ObjectiveThis study aims to analyze animal models of anxiety disorder based on the clinical characteristics of anxiety disorder in traditional Chinese and Western medicine， systematically assess the clinical compatibility， and provide suggestions for the construction of animal models with a high degree of clinical compatibility between traditional Chinese and Western medicine. MethodsRelevant literature on animal models of anxiety disorder was retrieved from global databases. Scoring scales were developed according to the etiology， pathogenesis， and diagnostic criteria of anxiety disorder in both traditional Chinese and Western medicine. The animal models of anxiety disorder in the literature were analyzed， and their clinical compatibility was systematically assessed to identify reference-worthy models. ResultsThe average clinical compatibility of existing animal models of anxiety disorder was 42.13% for traditional Chinese medicine and 50.94% for Western medicine. Among these， the chronic unpredictable mild stress （CUMS） model had the highest compatibility with both traditional Chinese and Western medicine. However， current models rarely reflect the clinical syndromes of traditional Chinese medicine in depth， and show limitations in syndrome differentiation. ConclusionThe existing animal models of anxiety disorder are mostly established using single-factor approaches， which fail to comprehensively simulate the onset process and physiopathological characteristics of anxiety disorder. These models also neglect the syndrome-based indicators emphasized in traditional Chinese medicine. In the future， the model development should incorporate the clinical characteristics of syndromes in both traditional Chinese and Western medicine， establish standardized evaluation criteria for anxiety disorder models， and utilize multifactorial approaches to enhance the representativeness of animal models in traditional Chinese medicine.

Objective:To screen the host interaction proteins of the severe fever with thrombocytopenia syndrome virus(SFTSV)nonstructural protein(NSs)by immunoprecipitation combined with mass spectrometry analysis,to discuss the functions,subcellular localization,and biological pathways of these interaction proteins,and to provide the basis for clarifying the replication and pathogenic mechanism of SFTSV.Methods:The eukaryotic expression vectors pSFTSV-NSs-Flag(experimental group)and Flag-CMV-3(negative group)were transfected into the human embryonic kidney 293T cells,and contorl group(no treatment)was set up.The lysates of the cells in various groups were collected,and the expression and localization of SFTSV NSs in the host cells were verified by indirect immunofluorescence and Western blotting methods.The protein lysates were treated with protein A/G and immunoprecipitation was used to enrich host proteins binding to NSs.The captured interaction proteins were initially analyzed by silver staining and Coomassie brilliant blue staining to observe the differential protein bands in various groups;liquid chromatography-tandem mass spectrometry was used to obtain the information of protein sequences;the reliable proteins were retained and searched by UniProt database;Gene Ontology(GO)functional enrichment analysis,IPR,eukaryotic orthologous groups(KOGs)functional annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis,subcellular localization,and transcription factor(TF)functional annotation were used to determine the subcellular structure,gene functions,and biological processes of the interaction proteins.Results:The immunofluorescence results showed that the SFTSV NSs expressed a single specific band at relative molecular mass 33 000 and was localized in the cytoplasm in a granular inclusion body-like manner.The silver staining and Coomassie brilliant blue staining results showed there were significant differential protein bands between experimental group and negative group.The mass spectrometry results identified 46 potential interaction proteins.The GO functional enrichment analysis,KOGs functional annotation,and KEGG signaling pathway enrichment analysis results showed that the biological pathways related to viral translation,cellular metabolism,and protein transport were enriched with a considerable number of proteins.Eight annotated proteins had intermediate filament domains.The highest percentage of subcellular localization was cytoplasmic proteins,consistent with the NSs localization site.The TF functional annotation analysis results showed one protein from the NF-Y family.Conclusion:The interaction proteins play roles in assisting the proper protein folding,participating in the cribosome translation,and forming the cytoskeleton,which may be involved in antiviral replication.These proteins can be used as candidate proteins for further study on the replication mechanism of SFTSV.

Objective:To explore the predictive value of pre-biopsy serum inflammatory markers on positive prostate biopsy results, establish a nomogram model based on pre-biopsy inflammatory markers combined with other parameters, and evaluate its predictive ability for prostate biopsy results.Methods:The clinical data of 601 patients undergoing transperineal prostate biopsy who were admitted to the Second Hospital of Tianjin Medical University from August 2019 to August 2021 were retrospectively analyzed. The median age was 68(35, 89)years, and the median tPSA was 9.56(4.01, 19.95)ng/ml. The median fPSA was 1.36(0.88, 2.02)ng/ml, the median PSAD was 0.16(0.11, 0.26)ng/ml 2, and the median platelet-to-lymphocyte ratio(PLR)was 129.90(98.95, 169.89). PI-RADS v2.1 score<3 points in 189 cases(31.45%), 3 points in 174 cases(28.95%), 4 points in 190 cases(31.61%), and 5 points in 48 cases(7.99%). A simple randomization method was used to obtain 421 cases(70.00%)in the modeling group and 180 cases(30%)in the validation group.There was no significant difference in the clinical data between the two groups ( P>0.05). Univariate and multivariate logistic regression analysis were performed in the modeling group to screen independent influencing factors for the prediction of positive prostate biopsy results. A nomogram model was established and internal verification was conducted. External validation of the model was performed in the validation group. Receiver operating characteristic(ROC)curve was used to verify model discrimination, Hosmer-Lemeshow goodness-of-fit test was used to verify model calibration, and decision curve analysis (DCA) was used to evaluate the net benefit and clinical utility of the predictive model. Results:The results of univariate analysis showed that the age( OR=1.060, P<0.01), histological inflammation( OR=0.312, P<0.01), the number of biopsy needles( OR=0.949, P=0.009), f/tPSA( OR=0.954, P=0.003), PV( OR=0.973, P<0.01), PSAD( OR=29.260, P<0.01), PI-RADS v2.1 score(3-point OR=3.766, P=0.001; 4-point OR=11.800, P<0.01; 5-point OR=57.033, P<0.01), lymphocyte count( OR=1.535, P=0.013), NLR( OR=0.848, P=0.044), PLR( OR=0.994, P=0.005)and SII( OR=0.999, P=0.009)were statistically different between the prostate patients and non-prostate cancer patients in the modeling group; Multivariate analysis showed that age( OR=1.094, P<0.001), fPSA( OR=0.605, P=0.002), histological inflammation ( OR=0.241, P<0.001), PSAD ( OR=7.57, P=0.013), PLR ( OR=0.994, P=0.005) and PI-RADS v2.1 Score(3-point OR=2.737, P=0.016; 4-point OR=8.621, P<0.001; 5-point OR=47.65, P<0.001) was an independent influencing factor for prostate cancer at initial biopsy; a nomogram model based on age, fPSA, PSAD, PLR and PI-RADS v2.1 scores was established. The AUC of the modeling group was 0.849(95% CI 0.810-0.888), and the sensitivity was 80.9%, and the specificity was 76.1%; the AUC of the validation group was 0.862(95% CI 0.809-0.915), and the sensitivity was 91.9%, and the specificity was 67.8%, suggesting that the diagnostic prediction model had a good discrimination. The calibration curve showed that the prediction model was well calibrated ( χ2=6.137, P=0.632). The decision curve analysis (DCA) of the modeling and validation groups indicated a larger net benefit of the predictive model. Conclusions:The nomogram model established in this study based on age, fPSA, PSAD, PLR and PI-RADS v2.1 score showed good predictive efficacy for prostate biopsy in patients with PSA between 4-20 ng/ml.

Objective:To investigate the role of IL-21/IL-21R-mediated CD4 + T cells in Chlamydia muridarum ( Cm) respiratory infection. Methods:C57BL/6 mice (WT mice) and IL-21R -/- mice were used to establish the models of Cm respiratory infection through intranasal inhalation of Cm. Flow cytometry was used to detect the proportion, number, activity and function of CD4 + T cells in lung and spleen tissues at 0, 3, 7 and 14 d after Cm respiratory tract infection. IFN-γ and IL-4 levels in spleen cell culture supernatants were detected by ELISA. Na?ve WT mice were transferred with CD4 + T cells in the spleen tissues of IL-21R -/- mice or WT mice on 7 d after infection and given Cm intranasally 2 h later. Then the mice were weighed daily and sacrificed on 14 d after infection. The bacterial load and pathological changes in lung were analyzed. Flow cytometry was performed to detect the proportions and numbers of neutrophils (CD45 + CD11b + Gr-1 high) and alveolar macrophages (CD45 + F4/80 + CD11c high)as well as the proportions of Th1 (IFN-γ + CD4 + ) and Th2 (IL-4 + CD4 + ) cells. ELISA was also performed to measure IFN-γ and IL-4 levels in spleen cell culture supernatants. Results:Compared with WT mice, IL-21R -/- mice showed elevated numbers and enhanced activation of CD4 + T cells, increased proportion of Th1 cells and decreased proportion of Th2 cells in spleen and lung tissues after Cm respiratory infection. Besides, IFN-γ levels increased, while IL-4 levels decreased in spleen cell culture supernatants of IL-21R -/- mice. After Cm infection, the na?ve WT transferred with CD4 + T cells from IL-21R -/- mice showed less body weight loss, reduced bacterial load and alleviated pathological changes in lung tissues, increased proportion of Th1 cells in lung tissue and higher IFN-γ level in spleen cell culture supernatants. Conclusions:IL-21/IL-21R-mediated CD4 + T cells could aggravate Cm respiratory infection by suppressing Th1 cell immune responses.

Objective To explore efficacy and safety of simulated artificial pancreas in modulating stress hyperglycemia in critically ill patients. Methods A prospective randomized controlled study was performed. Seventy-two critically ill patients with stress hyperglycemia, aged 18-85 years, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score over 15, two consecutive random blood glucose 11.1 mmol/L or higher, glycated hemoglobin (HbA1C) below 0.065, unable to eat food for 3 days after inclusion, or only accepting parenteral nutrition, admitted to intensive care unit (ICU) in Shanghai Punan Hospital of Pudong New District from January 1st, 2015 to June 30th, 2017 were enrolled. The patients were divided into three groups according to the random number table method, high-intensity group and low-intensity group were injected Novolin R (high-intensity group 2/3 dosage, low-intensity group 1/3 dosage) to modulate stress hyperglycemia by simulated artificial pancreas. Simulated artificial pancreas consisted of Guardian real time glucose monitoring system (GRT system), close-circle control algorithm and micro-pump;subcutaneous injection of Humulin 70/30 was applied to modulate stress hyperglycemia in humulin group. Real-time glucose levels of interstitial fluid in abdominal wall, equivalent to blood glucose levels, 10 minutes each time, were monitored by using of GRT system for all patients in three groups. Fasting serum levels of stress hormones including epinephrine and cortisol and insulin resistance index (IRI) were recorded within 24 hours after inclusion. Mean blood glucose, blood glucose variation coefficient, blood glucose target-reaching rate, blood glucose target-reaching time, hypoglycemia rate and 6-month mortality were measured. Twenty healthy adults from health administration department of the hospital were recruited as healthy control group. Results A total of 60 eligible critically ill patients were included in this study, each group with 20 patients. There was no significant difference in gender, age, APACHE Ⅱ scores among three groups. The levels of serum epinephrine, cortisol and IRI within 24 hours after inclusion in the three groups were significantly higher than those in healthy control group. The mean blood glucose levels of humulin group, low-intensity group, high-intensity group were decreased (mmol/L: 10.2±3.2, 8.4±2.6, 8.1±2.2), the blood glucose target-reaching rate were increased [40.2% (3 295/8 196), 71.1% (5 393/7 585), 80.4% (6 286/7 818)], the blood glucose target-reaching time were shortened (hours: 49.1±5.8, 24.6±4.6, 17.5±4.2), the hypoglycemia rates were increased respectively [1.3% (108/8 196), 2.8% (211/7 585), 4.0% (313/7 818)], with statistically significant differences (all 1 = 0.000). There was no significant difference in blood glucose variation coefficient and 6-month mortality among three groups [blood glucose variation coefficient: (29.4±3.7)%, (28.5±5.3)%, (26.1±4.6)%, 6-month mortality: 55.0%, 45.0%, 40.0%, all 1 > 0.05]. Conclusions Simulated artificial pancreas could effectively and safely modulate stress hyperglycemia in critically ill patients, high-intensity modulation could bring about better efficacy in the regulation of hyperglycemia. High-frequency blood glucose monitoring by using GRT system could promptly identify hypoglycemia and help it to be corrected.

Objective To evaluate effect of intensive insulin treatment(IIT)on healthcare-associated infection (HAI)rate in patients with acute stroke and stress hyperglycemia.Methods Databases,including PubMed,Em-base,Cochrane Library,WanFang,and China National Knowledge Infrastructure(CNKI)Data,were electronically searched,relevant journals and references of the included literatures were also searched manually,literatures were selected according to the uniform inclusion and exclusion criteria,incidence of HAI and mean blood glucose in patients who received IIT for acute stroke were assessed systematically.Results A total of 13 randomized controlled trials (RCT)involving 1 032 patients were included in this systematic review.Meta-analysis results showed that 10 studies involving 832 patients were finally enrolled for comparing HAI rate, HAI rates in IIT group and conventional insulin treatment group were 28.3% and 56.1 %,respectively(Z =4.50 ),difference between two groups was statistically significant (RR=0.53 [95 %CI :0.40 to 0.70],P <0.001 );A total of 328 patients in 5 studies were finally included in the comparison of blood glucose,difference in mean blood glucose between two groups was statistically significant(MD =-2.52 [95% CI :-4.30 to -0.74],P =0.006).Funnel plot of HAI rate revealed that there was publication bias.Conclusion IIT is used for the regulation of stress hyperglycemia in acute stroke,it can reduce the incidence of HAI and blood glucose in patients.

OBJECTIVETo investigate the levels and influencing factors of phthalate internal exposure in pregnant women (gestation age ≤ 16 weeks).

METHODSDuring April to June in 2013, 1 020 pregnant women (gestation age ≤ 16 weeks) who had established the maternal care manual were recruited in maternal and child health hospital of Siming District, Xiamen city. Participators were asked to complete a questionnaire to obtain information on socio-demographic characteristics, lifestyle behaviors, and antenatal examination and to provide a urine sample. Finally, 998 pregnant women who provided a urine sample and completed the questionnaire were enrolled. Adopting systematic sampling method, 100 ones were selected randomly among 998 pregnant women. High performance liquid chromatography-electrospray ionization-tandern mass was used to determine the concentration of five phthalate monoesters in each urine, including mono-n-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-ethylhexyl phthalate (MEHP). Based on the measurements and questionnaire data, multivariate logistic regression was used to analyze the association between the phthalate monoester levels and potential influential factors.

RESULTSThe detection rates of MMP, MEP, MBP, MBzP and MEHP in 100 pregnant urine samples were 94%, 93%, 87%, 83%, 99%, respectively. And the urinary median uncorrected concentrations of MMP, MEP, MBP, MBzP and MEHP in 100 urine samples were 20.56, 17.62, 10.15, 2.03, and 5.12 ng/ml, respectively. Specific gravity-corrected concentration were 20.81, 20.36, 12.88, 2.58, 5.00 ng/ml, respectively. The results of multivariate logistic regression analysis indicated that: education degree was negatively associated with urinary concentration of MMP, MEP, MBP, MBzP and MEHP, OR (95% CI) were 0.495 (0.253-0.966), 0.380 (0.191-0.755), 0.379 (0.186-0.774), 0.401 (0.196-0.819), 0.373(0.183-0.762), respectively. Participants who had hair permed and dyed during pregnancy had higher urinary level of MBP and MBzP, OR (95% CI) were 12.867 (1.240-133.525), 15.982 (1.367-186.911), respectively; Participants who use cosmetics during pregnancy had higher urinary level of MEP and MBP, OR (95% CI) were 2.977 (1.012-8.757), 4.440 (1.485-13.272), respectively; plastic bottled water consumption was positively associated with urinary concentrations of MEP and MEHP, OR (95% CI) were 3.780 (1.417-10.083), 2.699 (1.039-7.010), respectively; annual household income was negatively associated with urinary concentration of MMP, OR (95% CI) was 0.597 (0.372-0.959); individuals who took medications during pregnancy had higher urinary level of MEHP than non-takers, OR (95% CI) was 4.853 (1.084-21.732).

CONCLUSIONPregnant women whose gestation age was less than 16 weeks are generally exposed to phthalate. Phthalate internal exposure levels are significantly associated with most measured factors and the influencing factors with different phthalates internal exposure levels are different.

Chromatography, High Pressure Liquid ; Dibutyl Phthalate ; urine ; Female ; Humans ; Life Style ; Maternal Exposure ; Phthalic Acids ; urine ; Pregnancy ; Surveys and Questionnaires ; Tandem Mass Spectrometry

Objective To detect the difference of the expression of HLA-DQA1 genes polymorphism in the lung cancer patients with pneumoconiosis and the non-occupational lung cancer patients.Methods Multiple polymerase chain reaction-ligase detection reaction classification method (PCR-LDR) was used to detect 6 alleles in HLA-DQA1 and the expression of HLA-DQA1 gene between the 21 cases of pneumoconiosis complicated with lung cancer and 40 cases of non-occupational lung cancer respectively.The correlation between them with pneumoconiosis complicated with lung cancer was analysed.Results HLA-DQA1 0301 gene frequencies were 19％ in pneumoconiosis complicated with lung cancer group and 2.5％ in non-occupational lung cancer group respectively,with a statistically significant difference (x2 =10.022,P =0.002).There was no statistically significant difference in the other allele between the two groups.Conclusion HLA-DQA1 gene polymorphism may be related to the susceptibility of the pneumoconiosis complicated with lung cancer.DQA1 0301 is one of the important genes of pneumoconiosis complicated with lung cancer,which maybe the risk factor for the susceptibility of the pneumoconiosis complicated with lung cancer.

Objective To evaluate islet cells functional recovery and clinical effects of dynamic blood sugar monitoring combined with insulin pump in newly diagnosed type 2 diabetes mellitus in the elderly.Methods 300 cases with newly diagnosed type 2 diabetes mellitus were randomly divided into treatment group (n=150) and control group (n=150) accompanying with three months follow-up.Body mass indexes (BMI),levels of hemoglobin A1c (HbA1c),fasting plasma glucose (FPG),2-h postprandial blood glucose,fasting insulin,2-h postprandial insulin,fasting C-peptide,2-h postprandial C peptide,and the percentage of patients who took oral hypoglycemic drugs alone without insulin could well control the blood glucose were compared between the two groups before versus after treatment.Results The levels of BMI,HbA1c,FPG,2-h postprandial blood glucose,fasting insulin,2-h postprandial insulin,fasting C peptide,2-h postprandial C peptide in the two groups were significantly decreased after treatment as compared with the pretreatment (P ＜ 0.05).The improvement of blood sugar spectrum was better in treatment group than in control group(P＜0.05) and the percentage of patients who took oral hypoglycemic drugs alone without insulin could well control the blood glucose was significantly higher in treatment group than in control group(21％ vs.3％,x2 =22.475,P＜0.05).Conclusions The clinical effects of dynamic blood sugar monitoring combined with insulin pump on newly diagnosed type 2 diabetes mellitus in the elderly is definite and can improve the recovery of islet cells function.It is worthy of clinical promotion.

Objective To investigate the characteristics of blood pressure variability during 24 hours and pre-thrombotic state(PTS) in elderly patients with essential hypertension.Methods One hundred cases of old patients with essential hypertension in the department of Cardiology (hypertension group) and 65 controls with normal blood pressure from Punan Health Check Center (control group) were recruited.The systolic and diastolic blood pressure variability (SBPV,DBPV) during 24 h daytime and nighttime were monitored for all subjects by ambulatory blood pressure monitor.The plasma levels of P-selectin (PS),fibrinogen (Fg) and plasminogen activator inhibitor-1 (PAI-1) were measured.Results The systolic blood pressure variability (SBPV) in hypertension group was significantly larger than that of control group (P ＜ 0.05) in daytime,and no significant difference regarding of the diastolic blood pressure variability (DBPV) between two groups.While in nighttime,SBPV and DBPV in hypertension group were significantly higher than those of control group (P ＜ 0.05).The levels of plasma Fg and PAI-1 in hypertension group were significantly higher than those of control group ((2.8 ±0.9) g/L vs.(2.3 ±0.7) g/L and (29.8 ±2.7) μg/L vs.(25.6 ± 1.2) μg/L,respectively).While no significant difference was found between two groups for PS (P ＞ 0.05).Conclusion That indicated pre-thrombotic state including higher blood pressure variability during 24 hours,especially during nighttime in elderly patients with essential hypertension and plasma fibrinogen.