Background C57BL/6(B6) is a kind of routine mouse specie used in experimental autoimmune uveitis (EAU) research.Previous studies showed that the pathogenesis of uveitis related to inflammatory cytokines secreted by different helper T(Th) cells.However,the interaction of different Th cells in EAU is unclear.Objective This study was to investigate the dynamic changes of inflammatory factors in the spleen and serum after immunization in EAU mice.Methods Forty-four SPF B6 mice were immunized by injection of interphotoreceptor retinoid-binding protein (IRBP) and complete Freund adjuvant (CFA) emulsion via caudal vein and footpad.Indirect ophthalmoscope was used to examine the eyes 3 times per week and the inflammatory response was scored based on Thurau's criteria.In the thirty day after injection,20 model eyes were extracted and the sections of eye tissue were prepared for histopathological examination.The spleens of model mice were enucleated before injection and 2,5,10,15,20,25,30 days after injection,and reverse transcriptase PCR (RT-PCR) was used to detect the contents of interleukin-17 (IL-17) mRNA,interferon-γ (IFN-γ) mRNA,tumor necrosis factor-α (TNF-α) mRNA and IL-10 mRNA,and the contents of IL-17,IFN-γ,TNF-α and IL-10 in model serum were assayed by ELISA in 24 model mice.The experimental protocol and use of the animals were approved by Ethic Committee for Care and Use of Laboratory Animals of Shandong University of Traditional Chinese Medicine.Results Mild inflammatory response was seen in 12 days under the indirect ophthalmoscope with the scores of 0.5.The inflammatory scores peaked in 13-15 days with the scores of 1.0 and alleviated after that with the inflammatory scores of 0.5 in 30 days after injection.The histopathological score was consistent with the clinical score in the models on the 30 days.The serum IL-17 content of model mice was (0.98±0.05) ng/L before injection and increased to (51.85 ±2.42) ng/L on the fifth day,and decreased to (4.01±0.06)ng/L on the fifteen day.But,the serum IL-17 level increased to (25.00±0.94)ng/L again on the 25th day,and then lowed to (6.01 ±0.21)ng/L 30 days after injection,showing a significant elevation in comparison with that of before injection (P=0.000).The serum IFN-γ content of the model mice was (1.02±0.09)ng/L before injection and increased to (50.54±0.48) ng/L on the fifth day,and (73.21±0.12) ng/L on the tenth day,and then it declined gradually until (5.15±0.18)ng/L in the 30th day,which was still higher than that of before injection (P=0.000).After injection of IRBP+CFA,the serum TNF-α level upregulated from the second day to fifth day with the peak values (134.25±0.59)ng/L,and declined to valley on 15th day.A repeat elevation of serum TNF-α level was found on the 20th day with the values (60.54±0.62)ng/L and followed by decrease till the 30th day,which was higher than that of before injection (P=0.660).Serum IL-10 was detectable in the tenth day and peaked on the 15th day.Then a slight decrease was seen till the 30th day,compared with before injection(P =0.000).The contents of IL-10 mRNA,IL-17 mRNA,TNF-α mRNA,IFN-γmRNA in mice spleens followed the same pattern with serum levels of their proteins.Conclusions IL-17,IFN-γ,TNF-α and IL-10 are key inflammatory factors of Th1,Th2 and Th17,they present with specific changes during EAU,it confirming that IFN-γ probably play a pathogenic role in EAU,IL-17 and TNF-α levels probably associated with the chronic and recurrent procedure of uveitis,IL-10 plays an inhibit role in EAU.

Background Lewis rat is a commonly used specie in experimental autoimmune uveitis(EAU).However,the characteristics of EAU,especially ocular uhrastructural change,are rarely reported.Objective This study was to investigate the inflammatory characteristics and ocular uhrastructure of EAU models in Lewis rat.Methods EAU models were induced in 12 SPF female Lewis rats(6-8 weeks old)by injection of complete Freund adjuvant(CFA) containing interphotoreceptor retinoid-binding protein (IRBP,1177-1191) and tuberculin (TB) into footpads,napes and back of the body,and 6 normal matched rats were used as normal controls.The diet and drinking,temperature and behavior acts of the rats were recorded during the observational duration.Ocular manifestations were examined under the slit lamp biomicroscope after modeling and scored.Eyeballs were obtained in 12 days after modeling for histopathological examination,and the ultrastructures of eyeballs were observed under the scanning electron microscope and transmission electron microscope.The use and care of the animals complied with Statement of ARVO.Results The food-intake was (190.00± 18.03)g in the model group,and that in the control group was (285.33 ±28.02) g,showing a significant difference between them (t =4.955,P =0.012).The drinking-water volume of rats was (241.67±t 18.56)ml in the model group,which was significantly less than (289.67± 18.18)ml in the control group,showing a significant difference between them (t =3.201,P =0.033).In addition,elevated temperature and tiredness were found in the model rats.Anterior chamber empyema,iris hyperemia and occlusion of the pupil appeared in the models on the 6th day and peaked on the 12nd day after immunized,with the inflammatory scores of 3.83±0.41.The infiltration of inflammatory cells were seen in anterior chamber,ciliary body and vitreous cavity under the optical microscope in the model rats.Scanning electron microscopy found uneven iris texture,coarse ciliary surface and loosen villi of retinal pigment epithelial (RPE) cells in the model rats.Under the transmission electron microscope,the infiltration of macrophagocytes on the iris,wrinkle sparse of ciliary epithelium,myeloid bodies in retinal Müller cells and vacuolus in mitochondria of RPE cells were exhibited.No obvious abnormality was found in the control rats.Conclusions Lewis rats are autoimmune status following injection of CFA with IRBP(1177-1191) and TB.The morphology and ultrastructure of eyeballs in the EAU rats can explain the finding of eyes.

UDP glucosyltransferase (UDPGT) catalyzes the synthesis of secondary metabolites and plant hormones to regulate plant growth and development, pathogen defense and environmental adaptability. In this study 18 members of the RcUDPGT gene family were cloned from Tibetan Rhodiola crenulata and analyzed using bioinformatics. The tissue-specific expression, abiotic stresses and plant hormones (abscisic acid, auxin, methyl jasmonate) induced expression patterns were identified by real-time quantitative PCR. The bait vector of RcUDPGT (JX228125.1) was constructed to select interacting proteins from an Arabidopsis yeast library. The results of the bioinformatics analysis revealed that RcUDPGT nucleotide sequences were about 1 400 bp and encoded 452-498 amino acids. In the primary protein sequences, C-terminal sequences were more conserved compared with N-terminal regions, which held a PSPG (plant secondary product glycosyltransferase) domain. In the tertiary structures, RcUDPGTs contained a UDP sugar donor recognition binding site. In addition, all genes had multiple phosphorylation sites. The results of qRT-PCR showed that RcUDPGTs genes were expressed in root, stem and leaf. The expression levels were regulated by low temperature/ultraviolet light and various plant hormones (ABA, IAA, MeJA), but the expression patterns were quite different among them. For example, RcUDPGT6, RcUDPGT11, and RcUDPGT17 had the highest expression in leaves and were induced by all three hormones, suggesting that the functions of these genes might be to respond to environmental changes. RcUDPGT9, RcUDPGT10, RcUDPGT14 were most abundantly expressed in roots and were significantly induced by ABA and MeJA hormones, indicating that these genes may be involved in the synthesis and accumulation of salidroside. Yeast two-hybrid results showed that RcUDPGT did not exhibit autoactivation and cell toxicity, and two significant interactional genes were identified, AtKCR1 (AT1G67730.1) and AtSNL4 (AT1G70060). The AtKCR1 gene encodes a β-ketoacyl reductase (KCR) involved in synthesis of very long chain fatty acids. The AtSNL4 gene encodes a homolog of the transcriptional repressor SIN3, which could participate in the ABA hormone signaling pathway and enhance the transcriptional repression of AP2/EREBP class factors in Arabidopsis. These results suggest that the accumulation of the secondary metabolite salidroside in Rhodiola crenulata might be affected by several regulatory mechanisms. The above results may lay the foundation for understanding the adaptive mechanism of Rhodiola crenulata in a high altitude environment and stimulate an in-depth study of the synthesis and accumulation of secondary metabolites in this species.

Objective To evaluate the impact of BRAF(V600E) gene status on clinical outcome of radioiodine((131)I) therapy in low-intermediate risk recurrent papillary thyroid carcinoma (PTC). Methods Totally 135 PTC patients were enrolled and divided into two groups according to BRAF(V600E) gene status:BRAF(V600E) mutation group(n=105) and BRAF(V600E) wild group(n=30). The median follow-up time was 2.16 years(1.03-4.06 years),and clinical outcome after initial (131)I ablation therapy was divided into excellent response(ER),acceptable response(AR),and incomplete response(IR) according to the serological and imageological follow-up results. The cinical outcomes were then compared between these two groups. Results There was no significant difference in clinicopathological features and initial radioactive iodine dose between BRAF(V600E) mutation and wild groups (P>0.05). ER,AR,and IR after (131)I ablation therapy accounted for 74.3%,20.0%,and 5.7% in BRAF(V600E) mutation group and 73.3%,20.0%,and 6.7% in BRAF(V600E) wild group,and no statistical difference was found (P=0.891). Conclusion For low-intermediate risk recurrent PTC,BRAF(V600E) gene status may have no impact on the response to (131)I ablation therapy,and thus this molecular feature should not be used as an independent weighting factor for risk assessment in this population.
Carcinoma ; genetics ; radiotherapy ; Carcinoma, Papillary ; Humans ; Iodine Radioisotopes ; therapeutic use ; Mutation ; Prognosis ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroid Neoplasms ; genetics ; radiotherapy

Objective To predict the monthly reported echinococcosis cases in China with the autoregressive integrated mov-ing average(ARIMA)model,so as to provide a reference for prevention and control of echinococcosis. Methods SPSS 24.0 software was used to construct the ARIMA models based on the monthly reported echinococcosis cases of time series from 2007 to 2015 and 2007 to 2014,respectively,and the accuracies of the two ARIMA models were compared. Results The model based on the data of the monthly reported cases of echinococcosis in China from 2007 to 2015 was ARIMA(1,0,0)(1,1, 0)12,the relative error among reported cases and predicted cases was-13.97%,AR(1)=0.367(t=3.816,P<0.001),SAR (1)=-0.328(t=-3.361,P=0.001),and Ljung-Box Q=14.119(df=16,P=0.590).The model based on the data of the monthly reported cases of echinococcosis in China from 2007 to 2014 was ARIMA(1,0,0)(1,0,1)12,the relative error among reported cases and predicted cases was 0.56%,AR(1)=0.413(t=4.244,P<0.001),SAR(1)=0.809(t=9.584, P<0.001),SMA(1)=0.356(t=2.278,P=0.025),and Ljung-Box Q=18.924(df=15,P=0.217).Conclusions The different time series may have different ARIMA models as for the same infectious diseases.It is needed to be further verified that the more data are accumulated,the shorter time of predication is,and the smaller the average of the relative error is.The estab-lishment and prediction of an ARIMA model is a dynamic process that needs to be adjusted and optimized continuously accord-ing to the accumulated data,meantime,we should give full consideration to the intensity of the work related to infectious diseas-es reported(such as disease census and special investigation).

As an interdisciplinary subject of medicine and artificial intelligence, intelligent diagnosis and treatment has received extensive attention. The standardization of Chinese medicine (CM) diagnosis has been always a bottleneck in the modernization and globalization of CM. Studying the application technology of artificial intelligence in CM and solving the problems is an urgent need for the development of modern CM in the era of artificial intelligence. Taking the pneumonia with dyspnea and cough in CM as an example, this article gives an overview of intelligent medical technology and application development, brings forward the present technical problems faced and the new advances in intelligent technology on CM diagnosis and treatment.

OBJECTIVETo evaluate the response of (131)I therapy and to explore the influencing factors in non-metastatic differentiated thyroid cancer (DTC) patients with preablative stimulated thyroglobulin (ps-Tg) above 10 ng/ml.

METHODSThe study included 157 DTC patients who had undergone total or near total thyroidectomy and subsequent (131)I therapy with ps-Tg>10 ng/ml, and they were divided into 3 groups as excellent response (ER, 49 cases), acceptable response (AR, 36 cases), and incomplete response (IR, 72 cases) according to the response to (131)I therapy. We compared the clinicopathologic features and ps-Tg levels among 3 groups, as well as ps-Tg levels between IR and non-IR groups. The ROC curve was employed to evaluate the predictive value of ps-Tg levels in (131)I therapy responses.

RESULTSThe three groups showed significant difference in ps-Tg levels (H=35.142, P<0.001), gender (χ(2)=6.82, P=0.033), extrathyroid invasion (H=31.380, P<0.001), and lymph metastases (H=14.375, P=0.001). The ps-Tg level in IR is higher than that in non-IR (U=1384.5, P<0.001), while it was not significantly different between ER and AR (U=771.5, P=0.326). The diagnostic critical point (DCP) of ps-Tg to differentiate IR and non-IR was 28.3 ng/ml (sensitivity 57.5%, specificity 87.1%), with a corresponding area under the ROC curve (AUC) of 0.774 (95%CI: 0.701-0.847).

CONCLUSIONSNear-half (45.86%) non-metastatic DTC patients with ps-Tg above 10 ng/ml are more susceptible to IR. The level of ps-Tg>28.3 ng/ml may be a useful and sensitive diagnostic marker for predicting incomplete response.

Area Under Curve ; Cell Differentiation ; Humans ; Iodine Radioisotopes ; Lymphatic Metastasis ; ROC Curve ; Thyroglobulin ; Thyroid Neoplasms ; Thyroidectomy

Objective: This study aims to investigate the sleep quality of pregnant women in Xuhui District, Shanghai, and the related factors of sleep disturbances during pregnancy. Methods: From February 2019 to February 2021, we used online integrated sleep questionnaire (including PSQI, BQ, ESS, AIS) in Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, The International Peace Maternity and Child Health Hospitals of China Welfare Institution, and Shanghai Eighth People's Hospital, to investigate the sleep quality across pregnancy. We also collected maternal physical examination results, childbearing history, sociodemographic, and other clinical data. The prevalences and related factors of various sleep disturbances in pregnant women were analyzed, including insufficient/excessive nighttime sleep, low sleep efficiency, difficulty falling asleep, poor sleep quality, insomnia, daytime sleepiness, and high risk of sleep-disordered breathing (SDB). Results: This study includes 1 898 cases in the first trimester (T1), 3 099 cases in the second trimester (T2), and 1 539 cases in the third trimester (T3). Poor sleep quality (38.6%), daytime sleepiness (mild 41.9%, moderate 17.7%, severe 2.1%), and suspicious insomnia (32.3%) are most prevalent among women in T1 (P<0.01). In comparison, short sleep time (2.7%), long sleep time (8.6%), difficulty falling asleep (12.2%), poor sleep efficiency (35.4%), very poor sleep quality (6.7%), clinical insomnia (21.8%), and high-risk SDB (6.4%) are most prevalent among women in T3 (P<0.05). During pregnancy, late gestation (OR=1.016, 95%CI: 1.006-1.025) and multiple induced/drug abortions (OR=1.329, 95%CI: 1.043-1.692) are risk factors for poor sleep quality (PSQI>5), while multiple full-term deliveries (OR=0.800, 95%CI: 0.675-0.949) is its protective factor. Advanced maternal age (OR=0.976, 95%CI: 0.956-0.997), multiple full-term deliveries (OR=0.808, 95%CI: 0.680-0.959), late gestation (OR=0.983, 95%CI: 0.974-0.992) and hypertension (OR=0.572, 95%CI: 0.401-0.814) are protective factors for daytime sleepiness (ESS>6). The high-risk pregnancy category (OR=9.312, 95%CI: 1.156-74.978) is a risk factor for insomnia (AIS≥4), while multiple full-term deliveries (OR=0.815, 95%CI: 0.691-0.961) is its protective factor. High BMI (OR=1.334, 95%CI: 1.270-1.402) and hypertension (OR=4.427, 95%CI: 2.539-7.719) are risk factors for high-risk SDB in pregnant women. Conclusions: The prevalences of various sleep disturbances are high throughout pregnancy. Noticeably, symptoms of maternal SDB develop along with pregnancy. Different types of sleep disturbances are associated with different factors. Women of high-risk pregnancy category, in late gestation, with high BMI, hypertension, a history of induced/drug abortion, or without a history of full-term delivery can be at high risk of sleep disturbances during pregnancy.
Child ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Pregnancy ; Pregnancy Complications/epidemiology* ; Pregnant Women ; Sleep ; Sleep Quality

Baby Boom(BBM) gene is a key regulatory factor in embryonic development and regeneration, cell proliferation, callus growth, and differentiation promotion. Since the genetic transformation system of Panax quinquefolius is unstable with low efficiency and long period, this study attempted to transfer BBM gene of Zea mays to P. quinquefolius callus by gene gunship to investigate its effect on the callus growth and ginsenoside content, laying a foundation for establishing efficient genetic transformation system of P. quinquefolius. Four transgenic callus of P. quinquefolius with different transformation events were obtained by screening for glufosinate ammonium resistance and molecular identification by PCR. The growth state and growth rate of wild-type and transgenic callus were compared in the same growth period. The content of ginsenoside in transgenic callus was determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS). The results showed that transgenic callus growth rate was significantly higher than that of wild-type callus. In addition, the content of ginsenoside Rb_1, Rg_1, Ro, and Re was significantly higher than that in wild-type callus. The paper preliminarily proved the function of BBM gene in promoting growth rate and increasing ginsenoside content, which provided a scientific basis to establish a stable and efficient genetic transformation system for Panax plants in the future.
Female ; Pregnancy ; Humans ; Ginsenosides ; Panax/genetics* ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Cell Proliferation

OBJECTIVETo investigate the clinical outcome of (131)I therapy in differentiated thyroid cancer (DTC) with preablative stimulated thyroglobulin (ps-Tg) below 10 ng/ml and the value of ps-Tg for predicting clinical outcome.

METHODSTotally 167 DTC patients with ps-Tg below 10 ng/ml were included and divided into three groups [excellent response (ER, n=131), acceptable response (AR, n=34), and incomplete response (IR, n=2)] according to the response to initial (131)I therapy. One-way analysis of variance, χ(2) test, and Kruskal-Wallis test were used to evaluate the statistical differences of clinicopathological features, recurrence risk, and ps-Tg value among the three groups. The ps-Tg value between ER group and non-ER group were compared by Mann-Whitney rank-sum test. The ROC curve and optimal cut-off point were analyzed to evaluate the clinical value of ps-Tg for predicting disease-free status.

RESULTSThere was significant difference in ps-Tg level (H=14.305, P=0.001) among three groups but not in age (F=0.831, P=0.755), sex (χ(2)=0.178, P=0.915), cervical lymph node metastases (χ(2)=1.475, P=0.478), TNM stage (H=1.063, P=0.588), and recurrence risk (H=2.947, P=0.229). The median level of ps-Tg in ER group was 2.20 ng/ml (1.10, 4.40), which was significantly lower than 4.40 ng/ml (2.70, 5.90) of non-ER groups (U=1424.50, P=0.000). Area under the ROC curve was 0.717. The cut-off value of ps-Tg was 2.35 ng/ml,with a sensitivity of 83.33%, specificity of 53.43%, and negative predictive value of 92.11%.

CONCLUSIONThe serum ps-Tg value is a sensitive marker for predicting the disease-free status in DTC patients with ps-Tg below 10 ng/ml.

Adenocarcinoma ; Humans ; Iodine Radioisotopes ; Lymph Nodes ; Lymphatic Metastasis ; Neck ; Prognosis ; ROC Curve ; Thyroglobulin ; Thyroid Neoplasms ; Treatment Outcome