Objective To study the factors influencing the blood concentration of caspofungin(CPFG),construct a prediction model,and validate the predictive effect of the model,so as to provide reference for the individualised dosing of patients with fungal infections in haematology.Methods Seventy-five patients admitted to the Department of Haematology,General Hospital of Tianjin Medical University,who were treated with CPFG for antifungal therapy during the period of March 2021 to June 2022 were selected as the study subjects,and CPFG blood concentration monitoring was carried out to explore the influencing factors of CPFG blood concentration and to construct a prediction model accordingly.Hosmer-Lemeshow(H-L)was used to test the goodness-of-fit of the model,and another 30 patients were selected as the verification group,and the predictive effect of the model was verified by the receiver's operating characteristics(ROC)curve.Results The mean blood concentrations of the patients at 0.5,9 and 24 h were(12.54±4.38),(6.80±2.76),(4.13±2.16)μg·mL-1,and the mean AUC0-24h were(152.05±57.60)μg·mL-1·h.AUC0-24h was lower than the reference value(98 μg·mL-1·h)in two patients.The results of correlation analysis showed that gender showed a correlation with 0.5 h blood concentration(P＜0.05),and there was no correlation with the rest of the two time points blood concentration and AUC0-24h(P＞0.05).Body weight and albumin(Alb)concentration showed correlation with 0.5,9,24 h blood drug concentration and AUC0-24 h(P＜0.05),and the rest of the indicators showed no correlation with blood drug concentration and AUC0_24h at each time point(P＞0.05).The results of multifactorial analysis showed that the factors influencing the patients'0.5 h blood concentration were gender,Alb concentration and body weight,and the factors influencing the 9 and 24 h blood concentration and AUC0-24h were Alb concentration and body weight(P＜0.05).Correlation analysis showed that the daily dose was positively correlated with the plasma concentration of CPFG at 0.5,9 and 24 h and AUC0-24h(P＜0.05).The results of multivariate analysis showed that the daily dose was also one of the influencing factors of the plasma concentration of CPFG(P＜0.05).ROC curve shows that the model has good prediction ability.Conclusion Body weight and Alb are significantly associated with CPFG blood concentrations and area under the drug-time curve,which can be used as a basis for preventive risk avoidance.

Twelve compounds were isolated from Liquidambaris Resina by silica gel column chromatography and thin layer chromatography. Their structures were identified on the basis of spectral data, electron capture detector data, and physicochemical properties as(2'R, 3'R)-2',3'-dihydroxy-hydrocinnamyl-(E)-cinnamate(1),(E)-cinnamyl-(E)-cinnamate(2), cinnamic acid(3), 28-norlup-20(29)-en-3-one-17β-hydroperoxide(4), erythrodiol(5), 13β,28-epoxy-30-hydroxyolean-1-en-3-one(6),(3β)-olean-12-ene-3,23-diol(7), 2α,3α-dihydroxy-olean-12-en-28-oic acid(8), 28-hydroxyolean-12-en-3-one(9), 3-epi-oleanolic acid(10), 3-oxo-oleanolic acid(11), and hederagenin(12). Compound 1 was a new cinnamic acid ester derivative and compounds 2-4,6-8, and 12 were isolated from Liquidambaris Resina for the first time. Compounds 4, 5, 10, and 12 exerted inhibitory effects on the proliferation of human umbilical vein endothelial cells(HUVEC) with the IC_(50) values of(17.43±2.17),(35.32±0.61),(27.50±0.80), and(46.30±0.30) μmol·L~(-1), respectively.
Humans ; Oleanolic Acid ; Endothelial Cells ; Esters ; Cinnamates ; Triterpenes/chemistry* ; Molecular Structure

Objective To explore the potential biological functions and prognostic prediction values of non-apoptotic regulated cell death genes (NARCDs) in lung adenocarcinoma.Methods Transcriptome data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. We identified differentially expressed NARCDs between lung adenocarcinoma tissues and normal tissues with R software. NARCDs signature was constructed with univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression. The prognostic predictive capacity of NARCDs signature was assessed by Kaplan-Meier survival curve, receiver operating characteristic curve, and univariate and multivariate Cox regression analyses. Functional enrichment of NARCDs signature was analyzed with gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. In addition, differences in tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion score, and chemotherapeutic drug sensitivity were analyzed between the high and low NARCDs score groups. Finally, a protein-protein interaction network of NARCDs and immune-related genes was constructed by STRING and Cytoscape software. Results We identified 34 differentially expressed NARCDs associated with the prognosis, of which 16 genes (ATIC, AURKA, CA9, ITGB4, DDIT4, CDK5R1, CAV1, RRM2, GAPDH, SRXN1, NLRC4, GLS2, ADRB2, CX3CL1, GDF15, and ADRA1A) were selected to construct a NARCDs signature. NARCDs signature was identified as an independent prognostic factor (P < 0.001). Functional analysis showed that there were significant differences in mismatch repair, p53 signaling pathway, and cell cycle between the high NARCDs score group and low NARCDs score group (all P < 0.05). The NARCDs low score group had lower tumor mutational burden, higher immune score, higher tumor immune dysfunction and exclusion score, and lower drug sensitivity (all P < 0.05). In addition, the 10 hub genes (CXCL5, TLR4, JUN, IL6, CCL2, CXCL2, ILA, IFNG, IL33, and GAPDH) in protein-protein interaction network of NARCDs and immune-related genes were all immune-related genes. Conclusion The NARCDs prognostic signature based on the above 16 genes is an independent prognostic factor, which can effectively predict the clinical prognosis of patients of lung adenocarcinoma and provide help for clinical treatment.
Humans ; Prognosis ; Apoptosis ; Regulated Cell Death ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Tumor Microenvironment

Objective:To analyze the composition, the changes of expense structure and the influencing factors of hospitalization expenses, for reference in optimizing the cost control of day surgery.Methods:Collection of the first page data of patients with the top three diseases(varicose veins of lower limbs, chronic cholecystitis and varicocele)in the day surgery volume ranking in three tertiary general hospitals in a city in 2020. The confounding factors were eliminated through propensity matching. The structural change of hospitalization expenses was analyzed by structural change degree, and the influencing factors of hospitalization expenses were analyzed by grey correlation degree and multiple linear regression.Results:After 1∶1 propensity matching of the first page data of 752 patients with day surgery and non day surgery, 98 patients with lower extremity varicose veins, 356 patients with chronic cholecystitis and 38 patients with varicocele were finally included. Compared with non day hand, the total hospitalization cost of day surgical instruments decreased, and the cost structure changes of chronic cholecystitis, varicocele and varicose veins of lower limbs were 14.59%, 6.20% and 16.20% respectively. Among them, the general medical service fee, nursing fee and examination and laboratory fee showed a downward trend, and the fees of materials and drugs showed an upward trend. General medical service fee, nursing fee, examination and laboratory fee, clinical diagnosis fee, treatment fee, drug fee, material fee and other expenses presented a high correlation with the cost of day surgery(grey correlation>0.90). The payment method, wound healing type and discharge diagnosis can influence the cost of day surgery( P<0.05). Conclusions:Compared with non daytime surgery, the total hospitalization cost of day surgery has a certain cost control effect, but it can not reduce the cost of all projects. The main influencing factors are the internal composition of the cost, payment method and so on. The hospitals should focus on tapping the internal cost control potential of day surgery and further expanding the coverage of day surgery diseases.

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

OBJECTIVE: To evaluate the changes of heart structure and function in elite Chinese weightlifters by spot tracking technique. METHODS: Chinese elite male weightlifters (weightlifter group, n=16) and age-matched healthy men (control group, n=16) were included as subjects. Transthoracic echocardiography and speckle-tracking automatic functional imaging were used for two-dimensional myocardial strain measurements. RESULTS: The thickness of septum and left ventricular (LV) posterior wall and the myocardial mass index of LV were all higher than those of the control group [(9.3±1.3) mm vs. (8.0±0.4) mm, (9.2±0.8) mm vs. (8.0±0.8) mm, (77.8±12.8) g/m² vs. (67.8±11.2) g/m², all P < 0.05]. Although the LV ejection fraction (LVEF) and global long axis strain value (LVGLS) were not significantly different from those in the control group, the LV mean Sm and Em reflecting the systolic and diastolic functions of the LV were lower than those in the control group (P < 0.05). Further myocardial strain analysis showed that the absolute value of the long axial strain of the basal anteroseptal and mid-inferoseptal segments of the weightlifters were significantly lower than those of the control group [|(-15.1±4.2)%|vs.|(-18.7±3.0)%|, |(-18.8±2.6)%|vs.|(-21.3±2.8)%|, all P < 0.05]. There was no significant difference in other segments. The athletes were divided into two groups according to their best performance in the National Youth Games. The athletes were divided into two sub-groups according to their performance in the National Youth Games. The thickness of the septum in the sub-group with better performance (who ranked the 1^st to 8^th) was larger [(10.2±1.1) mm vs. (8.5±1.0) mm, P < 0.05], and the absolute value of the long-axis strain in the mid-inferoseptal segment was lower [|(-17.1±2.1)%|vs.|(-20.4±2.1)%|, P < 0.05]. CONCLUSION The thickening of septum is more obvious in the excellent weightlifters, accompanied by the decrease of myocardial systolic function. The speckle-tracking technique of echocardiography can identify the changes of the heart structure and function of elite athletes at an early stage, which may provide a basis for sports medicine supervision and the selection of excellent talents.
Adolescent ; China ; Echocardiography ; Humans ; Male ; Stroke Volume ; Ventricular Dysfunction, Left ; Ventricular Function, Left

Atherosclerosis ; Humans ; Lymphatic Vessels

OBJECTIVE: To establish a method for simultaneous determination of 12 kinds of chlorobenzene compound(CBs) in workplace air using portable gas chromatography-mass spectrometry(GC-MS) technique. METHODS: The GDH-3 air sampling tube was developed independently, and were used to collect the 12 kinds of CBs in the vapor state and aerosol state in the air. After elution with toluene solvent, portable GC-MS method was used for detection. Fast chromatographic column was used for separation, and then qualitatively analyzed with retention time and characteristics of the ions, and quantitative analyzed by standard curves. RESULTS: The quantitative determination ranges of the 12 kinds of CBs were 0.20-200.00 mg/L. All the correlative coefficients were greater than 0.998 3. All the minimum quantitative concentration was 0.01 mg/m~3, and all the minimum quantitative mass concentration was 0.04 mg/m~(3 )(15 L sample). The average elution efficiency was 88.97%-116.86%. The within-run and the between-run relative standard deviation was 10.15%-13.48% and 12.87%-19.66%, respectively. All the sampling efficiencies were>90.00%. CONCLUSION: The portable GC-MS technique could be used for rapid qualitative and quantitative detection of 12 kinds of CBs in workplace air.

OBJECTIVE: To prepare and develop a GDH-2 air sampling tube for detecting 12 kinds of chlorobenzenes(CBs) in workplace air and to establish a matching detecting method. METHODS: The self-developed GDH-2 air sampling tube was filled with ion exchange resin and activated carbon, and the mass ratio was 10 ∶1. The GDH-2 air sampling tube was used to collect 12 kinds of CBs with coexistence of gaseous and aerosol in the air. After elution with toluene, they were separated on a chromatographic column and determined by microcell electron capture detector. RESULTS: The quantitative detecting range of the method was 0.51×10~(-3)-6 000.00 mg/L, with the correlation coefficients greater than 0.999 4. The minimum detection concentration was 0.02-61.99 μg/m~3, and the minimum quantitative concentration was 0.05-206.62 μg/m~3. The average desorption efficiency was 90.8%-104.0%. The within-run relative standard deviation(RSD) was 1.0%-5.7%, and the between-run RSD was 3.0%-7.3%. The samples can be stored at room temperature for at least 26 days. CONCLUSION: The self-developed GDH-2 air sampling tube and its matching measuring method can be used for the collection and determination of the 12 kinds of CBs in the air of workplace.

Compared with crystalline drugs, their amorphous forms present long-range disordered molecular arrangements, and often exhibit higher apparent solubility and dissolution. However, several small molecule amorphous drugs may exhibit gelation phenomenon during the dissolution process, and show abnormal dissolution behavior with significantly lower dissolution than crystalline drugs. The current study aims to discover the relationship between the gelation of amorphous drugs and their abnormal dissolution, and further explore the internal gelation mechanism. Amorphous simvastatin (SIM), carvedilol (CAR), and irbesartan (IRB) were prepared by melt cooling method and characterized via X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). Gel formation causes the dissolution of these three amorphous drugs to be significantly lower than their crystalline state. The formed gels were characterized as three-dimensional dense network structures by scanning electron microscope (SEM). Furthermore, amorphous SIM, CAR and IRB showed the critical gel temperature at 8-15 ℃, 25-30 ℃ and 45-50 ℃, and amorphous CAR and IRB showed the critical gel pH at 1 and 0.25. The mechanism of gel formation was proposed to be closely related to the transformation of amorphous drugs into the supercooled liquid state (as the important driving force) and the protonation induced self-assembling under acidic conditions. In addition, the wettability and properties of amorphous drugs also affect the formation of gelation.