objective: To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou. Methods: The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio (HR) values and their 95%CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results: The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD (HR=1.42, 95%CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers (HR=2.49, 95%CI: 1.35-4.59, interaction P<0.001). Conclusion: Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

[Efficacy and safety of pulsed radiofrequency combined with gabapentin in the treatment of acute herpetic neuralgia].

Objective: To explore the clinical efficacy and safety of pulsed radiofrequency (PRF) combined with gabapentin in the treatment of acute herpetic neuralgia (AHN). Methods: A total of 123 AHN patients were retrospectively selected in Henan Provincial People's Hospital from November 2019 to July 2022, who were divided into two groups based on treatment methods: control group (treated with gabapentin, n=61) and study group (treated with gabapentin and PRF, n=62). The visual analog scale (VAS) was utilized for pain severity assessment and the self-rating scale for sleep (SRSS) was utilized for sleep quality evaluation. The differences in serum levels of interleukin (IL)-10, chemokine ligand 10 (CXCL-10), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), IL-2 and IL-6 before and after treatment were compared between the two groups. The overall treatment effectiveness and the occurrence rates of postherpetic neuralgia and adverse reactions were evaluated in both groups. Results: Among the study group patients, 28 were male and 34 were female, and the age was (62.8±8.5) years. Among the control group patients, 35 were male and 26 were female, and the age was (64.0±7.8) years. The VAS scores of the study group before and after treatment were 7.96±1.33 and 1.52±0.60, respectively, while the control group were 7.68±1.52 and 2.70±0.64. The SRSS scores before and after treatment in the study group were 31.74±5.90 and 12.06±2.81, respectively, while those in the control group were 33.10±5.54 and 14.14±2.96, respectively. Before treatment, there were no statistically differences of the VAS scores and SRSS scores in both groups (all P>0.05). After treatment, the VAS scores and SRSS scores in both groups decreased compared with before treatment (all P<0.05), the study group's VAS scores and SRSS scores were lower than those in the control group (all P<0.05). Before treatment, there were no statistically differences of the serum levels of IL-10, CXCL-10, PGE2, COX-2, IL-2 and IL-6 in both groups (all P>0.05). After treatment, the serum levels of IL-10, CXCL-10, PGE2, COX-2 and IL-6 in both groups decreased compared with before treatment, while the IL-2 level increased. Additionally, the study group had lower serum levels of IL-10, PGE2, COX-2 and IL-6 compared with the control group (all P<0.05). After treatment, the study group had 35 cases of cure, 26 cases of effectiveness, and 1 case of ineffectiveness, while the control group had 22 cases of cure, 31 cases of effectiveness, and 8 cases of ineffectiveness. The overall treatment efficacy of the study group was better than that of the control group (P=0.012). The incidence of postherpetic neuralgia in the study group after treatment was 16.1% (10/62), which was lower than that in the control group, which was 37.7% (23/61) (P<0.05). There were no statistically differences of the occurrence rates of adverse reactions in both groups (all P>0.05). Conclusion: Combining PRF with gabapentin for the treatment of AHN demonstrates better overall efficacy and safety, which can more effectively alleviate pain, improve sleep, and reduce inflammatory cytokine levels.

Investigating a Causal Relationship Between Diabetes Mellitus and Oropharyngeal Cancer: A Mendelian Randomization Study.

OBJECTIVE: Previous observational studies reported an association of diabetes mellitus (DM) with oropharyngeal cancer (OPC), however, the potential causality of the association between them remains unclear. METHODS: To explore this causal relationship in individuals of European descent, a two-sample Mendelian randomization (MR) study was conducted. A genome-wide association study (GWAS) of DM was used to represent the exposure factor (T1DM: n = 24,840; T2DM: n = 215,654), and GWAS of OPC represented the outcome (n = 3,448). RESULTS: Forty-one single nucleotide polymorphisms (SNPs) related to T1DM and fifty-four SNPs related to T2DM were identified as effective instrumental variables (IVs) in the two-sample MR analyses. In IVW estimates, neither T1DM nor T2DM significantly contributed to an increased risk of OPC [T1DM: OR 1.0322 (95% CI 0.9718, 1.0963), P = 0.3033; T2DM: OR 0.9998 (95% CI 0.9995, 1.0002), P = 0.2858]. Four other regression models produced similar results. MR-Egger regression results [Cochran's Q statistic was 47.1544 (P = 0.1466) in T1DM, and 35.5084 (P = 0.9512) in T2DM] suggested no horizontal pleiotropy between IVs and outcomes. CONCLUSION: Our findings suggest little evidence to support the genetic role of diabetes mellitus in OPC development in the European population.

[Incidence of chronic obstructive pulmonary disease and risk factors in the Suzhou cohort].

Objective: To understand the incidence of chronic obstructive pulmonary disease (COPD) in the Suzhou cohort, and explore the risk factors for the development of COPD in Suzhou, and provide a scientific basis for COPD prevention. Methods: This study was based on the China Kadoorie Biobank project in Wuzhong District, Suzhou. After excluding individuals with airflow obstruction and self-reported chronic bronchitis, emphysema, or pulmonary heart disease at baseline, 45 484 individuals were finally included in the analysis. Cox proportional risk models were used to analyze risk factors of COPD and calculate hazard ratios and 95% confidence interval (CI) in the Suzhou cohort. The effect modifications of smoking on the association between other risk factors and COPD were evaluated. Results: Complete follow-up was available through December 31, 2017. Participants were followed up for a median of 11.12 years, and 524 individuals were diagnosed with COPD during the follow-up period; the incidence was 105.54 per 100 000 person-years. Multivariate Cox proportional risk regression models showed that age (HR=3.78, 95%CI:3.32-4.30), former smoking (HR=2.00, 95%CI:1.24-3.22), current smoking (<10 cigarettes/day, HR=2.14, 95%CI:1.36-3.35;≥10 cigarettes/day, HR=2.69, 95%CI:1.60-4.54), history of respiratory disease (HR=2.08, 95%CI:1.33-3.26), daily sleep duration ≥10 hours (HR=1.41, 95%CI:1.02-1.95) were associated with increased risk of COPD. However, education level of primary school and above (primary or junior high school, HR=0.65, 95%CI:0.52-0.81; high school and above, HR=0.54, 95%CI:0.33-0.87), consuming fresh fruit daily (HR=0.59, 95%CI:0.42-0.83) and consuming spicy food weekly (HR=0.71, 95%CI:0.53-0.94) were associated with reduced risk of COPD. Conclusions: The incidence of COPD is low in Suzhou. Older age, smoking, history of respiratory disease, and long sleep duration were risk factors for the development of COPD in the Suzhou cohort.

[Follow-up study on the relationship between changes in waist circumference and body weight and changes in blood pressure levels among high cardiovascular risk population].

Objective: To investigate the relationship between changes in waist circumference, body weight, and blood pressure change in a high cardiovascular risk population and to provide a theoretical basis and reference for the prevention and treatment of hypertension and cardiovascular disease. Methods: A total of 12 931 patients with a high risk of cardiovascular disease participating in the follow-up survey in 2016 were selected as the study subjects, and their long-term follow-up data from 2017 to 2019 were included in the analysis. Statistical analysis was performed using a t-test, χ2 test, and generalized estimation equation (GEE). Results: Increased waist circumference, body weight, and BMI were associated with a higher risk of elevated blood pressure in people at high risk of cardiovascular disease. Waist circumference, weight, and BMI were reduced when blood pressure levels were lower. SBP and DBP increased by 0.200 (95%CI: 0.164-0.236) mmHg and 0.085 (95%CI: 0.066-0.105) mmHg for each 1 cm increase of waist circumference. SBP increased by 0.355 (95%CI: 0.289-0.421) mmHg and DBP increased by 0.182 (95%CI: 0.144-0.220) mmHg for each 1 kg increase in body weight. For each 1 kg/m2 increase in BMI, SBP increased by 1.100 (95%CI: 1.194-1.258) mmHg, and DBP increased by 0.365 (95%CI: 0.273-0.456) mmHg. Compared with urban residents, SBP changes more with waist circumference and body weight, and DBP changes more with waist circumference in high-risk cardiovascular disease groups (all P for interaction <0.05). SBP with waist circumference and BMI and DBP with BMI was greater in participants without hypertension than in those with hypertension (all P for interaction <0.05). Conclusion: There is a positive linear correlation between the changes in waist circumference, body weight, and BMI and the changes in blood pressure in a high-risk cardiovascular disease population.

A novel polychromator calibration method for Thomson scattering diagnostics.

Polychromators are most frequently used in Thomson scattering (TS) diagnostics to analyze the scattered light spectrum and intensity so that the plasma electron temperature (Te) and density (ne) can be derived. For Te measurements, the spectral response of the polychromator channels and the relative spectral responsivities need to be calibrated. The spectral response is calibrated with a bromine tungsten lamp and a monochromator in a conventional way. A novel method for calibrating the relative spectral responsivities of the polychromators is described in detail. A broadband pulsed Light Emission Diode (LED) is used, which has a spectral irradiance similar to that of the TS spectrum, and the LED can be driven in pulse mode with the pulse width similar to the TS signal pulse width of about 10-20 ns full width at half maximum. This new method allows for the calibration to be done after the polychromator is fully installed, and in situ system calibration can be easily performed, showing the advantages of accuracy, simplicity, efficiency, and flexibility. For ne measurements, absolute sensitivity calibration is done by Rayleigh scattering with argon gas. Formulas for calculating the plasma density from the calibration data and the polychromator signals from the off-laser wavelength channels are presented.

Thomson scattering diagnostic system for the XuanLong-50 experiment.

A 15-point Thomson scattering diagnostic system is developed for ENN's spherical torus experiment XuanLong-50 (EXL-50). A BeamTech laser with 3 J/pulse (1064 nm wavelength) at 50 Hz repetition rate is chosen for measurements during EXL-50 plasma operations. To enable measurements at low density (∼0.5 × 1018 m-3) plasma operations, the opto-mechanical subsystems are carefully designed to maximize the collection and transmission of the scattered light and to minimize the stray light level. In addition, the high bandwidth trans-impedance amplifiers and segmented high speed waveform digitizers allow for the application of muti-pulse averaging to further improve the signal-to-noise ratio. Details of the diagnostic system are described and initial experimental results are presented.

[Epidemiological characteristics and influencing factors for high risk cardiovascular disease population in Jiangsu province].

Objective: To investigate the detection types and aggregation of high-risk population of cardiovascular disease (CVD) in Jiangsu province and the related influencing factors to provide reference for the prevention and control of cardiovascular disease. Methods: A total of 120 211 participants were included in the investigation. Information was collected by questionnaire based survey, physical examination and biochemical tests. χ2 test and multivariate logistic regression were used for statistical analysis. Results: The detection rate of CVD high risk was 25.03%. The detection rates were 19.01%, 4.85%, 3.18% and 5.31% for hypertension, dyslipidemia, cardiovascular history and WHO assessed risk ≥20% types, respectively. Male, rural, old age, low education level, low family income, drinking, waist circumference exceeding standard, overweight and obesity were risk factors of CVD (all P<0.01). The composition ratios of aggregation of 1, 2 and ≥3 high risk types of CVD were 74.01%, 22.91% and 3.08%, respectively. With the increase of aggregation types, the correlation strength increased with age, rural residents, education level and annual family income. Conclusion: Targeted measures should be carried out according to different influencing factors for the prevention and control of CVD in Jiangsu province in order to achieve the maximum prevention and control effect with the minimum cost.

[Mediating effect of physical activity on association between sedentary leisure-time and obesity indexes among hypertensive individuals].

Objective: To explore the mediating effect of physical activity on association between sedentary leisure-time and obesity indexes among hypertensive individuals. Methods: After excluding of those with a prior history of heart disease, stroke and cancer, a total of 20 178 hypertensive participants in the China Kadooire Biobank (CKB) study from Wuzhong district of Suzhou city were included. Mediating effect analysis was used to analyze the mediating effect of physical activity (PA) on correlation between sedentary leisure-time and body fat percentage (BFP), waist circumference (WC) and body mass index (BMI). Results: After adjusted for age, gender, smoking status, alcohol consumption, education levels, intake frequencies of meat and intake frequencies of fresh fruit, sedentary leisure-time (SLT) was negatively correlated with PA (ß=-0.246, P<0.001), but positively associated with BFP (ß=0.061, P<0.001), WC (ß=0.087, P<0.001) and BMI (ß=0.071, P<0.001). After including the mediator variable PA, the direct effect of SLT on obesity index was still significant. PA was negatively correlated with BFP, WC and BMI (ß=-0.052, -0.083 and -0.028, respectively, P<0.001). Analysis of mediating effect indicated that the association of SLT with BFP, WC and BMI were partly mediated by PA, the proportion of mediating effect was 20.820%, 23.421% and 9.915%. Stratified by gender, PA had mediating effect on SLT and all obesity indexes in women, while only on SLT and BFP and WC in men. Conclusions: There is a significant mediating effect of PA on correlation between SLT and obesity indexes among hypertensive individuals. Hypertensive patients should increase the level of physical activity and reduce sedentary behavior to achieve a profounder healthy effect.

[Association between occupational hazard exposures and small airway function among middle-aged and elderly people].

Objective: To investigate the association between occupational hazard exposures and small airway function among middle-aged and elderly people. Methods: From July to December in 2015, a multistage cluster random sampling method was used to select 3 600 residents aged 40 years old and above from 6 chronic obstructive pulmonary disease surveillance points in Jiangsu province. A cross-sectional survey was conducted to collect relevant information. Multivariable linear regression model was performed to determine the relationship between occupational hazard exposures and small airway function. Results: A total of 3 347 participants were included in the final analysis, and 44.6% of participants had been exposed to occupational hazard exposures. Compared with participants without the exposure history of occupational hazards, the significantly lower post-bronchodilator FEF50%, FEF75% and MMEF levels were observed in those with the exposure history of occupational hazards (ß=-82.74, -55.43 and -91.57, respectively). Post-bronchodilator FEF75% and MMEF (ß=-51.78 and -79.47, respectively) in the participants with the exposure history of occupational dust and post-bronchodilator FEF50%, FEF75% and MMEF (ß=-96.84, -32.87 and -75.72, respectively) in the participants with the exposure history of occupational harmful gas all showed a lower level. Post-bronchodilator FEF75% was negatively associated with occupational hazard exposures in males (ßmale=-91.65 vs. ßfemale=-27.21, P for interaction=0.022). Conclusions: The small airway function is worse in the middle-aged and elderly population with the exposure history of occupational hazards, and it is more significant in the male population.

[Analysis on prediction power of HIV infection risk assessment tool in men who have sex with men in Guizhou province].

Objective: To evaluate the prediction power of HIV infection risk assessment tool and the applicability in MSM in Guizhou province. Methods: MSM were recruited through snowball sampling method. Questionnaire surveys were conducted among the MSM using HIV infection risk assessment tool, and combined with HIV serologic test results, the risk prediction power of HIV infection risk assessment tool was evaluated. Results: A total of 3 379 MSM were recruited from January 2018 to December 2019 in Guizhou. The HIV infection rate was 3.3%(111/3 379). The mean risk scores of HIV positive and HIV negative MSM were (12.15±3.08) and (12.07±3.07), respectively. The difference in risk score was significant between MSM with different HIV status (t=8.69, P<0.001). According to the principle of decision tree, individual risk scores were divided into following three categories: ≤11.96, 11.97-14.80 and >14.80, the HIV infection rate was 0.8%, 4.3% and 8.6% respectively, suggesting that the higher the individual risk score was, the higher the HIV infection rate was (trend χ2=88.18, P<0.001). Multivariate logistic regression analysis showed that the higher the individual risk score was, the higher the risk of HIV infection was. Compared to the total score ≤11.96, the aOR values at total scores of 11.97-14.80 and >14.80 were 6.34 (95%CI: 3.38-11.88) and 14.07(95%CI: 7.44-26.61), respectively. The risk of HIV infection in Miao ethnic group was higher than that in Han ethnic group (aOR=1.83, 95%CI:1.04-3.21), and the risk of HIV infection in those with education level of primary school and below was higher than that in undergraduates or those with education level of junior college and above (aOR=2.50, 95%CI:1.06-5.88), and the risk of HIV infection was higher in those who had bisexual behaviors than in those who had homosexual behaviors (aOR=1.95, 95%CI:1.19-3.19). The risk of HIV infection was higher in those who had never received HIV testing (aOR=1.53, 95%CI:1.01-2.33). The area under the receiver operating characteristic (ROC) curve and area under ROC (AUC) for HIV infection prediction was 0.751 (95%CI:0.710-0.792, P<0.001). The maximum Youden's index was individual risk score of 12.56, and the sensitivity of the risk assessment tool was 0.838, and its specificity was 0.412. Conclusions: The results of HIV infection risk assessment tool in Guizhou indicated that in MSM the higher the individual risk score, the higher the risk of HIV infection is. The tool can be used to evaluate the risk of HIV infection in MSM, but the specificity should be improved.

Time resolved absolute extreme ultraviolet radiation measurement on the ENN XuanLong-50 spherical tokamak.

A plasma radiation measurement system for a wide spectral range, based on compact Absolute eXtreme UltraViolet (AXUV) silicon photodiodes, has been implemented on the newly constructed ENN XuanLong-50 (EXL-50) spherical tokamak. The system consists of two 16-channel AXUV16ELG arrays and one AXUV63HS1 single-cell detector mounted on ceramic sockets. The two arrays, facing toward the EXL-50 slim central post from two locations inside a top and a side ConFlat 400 port, have 32 view chords covering the interested plasma region in a poloidal cross section at toroidal 330°. The single-cell detector, seated on a retractable feedthrough, could be arranged flexibly with the help of an ultra-high vacuum compatible gate valve. The design details together with considerations on the EXL-50 specific engineering realities and physics requirements are described. Preliminary results from the EXL-50 2020 experimental campaign are presented.

Toroidal soft x-ray array on the EXL-50 spherical tokamak.

A toroidal soft x-ray array system for spectrum and intensity measurements on the EXL-50 spherical tokamak is described. Silicon drift detectors and digital multichannel analyzers are adopted for all 21 channels of the array, and an average energy resolution of 147 eV at 5.89 keV has been achieved at count rates over 500 kcps. In total, 20 channels of the array are symmetrically observed in both co- and counter-current directions on the EXL-50 mid-plane with a spatial resolution of around 10 cm, and the remaining one serves as a background reference channel. Tungsten emissions from tungsten coating of the limiters on the central post are observed. The influence of hard x rays on measured soft x-ray spectra and system operation is discussed.

[A birth cohort study on the effect of chronotype during pregnancy on small for gestational age and the mediating effect of glucose-lipid metabolism].

Objective: To explore the relationship between maternal sleep time and the risk of small for gestational age (SGA), and to evaluate the role of glucose-lipid metabolism in the association. Methods: A total of 6 821 women who was second pregnancy were recruited from pregnancies consulted at Hefei First People's Hospital, Anhui Province Maternity & Child Health Hospital and the First Affiliated Hospital of Anhui Medical University from March 2015 to April 2019, and a face-to-face questionnaire survey was conducted to collect general demographic characteristics, dietary habits and routine lifestyles. Sleep information including bedtime, getup and sleep duration were reported by pregnant woman herself, and this survey as well as the third trimester of gestation. Pregnancy and birth outcomes were collected at delivery. A total of 5 488 mother-pairs with complete data were obtained in the final data. The non-linear relationship between chronotype and SGA risk was explored by restricted cubic spline regression model, and the role of glucose-lipid metabolism in the association between sleep midpoint and SGA was explored by using the mediating model based on bootstrap method. Results: The incidence of SGA was 8.4% (459/5 488) in eligible pregnant women. Compared with the pregnant women who went to bed before 21∶00, the risk of SGA of women who went to bed after 23∶00 am (OR=1.54, 95%CI: 1.01-2.34) was significantly higher in the multivariate logistic regression model. Additionally, the risk of SGA in pregnant women who got up after 8∶00 am was significantly higher than those women who got up before 8 o'clock (OR=1.31, 95%CI:1.05-1.62). However, the significant association between sleep duration and SGA was not found. In the restricted cubic spline regression, the risk of SGA was significantly increased from the specific midpoint of 02∶45 am (P<0.05). Moreover, mediation model showed that the negative effect of late sleep in the second trimester on SGA may be partially explained through glucose-lipid metabolism(all P<0.05). Conclusion: Maternal sleep status at the second trimester of gestation may be more susceptible to SGA. Lately sleep midpoint may be a potential independent risk factor for increased risk of SGA, and furtherly affect the occurrence of SGA by changing the level of glucose and lipid metabolism.

Large trans-ethnic meta-analysis identifies AKR1C4 as a novel gene associated with age at menarche.

STUDY QUESTION: Does the expansion of genome-wide association studies (GWAS) to a broader range of ancestries improve the ability to identify and generalise variants associated with age at menarche (AAM) in European populations to a wider range of world populations? SUMMARY ANSWER: By including women with diverse and predominantly non-European ancestry in a large-scale meta-analysis of AAM with half of the women being of African ancestry, we identified a new locus associated with AAM in African-ancestry participants, and generalised loci from GWAS of European ancestry individuals. WHAT IS KNOWN ALREADY: AAM is a highly polygenic puberty trait associated with various diseases later in life. Both AAM and diseases associated with puberty timing vary by race or ethnicity. The majority of GWAS of AAM have been performed in European ancestry women. STUDY DESIGN, SIZE, DURATION: We analysed a total of 38 546 women who did not have predominantly European ancestry backgrounds: 25 149 women from seven studies from the ReproGen Consortium and 13 397 women from the UK Biobank. In addition, we used an independent sample of 5148 African-ancestry women from the Southern Community Cohort Study (SCCS) for replication. PARTICIPANTS/MATERIALS, SETTING, METHODS: Each AAM GWAS was performed by study and ancestry or ethnic group using linear regression models adjusted for birth year and study-specific covariates. ReproGen and UK Biobank results were meta-analysed using an inverse variance-weighted average method. A trans-ethnic meta-analysis was also carried out to assess heterogeneity due to different ancestry. MAIN RESULTS AND THE ROLE OF CHANCE: We observed consistent direction and effect sizes between our meta-analysis and the largest GWAS conducted in European or Asian ancestry women. We validated four AAM loci (1p31, 6q16, 6q22 and 9q31) with common genetic variants at P < 5 × 10-7. We detected one new association (10p15) at P < 5 × 10-8 with a low-frequency genetic variant lying in AKR1C4, which was replicated in an independent sample. This gene belongs to a family of enzymes that regulate the metabolism of steroid hormones and have been implicated in the pathophysiology of uterine diseases. The genetic variant in the new locus is more frequent in African-ancestry participants, and has a very low frequency in Asian or European-ancestry individuals. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Extreme AAM (<9 years or >18 years) were excluded from analysis. Women may not fully recall their AAM as most of the studies were conducted many years later. Further studies in women with diverse and predominantly non-European ancestry are needed to confirm and extend these findings, but the availability of such replication samples is limited. WIDER IMPLICATIONS OF THE FINDINGS: Expanding association studies to a broader range of ancestries or ethnicities may improve the identification of new genetic variants associated with complex diseases or traits and the generalisation of variants from European-ancestry studies to a wider range of world populations. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by CHARGE Consortium grant R01HL105756-07: Gene Discovery For CVD and Aging Phenotypes and by the NIH grant U24AG051129 awarded by the National Institute on Aging (NIA). The authors have no conflict of interest to declare.

Forensic Application of Next Generation Sequencing Technology in the Typing of Y Chromosome Genetic Markers.

ABSTRACT: The paternal inheritance characteristics of Y chromosome have been widely used in the forensic genetics field to detect the genetic markers in the non-recombining block, and used in the studies such as, genetic relationship identification, mixed stain detection, pedigree screen and ethnicity determination. At present, capillary electrophoresis is still the most common detection technology. The commercial detection kits and data analysis and processing system based on this technology are very mature. However, the disadvantages of traditional detection technology have gradually appeared with the rapid growth of bio-information amount, which promotes the renewal of forensic DNA typing technology. In recent years, next generation sequencing （NGS） technology has developed rapidly. This technology has been applied to various fields including forensic genetics and has provided new techniques for the detection of Y chromosome genetic markers. This article describes the current situation and application prospects of the NGS technology in forensic Y chromosome genetic markers detection in order to provide new ideas for future judicial practice.

[Methods of repairing large soft tissue defect with latissimus dorsi myocutaneous flap and management of secondary wound in donor site].

Objective: To explore the methods of repairing large soft tissue defect with latissimus dorsi myocutaneous flap and the management of secondary wound in donor site. Methods: From June 2015 to June 2019, 30 patients with soft tissue defect caused by various reasons or hyperplastic scar were hospitalized in the First Medical Center of Chinese PLA General Hospital, including 10 males and 20 females, aged 25-64 years, with 18 cases of head soft tissue defects caused by the growth and rupture of tumor, 7 cases of hypertrophic scar in trunk and limbs, and 5 cases of facial and neck soft tissue defects caused by trauma. The area of primary wound after debridement or enlarged lesion resection was 14 cm×10 cm-18 cm×16 cm. Preoperative evaluation of 20 patients showed that the wound was relatively large, and the donor site could not be directly closed by suturing after resection of conventional single-lobe latissimus dorsi myocutaneous flap, so the bilobed latissimus dorsi myocutaneous flap with area of 14 cm×5 cm-18 cm×8 cm was cut to repair the wound, and the donor site was directly closed by suturing. Preoperative evaluation of 10 patients showed that the donor site could be directly closed by suturing after resection of conventional single-lobe latissimus dorsi myocutaneous flap, so that conventional single-lobe latissimus dorsi myocutaneous flap with area of 11 cm×9 cm-13 cm×10 cm was resected to repair the primary wound, resulting in big tension in donor site and secondary wound with area of 6 cm×4 cm-8 cm×6 cm that couldn't be directly sutured, which was repaired with donor site local flap with area of 7 cm×4 cm-9 cm×6 cm, and the second donor site was directly closed by suturing. Intraoperative end-to-end anastomosis was performed between the thoracodorsal arteries and veins of the latissimus dorsi myocutaneous flap and the arteries and veins of the primary recipient wound. The survival of latissimus dorsi myocutaneous flaps and local flaps were observed after surgery, and the appearance and function of the donor and recipient areas were observed during follow-up. Results: All the latissimus dorsi myocutaneous flaps and local flaps survived in the patients after surgery. Follow-up of 6-12 months showed that the latissimus dorsi myocutaneous flap was similar in color to the surrounding normal skin, with soft texture and good elasticity. The donor site of 20 patients repaired with bilobed latissimus dorsi myocutaneous flaps were only left with linear scars, among which 2 patients had hypertrophic scars and none had functional impairment. The donor site of 10 patients repaired with single-lobe latissimus dorsi myocutaneous flaps and donor site local flaps had good appearance, left with linear scar, irregular shape, but no local traction or dysfunction. Conclusions: When repairing a large soft tissue defect, the bilobed latissimus dorsi myocutaneous flap or the single-lobe latissimus dorsi myocutaneous flap combined with the local flap transfer in the donor site can be used after preoperative evaluation so that the donor site wound can be closed at one time while repairing the primary wound. The donor site has less scar, and both the recipient and donor sites have good appearance and function after surgery.