Objective To analyze the composition characteristics and biological functions of tumor cell subpopulations in glioblastoma(GBM)through multi-transcriptomics sequencing technology,and explore the hypoxia characteristics and spatial localization features of the mesenchymal-like(MES-like)tumor cell subpopulation in GBM and the influence on malignant biological behaviors.Methods Multi-transcriptomics sequencing data,including single-cell RNA sequencing(scRNA-seq)data(18 patients),bulk RNA sequencing(bulk RNA-seq)and spatial transcriptomics(ST)data of GBM,were employed to define cell subpopulations in GBM,and Gene Ontology(GO)and Gene Set Enrichment Analysis(GSEA)were utilized to analyze their functions.The proportions and locations of cell subpopulations in bulk RNA-seq data were evaluated with BayesPrism deconvolution.Immunofluorescence assay was conducted for verification on 12 paraffin samples of GBM from patients who visited the neurosurgical department of our hospital from 2015 to 2023 and met the pathological diagnostic criteria for GBM(10 males and 2 females,at an average age of 53.50 years and a median age of 54.50 years).pySCENIC was applied to predict specific transcription factors of tumor cell subpopulations.Results Tumor cells in GBM were highly heterogeneous,and could be mainly divided into 4 subpopulations:astrocyte-like(AC-like),neural progenitor-like(NPC-like),oligodendrocyte progenitor-like(OPC-like)and MES-like.Differential gene analysis found that the MES-like tumor cells highly expressed vascular endothelial growth factor A(VEGFA),adrenomedullin(ADM),N-myc downstream regulated 1(NDRG1),insulin like growth factor binding protein 5(IGFBP5),and A-kinase anchoring protein 12(AKAP12)(P<0.001).pySCENIC transcription factor prediction found that the high-active transcription factors of the MES-like tumor cells were AT-rich interaction domain 3A(ARID3A),FOS like 2,AP-1 transcription factor subunit(FOSL2),endothelial PAS domain protein 1(EPAS1),CCAAT enhancer binding protein delta(CEBPD),and CCAAT enhancer binding protein beta(CEBPB)(P<0.05).GO and GSEA enrichment analyses found that the MES-like tumor cells were enriched in hypoxia-related pathways,especially the pathway of cell responses to hypoxia levels(NES=2.437,P<0.001).BayesPrism deconvolution showed that the MES-like tumor cells mainly existed in PAN(Pseudopalisading cells around necrosis)and perinecrotic zone.Immunofluorescence assay confirmed CD44+(CD44 antigen)MES-like tumor cells were mainly located in hypoxia areas with highly expression of hypoxia inducible factor 1 subunit alpha(HIF1α)(P<0.01).Multivariate Cox regression analysis indicated that the MES-like tumor cells were significantly correlated with the adverse prognosis of GBM patients(HR=1.71,95%CI:1.38～2.11,P<0.001).Conclusion Tumor cells in GBM are of highly heterogeneity.They could be mainly divided into 4 subpopulations:AC-like,NPC-like,OPC-like and MES-like.MES-like tumor cells,mainly locating in PAN and perinecrotic zone,are characterized by hypoxia,which can promote the malignant progression of GBM.

Objective:To analyze the trend of infertility disease burden from 1990 to 2019 and predict the age-standardized prevalence rate (ASPR) and age-standardized disability-adjusted life-year (DALY) rate of male and female infertility for 2020—2029, providing a certain reference for the prevention and treatment of infertility diseases.Methods:Based on the Global Burden of Disease 2019, prevalence, ASPR, DALY rate, and age-standardized DALY rate were used to evaluate the global burden of infertility comprehensively. The estimated annual percentage change was used to describe trends in the disease burden of infertility in 21 regions worldwide. The Bayesian age period cohort model was used to predict the ASPR and age-standardized DALY rate for male and female infertility in 204 countries and regions from 2020 to 2029. Sensitivity analysis was performed using the autoregressive integrated moving average model.Results:The prevalence, DALY rate, ASPR and age-standardized DALY rate of global male infertility increased from 319.52 per 100 000,1.82 per 100 000, 2 856.53 per 100 000, and 16.19 per 100 000 in 1990 to 565.30 per 100 000, 3.22 per 100 000, 3 398.53 per 100 000, and 19.36 per 100 000 in 2019, respectively. The prevalence, DALY rate, ASPR, and age-standardized DALY rate of global female infertility increased from 656.67 per 100 000, 3.53 per 100 000, 6 036.36 per 100 000, and 32.27 per 100 000 in 1990 to 1 223.78 per 100 000, 6.59 per 10 000, 7 483.12 per 100 000, and 40.33 per 100 000 in 2019, respectively. The burden of infertility disease was the highest in men and women aged 30-34 years, and the ASPR and age-standardized DALY rates were 4 407.47 per 100 000, 25.08 per 100 000, 10 270.55 per 100 000 and 55.65 per 100 000, respectively. Only in 45-49 years of age, the prevalence of infertility (11.31 per 100 000) and DALY rate (0.06 per 100 000) in women were lower than those in men (15.68 per 100 000 and 0.08 per 100 000). In addition, the burden of infertility was the lowest in high socio-demographic index regions. Cameroon had the highest ASPR (7 652.40 per 100 000) and age-standardized DALY rate (43.94 per 100 000) for male infertility. Chinese women had the highest ASPR (20 402.30 per 100 000) and age-standardized DALY rate (106.16 per 100 000) of infertility. The forecast results show that the burden of male and female infertility diseases will increase in 204 countries and regions from 2020 to 2029.Conclusion:The burden of infertility diseases in men and women increased in 204 countries and regions from 1990 to 2019, and it is predicted that the global burden of infertility diseases will continue to rise in 2020—2029. Preliminary screening of infertility should be carried out as soon as possible, health education should be strengthened and effective prevention and treatment strategies should be formulated.

Objective:To analyze the trend of infertility disease burden from 1990 to 2019 and predict the age-standardized prevalence rate (ASPR) and age-standardized disability-adjusted life-year (DALY) rate of male and female infertility for 2020—2029, providing a certain reference for the prevention and treatment of infertility diseases.Methods:Based on the Global Burden of Disease 2019, prevalence, ASPR, DALY rate, and age-standardized DALY rate were used to evaluate the global burden of infertility comprehensively. The estimated annual percentage change was used to describe trends in the disease burden of infertility in 21 regions worldwide. The Bayesian age period cohort model was used to predict the ASPR and age-standardized DALY rate for male and female infertility in 204 countries and regions from 2020 to 2029. Sensitivity analysis was performed using the autoregressive integrated moving average model.Results:The prevalence, DALY rate, ASPR and age-standardized DALY rate of global male infertility increased from 319.52 per 100 000,1.82 per 100 000, 2 856.53 per 100 000, and 16.19 per 100 000 in 1990 to 565.30 per 100 000, 3.22 per 100 000, 3 398.53 per 100 000, and 19.36 per 100 000 in 2019, respectively. The prevalence, DALY rate, ASPR, and age-standardized DALY rate of global female infertility increased from 656.67 per 100 000, 3.53 per 100 000, 6 036.36 per 100 000, and 32.27 per 100 000 in 1990 to 1 223.78 per 100 000, 6.59 per 10 000, 7 483.12 per 100 000, and 40.33 per 100 000 in 2019, respectively. The burden of infertility disease was the highest in men and women aged 30-34 years, and the ASPR and age-standardized DALY rates were 4 407.47 per 100 000, 25.08 per 100 000, 10 270.55 per 100 000 and 55.65 per 100 000, respectively. Only in 45-49 years of age, the prevalence of infertility (11.31 per 100 000) and DALY rate (0.06 per 100 000) in women were lower than those in men (15.68 per 100 000 and 0.08 per 100 000). In addition, the burden of infertility was the lowest in high socio-demographic index regions. Cameroon had the highest ASPR (7 652.40 per 100 000) and age-standardized DALY rate (43.94 per 100 000) for male infertility. Chinese women had the highest ASPR (20 402.30 per 100 000) and age-standardized DALY rate (106.16 per 100 000) of infertility. The forecast results show that the burden of male and female infertility diseases will increase in 204 countries and regions from 2020 to 2029.Conclusion:The burden of infertility diseases in men and women increased in 204 countries and regions from 1990 to 2019, and it is predicted that the global burden of infertility diseases will continue to rise in 2020—2029. Preliminary screening of infertility should be carried out as soon as possible, health education should be strengthened and effective prevention and treatment strategies should be formulated.

Objective Metabolomics was used to analyze the changes of metabolites in the plasma of Fenpropathrin-contaminated rats to find potential biomarkers for forensic identification of Fenpropathrin poisoning.Methods SD rats in the two experimental groups were given 20.5 mg/kg and 41 mg/kg doses of fenpropathrin respectively by gavage.The rats in the control group were given equivalent volume of normal saline.The angular vein blood of rats was collected 24 hours after gavage,and endogenous small molecule metabolites in plasma were investigated by ultra-performance liquid chromatography-time-of-flight mass spectrometry(UPLC-TOF-MS).The data was processed by SIMCA14.1.The differential metabolites in plasma of fenpropathrin-infected rats were screened out according to the Variable Importance in Projection(VIP)and p<0.05 in the OPLS-DA model.Finally,the pathways were analyzed.Results There were significant differences in plasma metabolite levels between the control group and the experimental group,and 17 biomarkers were selected to identify whether the rats had received fenpropathrin,which mainly affected purine metabolism,Alanine,aspartate and glutamate metabolism,arginine biosynthesis,biosynthesis of unsaturated fatty acids and pyrimidine metabolism.Conclusion Fenpropathrin can change the composition of metabolites in rats,and the differential markers screened can provide supportive forensic evidence for cases related to deltamethrin poisoning.

Objective To study the effects of different doses of vancomycin bone cement on serum inflammatory factors and joint function in patients undergoing total knee arthroplasty.Methods A total of 128 patients who underwent total knee arthroplasty admitted to Handan First Hospital from August 2021 to January 2023 were selected as the study subjects.They were divided into group A(acrylic bone cement without vancomycin),group B(0.5 g vancomycin per 40 g acrylic bone cement),group C(1.0 g vancomycin per 40 g acrylic bone cement)and group D(2.0 g vancomycin per 40 g acrylic bone cement)by random number table method,with 32 patients in each group.High performance liquid chromatography was used to detect the concentration of vancomycin in drainage fluid at different time points after operation of patients in group B,group C,and group D.Immune scattering turbidimetry and Westergren method were used to detect the levels of serum C-reactive protein(CRP)and erythrocyte sedimentation rate(ESR)of patients in the four groups before operation,7 days and 6 months after operation.Hospital for special surgery knee score(HSS)was used to evaluate the knee joint function of patients in the four groups before operation and 6 months after operation.Results The concentration of vancomycin in drainage fluid of patients in group B,group C,and group D increased with the increase of dose(P<0.05),and decreased with the extension of time(P<0.05).The postoperative serum CRP and ESR levels in the four groups increasing first and then decreased with time(P<0.05).The levels of serum CRP and ESR 7 days and 6 months after operation of patients in group B,group C,and group D were significantly lower than those in group A(P<0.05).The levels of serum CRP and ESR 7 days and 6 months after operation of patients in group C and group D were significantly lower than those in group B(P<0.05),while there was no significant difference in serum CRP and ESR levels between group C and group D(P>0.05).The HSS scores 6 months after operation of patients in the four groups obviously improved(P<0.05);the HSS scores 6 months after operation of patients in group B,group C and group D were higher than those in group A(P<0.05);the HSS scores 6 months after operation of patients in group C and group D were obviously higher than those in group B(P<0.05),while there was no obvious difference in the HSS scores 6 months after operation between group C and group D(P>0.05).Conclusion The use of bone cement containing vancomycin can obviously reduce the levels of serum inflammatory factors CRP and ESR in patients undergoing total knee arthroplasty,prevent postoperative infection,and improve joint function of patients.The degree of action of different doses of vancomycin also varies,and it is recommended to use 1.0 g of vancomycin in clinical practice.

Objective To investigate the effects of glutathiones-transferase (GST) T1, GSTM1 and epoxide hydrolase (EPHX1) genes on skin injury in workers exposed to coal tar pitch. Methods Workers from a carbon manufacturing company involved in coal tar pitch production and use were selected as the study subjects using a judgment sampling method. Workers with skin injury after exposed to coal tar were selected as the case group (55 cases), and those with the same workshop and type of work but without skin abnormalities were selected as the control group (197 cases). Urine and blood samples were collected from the workers, and levels of polycyclic aromatic hydrocarbon metabolites, including 1-pyrenol (1-OH-P), 1-naphthol (1-OH-N) and 2-naphthol (2-OH-N), in urine were measured using ultra high-performance liquid chromatography tandem mass spectrometry. The GSTT1, GSTM1 and EPHX1 genes in blood were detected by polymerase chain reaction. Results In the case group, all 55 workers reported skin stinging, 25 workers reported itching and flaking, and 15 workers reported blackheads and pigmentation. Urinary levels of 1-OH-N and 2-OH-N were lower in the worker in the case group than that in the control group (all P<0.05). However, there was no significant difference in the level of 1-OH-P between the two groups (P>0.05). There were significant differences in the number of workers with GSTT1, GSTM1 and EPHX1(His139His) genes between the two groups (all P<0.01). The GSTT1 and GSTM1 genes were positively correlated with post-shift urinary levels of 1-OH-N, 1-OH-P, and 2-OH-N (all P<0.01). The EPHX1 (139Arg locus) gene was positively correlated with post-shift 2-OH-N levels (P=0.03). The GSTT1, GSTM1, and EPHX1 (139Arg locus) genes were associated with reduced skin damage among coal tar workers (all P<0.01), after controlling for age, length of service, gender, smoking, and alcohol consumption. Conclusion Exposure to coal tar pitch can cause skin injury in workers, and the GSTT1, GSTM1, and EPHX1 (139Arg locus) genes are protective factors against skin injury in those workers.

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.
Female ; Humans ; Antibodies, Antineutrophil Cytoplasmic ; Organizing Pneumonia ; Autoantibodies ; Glomerulonephritis ; Anti-Glomerular Basement Membrane Disease ; Pneumonia ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications*

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*

Objective: To explore the correlation between serum vitamin D level and glucose and lipid metabolism among primary and middle school students in Inner Mongolia, so as to providing a scientific basis for guiding rational vitamin D supplementation among primary and middle school students in Inner Mongolia Region. Methods: A total of 2 206 students of primary and middle school students from 8 counties (districts) in Inner Mongolia were enrolled for a questionnaire survey, physical examination, and laboratory test by a multi stage stratified random sampling approach.The levels of fasting blood glucose, blood lipid and other related indexes with different vitamin D levels were analyzed, and their correlation was further discussed. Results: The deficiency and insufficiency rates of vitamin D among primary and middle school students were 33.2% and 42.8%, respectively, and the suitable rate was 24.0%. The body mass index (BMI) and waist height ratio (WHtR) of the vitamin D deficiency group [(22.87±7.41) kg/m 2 , 0.46±0.08)]were higher than the insufficiency [(20.59±8.00)kg/m 2, 0.44±0.09)] and suitable group [(18.01±7.38)kg/m 2, 0.43 ±0.08)] ( P <0.05). Compared with the vitamin D suitable group [(3.87±0.85) mmol/L], the total cholesterol (TC) level in the deficiency group [(3.73±0.67)mmol/L] decreased, with a statistically significant difference ( P <0.05). The levels of high density lipoproteins (HDL) in the vitamin D insufficiency[(1.40±0.33)mmol/L] and deficiency groups [(1.34±0.31)mmol/L] were lower than the suitable group [(1.48±0.34)mmol/L], with a statistically significant difference ( P <0.05). The detection rate of hyperuricemia (HUA) in the vitamin D deficiency group (22.95%) was higher than the suitable group (17.20%), with a statistically significant difference ( P <0.016 7). Pearson correlation analysis showed that vitamin D was negatively correlated with BMI and WHtR ( r =-0.23, -0.11), and positively correlated with TC and HDL level ( r =0.06, 0.16) ( P <0.05). Conclusions The deficiency and insufficiency rates of serum vitamin D among primary and middle school students in Inner Mongolia are high which are associated with several indicators of blood lipids. Therefore, it is recommended to supplement vitamin D preparations in moderation in daily life.