A new method was developed for simultaneous detection of total 19 kinds of organophosphate esters(OPEs)and their diester metabolites(di-OPEs)in human serum(1.0 mL)and urine(1.5 mL)with low volume of samples.The target compounds were determined using ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)after acetonitrile liquid-liquid extraction combined with purification using an ENVI-18 solid-phase extraction(SPE)column.OPEs and di-OPEs were separated using a Shim-pack GIST C18 column(100 mm×2.1 mm,2 μm)with a Shim-pack GIST-HP(G)C18 guard column.An electrospray ionization source(ESI)was employed in mass spectrometry analysis,with positive/negative ion mode using the multiple reaction monitoring(MRM).All target compounds were separated within 15 min,and exhibited good linear relationships in the concentration range of 2-100 ng/mL,with correlation coefficients(R2)above 0.994.The method detection limits(MDL)in serum ranged from 0.001 to 0.178 ng/mL and the MDL in urine ranged from 0.001 to 0.119 ng/mL.The recoveries of the analytes spiked in serum and urine matrices at two concentration levels were 30.5%-126.8%,with the relative standard deviations(RSDs)ranged from 1%to 23%.In addition,paired serum and urine samples from 11 patients were analyzed.For all samples tested,the internal standards of OPEs exhibited recoveries between 61%and 114%,whereas the internal standards for di-OPEs had recoveries ranging from 43%to 103%.OPEs and di-OPEs exhibited high detection frequencies in 22 serum and urine samples.Triethyl phosphate(TEP),tributyl phosphate(TBP),tris(2-ethylhexyl)phosphate(TEHP),tris(2-butoxyethyl)phosphate(TBEP),tris(1-chloro-2-propyl)phosphate(TCIPP),triphenyl phosphate(TPHP),tri-m-tolyl-phosphate(TMTP)and 2-ethylhexyl diphenyl phosphate(EHDPP)were universally detected in all serum samples.TCIPP was identified at the highest concentrations(median 0.548 ng/mL)in serum samples.In urine samples,the detection frequency for 12 kinds of target compounds reached 100%.Notably,TBP emerged as the predominant OPE in urine,demonstrating a median concentration of 0.506 ng/mL.Regarding di-OPEs,bis(2-chloroethyl)phosphate(BCEP)and bis(2-butoxyethyl)hydrogen phosphate(BBOEP)were the most abundant in urine,with median concentrations of 6.404 and 2.136 ng/mL,respectively.The total concentrations of OPEs and di-OPEs in serum and urine were 1.580-3.843 ng/mL and 5.149-17.537 ng/mL,respectively.These results not only confirmed the effectiveness of the method in detection of OPEs and di-OPEs in biological matrices,but also revealed the widespread presence of OPE compounds in human body and pointed to potential exposure risks.

Arthropods of medical importance such as mosquitoes, ticks and sandflies are one of the key drivers of arthropod-borne diseases outbreak, posing a great threat to global public health security. For further understanding the transmission mechanisms of arthropod-borne diseases and establishing the prevention and control measures, a series of experiments of arthropods infection need to be carried out under laboratory conditions. Besides the regular biosafety requirements, some specific considerations need to be taken into account when performing arthropod infection and the infected arthropod rearing. Except for the physical containment composed of biosafety facilities, a comprehensive assessment of the biosafety risks during operations and corresponding preventive measures are also critical to eliminate or mitigate the biosafety risks. In this paper, we introduce our practice in handling mosquito infection with Risk Group 2 pathogens in Arthropod Containment Level-2 (ACL-2) laboratory, with an aim to provide a reference for researchers in related fields.

Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.
Humans ; Cleft Palate/genetics* ; Cleft Lip/genetics* ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Risk Factors ; Polymorphism, Single Nucleotide

OBJECTIVES: To study the factors influencing the short-term (28 days) efficacy of initial adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasms syndrome (IESS), as well as the factors influencing recurrence and prognosis. METHODS: The clinical data were collected from the children with IESS who received ACTH therapy for the first time in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from April 2008 to January 2018 and were followed up for ≥2 years. The multivariate logistic regression analysis was used to evaluate the factors influencing the short-term efficacy of ACTH therapy, recurrence, and long-term prognosis. RESULTS: ACTH therapy achieved a control rate of seizures of 55.5% (111/200) on day 28 of treatment. Of the 111 children, 75 (67.6%) had no recurrence of seizures within 12 months of follow-up. The possibility of seizure control on day 28 of ACTH therapy in the children without focal seizures was 2.463 times that in those with focal seizures (P<0.05). The possibility of seizure control on day 28 of ACTH therapy in the children without hypsarrhythmia on electroencephalography on day 14 of ACTH therapy was 2.415 times that in those with hypsarrhythmia (P<0.05). The possibility of recurrence within 12 months after treatment was increased by 11.8% for every 1-month increase in the course of the disease (P<0.05). The possibility of moderate or severe developmental retardation or death in the children without seizure control after 28 days of ACTH therapy was 8.314 times that in those with seizure control (P<0.05). The possibility of moderate or severe developmental retardation or death in the children with structural etiology was 14.448 times that in those with unknown etiology (P<0.05). CONCLUSIONS Presence or absence of focal seizures and whether hypsarrhythmia disappears after 14 days of treatment can be used as predictors for the short-term efficacy of ACTH therapy, while the course of disease before treatment can be used as the predictor for recurrence after seizure control by ACTH therapy. The prognosis of IESS children is associated with etiology, and early control of seizures after ACTH therapy can improve long-term prognosis.
Child ; Humans ; Infant ; Adrenocorticotropic Hormone/therapeutic use* ; Spasms, Infantile/drug therapy* ; Treatment Outcome ; Seizures ; Electroencephalography/adverse effects* ; Spasm/drug therapy*

Objective To explore the optimal administration route of tranexamic acid (TXA) in shoulder arthroscopic surgery. Methods Patients undergoing arthroscopic rotator cuff repair were randomly divided into four groups: control group (without TXA treatment), intravenous group (TXA was intravenously administered 10 minutes before surgery), irrigation group (TXA was added to the irrigation fluid during subacromial decompression and acromioplasty), and intravenous plus irrigation group (TXA was applied both intravenously and via intra-articular irrigation). The primary outcome was visual clarity assessed with visual analog scale (VAS) score, and the secondary outcomes included irrigation fluid consumption and time to subacromial decompression and acromioplasty procedure. Results There were 134 patients enrolled in the study, including 33 in the control group, 35 in the intravenous group, 32 in the irrigation group, and 34 in the intravenous plus irrigation group. The median and interquartile range of VAS scores for the intravenous, irrigation, and intravenous plus irrigation groups were 2.70 (2.50, 2.86) (Z = -3.677, P = 0.002), 2.67 (2.50, 2.77) (Z = -3.058, P < 0.001), and 2.91 (2.75, 3.00) (Z = -6.634, P < 0.001), respectively, significantly higher than that of the control group [2.44 (2.37, 2.53)]. Moreover, the control group consumed more irrigation fluid than the intravenous group, irrigation group, and intravenous plus irrigation group (all P < 0.05). The intravenous plus irrigation group consumed less irrigation fluid than either the intravenous group or the irrigation group (both P < 0.001). There was no difference in subacromial decompression and acromioplasty operative time among the four groups. Conclusion TXA applied both topically and systematically can improve intraoperative visual clarity, and the combined application is more effective.
Humans ; Tranexamic Acid/therapeutic use* ; Shoulder ; Arthroscopy/methods* ; Decompression, Surgical/methods* ; Treatment Outcome

Objective:To investigate clinical and histopathological features of adult erythema nodosum (EN) .Methods:Clinical data were collected from 54 adult inpatients with histopathologically confirmed EN in Department of Dermatology and Venereology, the First Affiliated Hospital of Wannan Medical College from November 2019 to July 2022, and analyzed retrospectively.Results:Among the 54 EN patients, there were 6 males and 48 females, their ages were 42.50 ± 11.68 years (range, 18 - 73 years), and their disease course ranged from 1 day to 10 years; 30 patients (55.56%) were diagnosed with idiopathic EN, and 24 (44.44%) with secondary EN. The most common etiological factor in secondary EN was infection (17 cases), including respiratory tract infection (9 cases), tuberculosis infection (6 cases), upper respiratory tract infection comorbid with active hepatitis B virus infection (2 cases) ; the following common etiological factor was connective tissue disease (7 cases), including Behcet′s syndrome (4 cases), Sj?gren′s syndrome (1 case), and undifferentiated connective tissue diseases (2 cases). The patients′ ages were significantly younger in the secondary EN group (38.33 ± 12.15 years) than in the idiopathic EN group (46.17 ± 10.20 years, t = 2.58, P = 0.013). All patients had skin lesions on their lower limbs, lesions were limited to both lower limbs in 24 patients with idiopathic EN and 12 with secondary EN, and the proportion of patients with lesions limited to both lower limbs was significantly lower in the secondary EN group than in the idiopathic EN group ( χ2 = 5.44, P = 0.020). Compared with the idiopathic EN group, the secondary EN group showed significantly increased white blood cell counts ([7.56 ± 2.46] × 10 9/L vs. [6.04 ± 1.60] × 10 9/L, t = 2.62, P < 0.05) and C-reaction protein levels (34.34 ± 46.48 mg/L vs. 11.45 ± 18.13 mg/L, t = 2.28, P < 0.05). In the idiopathic EN group, 23 patients mainly showed histopathological features of septal panniculitis, while 17 patients in the secondary EN group mainly showed histopathological features of mixed panniculitis or lobular panniculitis, and the proportion of patients with histopathological features of mixed panniculitis or lobular panniculitis was significantly higher in the secondary EN group than in the idiopathic EN group ( χ2 = 12.18, P < 0.001) . Conclusion:EN was more common in female adults; idiopathic EN was the most common type, and secondary EN may be a cutaneous sign of systemic diseases; for EN patients at a relatively young age, with lesions involving both lower limbs or more sites, higher white blood cell counts and C-reaction protein levels, and histopathological manifestations of lobular panniculitis, systemic examinations were required to rule out underlying causes.

Humans ; Temperature ; Cities/epidemiology* ; Hot Temperature ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Mortality

Objective: To examine the association of long working hours and shift work with occupational stress among medical staff in level A tertiary hospitals, so as to provide insights into promotion of physical and mental health among medical personnel. Methods: One level A tertiary hospital was sampled using a stratified cluster sampling method from southern and northern Xinjiang Uygur Autonomous Region, and all medical personnel were recruited from these two hospitals. Participants' demographics, working duration, and working in shifts were collected using questionnaires, and occupational stress was measured using the Core Scale for Measurement of Occupational Stress proposed by National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention. The associations of long working hours (weekly working duration of >40 hours) and shift work with occupational stress were examined using a multiple linear regression model. Results: A total of 2 529 questionnaires were allocated, and 2 262 were valid, with an effective rate of 89.44%. The respondents had a mean age of (35.12±8.71) years, and included 1 696 women (74.98%). Of all respondents, there were 722 doctors (31.92%), 1 033 nurses (45.67%), 361 medical or pharmaceutical technicians (15.96%), 1 808 with long working hours (79.93%) and 1 264 with shift work (55.88%). The score of occupational stress was (44.79±8.49) points, and the prevalence of occupational stress was 28.69% among respondents. Multiple linear regression analysis showed that after adjustment for age, marital status, length of service, position, smoking and physical exercise, long working hours (>40 h, β'=0.124; >48 h, β'=0.175; ≥55 h, β'=0.323) and shift work (β'=0.203) were influencing factors for occupational stress among medical personnel（P<0.05）; however, there was no interaction between long working hours and shift work (P>0.05). Conclusion Long working hours and shift work may increase the risk of occupational stress among medical personnel in level A tertiary hospitals.

Cell Cycle Proteins ; Microtubule-Associated Proteins

Next-generation sequencing has revolutionized family-based association tests for rare variants. As the lower power of genome wide association study for detecting casual rare variants, methods aggregating effects of multiple variants have been proposed, such as burden tests and variance component tests. This paper summarizes the methods of rare variants association test that can be applied for family data, introduces their principles, characteristics and applicable conditions and discusses the shortcomings and the improvement of the present methods.
Computer Simulation ; Family Relations ; Genetic Association Studies ; Genetic Variation ; Genome-Wide Association Study/methods* ; Humans