Impact of the Learning Curve on the Survival of Abdominal or Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The objective of this study was to define the learning curve required to attain satisfactory oncologic outcomes of cervical cancer patients who were undergoing open or minimally invasive surgery for radical hysterectomy, and to analyze the correlation between the learning curve and tumor size. @*Materials and Methods@#Cervical cancer patients (stage IA-IIA) who underwent open radical hysterectomy (n=280) or minimal invasive radical hysterectomy (n=282) were retrospectively reviewed. The learning curve was evaluated using cumulative sum of 5-year recurrence rates. Survival outcomes were analyzed based on the operation period (“learning period,” P1 vs. “skilled period,” P2), operation mode, and tumor size. @*Results@#The 5-year disease-free and overall survival rates between open and minimally invasive groups were 91.8% and 89.0% (p=0.098) and 96.1% and 97.2% (p=0.944), respectively. The number of surgeries for learning period was 30 and 60 in open and minimally invasive group, respectively. P2 had better 5-year disease-free survival than P1 after adjusting for risk factors (hazard ratio, 0.392; 95% confidence interval, 0.210 to 0.734; p=0.003). All patients with tumors < 2 cm had similar 5-year disease-free survival regardless of operation mode or learning curve. Minimally invasive group presented lower survival rates than open group when tumors ≥ 2 cm in P2. Preoperative conization improved disease-free survival in patients with tumors ≥ 2 cm, especially in minimally invasive group. @*Conclusion@#Minimally invasive radical hysterectomy required more cases than open group to achieve acceptable 5-year disease-free survival. When tumors ≥ 2 cm, the surgeon’s proficiency affected survival outcomes in both groups.

Comparison of Serum Anti-Mullerian Hormone-Level Changes in Single-Port Laparoscopic Endometriotic and Non-Endometriotic Ovarian Cyst Enucleations

Objectives@#This study compared serum anti-Mullerian hormone (AMH) levels in endometriotic cysts (ECs) with those in non-ECs and analyzed changes thereof after single-port laparoscopic (SPL) ovarian cyst enucleation using vasopressin injection. @*Methods@#In total, 180 patients (EC group, n = 112; non-EC group, n = 68) who underwent SPL ovarian cyst enucleation were retrospectively reviewed. Their AMH levels were checked preoperatively, on postoperative day 10 (POD10), and on postoperative month 3 (POM3). Changes in AMH levels were analyzed according to tumor type and vasopressin use. @*Results@#The median initial and postoperative serum AMH levels in the EC group were significantly lower than those in the nonEC group (preoperation: 2.0 vs 3.8 ng/mL, P < 0.001; POD10: 1.0 vs 3.2 ng/mL, P < 0.001; POM3: 1.2 vs 3.6 ng/mL, P < 0.001). The postoperative decrease in AMH levels was higher in the EC group than the non-EC group on POD10 (0.8 vs 0.5 ng/mL, P = 0.011) but not on POM3 (0.7 vs 0.5 ng/mL, P = 0.164). Vasopressin injection during EC enucleation had no significant effect on the decrease in AMH levels on POD10 (vasopressin group vs non-vasopressin group: 1.0 vs 0.8 ng/mL, P = 0.253) and POM3 (vasopressin group vs nonvasopressin group: 1.4 vs 1.1 ng/mL, P = 0.242). @*Conclusions@#AMH levels were lower at baseline and had higher decreasing rates after SPL surgery in the EC group relative to the nonEC group. Vasopressin injection might not protect the ovary from the postoperative decrease in AMH levels.

Experiences of prevention and control of hospital infection in the emergency wards:the designated hospital treating new novel coronavirus disease in Shanghai as an example / 上海预防医学

Since the outbreak of novel coronavirus pneumonia, the World Health Organization and the National Health Commission have issued multiple guidance documents.Medical facilities across the nation have actively implemented the countermeasures in response to the epidemic.However, in the real scenario of prevention and control, hospital infection remains a great concern.It is crucial to formulate measures and procedures based on standard prevention and transmission route prevention to avoid cross infection between medical workers and patients.Based on the practice, we summarize the institutional management, layout process, prevention and control of hospital infection in the emergency wards for further discussion and improvement.

Genetic Profiles Associated with Chemoresistance in Patient-Derived Xenograft Models of Ovarian Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. MATERIALS AND METHODS: To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA). RESULTS: Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25,HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845). CONCLUSION: We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.

The warning function of PEWS on septic shock of children with acute lymphoblastic leukemia after chemotherapy / 中华护理杂志

Objective To explore the application and effects of pediatric early warning score (PEWS) on the early warning and identification of septic shock in acute lymphoblastic leukemia children with neutropenia and coinfection at bone marrow suppression period after chemotherapy. Methods A retrospective study of 57 acute lymphoblastic leukemia children with neutropenia and coinfection in a tertiary hospital in Changsha from January 2015 to May 2016 was conducted. PEWS was performed based on vital sign monitoring of children. ROC curve was established to evaluate the PEWS warning value when the sick children had septic shock. The obtained PEWS system was applied in the early warning of acute lymphoblastic leukemia children with neutropenia and coinfection from October 2016 to March 2017,and relative intervention measures including setting corresponding monitor level, oxygen uptake and fluid resuscitation were provided according to various PEWS warning value. The incidence of shock,death rate and the time of recovery between two groups before and after intervention were compared. Results The optimal cut off point of PEWS when children with neutropenia and coinfection had septic shock was 3.5. After intervention,the incidence of shock,death rate and the time of recovery were lower than those before intervention (P<0.05). Conclusion PEWS can provide effective early warnings for acute lymphoblastic leukemia children with neutropenia and coinfection. It is beneficial for disease recovery and subsequent chemotherapy of the patients.

Polyinosine-polycytidylic acid promotes excessive iodine intake induced thyroiditis in non-obese diabetic mice via Toll-like receptor 3 mediated inflammation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Excessive iodine intake and viral infection are recognized as both critical factors associated with autoimmune thyroid diseases. Toll-like receptors (TLRs) have been reported to play an important role in autoimmune and inflammatory disorders. In this study, we aimed to clarify the possible mechanism of TLR3 involved in polyinosine-polycytidylic acid (poly(I:C)) promoting excessive iodine intake induced thyroiditis in non-obese diabetic (NOD) mice.</p><p><b>METHODS</b>Both NOD and BALB/c mice were randomly assigned to four groups: control group (n = 5), high iodine intake (HI) group (n = 7), poly(I:C) group (n = 7) and combination of excessive iodine and poly(I:C) injection (HIP) group (n = 7). After 8 weeks, mice were weighed and blood samples were collected. All the mice were sacrificed before dissection of spleen and thyroid gland. Then, thyroid histology, thyroid secreted hormone, expression of CD3(+) cells and TLR3 as well as inflammatory mRNA level were evaluated.</p><p><b>RESULTS</b>Both NOD and BALB/c mice from HI and HIP group represented goiter and increasing thyroid relative weight. Thyroid histology evidence indicated that only HIP group of NOD mice showed severe thyroiditis with lymphocytes infiltration in majority of thyroid tissue, severe damage of follicles and general fibrosis. Immunofluorescence staining results displayed a large number of CD3(+) cells in HIP NOD mice. Real-time polymerase chain reaction (PCR) results suggested interferon (IFN)-α increased over 30 folds and IFN-γ expression was doubled compared with control group, but interleukin (IL)-4 remained unchanged in HIP group of NOD mice thyroid. Meanwhile, over one third decrease of blood total thyroxine (TT4) and increased thyroid-stimulating hormone (TSH) was observed in HIP group of NOD mice. Only HIP group of NOD mice represented significantly elevation of TLR3 expression.</p><p><b>CONCLUSION</b>Poly(I:C) enhanced excessive dietary iodine induced thyroiditis in NOD mice through increasing TLR3 mediated inflammation.</p>

Tissue-engineered calcium phosphate cement in rabbit femoral condylar bone defects / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Calcium phosphate cement (CPC) is a favorable bone-graft substitute, with excellent biocompatibility and osteoconductivity. However, its reduced osteoinductive ability may limit the utility of CPC. To increase its osteoinductive potential, this study aimed to prepare tissue-engineered CPC and evaluate its use in the repair of bone defects. The fate of transplanted seed cells in vivo was observed at the same time.</p><p><b>METHODS</b>Tissue-engineered CPC was prepared by seeding CPC with encapsulated bone mesenchymal stem cells (BMSCs) expressing recombinant human bone morphogenetic protein-2 (rhBMP-2) and green fluorescent protein (GFP). Tissue-engineered CPC and pure CPC were implanted into rabbit femoral condyle bone defects respectively. Twelve weeks later, radiographs, morphological observations, histomorphometrical evaluations, and in vivo tracing were performed.</p><p><b>RESULTS</b>The radiographs revealed better absorption and faster new bone formation for tissue-engineered CPC than pure CPC. Morphological and histomorphometrical evaluations indicated that tissue-engineered CPC separated into numerous small blocks, with active absorption and reconstruction noted, whereas the residual CPC area was larger in the group treated with pure CPC. In the tissue-engineered CPC group, in vivo tracing revealed numerous cells expressing both GFP and rhBMP-2 that were distributed in the medullar cavity and on the surface of bony trabeculae.</p><p><b>CONCLUSION</b>Tissue-engineered CPC can effectively repair bone defects, with allogenic seeded cells able to grow and differentiate in vivo after transplantation.</p>

Impact of iodine deficiency on expression of thyroid stimulating hormone β splice variant in BALB/c mice / 中国地方病学杂志

ObjectiveTo find out if the immune system derived thyroid stimulating hormone(TSH) β splice variant(TSHβ-Ⅴ) would be regulated by circulating thyroid hormone levels to get a further understanding of the function and mechanism of this TSHβ-Ⅴ in thyroid homeostasis.MethodsA total of 20 weaning Balb/c mice (half male and half female) were selected and randomly divided into two groups according to their body mass and gender(n =10).Mice of control group were fed with common diet and deionized water.Mice of the low-iodine(LI) group were fed with low-iodine diet(containing iodine 20 - 40 μg/kg,iodine-intake about 0.25 μg/d) and deionized water.The experimental period was 3 months.At the end of the experiment,mice were executed and the blood was collected to observe the levels of TSH and thyroid hormone by chemiluminescence immunoassay (CIA) ; bone marrow (BM),peripheral blood(PBL),thyroid gland and pituitary were collected to assay the TSHβ-Ⅴ mRNA expression by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR).ResultsThe serum free thyroxine(FT4) and total thyroxine(TT4) levels in LI group of mice[(0.47 ± 0.70)nmol/L,(2.41 ± 0.28)pmol/L] were significantly lower than that of the control group of mice [(55.2 ± 3.68) nmol/L, (32.72 ± 1.02) pmol/L,t =43.81,86.04 、all P ＜ 0.01 ] and the serum total triiodothyronine(TT3) and free triiodothyronine(FT3) reduction in LI group of mice[ (0.76 ± 0.08)nmol/L,(4.01 ± 0.40)pmol/L] were significantly lower than that of the control group of mice [ (1.10 ± 0.06)nmol/L,(5.40 ± 0.38)pmol/L,t =9.81,7.5 1,P ＜ 0.01 ].Iodine insufficiency strongly elevated the serum TSH in LI group of mice[ (35.67 ± 17.39)mU/L] than that in control group of mice[ (0.24 ± 0.10)mU/L,t =- 6.11,P ＜ 0.01 ].The mRNA levels of TSH β-Ⅴ in BM (9.62 ± 0.60) and in PBL( 9.25 ± 0.83 ) of LI group of mice were lower than those in control group of mice (7.69 ± 0.36,7.11 ± 0.41,t =6.77,5.64,P ＜ 0.01),while the mRNA level of TSH β-Ⅴ in pituitary of LI group of mice (1.99 ± 0.61) was increased compared with that in control group of mice (5.75 ± 0.98,t =- 8.02,P＜ 0.01).Compared with control group of mice(9.12 ± 0.62),the level of thyroid TSH β-Ⅴ mRNA in LI group of mice (9.32 ± 0.91 ) was not significantly changed (t =0.45,P ＞ 0.05).There was no detectable native TSHβ in BM,PBL and thyroid.The mRNA level of native TSHβ in pituitary in LI group of mice( - 7.17 ± 1.78) was dramatically elevated compared to that in control group of mice( - 1.43 ± 0.51,t =- 7.60,P ＜ 0.01 ).ConclusionsThe mRNA levels of TSHβ-Ⅴ are suppressed in BM and PBL in low iodinediet induced hypothyroidism mice,which suggest that immune system derived TSHβ-Ⅴ may be more important thannative TSHβ in immune-thyroid regulation.

Effects of naloxone on the expression of stem cell factor and C-kit receptor in combined oxygen-glucose deprivation of primary cultured human embryonic neuron in vitro / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the effects of naloxone on the expression of c-kit receptor (c-kit R) and its ligand stem cell factor (SCF) in human embryo neuronal hypoxic injury.</p><p><b>METHODS</b>Serum-free cerebral cortical cultures prepared from embryonic human brains were deprived of both oxygen and glucose which would set up an environment more likely with that of in vivo ischemic injury. Neurons in 24-well culture plates were randomly divided into four groups: control group, hypoxia group, naloxone 0.5 microg/ml group and naloxone 10 microg/ml group. MTT assay and biological analysis were performed to study the cell death and the changes of extracellular concentrations of lactate dehydrogenase (LDH) after combined oxygen-glucose deprivation. Neurons in 25 ml culture flasks were also randomly allocated into four groups as previously described. Intracellular total RNA were extracted at different time points: pre-hypoxia, immediately after hypoxia, and 3, 6, 12, and 24 hours after reoxygenation. The changes of SCF/c-kit R mRNA expression in hypoxic neurons treated with different concentrations of naloxone pre and post oxygen-glucose deprivation were determined with RT-PCR.</p><p><b>RESULTS</b>The cell vitality detected by MTT assay decreased significantly in hypoxia group and naloxone 0.5 microg/ml group when compared with control group (P<0.01), while no significant difference was found between naloxone 0.5 microg/ml group and hypoxia group or between naloxone 10 microg/ml group and control group. Extracellular concentration of LDH significantly increased in hypoxia group (P<0.05), while no difference was found between naloxone 0.5 microg/ml group and control group, between naloxone 0.5 microg/ml and hypoxia group, or between naloxone 10 microg/ml and control group (all P>0.05). Immediately after oxygen-glucose deprivation, the expression of SCF/c-kit R mRNA increased significantly (P<0.01). Among those the expression of SCF presented a distribution of double-peak value within 24 hours. After treated with different concentrations of naloxone, the peak value of each group were delayed to appear and went down with the increasing of naloxone concentration. The peak values in all treated groups were significantly different from that in control group (P<0.01).</p><p><b>CONCLUSIONS</b>The expression of SCF/c-kit R mRNA increases at the early stage after combined oxygen-glucose deprivation. Naloxone 0.5 microg/ml can attenuate cell injuries and regulate the expression of SCF/c-kit R. Naloxone may protect neurons by modulating the expressions of some cytokines.</p>

Effects of iodine excess on mitochondrial superoxide production and mitochondrial membrane potential in rat thyroid cell line cells / 中国地方病学杂志

Objective To investigate the effects of iodine excess on mitochondrial superoxide production and mitoehondrial membrane potential(△ψ)changes in Fisher rat thyroid cell line(FRTL)cells.Methods FRTL cells were treated with 10-4mol/L potassium iodine(KI),10 U/L thyrotropin(TSH),10-4 mol/L KI+10 U/L TSH respectively for 24 h.Effects on cell proliferation were assayed by methyl thiazolyl tetrazolium(MTT)colorimetric method.Changes of mitochondrial superoxide production and △ψ were measured by live cell imaging and spectrofluorometer using MitoSOX and rhodamine 123(rh123)respectively.Results Absorbance(A)in the KI group (0.794±0.144)showed a significant decline compared to the control group(1.000 ±0.183,P<0.05),whereas a significant elevation was observed in the TSH group(1.215±0.156,P<0.05).No significant differences was found between the KI+TSH group(1.025±0.254)and the control group(P>0.05),but the former was marked higher than the KI group(P<0.05).Compared to the control group(9.74±3.24).MitoSOX mean fluorescence intensity (MFI)in the KI and KI+TSH groups(18.16±6.57,13.33±2.92)were significantly increased(all P<0.05),which was a significant decline in the TSH group(6.64±2.15,P<0.05).MitoSOX MFI in the KI+TSH group was lower than the KI group(P<0.05).Rh123 MFI in the KI and KI+TSH groups(210 593±31 328,295 525±34 243)showed significant decline than the control group(407 824±37 198,all P<0.05).Compared with the KI group.the KI+TSH group pronouncedly attenuated the reduction of Rh 123 MFI(P<0.05).No significant differences of Rh 123 MFI were found between the TSH group(411 187 ± 72 852) and the control group(P > 0.05). Conclusion Iodine excess (10-4 mol/L KI) may lead to peroxide damage on the mitochondria of FRTL cells, and cell proliferation is inhibited. Combining treatment with 10 U/L TSH may attenuate mitochondrial peroxide damage and inhibition of cell proliferation caused by iodine excess.

Effects of Iodine excess,polyinosinic-polycytidylic acid and thyroglobulin induced thyroiditis in mice on Toll-like receptor 3 expression / 中国地方病学杂志

Objective To observe the effect of iodine excess(HI),polyinosinic-polycytidylic acid[Poly(I:C),Poly]and thyroglobulin(TG)on the thyroid of mice by the expression of Toll-like receptor 3(TLR3)to reveal the functional role of TLR3 in autoimmune thyroiditis.Methods Forty-two non-obese diabetic mice,body weight (20±3)g,were divided into six groups:control group,HI group,Poly group,TG group,HI+TG group,HI+Poly group. Fed with deionized water and injected intraperitoneally with physiological saline 0.1 ml each day for a week, the mice in control group were injected with physiological saline every other day at the same dose for 1 week before they were sacrificed; HI group drank 0.05% NaI water and were injected intraperitoneally with physiological saline same as control group; Poly group drank deionized water and were injected intraperitoneally with poly 0.1 ml (1 g/L)each day of the week, then the mice were injected with Poly every other day at the same dose for 1 week before they were sacrificed; TG group drank deionized water and were injected intraperitoneally with physiological saline same as control group, immunized with 0.1 mg TG by subcutaneously injecting and the immunization was enhanced after they were fed half dose for 4 and 8 weeks separately. In HI + Poly group, the treatment was the same as HI group and Poly group; HI + TG group: the treatment was the same as HI group and TG group. Eight weeks later, mice were sacrificed and thyroids were taken to make frozen sections, Hematoxylin-Eosin (HE) staining was employed to observe the morphological change of the thyroids. The expression of TLR3 of thyroids was observed under fluorescence microscope after Immumofluorescence using TLR3 antibody and TR3-positive cells were analyzed in the thyroid density. Results HE staining showed thyroids of Poly group had no inflammation under microscope.There were different degrees of inflammatory cell infiltration in HI group and TG group. The inflammatory cell infiltration and the damage of follicular thyroid of HI + TG group and HI + Poly group were serious, and the degrees of inflammation were higher over "++". Thyroid follicular epithelial cell with TLR3 expression could be seen in Poly group and HI group, meanwhile, there were TLR3 strong positive inflammatory cells in HI group under fluorescent microscope. Using stereological analysis of TLR3-positive cell density in the thyroid, the difference between groups was statistically significant(F=7.870, P<0.01 ). TLR3-positive cell density in the thyroid of HI + Poly group was higher[ (9.287 ± 0.522)mm2] than control group[ (0.062 ± 0.025)mm2, P < 0.01] significantly, meanwhile, the density in HI + Poly group was higher than HI group [ (2.574 ± 0.257 )mm2] and Poly group[ (1.361 ± 0.148 )mm2, all P < 0.01]. The density in HI + TG group[ (4.843±0.405)mm2] was higher than HI group and TG group[(1.601 ±0.268)mm2, all P < 0.01 )]. Conclusions Excessive iodine and thyroglobulin can induce thyroiditis, and stimulate the expression of TLR3 in the thyroid follicular epithelial, Poly aggravated thyroiditis induced by iodine excess in NOD mice; TLR3 positive inflammatory cells also appeared in inflammatory region, suggesting that TLR3 is involved in the pathogenesis of autoimmune thyroiditis

Effect of iodine excess on TRAIL and TRAIL-sR1 expression of thyroid in Balb/c and NOD mice / 中国地方病学杂志

Objective To investigate the influence of iodine excess on expression of TRAIl/TRAIL-sR1 in NOD and Balb/c mice and to study the effect of TRAIl/TRAIL-sR1 on the pathogenesis of experimental autoimmune thyroiditis(EAT). Methods Both Balb/c and NOD mice were divided randomly into control and iodine excess group by feeding with water containing no NaI or 0.05% Nal. The mice were sacrificed after 8 weeks. TRAIL and TRAIL-sR1 mRNA levels were detected by RT-PCR. The function, morphology and apoptosis of thyroids were also observed by ELISA and Tunnel stain. Results Treated by HI, enlarged follicles and flattened epithelium by accumulation of colloid were found in thyroids of both NOD and Balb/c mice. But significant lymphoid cell infiltration and local fibrosis were only found in thyroids of NOD HI group. The relative weight of thyroids of NOD mice in HI group[(104.8±14.5)mg/kg]was heavier than that of control group [(71.8±20.4)mg/kg]. The level of TT4 declined in HI group[(30.77±3.59)mmol/L]compared with control group[(36.43±2.66)mmol/L], meanwhile, the level of TSH was higher in HI group[(6.98±0.66)μg/L]than that in control group [(5.55±0.56)μg/L]. The difference being statistically significant(t=7.773,-9.526,-4.458, all P < 0.05). The relative weight of thyroids of Balb/c mice of HI group[(155.8±20.8)mg/kg]also heavier than that of control group [(105.1±22.0) mg/kg]. The level of TT4 droped in HI group [(19.75±3.32) mmoL/L]was higher than that in control group[(23.46±6.21)mmoL/L], the level of TSH in HI group[(4.14±1.71)μg/L]was higher than that in control group[(3.55±1.41)μg/L], the difference being statistically significant(t=7.554,-7.239,3.140, all P< 0.05). A great deal of apoptotie ceils observed in NOD (3.97±0.91) and Balb/c mice (1.05±0.45) by Tunnel stain were greater than control groups (0.21±0.15, 0.10±0.03), the difference being statistically significant in beth of the two species(t=-7.167,-17.772, both P < 0.05). The apoptosis index of thyroid follicular epithelium in NOD was obviously higher than Balb/c(t=-7.625, P<0.05). The level of TRAIL mRNA did not remarkably change in Balb/c between control group(0.000 59±0.000 39) and HI group(0.001 24±0.000 46, t=-1.940, P>0.05), but it increased apparently in NOD mice HI group(0.018 88±0.005 77) than that of control group(0.009 61± 0.00591, t=-2.71, P<0.05). The level of the expression of TRAIL-sR1 mRNA increased in HI groups of NOD (0.000 53±0.000 15) and Balb/c mice(0.000 42±0.000 09) than that in control groups of NOD(0.000 28± 0.000 05) and Balb/c mice (0.000 17±0.000 06) and the differences were statistically significant between the two species(t=3.050,3.990, all P<0.05). The differences of the expression of TRAIL and TRAIL-sR1 mRNA between the two species were significant(t=-3.37,-4.76, all P<0.05). Conclusions Iodine excess induces colloid goiter in beth species of mice and thyroiditis in NOD mice. The increase of TRAIL and TRAIL-sR1 influenced by iodine excess is one of the molecular bases of follicular epithelium apoptosis and inflammation in thyroids. Genetic factor is a key factor in the pathogenesis of thyroiditis.

Levels of serum leptin in the autoimmune thyroid diseases / 中国地方病学杂志

Objective To observe the levels of serum leptin in Gaves disease(GD)and thyroiditis(HT)Datients and to discuss the immunological role of leptin in the pathogenesis of autoimmune thyroid disease(AITD).Methods 102 newly diagnosed female AITD patients were divided into 3 groups:GD hyperthyroid group,HT hypothyroid group and subclinical hypothyroid group.Age,sex and BMI-matched 27 euthyroid,healthy subjects served as controis.The levels of FT3,FT4 and sTSH were determined by immunofluorometrie assay.ELISA kit was aDplied to measure the levels of serum leptin.Results Serum FT3 and FT4[(19.74±15.39),(78.25±58.68)pmol/L]levels of GD hyperthyroid patients were obviously higher than those of the controls[(4.87±0.25),(15.96±3.15)pmol/L,P＜0.01],but serum sTSH and leptin levels[(0.15±0.08)mU/L,(8.73±1.92)μg/L]were obviously lower than those of the controls[(3.81±0.19)mU/L,(12.38±3.51)μg/L,P＜0.01or＜0.05].Serum FT3 and FT4[(3.36±0.26),(6.95±3.29)pmol/L]levels of HT hypothyroid patients were obviously lower than those of the controls(P＜0.05),but serum sTSH and leptin levels[(45.48±35.83)mU/L,(17.17±3.82)μg/L]were obviously higher than those of the controls(P＜0.01 or＜0.05).Serum FT3 and FT4[(4.67±0.60),(14.87±2.14)pmol/L]levels of subclinical hypothyroid patients had not statistical difference comparing with those of the controls(P＞0.05),but serum sTSH and leptin levels[(13.67±8.66)mU/L,(16.25±3.67)μg/L]were obviously higher than those of the controls(P＜0.01 or＜0.05).Conclusions Leptin might have an immuoregulation role in the pathogenesis of AITD.In addition,serum levels of leptin in AITD is also influenced by many other related hormones.

Induction of experimental Graves' disease in Balb/c mice immunized with human thyrotropin receptor ectodomain amino terminus gene / 中国地方病学杂志

Objective To study the antigenicity of human thyrotropin receptor(hTSHR)amino terminus (amino acid 29～280)and its association with Graves' disease.Methods Total thyroid RNA was prepared from human normal thyroid tissue.RNA was then reversely transcripted and cDNA was subjected to PCR amplification.PCR product was cloned into pcDNA3.1 and the recombinant plasmid was named pcDNA3.1/hTSHR188～940bp. Balb/c mice were immunized with peDNA3.1/hTSHR188～940bp. The levels of serum thyroxin,anti-TSHR antibody(TRAb)and thyroid stimulating antibody(TSAb)were measured,and the pathological changes of thyroid tissue were also observed.Results A 753 bp fragment encoding hTSHR ectodomain amino end was obtained after PCR amplification.Confirmed by Hind Ⅲ restriction enzyme digestion and DNA sequencing,pcDNA3.1/hTSHR188～940bphad been constructed successfully,with the correct sequence and direction of hTSHR188～940bp.In the Balb/c mice treated with pcDNA3.1/hTSHR188～940bp,elevated TRAb in week 6(0.148±0.018)were observed compared with those at week o(0.106±0.006,P＜0.01),and kept a higher level till week 10(0.134±0.011,P＜0.01).T4 and TSAb index values were significantly increased in week 10.Serum T4 concentration increased from(41.02±7.97)μg/L in week 0 to(62.20±12.77)μg/L in week 10(P＜0.01);TSAb index values rose from 0.864±0.076 at week 0 to 1.392±0.615(P＜0.01).Thyroid pathological examination showed that proliferated thyroid follicular epithelial cells and foll icular eapacity increased.Inflammatory cells were occasionally found.Conclusions There are antigen epitopes in hTSHR ectodomain amino acid 29～280,which can stimulate the production of TSAb.And the latter induces hyperthyroidism and Graves' disease like manifestations.It suggests that hTSHR ectodomain amino acid 29～280 is closely associated with Graves' disease,and maybe one of important etiological factors leading to the disease.

Detection of serum fibrosis markers in patients with autoimmune thyroid diseases / 中国地方病学杂志

Obecfive To study the clinical significance of detecting serum proeollagen type Ⅲ(PCⅢ) and hyaluronie acid(HA)in patients with autoimmune thyroid diseases(AITD).Methods According to the thyroid function,the 114 patients with AITD were divided into hyperthyroidism group(38),hypothyroidism group(35),and sub-hypothyroidism group(41).In addition,40 healthy persons were served as controls.The level of serum PCⅢ was determined with ELISA and that of serum HA with RIA.The level of FT3,FT4 and sTSH were detected by immumnofluorometric assay.Results Serum FT3(18.35±6.19)pmol/L]and FT4[(76.28±23.49)pmol/L]level of patients with hyperthyroidism were obviously higher than those of the controls[(4.75±0.31),(16.12±3.27) pmol/L],but serum sTSH[(0.15±0.07)mU/L]was obviously lower than that of the control[(3.78±0.15)mU/L],the differences were statically significant(P＜0.01).Serum FT3[(3.36±0.26)pmol/L]and FT4 [(6.37±2.19) pmol/L]level of patients with hypothyroidism were both lower than those of the controls(P＜0.05).but serum sTSH[(44.58±13.29)mU/L]was obviously higher than that of the control(P＜0.01).Serum FT3 [(4.86±0.45)pmol/L]and FT4[(15.26±2.78)pmol/L]level of patients with sub-hypothyroidism had no statistical difference compared with those of the controls(P＞0.05),but serum sTSH[(14.26±4.73)mU/L] was obviously higher than that of the controls(P＜0.01).The level of sernm PCⅢ[(4.63±1.22)μg/L]in pafients with hyperthyroidism was significantly higher than that of any other group(P＜0.05).There waB no statistical significant difference in PCⅢ among the patients with hypothyroidism,the patients with sub-hypothyroidism and controls [(3.64±1.12),(3.54±1.17)and(3.56±1.07)μg/L],respectively(P＞0.05).The level of serum HA [(31.13±10.28)μg/L]in patients with hypothyroidism was significantly higher than that of any other group(P＜0.05).There was no statistical significant difference in HA among the patients with hyperthyroidism,the patients with sub-hypothyroidism and controls[(22.24±7.22),(22.43±7.99)and(23.09±9.19)μg/L,respectively,P＞0.05].Conclusions It is very significant to understand myocardial fibrosis early through detecting sernm PCⅢ in patients with hyperthyroidism.Measurement of serum PCⅢ and HA will be useful to discovery hepatic fibrosisearly in patients with a long course of hyperthyroidism.

Effect of iodine on the pathogenesis of postpartum thyroiditis / 中国地方病学杂志

Objective To explore the effect of iodine on the pathogenesis of postpartum thymiditis.Methods Forty-four female C57BL/6J mice,8-week old,fed by low iodine dietary(the concentration of iodine≤35 μg/kg),were randomly divided into 4 groups:non-pregnancy experimental autoimmune thymiditis(non-pregnancy EAT)group with 8 mice,EAT of mice was induced by immunization with pig's thyroglobulin(Tg)in the presence of complete Freund's adjuvant.Six mice in non-pregnancy EAT group survived at the end of experiment;normal iodine-PPT(NI-PPT)group,10-fold high iodine-PPT(10HI-PPT)group and 50-fold high iodine-PPT(50HI-PPT)group with 12 mice in each group.The last 3 groups mice,who received the same immunization schedule as the above,were mated with adult male mice followed by induction of EAT.In the end,7,6 and 6 mice were noticed to be pregnant in each group.All animals were killed 4 weeks after postpartum.Histological severity of thyroid specimens was evaluated.The serum level of thyroglobulin antibody(Tg-Ab),thyroid pomxidase antibody(TPO-Ab),TT3 and TT4 were measured by radioimmunoassay(RIA).The expression level of IFN-γ/IL-4 mRNA in spleenwere assayed by RT-PCR.Results Pathological examination showed the infiltration of inflammatory cells.epithelial cell applanation,follicle atrophy or destruction.The severity of inflammation in non-pregnancy EAT bgroup.NI-PPT group and 10HI-PPT group was less serious than that in the 50HI-PPT group,the difference has bstatistical significance(P＜0.05).The level of TPO-Ab in non-pregnancy EAT group,NI-PPI-group,10HI-PPTgroup and 50HI-PPT group wag(14.32±8.85)%,(64.45±10.52)%,(38.46±5.57)%and(90.09±9.98)%.respectively the difference being statistically significant between any two groups(P＜0.05).There was no statisticaldifference(F＝0.484,P＞0.05)of Tg-Ab among non-pregnancy EAT group[(33.74±3.71)%],NI-PPT group [(29.65±2.06)%],10HI-PPT group[(37.21±3.87)%]and 50HI-PPT group[(33.87±4.17)%].There was no statistical difference(F＝1.596,P＞0.05)of TT3 among non-pregnancy EAT group (2.47±0.69)%,NI-PPT group(1.57±0.25)%,10HI-PPT group[(1.60±0.28)%]and 50HI-PPT group[(1.82±0.75)%].The level of TT4 in 50HI-PPT group[(66.68±5.47)%]was lower than that in non-pregnancy group,NI-PPT group and 10HI-PPTgroup[(99.87±5.97)%,(89.13±7.64)%and(91.05±5.82)%],the difference being statistically significant(P＜0.05).The expression level of IFN-γ mRNA was increasing,being 1.02±0.10,1.37±0.10,1.39±0.12 and 1.68±0.06 in non-pregnancy EAT group,NI-PPT group,10HI-PPT group and 50HI-PPT group.The difference had a statistical significance between any two groups except for NI-PPT group and 10HI-PPT group(P＜0.05).The expression level of IL-4 mRNA in 10HI-PPT group(0.49±0.04)and 50HI-PPT group(0.53±0.06)were all higher than non-pregnancy EAT group(0.24±0.05)and NI-PPT group(0.35±O.05),the differences being statistically significant (P＜0.05).Conclusions Adequate iodine supplementation during pregnancy and postpartum period is necessary,but iodine excess could induce postpartum thyroiditis.So iodine supplementation during pregnancy and postpartum should be adequate and reasonable.

Effects of naloxone on glutamate release in combined oxygen-glucose deprivation of primary cultured human embryo neuron / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effects of naloxone on glutamate release in combined oxygen-glucose deprivation of primary cultured human embryo neurons.</p><p><b>METHODS</b>The primary cultured embryonic human cortical neurons were demonstrated by immunocytochemical stain of neural filament (NF). The neurons were randomly allocated into control group, hypoxic group, and experimental group. The experimental group was further divided into three subgroups pretreated with different concentrations of naloxone (0.25, 5, 10 microg/ml). The neurons of hypoxic group and experimental group were deprived both oxygen and glucose for 1 hours followed by 24 hours of reoxygenation. Meanwhile, we used 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, high performance liquid chromatography (HPLC), and biological analysis to study the survival rate of neurons and the changes of extracellular glutamate and lactate dehydrogenase (LDH) levels after 24 hours of reoxygenation.</p><p><b>RESULTS</b>One hour of oxygen-glucose deprivation followed by 24 hours of reoxygenation was associated with a large increase in extracellular LDH and glutamate and a significant decrease of cell vitality (P < 0.01). Naloxone exerted a concentration-dependent protection against neuronal injury provoked by combined oxygen-glucose deprivation. After reoxygenation, the extracellular concentrations of glutamate gradually decreased (P < 0.05, P < 0.01, respectively) and cell vitality increased (P < 0.01) with increase of the concentration of naloxone compared with control group. All of them returned to control level when naloxone was up to 10 microg/ml (P > 0.05).</p><p><b>CONCLUSION</b>Naloxone protects neurons from hypoxic injury by inhibiting the release of glutamate and therefore alleviating the exciting toxicity.</p>

Anti-fungal test of composite agastache lotion on seven pathogenic fungi and its clinical application / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Chinese composite recipe in treating mycotic infection.</p><p><b>METHODS</b>The growth condition of 7 kinds of fungi cultured on the media containing composite agastache lotion (CAL, consisted of 5 Chinese drugs) of different concentration was observed. Result showed that CAL could inhibit 7 kinds of fungi. Based on the above anti-fungus test, 110 patients with skin tinea or genital candidiasis were treated separately with CAL, western medicine and combined (CAL and western) medicines, the therapeutic effects of the 3 groups were observed and compared.</p><p><b>RESULTS</b>The therapeutic effect in patients treated with combined medicine was significantly better than that in the other two groups (P < 0.05).</p><p><b>CONCLUSION</b>Combined use of CAL and western medicine could enhance the cure rate in treating skin tinea and genital candidiasis. Attention should be paid on studying Chinese anti-fungal agents.</p>