Objective To evaluate the effects and toxicities of the hyperthermic peritoneal peffusion with oxaliplatin (L-OHP) and interleukin-2 (IL-2) combined with chemotherapy for treatment malignant asci-tes. Methods 42 patients with malignant aacites from assimilation system tumor were catheterized,drained and flushed with L-OHP 85 mg/m2 in 2 000 ～2 500 ml of 5 % glucose and IL-2(2 MU),NRL-001 Double RF tumor hyperthermia system was applied to heat the abdominal part for 60 ～ 120 minutes at an intraperitoneal temperature of 41 -43 ℃ ,next day,all the patients were treated with calcium folinate(CF)0. 2 g/m2 by 2 hours intravenous infusion,5-fluorouracil (5-FU) 0. 4 g/m2 intravenously, followed by 46 hours continuous infusion of 5-FU (1 600 mg/m2), 2 weeks a cycle. Results The overall response rate was 66. 67%, including CR : 6 cases, PR:22 cases, NC:6 cases, and PD:8 cases. MST is 5.6 months. The main toxicity was impatient abdomen ache,paralysis intestinal obstruction. Conclusion Hyperthermic peritoneal perfusion with oxaliplatin and inter-leukin-2 combined with chemotherapy is efficient and safe in the treatment malignant ascites and can improve the quality of life. It is worthing wildly using and research.

Objective To investigate the effect of early screening and intervention on congenital hypothyroid-ism.Methods Thyroid stimulating hormone (TSH),three thyroid stimulating hormone (T3 )and thyroid hormone (T4 )were screened in 72h after birth,and thyroid ultrasound examination.All the patients were treated with the treat-ment of the left -to -thyroid hormone,0 -6 months medication dose 25 -50g/d,6 -12months medication dose 50 -100g/d,1 -3months medication dose 75 -100g/d.Serum TSH was reviewed every three months in the age of 1 years, 2 -3 years old every six months to review the serum TSH.Results The mean value of TSH in children with congeni-tal hypothyroidism was (68.7 ±15.3)mU /L.The mean value of T4 was (42.4 ±13.1)nmol/L.100 cases of chil-dren,including 38 cases of primary congenital hypothyroidism,transient congenital hypothyroidism in 62 cases.Ultra-sound examination showed primary congenital hypothyroidism were developmental abnormalities,and abnormal absence of a total of 18 cases (47.4%),Abnormal blood flow in 15 cases (39.5%);No abnormalities were found in the ultrasound examination of the transient congenital hypothyroidism.Before treatment,TSH in children with congenital hypothyroidism was significantly higher than that in the control group[(68.7 ±15.3)mU /L vs (4.6 ±1.1)mU /L], T4 was significantly lower than the control group[(42.4 ±13.1)nmol/L vs (124.4 ±45.5)nmol/L],the differences
were statistically significant (t =22.867,16.058,all P <0.05);After treatment,the TSH of the children was signifi-cantly decreased[(5.3 ±1.1)mU /L vs (68.7 ±15.3)mU /L],and the T4 was significantly increased[(114.5 ± 35.4)nmol/L vs (42.4 ±13.1)nmol/L],compared with before treatment,the differences were statistically significant (t =41.331,19.101,all P <0.05 ),but compared with the control group,there were no significant differences between TSH and T4 (all P >0.05).After 1 -3 years follow -up observation,children with Gesell development scale test showed that children with adaptability,large movements,fine movements,language and social skills to reach the normal level.Conclusion Early screening and treatment of the patients with congenital hypothyroidism is beneficial to the rehabilitation of the patients with congenital hypothyroidism.

Objective To explore the cause, clinical characteristic and the relation to the alterations of bone metabolism and bone mineral density (BMD) in senile male patients with chronic obstructive pulmonary disease (COPD). Methods Fifty senile male patients with simple stable COPD were divided into moderate and severe groups based on the diagnostic criteria of pulmonary function. Thirty senile male health volunteers were considered as control group. Blood gas analysis, BMD, bone mineral content (BMC), biochemical indexes relative to the bone formation and bone absorption in blood and urine were measured and analyzed. Results Reductions in BMD and BMC were more significant in two COPD groups than those in control group (P

Objective:To prepare dendritic cell (DC)-cytokine induced killer (CIK) tumor vaccine using DCs of patients with nonsmall-cell lung cancer (NSCLC) harboring autologous tumor antigens and to observe its inhibitory effect on autologous tumor cells in vitro. Methods: Peripheral blood mononuclear cells (PBMCs) extracted from NSCLC patients were cultured into DCs and CIKs in presence of different cytokines. Cancer cells from the patients were cultured in vitro and were used to prepare different tumor antigens: tumor cell lysates, necrotic tumor cells and normally-grown tumor cells. The DCs were stimulated by OK-432 and the phenotypes of the DCs were analyzed by flow cytometer. Then the DCs were co-cultured with CIKs. The anti-tumor effect of DC-CIK was evaluated by MTT assay. Results: Compared with the DCs harboring the antigens of necrotic tumor cells and normally-grown tumor cells, DCs pulsed with tumor cell lysates had significantly higher expression of surface molecules such as CD1a (85.1?2.7), CD80 (80.0?4.4), CD83 (75.4?5.3), and HLA-DR(80.5?7.8, all P

To generate a mWAP-hLF hybrid locus that the transcription of human lactoferrin (hLF) genomic sequence is directed by the up & down stream regulatory sequence of murine whey acidic protein (mWAP) gene locus, we describe here a successive three-step 'Gap-repair' method. First, a gap-repair vector based on pBR322 vector backbone by inserting six joint homologous arms was constructed. Then using 'Gap-repair 'method mediated by Red recombination system of lambda-prophage in Escherichia coli, in the first step, the 8 kb 3' flanking region of the mWAP gene was subcloned from the Bacterial artificial chromosome which harbors the mWAP gene locus(mWAP BAC) into the gap-repair vector; in the second step, the 29 kb hLF genomic sequence from the ATG code to the TAA code was subcloned from the hLF BAC; in the third step, the 12 kb 5' flanking region of the mWAP gene was subcloned from the mWAP BAC. Finally, all these three DNA fragments were automatically combined together without any gap in the gap-repair vector, and a 49 kb mWAP-hLF hybrid locus that the hLF genomic sequence was flanked by the 5' & 3' flanking region of mWAP gene locus was constructed. The result was confirmed by PCR, restriction enzyme digestion and sequencing. Our method provide a new way for the construction of large mammary-gland expression vector.
Animals ; Bioreactors ; DNA Repair ; genetics ; Genetic Engineering ; methods ; Humans ; Hybridization, Genetic ; Lactoferrin ; genetics ; Mammary Glands, Animal ; metabolism ; Mice ; Mice, Transgenic ; Milk Proteins ; genetics

Objective To find the effects of varus degree on the early metabolic changes of the lateral compartment cartilage in knees with medial unicompartmental osteoarthritis by detecting glycosaminoglycan (GAG) in varus knees.Methods From June 2016 to December 2017,twenty middle-aged volunteers without osteoarthritis or coronal deformities were recruited as the control group.Sixty patients diagnosed as medial unicompartmental osteoarthritis were recruited as the osteoarthritis group.The patients were further divided into four groups according to the degrees of varus angle,namely 2°-5° varus group,5°-10° varus group,10°-15° varus group and ＞15° varus group with 15 patients in each group.Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) was performed in all participants.The dGEMRIC indices (T1Gd) representing GAG content were calculated in the weight-bearing femoral cartilage (wbFC),the posterior non-weight-bearing femoral cartilage (pFC),the lateral femoral cartilage (FC,wbFC+pFC) and the tibial cartilage (TC) in the lateral compartment by using Matlab 7.1 and MRIMapper software.Results T1Gd of wbFC,pFC,FC and TC were 400.3±51.5 ms,393.6±57.9 ms,397.5±52.3 ms and 448.6±62.5 ms in the control group,391.8±41.5 ms,407.2±43.8 ms,400.1±37.8 ms and 461.3±41.6 ms in 2°-5° varus group and 386.9±57.1 ms,401.3±73.5 ms,397.7±59.6 ms and 438.9±42.8 ms in 5°-10° varus group.There was no significant difference among the above three groups in T1Gd in any of the analyzed cartilage regions (P＞0.05).In 10°-15° varus group,T1Gd of wbFC,pFC,FC and TC were 380.1±45.5 ms,385.5±76.6 ms,384.0±53.5 ms and 400.2±43.8 ms,respectively.Although T1Gd of wbFC,pFC and FC in 10°-15° varus group were similar with that in the control group,2°-5° varus group and 5°-10° varus (P＞0.05),T1Gd of TC in 10°-15° varus group decreased significantly (P＜0.05).In addition,T1Gd of wbFC,pFC,FC and TC in ＞15° varus groupwere 327.7±54.3 ms,340.1±33.0 ms,334.9±36.0 ms and 363.6±48.6 ms,respectively.T1Gd of all regions of interest in ＞15° varus group were significantly lower than that informer four groups (P＜0.05).Conclusion In medial unicompartmental knee osteoarthritis,there is a relationship between varus degree and GAG content of the lateral compartment cartilage.If varus angle ≤10°,the GAG content of the lateral compartment cartilage was similar with the similar aged subjects without osteoarthritis.If varus angle ＞ 10°,GAG content of the lateral compartment decreases significantly.

Objective:To analyze the prognosis and influencing factors of patients with brain metastases from non-small cell lung cancer (NSCLC) treated with different doses of whole brain radiotherapy (WBRT).Methods:A total of 244 NSCLC patients with brain metastases who underwent WBRT in the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different doses of WBRT (EQD 2Gy), they were divided into the 30-39 Gy group ( n= 104) and ≥40 Gy group ( n= 140). The intracranial progression-free survival (iPFS) and overall survival (OS) were compared betweentwo groups. According to the number of brain metastases, GPA score, KPS score, chemotherapy and targeted therapy, the prognosis of different doses of WBRT was further analyzed. Results:The median iPFS and OS of all patients were 6.9 months and 11.8 months, respectively. Univariate survival analysis: the 1-year iPFS and 1-year OS between two groups were 22.5% and 25.4%( P=0.430) and 41.1% and 46.4%( P=0.068), respectively. Multivariate survival analysis: different doses of WBRT were not associated with the improvement of iPFS and OS; independent factors influencing iPFS included local boost, gender, number of brain metastases, chemotherapy and targeted therapy; independent factors influencing OS included gender, number of brain metastases, chemotherapy and targeted therapy. Subgroup analysis: in patients with KPS≥90, the 1-year iPFS and OS of patients with WBRT ≥ 40 Gy were seemingly better than those of their counterparts with 30-39 Gy, but the difference was statistically significant only in OS ( P=0.047), the difference was not statistically significant in iPFS ( P=0.068); in patients with chemotherapy, the 1-year iPFS and OS of patients with WBRT≥40 Gy were better than those of their counterparts with 30-39 Gy ( P=0.017, P=0.012); in patients with targeted therapy, the 1-year iPFS and OS in the WBRT≥40 Gy group were better than those in the 30-39 Gy group ( P=0.012, P=0.045). Conclusions:The 30-39 Gy may be the appropriate dose of WBRT for NSCLC patients with brain metastases. WBRT≥40 Gy does not bring more benefits. WBRT≥40 Gy may benefit NSCLC patients with brain metastases with high KPS score or active systemic therapy.

Objective:To analyze the prognosis and influencing factors of different radiotherapy modes in patients with brain metastases from non-small cell lung cancer (NSCLC), and to explore the best benefit population with radiotherapy boost under different prognostic scores.Methods:634 patients with brain metastasis from NSCLC admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different radiotherapy modes, they were divided into three groups: no radiotherapy group ( n=330), whole-brain radiotherapy group (WBRT)( n=127) and whole-brain radiotherapy combined with boost group (WBRT+ boost)( n=177). The intracranial progression-free survival (iPFS) and overall survival (OS) were calculated by Kaplan-Meier method. The multivariate prognostic factors were analyzed by the Cox models. Results:The median iPFS and OS of all patients were 6.9 months and 9.0 months, respectively. In the no radiotherapy, WBRT and WBRT+ boost groups, the 1-year iPFS was 15.1%, 16.3% and 40.2%( P=0.002), and the 1-year OS was 33.7%, 38.2% and 48.1%( P<0.001), respectively. Multivariate survival analysis demonstrated that different radiotherapy modes were the independent factors affecting iPFS and OS. Subgroup analysis revealed that for patients with 1-3 brain metastases, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone ( P=0.026, P=0.044) when GPA score was 2.5-4.0; the 1-year OS and iPFSin the WBRT+ boost group were better than those of WBRT alone ( P=0.036, P=0.049) when there was no targeted therapy; for patients with ≥4 brain metastases, the 1-year iPFS in the WBRT+ boost group was better than that of WBRT alone ( P=0.019, P=0.012) when GPA score was 2.5-4.0 and there was no targeted therapy. When the GPA score was 0-2 or there was targeted therapy, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone, but the difference was not statistically significant (all P>0.05). Conclusions:Radiotherapy can significantly improve the iPFS and OS of NSCLC patients with brain metastases. When the number of brain metastases is 1-3, GPA score is 2.5-4.0 or no targeted therapy, boost may improve the iPFS and OS; when the number of brain metastases is more than 4, GPA score is 2.5-4.0 or no targeted therapy, boost may only bring iPFS benefit; when GPA score is 0-2 or targeted therapy, boost may not benefit significantly.

Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.
Humans ; Paxillin/metabolism* ; Protein-Lysine 6-Oxidase/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Epithelial-Mesenchymal Transition ; Integrin alpha2beta1/metabolism* ; Mouth Neoplasms/pathology* ; Collagen/metabolism* ; Fibroblasts ; Extracellular Vesicles/metabolism* ; Cell Line, Tumor ; Tumor Microenvironment

OBJECTIVETo understand the transmission mode of human infection with avian influenza A (H7N9) virus.

METHODSField epidemiological investigation was conducted for a family clustering of human infection with H7N9 virus in Hengxian county, Guangxi Zhuang Autonomous Region in February 2014. Two patients and their 82 close contacts were surveyed. The samples collected from the patients, environments and poultry were tested by using real time reverse transcriptase-polymerase chain reaction (rRT-PCR), and the samples from patients were used for virus isolation. The samples from 5 close contacts were tested with RT-PCR. The clinical data, exposure histories of the patients and the detection results of the isolates and their homology were analyzed.

RESULTSPatient A became ill 4 days after her last exposure to poultry in Zhongshan, Guangdong province, and returned to her hometown in Hengxian 2 days after onset. Patient B was patient A's 5 years old son, who had no known exposure to poultry but slept with patient A for 4 days. He developed symptoms 4 days after last contact with his mother. Two strains of H7N9 virus were isolated from the two patients. The 2 isolates were highly homogenous (almost 100%) indicated by gene sequencing and phylogenetic tree. None of the other 81 close contacts developed symptoms of H7N9 virus infection.

CONCLUSIONPatients B was infected through close contact with patient A, indicating that avian H7N9 virus can spread from person to person, but the transmissibility is limited and non-sustainable.

Animals ; Child, Preschool ; China ; Cluster Analysis ; Contact Tracing ; Family ; Female ; Homozygote ; Humans ; Influenza A Virus, H7N9 Subtype ; genetics ; isolation & purification ; Influenza, Human ; transmission ; virology ; Male ; Phylogeny ; Poultry ; virology ; Real-Time Polymerase Chain Reaction ; Sleep