Objective To evaluate the diagnostic efficacy of Kwak and ACR( 2017 ) thyroid imaging reporting and data systems ( T I‐RADS ) for thyroid nodules . Methods Cases of thyroid nodule who underwent surgery from January 2015 to M arch 2018 in 15 hospitals in Sichuan province were collected and the ultrasonographic features of thyroid nodules were retrospectively analyzed by trained senior ultrasound physicians using Kwak and ACR T I‐RADS classification methods . Totally ,12 712 thyroid nodules were observed ,7 023 thyroid nodules in 7 023 cases with complete ultrasound and surgical and pathological data were eventually enrolled in the study . T hyroid nodules with solid ,hypoechoic or very hypoechoic ,tall/wide ratio ≥ 1 , margin ill‐defined and microcalcification were classified as malignant signs of ultrasound . M alignant percentage was calculated and diagnostic tests were performed . Results ① T here was a statistical difference between the benign and malignant nodules in the two types of T I‐RADS classification ( P＜0 .01) . ② T he area under ROC curve of Kwak and ACR in the diagnosis of malignant nodules were 0 .89 and 0 .84 ,respectively . T he Youden index of Kwak and ACR were 0 .66 and 0 .57 ,respectively . ③Taking Kwak T I4B and ACR T R4 as critical points for malignancy ,the sensitivity ,specificity ,positive predictive value and negative predictive value of Kwak T I 4B were 75 .0% ,90 .9% ,83 .2% ,and 85 .9% , respectively . T he accuracy of Kwak T I4B was 84 .9% ; T he sensitivity ,specificity ,positive predictive value and negative predictive value of ACR T R4 were 88 .2% ,68 .9% ,62 .9% ,and 90 .8% ,respectively . T he accuracy of ACR T R4 was 76 .2% . T he Kappa value of Kwak TI4B and ACR T R4 was 0 .52 . T he χ2 value of Kwak T I4B and ACR T R4 was 2 174 .6 ( P ＜ 0 .01 ) . Conclusions T he diagnostic values of two T I‐RADS classification methods for thyroid malignant nodules are high . T he overall efficiency of Kwak T I‐RADS classification method is better than that of ACR TI‐RADS classification method .

In order to provide enlightening experience for the establishment of reasonable and diversified orphan drugs into the reimbursement system in China, the official websites of the National Institute for Health and Care Excellence(NICE)and the National Health Service(NHS)in the UK were inspected, collecting and summarizing the relevant documents, on the inclusion of orphan drugs into the reimbursement system. Relevant literatures were analyzed with theoretical studies on the accessibility of medicines for patients with rare diseases. In the NHS system, the inclusion of orphan drugs into the reimbursement system in the UK can be achieved mainly through seven routes, with three routes that are evaluated by NICE(MTA, STA and HST)and four are directly managed by the NHS(specialized commissioning, CDF, IFRs, CtE). Through the analysis of the inclusion of orphan drugs into the reimbursement system and the various problems in the UK, we have found some enlightening experience for the establishment of the reimbursement system for orphan drugs in China.

Objective To explore the clinical features, diagnosis, and treatment of congenital disorder of glycosylation type 1a (CDG-Ⅰa), a rare inherited metabolic disease. Methods The clinical data and the gene detection results of one case of CDG-Ia which was discovered because the case had encephalopathy and hepatopathy were retrospectively analyzed. The related literatures were reviewed. Results Male infant suffered with face and trunk rash, motor development retardation, malnutrition, cheek fat plump, low limbs muscle tone, and bilateral crater nipple at 3 months old. Abnormal liver function and mild renal impairment were found after examination. The development quotient was low. Head MRI showed that bilateral frontal and temporal sulcus widening, and cerebellar atrophy. Urinary organic acids, amino acids, carnitine, and biotin activities were normal. Gene sequencing revealed that there were two heterozygous mutations, c.430T>C (p.F144L) and c.713G>C (p.R238P), in the PMM2 gene. The diagnosis of CDG-Ⅰa was confirmed. Both of the infant's parents were healthy, and each of them carries a pathogenic mutation. The infant had an elder brother who had mental disorder and died for liver and kidney function damage and hydronephrosis at 8 months old. Conclusion CDG-Ⅰa is an autosomal recessive disease. For infants with unexplained multiple organ damage, especially combined with intelligent and motor development retardations, strabismus, nipple retraction, and cerebellar atrophy, the possibility of CDG-Ⅰa should be considered. Gene detection of PMM2 can help the diagnosis.

Objective To investigate the correlation between the expression of CD147 and MUC5ac in peripheral small cell lung cancer and the computed tomography (CT) signs.Methods Forty two cases of peripheral non-small cell lung cancer (NSCLC) confirmed by operation and pathology were examined by CT.The positive expression of CD147 and MUC5ac was detected by immunohistochemical staining and the relationship between the expression of CD147 and MUC5ac was analyzed.Results CD147 and MUC5ac were closely related to the lymphatic metastasis of peripheral non-small cell lung cancer (P ＜ 0.05).The positive expression of CD147 is significantly related to tumor size,deep lobulation,spinous process and lymphadenopathy (P ＜ 0.05).MUC5ac is significantly related to tumor size,deep lobulation,spiculation,vascular convergence sign,extrapleural fat Line disappearance,and mediastinal lymphadenopathy (P ＜0.05).Conclusions These results indicate that CD147 and MUC5ac play an important role in the invasion and metastasis of peripheral lung cancer.

Objective To investigate the radiosensitization effects of the combination treatment of clioquinol (CQ) and zinc on human cervical cell line HeLa in vitro.Methods Cells were divided into the 4 groups:controls,drug,radiation,and combined drug and radiation group.Cytotoxic effect of CQ and zinc on cell viability was determined by CCK-8 assay.Radiosensitization effect of CQ and zinc on HeLa cells was detected by colongenic assay,and the single-hit multi-target model was used to stimulate the doseresponse curve of survival and to calculate radiosensitization parameters.The cell cycle and apoptosis of HeLa cells were analyzed with flow cytometry.Luciferase reporter assay was used to study NF-κB activity of HeLa cells.Results The combination of CQ and zinc inhibited cell growth in a dose-dependent manner (F =188.00,P ＜ 0.01).The mean lethal dose was 3.16 and 2.04 Gy for radiation group and combined drug and radiation group,respectively,and hence the SER was 1.55.Compared with the radiation group,the ratio of G2-phase cells in the combined drug and radiation group decreased(t =10.39,P ＜ 0.05),the apoptosis rate increased at 24 h post-irradiation (t =5.64,P ＜ 0.01),and the NF-κB activity decreased (t =21.42,P ＜ 0.05).Compared to the control group,the NF-κB activity increased in the radiation group(t=6.23,P＜0.05),but decreased in the drug group(t =12.48,P＜0.05).Conclusions The combination of CQ and zinc could increase the radiosensitivity of HeLa cells by decreasing the ratio of G2-phase cells,increasing apoptosis and the inhibiting of NF-κB activity.

ObjectiveTo investigate the regulatory effects of traditional Chinese medicine (TCM) Shufengxuanfeijiedu formula on Janus kinase signal transducer and activators of transcription (JAK-STAT) of lung tissues in mice with influenza viral pneumonia.Methods According to random number table, 60 mice were randomly divided into six groups with 10 mice in each group: normal group (N), model group (M), Tamiflu control group (C) and low (SL), medium (SM), high dose (SH) Shufengxuanfeijiedu formula groups. The mouse model of influenza virus pneumonia was reproduced by dropping of 0.05 mL 4LD50 inflluenza virus FM1 strain which can be adapted to lung tissue into the nose; while the N received nose instillation of 0.05 mL normal saline. After successful modeling for 2 hours, distilled water was given orally (by lavage) to N and M; Duffy (oseltamivir) 2.5 g·mL-1·d-1 was administrated to C; the TCM SL, SM, SH were intragastrically administered with different doses of shufengxuanfeijiedu decoction into the corresponding groups respectively (the ingredients of prescription: chrysanthemum, mulberry leaf, almond, platycodon root, forsythia, bupleurum etc. forming granules), according to the suitable dose of granules used for human body surface, the dose used for mouse surface area was calculated, the high dose means the dose used in the medium dose group doubled, the low dose means 1/2 dose used in medium group, once a day, once 0.2 mL for consecutive 4 days. Afterwards, the lung tissues were collected, the mouse differential gene expressions related to JAK-STAT pathway were detected by gene chip technology, the standards for screening of differential gene expression were as follows: up-regulated gene was P < 0.05, and the log2ratio > 1; down-regulation gene wasP < 0.05, and log2ratio < -1. The levels in lung tissue kinase (JAK) andγinterferon (IFN-γ) mRNA expressions were determined by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR).Results Compared with those in N, the differential expression gene transcription activator, STAT5 [log2 (N/M) = 2.32], interleukin 4 receptor alpha subunit [IL4RA, log2 (N/M) = 4.77], interleukin 12 receptor [IL12R, log2 (N/M) = 1.58], JAK [log2 (N/M) = 2.41] were all obviously up-regulated, and IFN was significantly down-regulated [log2 (N/M) = -1.45] in M. Compared with those in M, C group IFN [log2 (C/M) = 1.51], various TCM dose groups [log2 (SL/M) = 1.46, log2 (SM/M) = 1.72, log2 (SH/M) = 1.40] differential expression gene IFN was significantly up-regulated, STAT5 [log2 (C/M) = -2.06, log2 (SL/M) = -1.41, log2 (SM/M) = -2.10, log2 (SH/M) = -1.89], IL4RA [log2 (C/M) = -2.52, log2 (SL/M) = -1.85, log2 (SM/M) = -2.74, log2 (SH/M) = -1.39), IL12R [log2 (C/M) = -1.48, log2 (SL/M) = -0.10, log2 (SM/M) = -1.58, log2 (SH/M) = -0.53], JAK [log2 (C/M) = -1.44, log2 (SL/M) = -0.88, log2 (SM/M) = -1.74, log2 (SH/M) = -0.53] were significantly down-regulated. In M, the JAK mRNA expression was obviously elevated (2-ΔΔCt: 3.17±0.94 vs. 1.01±0.13,P < 0.05), while the IFN-γ mRNA expression was decreased (2-ΔΔCt: 0.15±0.48 vs. 1.01±0.12,P < 0.05); compared with M, the JAK mRNA expressions in C, SM and SH groups were all obviously decreased (2-ΔΔCt: 2.02±0.63, 1.19±0.30, 1.59±0.67 vs. 3.17±0.94, allP < 0.05); while the IFN-γmRNA expressions in C, SL, SM and SH groups were elevated (2-ΔΔCt: 0.61±0.12, 0.41±0.13, 0.85±0.14, 0.78±0.20 vs. 0.15±0.48, allP < 0.05).Conclusions Shufengxuanfeijiedu formula can ameliorate the mice immune pathological injury of lung tissues induced by influenza virus by regulating JAK-STAT signal pathway and balancing Th1/2 via up-regulating the expression of IFN-γ.

BACKGROUND/AIMS: This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. METHODS: Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. RESULTS: The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%+/-1.2% in controls and was significantly increased to 7.2%+/-1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. CONCLUSIONS: There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability.
Animals ; Apoptosis/*physiology ; Claudins/*metabolism ; Colitis/chemically induced/immunology/*physiopathology ; Colon/immunology/physiopathology ; Dextran Sulfate ; Intestinal Mucosa/*physiopathology ; Lactulose/metabolism ; Mannitol/metabolism ; Mannose-Binding Lectin/*immunology ; Permeability ; Rats ; Rats, Sprague-Dawley ; Sucrose/analogs & derivatives/metabolism ; Up-Regulation

OBJECTIVEWe report the first case of acute encephalopathy induced by vaccination in an infant with methylmalonic aciduria cblA in China.

METHODThe clinical presentation, blood acylcarnitines analysis, urine organic acids analysis and gene studies of the patient were summarized.

RESULTThe proband, a boy, was admitted at the age of 15 months because of recurrent vomiting, acidosis and development delay for 8 months. The previously healthy boy presented vomiting and coma just one hour after hepatitis B vaccination at the age of seven months. Moderate dehydration, electrolyte disturbance and metabolic acidosis had been found. Although his acute metabolic crisis had been corrected soon after intravenous transfusion, psychomotor retardation and recurrent vomiting had been observed. When he was 15 months old, vomiting and lethargy occurred again 3 hours after DTaP vaccination. He was weakened as the illness became worse and got coma with dyspnea 7 days later. He was hospitalized with the suspected diagnosis of viral encephalitis. Blood acylcarnitines analysis, urine organic acids analysis and gene study had been performed for the etiologic investigation.His blood propionylcarnitine (16.3 µmol/L vs. normal range 1.0-5.0 µmol/L) and propionylcarnitine/free carnitine ratio (0.27 vs. normal range 0.03 to 0.25) increased. Markedly elevated urinary methylmalonic acid (388.21 mmol/mol creatinine vs. normal range 0.2 to 3.6 mmol/mol creatinine) and normal plasma total homocysteine supported the diagnosis of isolated methylmalonic aciduria. Two mutations, c.650 T>A (p.L217X) and c.742 C>T (p.Q248X), were identified in his MMAA gene, confirmed the diagnosis of cblA. Each parent carried one of the two mutations. Progressive clinical and biochemical improvement has been observed after hydroxylcobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine. He is currently 2 years and 7 months old with normal development and general condition.

CONCLUSIONA boy with cblA was firstly detected after the acute encephalopathy induced by vaccination in China. It is important to pay more attention to the patients with metabolic crisis or organ damage after vaccination. Metabolic studies are keys to the diagnosis of potential diseases and improve the outcome.

Amino Acid Metabolism, Inborn Errors ; complications ; Brain Diseases ; chemically induced ; Carnitine ; analogs & derivatives ; Diet, Protein-Restricted ; Hepatitis B Vaccines ; adverse effects ; Humans ; Infant ; Male ; Methylmalonic Acid ; urine ; Mutation ; Vaccination ; adverse effects ; Vitamin B Complex ; Vomiting

Objective To master the rehabilitation in patients with traumatic brain injury in Eastern China, and provide evidence for clinicians to rehabilitate early,correctly and effectively.Methods All sampling of the TBI patients from 80 hospitals in Eastern China were clustered and were analyzed using SPSS 13.0.Results The rate of in -patients in Eastern China with early rehabilitative intervention was 4.68%,and the rate of male was higher than female(male to female ratio was 3.80:1),mean age was (40.10 ±16.33)years old,but there was no difference in gender(χ2 =3.23,P =0.072)and age(t =-0.819,P =0.413)for the early rehabilitative intervention.Local resi-dent patients in early rehabilitative intervention was lower(χ2 =8.28,P <0.05).The average length of stay for the early rehabilitative intervention patients was(39.57 ±34.22)d(t =-17.74,P <0.05),the average cost of hospitali-zation was(42 741.50 ±43 186.69)yuan(t =-18.96,P <0.05).The rate of average length of stay and average cost of hospitalization of the rehabilitative intervention patients were higher and more expensive than the patients who did not obtain early rehabilitative intervention,but did have higher unfavourable prognosis rate(χ2 =85.45,P <0.05). Conclusion We advocate correct and early rehabilitative intervention for traumatic brain injury in patients with different degree,and promote not only the physical and functional rehabilitation,but also comprehensive rehabilitation such as the psychological treatment,family treatment and social regression.

Objective Antiangiogenesis therapy has been shown to prolong survival for patients with malignant tumor .However the present study has not been observed the clinical benefit of antiangiogenesis therapy combination with chemotherapy treated with gastric canc-er.Human recombinant vascular endothelial inhibition (endostar) as a multi-targeted anti-angiogenesis drug, the mechanism is different from other Antiangiogenesis drugs.It can block different pathways of signal transduction to inhibit angiogenesis .This study aimed to observe the effect of combined application of endostar and paclitaxel on biological behavior of gastric cancer cell lines . Methods MMT assay and Tr-answell invasion assay were respectively used to examine the inhibition rate of cell growth and invasion ability when cells were treated with va-rious concentrations of endostar and paclitaxel alone or in combination.The protein expressions of VEGF,MMP-2 and MMP-9 were examined by Western blot. Results Endostar or paclitaxel effectively inhibited the growth of MGC803 cells and the in vitro invasion of MGC803 cells in a concentration-dependent manner.The proliferation and invasion ability of combined treatment with endostar and paclitaxel was significantly lower than that of endostar or paclitaxel alone (P<0.05).Compared with con-trol group, the VEGF,MMP-2 and MMP-9 protein expressions were de-creased in experimental groups ( P <0.05).Compared with paclitaxel group, the VEGF, MMP-2 and MMP-9 protein expressions were relatively reduced in combination groups (P<0.05). Conclusion Endostar combined with paclitaxel can suppress the growth and invasion of MGC803 cells, and the decreasing VEGF , MMP-2 and MMP-9 expressions may be involved in the mechanism .