Ebolavirus can cause hemorrhagic fever in humans with a mortality rate of 50%-90%. Currently, no approved vaccines and antiviral therapies are available. Human TIM1 is considered as an attachment factor for EBOV, enhancing viral infection through interaction with PS located on the viral envelope. However, reasons underlying the preferable usage of hTIM-1, but not other PS binding receptors by filovirus, remain unknown. We firstly demonstrated a direct interaction between hTIM-1 and EBOV GP in vitro and determined the crystal structures of the Ig V domains of hTIM-1 and hTIM-4. The binding region in hTIM-1 to EBOV GP was mapped by chimeras and mutation assays, which were designed based on structural analysis. Pseudovirion infection assays performed using hTIM-1 and its homologs as well as point mutants verified the location of the GP binding site and the importance of EBOV GP-hTIM-1 interaction in EBOV cellular entry.
Ebolavirus ; metabolism ; Flow Cytometry ; Glycoproteins ; metabolism ; Hepatitis A Virus Cellular Receptor 1 ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Membrane Glycoproteins ; metabolism ; Membrane Proteins ; metabolism ; Protein Binding ; Receptors, Virus ; metabolism ; Surface Plasmon Resonance ; Viral Envelope Proteins ; metabolism ; Viral Proteins ; metabolism

BACKGROUNDRathke's cleft cyst (RCC) is one of the most common incidentally discovered sellar lesions, while symptomatic cases are relatively rare. Surgical treatment is recommended for symptomatic patients to drain the cyst content and to remove the capsule safely. The aim of this study was to clarify the clinical features, surgery considerations and therapy outcomes of symptomatic RCCs.

METHODSTotally 42 patients (19 males and 23 females) were retrospectively reviewed with the diagnosis of RCCs under surgery resection at the Affiliated Hospital of Medical College, Qingdao University between January 2005 and December 2010.

RESULTSPatients' age ranged from 6 to 67 years (mean of 41.6 years). The duration of symptoms ranged from 4 days to 10 years. Headache (69%), visual impairment (36%), and pituitary dysfunction (10%) were the most common presenting symptoms. The maximum diameter of cysts ranged from 6.0 to 46.7 mm (mean of 20.07 mm). Of the 42 patients, 36 underwent endonasal transsphenoidal approach and the others underwent transcranial approach. Thirty patients had a subtotal resection and decompression, while 12 patients had a total cyst resection. Cysts of 28 patients were lined by simple cubical or columnar epithelium, and cysts of 34 patients were filled by amorphous colloid material, that was the characteristic of RCCs. The majority of patients presented with a simple headache, and 93% of this group experienced a complete improvement after surgery. Twelve of 15 patients (80%) with preoperative visual deficits experienced an improvement in their vision after surgery. All of those patients with pituitary dysfunction experienced an improved endocrine status. The endocrinological complication usually was diabetes insipidus, and postoperative transient diabetes insipidus occurred in 13 (31%) patients without any permanent diabetes insipidus. The overall recurrence rate was 7% at a mean follow-up of 22 months (range 12 - 60 months).

CONCLUSIONSSurgical treatment is to drain the contents of the cyst and to remove the capsule as much as possible under the precondition that does not increase the complications. Biopsy and decompression procedures are recommended for most cases.

Adolescent ; Adult ; Aged ; Central Nervous System Cysts ; diagnosis ; pathology ; surgery ; Child ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Objective:To explore the clinical characteristics of Mycoplasma pneumoniae (MP) bronchiolitis to provide references for clinical prevention and treatment.Methods:From January 2019 to January 2020, the clinical data of children diagnosed with MP bronchiolitis in the Department of Respiratory 2 of Hebei Children′s Hospital were retrospectively collected and analyzed, and the patients were followed up to observe the prognosis.Results:Among the 67 children, there were 39 boys and 28 girls, with age of 5 (1-14) years.All the children had cough, 63 cases (94.0%) had fever, 49 cases (77.8%) had high fever (≥39.0 ℃), and the median total fever course was 8(1-27) d; 10 cases (14.9%) had wheezing; 5 cases (7.5%) had dyspnea; 3 cases (4.5%) had hypoxemia; wet rales were heard in 58 cases (86.6%) and wheezing in 10 cases (14.9%). Forty-eight patients (71.6%) had family allergy history or personal allergy history.The average value of peripheral blood white blood cells was (8.6±2.6)×10 9/L; the me-dian of C reactive protein was 9.1(0.5-55.6) mg/L, of which 7 cases (10.4%) were ≥30 mg/L; the median of lactate dehydrogenase was 278(181-590) U/L.Tree bud sign and central lobular nodules were the main findings of high-resolution CT of the chest.Among them, 45 cases (67.2%) had bilateral lesions, 38 cases (56.7%) involved ≥3 lung lobes, and 22 cases (32.8%) had a little lung consolidation, 19 cases (28.4%) had a small amount of pleural effusion.The bronchoscopic features of 35 children (52.2%): 71.4%(25/35 cases) showed white flocculent and cord-like secretions, 17.1%(6/35 cases) displayed mucus plugs blocking the lumen, and 10.9%(4/35 cases) showed no-dular protrusions and granulation tissue hyperplasia.All children were treated with Azithromycin sequentially; 42 children (62.7%) were treated with low-dose hormones, and the average initiation time was on day (10.62±2.71) and the median course was 14(2-42) d. Sixty-seven cases were followed up for half a year, of which 61 cases (91.0%) had almost complete lung recovery, and 6 cases (9.0%) developed bronchiolitis obliterans (BO). Conclusions:MP bronchiolitis mostly occurs in infants and preschool children with a family history of allergies or personal allergies.Fever and cough are the main clinical manifestations.In severe cases, dyspnea and hypoxemia may occur.The physical signs of the lungs are mainly include wet rales, some of which are wheezing.White flocculent and cord-like secretions are the main manifestations of bronchoscopy.After active treatment, most children have a good prognosis, and some children may develop BO.

OBJECTIVETo investigate the mutations of epidermal growth factor receptor (EGFR) in tumor tissue and pleural effusion in advanced non-small cell lung cancer (NSCLC) patients, and to analyze the relationship between EGFR mutations and the clinicopathologic characteristics.

METHODSTwo-hundred and forty-one cases of formalin-fixed, paraffin-embedded tumor tissues and 14 paired pleural effusions from advanced NSCLC patients were collected. Twenty-nine different EGFR mutations in exons 18-21 were assessed by scorpions and amplification refractory mutation system (scorpions ARMS) using real time PCR. The relationship between the EGFR mutations and clinical parameters was analyzed using statistical methods. EGFR mutation of 37 cases were detected with direct sequencing, and assessed the sensitivity, the specificity and the accuracy of scorpions ARMS.

RESULTSEGFR somatic mutations were detected in 114 of 234 advanced NSCLC patients, with the mutation rate of 48.7%, including deletions in exon 19 in 65 patients and point mutation of L858R in exon 21 in 39 patients; both accounting for 91.2% (104/114) of all types of EGFR mutations. The test results of 14 paired pleural effusion specimens were entirely the same to the tissues. The concordance rate of 2 different detection methods was 94.6%. Mutation rate was higher in women (55.9%) than in men (42.2%), and there was no difference in mutation rates between smokers and non-smokers; patients in stage IIIB and stage IV; adenocarcinoma and non-adenocarcinoma.

CONCLUSIONSEGFR somatic mutations appear to occur frequently in Chinese. Scorpions ARMS technology is a sensitive method to detect EGFR mutations and is suitable for screening patients who would likely respond to EGFR inhibitors therapy.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; pathology ; Exons ; Female ; Gene Deletion ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Point Mutation ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Young Adult

OBJECTIVETo assess the association of VKORC1 gene -1639G/A polymorphism with atrial fibrillation (AF) in ethnic Uygurs and Hans from Xinjiang.

METHODSThe above polymorphism was detected among 100 Uygur and 102 Han AF patients and 103 Uygur and 111 Han subjects that have no AF with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

RESULTSA statistically significant difference was detected between the patient and control groups of Uygur origin in terms of genotypic and allelic frequencies (P<0.05). Logistic regression analysis also indicated the -1639G/A polymorphism as an independent risk factor for AF in Uygur population (OR=2.085, 95% CI: 1.067-4.072, P=0.031). No similar statistical difference was found between the patient and control groups of Han origin (P>0.05).

CONCLUSIONThe -1639G/A polymorphism of VKORC1 gene is associated with AF in the Uygur population but not in Hans.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Atrial Fibrillation ; ethnology ; genetics ; Base Sequence ; China ; ethnology ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Vitamin K Epoxide Reductases ; genetics

To study pharmacokinetic characteristics of epimedin A, B, C and icariin after intermuscular administration of Chuankezhi injection to rat. The established RRLC-MS/MS method was applied for simultaneous determination of four analytes in rat plasma and calculating their pharmacokinetic parameters. As a result, each analyte showed a good linear relationship in the concentration range of 1-1 000 μg•L⁻¹.The intra-day precise was 96.9%-107.5% with RSD<5.99%, inter-day precise was 92.3%-105.0% with RSD<10.16%. The relative recovery of four analytes was 88.1%-101.1% with RSD<7.9% and their absolute recovery was 72.0%-86.6% with RSD<6.3%. After intermuscular administration of Chuankezhi injection, the plasma concentration of four flavonoid glycosides rapidly arose to peaks at about 10 min, and then quickly declined in rat. Tmax of epimedin A, B, C and icariin was 0.21, 0.19, 0.16 and 0.49 h, respectively, and their mean elimination half-life(t1/2z) was 0.60, 0.62, 0.47 and 0.49 h. The established method was validated to be sensitive, rapid and specific for determination of the four analytes. Serum concentration of 4 species of epimedium flavonoids in Chuankezhi injection was low, and their absorption and elimination seem quickly, displaying similar pharmacokinetic characteristics in this study.

To analyze the clinical application of Cervus and Cucumis Polypeptide injection in the real world, in order to define the characteristics of clinical drug use and correlation, and provide reference for risk management and further study for Cervus and Cucumis Polypeptide injection. Descriptive analysis and association rules analysis were performed on 37 721 cases using Cervus and Cucumis Polypeptide injection in 26 hospitals nationwide. Cervus and Cucumis Polypeptide injection were mostly adopted by patients aged between 45 and 64(39.84%); mainly used to treat fracture patients in clinic(17 362 cases, 33.97%); 12 mL(41.81%) was the commonest dosage. And the course of treatment mainly lasted for 1-3 days(28 467 cases, 76.26%), which was basically consistent with the description of package insert. In clinic, traditional Chinese medicines, such as blood activating and stasis removing agents and Bushen Zhuanggu agents, were frequently combined with it(rule support degree of 19.38%). Such western medicine as antibiotics and nutritional drugs were frequently combined with it(rule support 39.9%). The main single combined medicine were vitamin C(13 202 cases, 35%), and Jintiange capsule(7 285 cases, 19.31%). The commonly used combined drug pairs were Hulisan capsule and Jintiange capsule (rule support 4.458%), phenobarbital and ceftazidime azole oxazoline(rule support degree of 10.62%). Cervus and Cucumis Polypeptide injection is mainly adopted by elderly patients in clinic, used to treat fracture patients, and often combined with blood activating and stasis removing agents, Bushen Zhuanggu agents, antibiotics, and nutritional medicine to enhance fracture healing. In clinical application, attention shall be paid to drug safety of elderly patients and types of combined medicines and their interaction, so as to prevent adverse reactions.

Objective To compare the therapeutic effects between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in patients with stage Ⅱ/Ⅲ esophageal cancer and investigate the prognostic factors.Methods Medical record of 2 132 patients with stage Ⅱ/Ⅲ esophageal cancer who underwent definitive radiotherapy with/without chemotherapy in 10 hospitals from January 2002 to December 2016 from were retrospectively analyzed.Among these patients,37.9％ of them were aged ≥ 70 years,33.9％ with neck and upper esophageal tumors and 66.1％ with middle and lower esophageal and borderline tumors.The median gross tumor volume (GTV) and lymph node gross tumor volume (GTVnd) was 41.6 cm3.Among them,32％ were stage Ⅱ] and 68％ were stage Ⅲ.A total of 723 patients received 3DCRT and 1 409 cases received IMRT.Patients received an equivalent dose in 2 Gy (EQD2) ≥ 60 Gy accounted for 86.1％,and 41.1％ of them received concurrent chemoradiotherapy.Results The median follow-up time was 60.8 months.The 1-,3-and 5-year overall survival (OS) of all patients was 73.9％,41.7％ and 32.6％,and the 1-,3-and 5-year progression-free survival (PFS) was 62.2％,37.3％ and 32％,respectively.Multivariate analysis demonstrated that age,primary tumor location,clinical stage,tumor target volume,EQD2 and concurrent chemoradiotherapy were the independent prognostic factors for OS.Age,primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS.The OS and PFS did not significantly differ among the low-risk,low-/moderate-risk,moderate-/high-risk and high-risk groups according to age≥70 years,tumor diameter＞5 cm,tumor volume ≥41.6 cm3 and stage Ⅲ (P＜0.001).After the propensity score matching (PSM) method,neither 3DCRT nor IMRT yielded significant advantages in OS or PFS (P=0.971;P=0.658).However,IMRT tended to yield survival benefits in low-risk patients (P=0.125).Conclusions Both 3DCRT and IMRT yield relatively high OS rate in patients with stage Ⅱ/Ⅲ esophageal cancer.The prognosis model established in this investigation can properly predict the survival of patients.Low-risk patients tend to obtain survival benefits from IMRT.

Objective To retrospectively analyze the effect of tumor length on the prognosis in stage Ⅱ/Ⅲ esophageal squamous cell carcinoma (ESCC) patients treated with definitive radiotherapy and to evaluate the role of tumor length in clinical stage for non-operative ESCC patients.Methods The data of 2 086 ESCC patients who were treated with definitive radiotherapy from 2002 to 2016 in 10 hospitals (3JECROG) were analyzed.The effect of tumor length on overall survival (OS) was analyzed and stratified analysis of tumor length was done in different stages of ESCC.Results The median OS and median progression-free survival (PFS) time of the whole group were 25.6 months and 18.2 months respectively.The Cox multivariate analysis showed that treatment moda,aga,alinical stage and tumor length were independent prognostic factors.The median,1-,3-,and 5-year OS were 28.9 months,77.3％,45.0％,and 36.3％ versus 21.9 months,69.9％,37.9％,and 28.1％ for patients with ≤ 5 cm and patients ＞ 5 cm respectively (P＜0.05).For stage Ⅱ patienta,abe median OS were 42.1 and 38.9 months respectively in ≤ 5 cm group and＞5 cm group (P=0.303).And for stage Ⅲ patienta,abe median OS were 23.9 and 19.3 months respectively in ≤5 cm group and＞5 cm group (P＜0.001).The median OS with N1was 24.1 and 18.4 montha,aespectively in ≤5 cm group and＞5 cm group (P＜0.001).Conclusions The tumor length was an independent prognostic factor for stage Ⅱ/Ⅲ patients treated definitive radiotherapy.The tumor length may be helpful in clinical staging of ESCa,aspecially for stage Ⅲ and N1.

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.