OBJECTIVE To compare the metabolomic characteristics of stage T1 papillary thyroid carcinoma(PTC)and nodular goiter(NG),and the relationship between metabolites and lymph node metastasis of PTC.METHODS Serum samples were collected from 60 patients with stage T1 PTC and 30 patients with NG who underwent thyroidectomy at the Department of Otolaryngology Head and Neck Surgery,Civil Aviation General Hospital between September 2021 and April 2022.The PTC group was divided into the N+ group with lymph node metastasis and the N-group without lymph node metastasis according to the presence or absence of lymph node metastasis.The serum metabolites of the N+ and N-groups and the PTC and NG groups were compared and analyzed using an ultra-performance liquid chromatography-mass spectrometry(UPLC-Q-Exactive-MS)coupled platform,and principal component analysis(PCA),partial least squares discriminant analysis(PLS-DA),and orthogonal partial least squares discriminant analysis(OPLS-DA)was performed using SIMCA-P 14.1 software.OPLS-DA modeling,combined with FDR-corrected Mann-Whitney-Wilcoxon test results and metabolite difference multiples in the two groups undergoing comparison,etc.to screen for potential small molecule metabolic markers,and to establish a joint diagnostic model by binary logistic regression analysis.RESULTS There were no significant differential metabolites between the N+ group with lymph node metastasis and the N-group without lymph node metastasis.Seven differential metabolites were found between PCA patients and NG patients,and the five relevant metabolic pathways were the pentose phosphate pathway,pentose and glucuronide interconversion,glycolysis/gluconeogenesis,fructose,and mannose metabolism,and fatty acid biosynthesis.The differential metabolite with an area under the ROC curve>0.9 was D-glyceraldehyde 3-phosphate,and another N-undecanoylglycine,uronic acid,and the area under the ROC curve for three metabolites,N-undecanoylglycine,uric acid,and triiodothyronine glucuronide,was>0.8.CONCLUSION PTC patients differed from NG patients mainly in glucose metabolism and lipid metabolism,and D-glyceraldehyde 3-phosphate could be distinguished from NG patients with the aid of N-undecanoylglycine,uric acid,and triiodothyronine glucuronide,combined with imaging findings.Also,no significant differences in serum metabolites were found in the N+ group compared with the N-group,and the presence or absence of lymph node metastases did not affect serum metabolites in patients with stage T1 PTC.

Objective To grasp the main environmental factors affecting the growth of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao;To predict the distribution of suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province;To provide references for the rational distribution of the resources in Shanxi Province.Methods This study utilized the sample point longitude and latitude information collected in the"Fourth Survey of Chinese Materia Medica Resources"database in Shanxi Province.The data were supplemented by searching the China Digital Herbarium and retrieving related literature records.347 sample points distribution data and environmental factors were added to the MaxEnt model.The main environmental factors and contribution rates affecting the geographical distribution of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao were screened out.The ArcGIS software was used to divide the ecological suitable area of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province.Results The area under the ROC curve of the established MaxEnt model was 0.909,indicating that the model prediction results were accurate.The model screened 19 environmental factors.Among them,climate factor was the most important environmental factor,followed by biological factor and topographic factor,and soil factor had the least influence.The potential suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province were mainly distributed in the northern mountainous areas,presenting a trend of gradually decreasing suitability levels from north to south.Under the current climate conditions,the most suitable area for Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province was 15 424 km2,the suitable area was 19 856 km2,the sub suitable area was 59 436 km2,and the unsuitable area was 61 894 km2.Conclusion Based on MaxEnt model and ArcGIS software,this study predicts the distribution of suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province,which has certain reference value for the protection and rational distribution of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao resources in Shanxi Province.

Objective To analyze the bed utilization efficiency of various clinical departments in a public hospital and provide reference for the rational allocation of departmental bed resources.Methods Based on the data from a tertiary specialized hospital in 2022,traditional bed efficiency indicators were used as the basis.The Case Mix Index(CMI)was introduced for ad-justment,and the reasonable range of beds for each department was calculated.Data Envelopment Analysis(DEA)was em-ployed to comprehensively evaluate the input-output efficiency of each clinical department and determine the direction for optimi-zing bed allocation.Results Among the 39 departments included in the study,10 departments had inappropriate bed settings.Among them,5 departments needed additional beds,while 5 departments needed to reduce the number of beds.Conclusion By adjusting the bed efficiency indicators using CMI and combining the DEA method,hospitals can obtain a scientific basis for dy-namically adjusting the number of beds in clinical departments.Hospitals should make rational use of bed resources and scientifi-cally plan departmental beds.

Background::The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate. Some algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome, who subjected to preimplantation genetic testing for aneuploidy (PGT-A) treatment. However, it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal rearrangement.Methods::From February 2020 to May 2021, we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos, the clinical information of couples, and the comprehensive chromosome screening results of those blastocysts that had received PGT treatment. Initially, we developed a novel deep learning model called the Attentive Multi-Focus Selection Network (AMSNet) to analyze time-lapse videos in real time and predict blastocyst formation. Building upon AMSNet, we integrated additional clinically predictive variables and created a second deep learning model, the Attentive Multi-Focus Video and Clinical Information Fusion Network (AMCFNet), to assess the euploidy status of embryos. The efficacy of the AMCFNet was further tested in embryos with parental chromosomal rearrangements. The receiver operating characteristic curve (ROC) was used to evaluate the superiority of the model. Results::A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task, and 1422 qualified blastocysts received PGT-A ( n = 589) or PGT for chromosomal structural rearrangement (PGT-SR, n = 833) were enrolled for the euploidy assessment task in this study. The AMSNet model using seven focal raw time-lapse videos has the best real-time accuracy. The real-time accuracy for AMSNet to predict blastocyst formation reached above 70% on the day 2 of embryo culture, and then increased to 80% on the day 4 of embryo culture. Combing with 4 clinical features of couples, the AUC of AMCFNet with 7 focal points increased to 0.729 in blastocysts derived from couples with chromosomal rearrangement. Conclusion::Integrating seven focal raw time-lapse images of embryos and parental clinical information, AMCFNet model have the capability of assessing euploidy status in blastocysts derived from couples with chromosomal rearrangement.

Humans ; Asthma/diagnosis* ; HMGB1 Protein

Objective:To compare the social support levels as understood by family doctor team members in township hospitals/community health centers, and village clinics/community clinics, and their influencing factors, in order to provide reference for improving the work status of family doctor team members and enhancing the quality of family doctors′ contracted services.Methods:A multi-stage random cluster sampling method was used to sample medical workers from contracted family doctor teams in township hospitals/community health centers and their subordinate village clinics/community clinics in 6 counties (cities, districts) of Tai′an city, Shandong province. In August 2020, a questionnaire survey was conducted on the perceived level of social support among family doctor team members using the perceived social support scale. Descriptive analysis was conducted on the data, and independent sample t-tests and one-way ANOVA were used to conduct univariate analysis on the influencing factors of perceived social support scores of family doctor team members at different levels, while multiple linear regression analysis was used to conduct multivariate analysis. Results:A total of 765 valid questionnaires were collected, with 203 and 562 from township hospitals/community health centers and village clinics/community clinics, respectively. The total perceived social support scores of family doctor team members in township hospitals/community health centers and village clinics/community clinics were (65.56±10.29) and (67.31±10.14), respectively, featuring statistically significant differences ( t=-2.11, P<0.05). In-mirage marital status ( β=0.18, P=0.008), good/very good self-rated health status ( β= 0.25, P=0.048), participation of work-related training within one year ( β=0.17, P=0.010), relatively satisfied/very satisfied for job promotion ( β= 0.17, P=0.046), as well as above/far above average self-rated economic status as ( β=-0.15, P=0.027), were the influencing factor on the perceived social support scores of family doctor team members in township hospitals/community health centers. In-marriage marital status ( β= 0.12, P=0.002), good/very good self-rated health status ( β=0.14, P=0.026), junior or intermediate level or above professional title ( β=-0.11, P=0.003; β=-0.10, P=0.006), participation of work-related training within one year ( β= 0.14, P<0.001), and relatively satisfied/very satisfied for job promotion ( β= 0.16, P<0.001) were the influencing factors on the perceived social support scores of family doctor team members in village clinics/community clinics. Conclusions:Members of the family doctor teams in primary medical institutions in Tai′an city had a higher level of understanding of social support. There were differences in the social support levels of family doctor team members between the two levels of primary medical and health care institutions, and the influencing factors were not completely consistent. Targeted measures should be taken based on specific circumstances to enable them to better receive and perceive support from family and friends, and to improve the quality of family doctors′ contracted services.

Objective: To evaluate the value of cerebrospinal fluid markers expecially total-tau protein (T-tau), phosphorylated-tau protein (P-tau) in diagnosis and differentiation of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: sCJD (according to 2009 Brain criteria, 2018 Neurology amended criteria), Alzheimer's disease (AD; the National Institute on Aging at National Institutes of Health and the Alzheimer's Association revised guidelines 2011 criteria) and other patients without cognitive impairment, matched for sex and age, in the Department of Neurology, Peking Union Medical College Hospital from 2018 to 2019 were enrolled. Twelve sCJD patients, 49 AD patients and 14 normal controls were enrolled. Cerebrospinal fluid (CSF) specimens were collected through gravity dropping directly, and further stored in -80 ℃ and disposed according to widely used standards. The levels of T-tau and P-tau were measured by ELISA. The data on electroencephalogram and neuroimaging findings of sCJD patients were recorded. Moreover, specimens of sCJD patients were sent to the Chinese Center for Disease Control and Prevention to test 14-3-3 protein and PRNP genotype. Results: Using Mann-Whitney U test, T-tau concentrations were found higher in patients with sCJD (1 211(448, 2 227) pg/ml) than in AD patients (549(314, 1 078) pg/ml; U=178, P=0.034 9), and both groups had higher T-tau than the control group (127(79, 192) pg/ml; U=20, 73, P<0.01). The level of P-tau was significantly increased in AD patients (72(58,109) pg/ml) compared to the control group (27(15, 42) pg/ml; U=82, P<0.01), but not in sCJD patients (32(24, 47) pg/ml). The T-tau/P-tau ratio was higher in sCJD patients (29.77(20.01, 54.53)) than in AD patients (7.45(4.79, 10.43); U=87, P<0.01). Twelve sCJD patients had cotical hyperintensity on diffusion weighted imaging and five had periodic three-phase waves on electroencephalogram. Nine sCJD patients, whose CSF samples were tested in the Chinese Center for Disease Control and Prevention, carried an M/M genotype at codon 129 and E/E at codon 219. Conclusion The CSF tau level and T-tau/P-tau ratio are significantly increased in sCJD, which may promote the diagnosis and differentiation of sCJD in routine clinical setting.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Objective:To investigate the feasibility and clinical outcome of single-stage posterior total en bloc spondylectomy via posterior approach for lowerlumbar spinal malignant tumors.Methods:The clinical data of 23 patients with metastatic tumors of the lower lumbar spine who underwent single-stage posterior total En bloc spondylectomy in our hospital from January 2012 to June 2018 were analyzed retrospectively. There were 14 males and 9 females, age 57.9±10.8 years old (range, 37-74 years old). All patients were treated with single-stage posterior total en blocspondylectomy, titanium mesh implantation and posterior pedicle screw fixation. Observation items included operation time, intraoperative blood loss, postoperativehospital stays,the visual analogue scale (VAS) and the Eastern Cooperative Oncology Group (ECOG) physical condition score of the patients before operation,1 month after operationand 6 months after operation, the American spinal injury association (ASIA) spinal cord injury grade pre-operation andpostoperation, perioperative complications, local recurrence and survival state.Results:The median fellow-up time of this group was 20 months (range 6-56 months). At the end of the last follow-up, there were 3 patients who survived, the average follow-up time of the three patients who survived to the last follow-up was 37.3±11.7 months. One of them had local recurrence, but survived with tumor. The operative time was 155-510 min, with an average of 258±96 min, the intraoperative blood loss was 750-2 500 ml, with an average of 1 258.7±528.6 ml, and the postoperative hospital stay was 10-30 d, with an average of 18.4±4.6 d. VAS score decreased from 7.4±0.8 before operation to 2.6±0.6 1 month after operation, and ECOG score decreased from 1.6±0.9 before operation to 0.9±0.76 months after operation, showing statistically significant differences ( P<0.05). 6 patients presented with postoperative acute nerve root stimulation, 3 patients presented with postoperative cerebrospinal fluid leakage, 3 patients presented with postoperative surgical site infection, 1 with pulmonary infection, and 3 patients presented with titanium mesh displacement. Conclusion:Single-stage posterior total En bloc spondylectomy is feasible for the treatment of metastatic tumors of the lower lumbar spine. Although the operation is quite challenging due to its special anatomical structure and biomechanical characteristics,the long-term follow-up effect is satisfactory.

Objective To explore some reasonable ways of anticoagulation for pregnant women with mechanical prosthetic valves.Methods Retrospective analysis was conducted for 27 women with mechanical prosthetic valves who have born children after their cardiac surgeries.Numbers of pregnancies,ages,ways of anticoagulation during pregnancy,ways of anticoagulation before pregnancy,valve thrombosis events,thromboembolism events,bleeding events,outcomes of pregnancy and ways of delivery were collected and studied.Comparing adverse events and outcomes of different ways of anticoagulation which those women used during their pregnancies.Results 27 women with mechanical prosthetic valves experienced 41 pregnancies,and bore 28 children.24 pregnancies used oral low does warfarin(＜ 5 mg/day) to anticoagulate,2 minor bleeding events and 10 early abortion occurred,no abnormal neonates were found,14 healthy neonates were born.6 pregnancies used low-molecularweight heparin to anticoagnlate from 6th week to 12th week,they used oral warfarin to anticoagulate in rest weeks of pregnancy.1 late abortion occurred,1 fetus with hydrocephalus was found at 20th week,then induced labour was conducted.4 healthy neonates were born.11 pregnancies used low-molecular-weight heparin to anticoagulate until delivery,1 early abortion,2 minor bleeding events and 1 valve thrombosis occurred.10 neonates were born,and 1 of them has hypoxic-ischemic encephalopathy,the other 9 neonates were healthy.Conclusion For pregnant women with mechanical prosthetic valves,using oral low does warfarin throughout pregnancy is a reasonable way of anicoagnlation with low risk of maternal and fetal adverse events except high risk of abortion.Low-molecular-weight heparin is hopeful anticoagulant agent for pregnant women with mechanical prosthetic valves,but more studies about its safety and effectiveness should be conducted.