Objective To detect p27 expression in rectal carcinoma and serum transforming growth factor ? 1 (TGF ? 1) level in these patients, and to elucidate the modulatory effect of serum TGF ?1 on p27 expression in rectal carcinoma. Methods Expression of p27 was measured in 37 cases of rectal carcinoma, 22 of rectal adenoma and 19 of normal control specimens by immunohistochemical staining using antibodies to p27. Serum level of TGF ?1 was measured in these patients by enzyme linked immunosorbent assay (ELISA) method. Results p27 protein was expressed in normal rectal tissue, rectal adenoma and rectal carcinoma, and the positive rate was 89.47%, 90.91% and 64.87%, respectively. The positive rate of p27 in rectal carcinoma was significantly lower than that of normal rectal tissue and rectal adenoma ( P =0.025). p27 was mainly located in nucleolus of normal rectal tissue and rectal adenoma, and the positive rate of p27 in cytoplasm of rectal carcinoma was higher than that of normal and rectal adenoma. The positives rates of serum TGF ?1 in normal group, rectal adenoma group and rectal carcinoma group were 21.05%, 27.27% and 51.35%( P =0.045),respectively. The expression of p27 related to histological differentiation, lymph node metastasis and infiltration depth. Serum level of TGF ?1 related to lymph node metastasis, infiltrated depth and CEA level. The positive rate of p27 in TGF ?1 negative group and positive group was 88.89% and 42.11%(Mantel Haenszel ? 2=6.755, P =0.009), respectively. Conclusion TGF ?1 may be useful in assessment of malignance and prognosis of rectal carcinoma. TGF ?1 can down regulate p27 expression in rectal carcinoma.

A plasmids of continuous expressing shRNAs targeting the NDV NA-1 Phosphoprotein (P) gene was designed.Virus titration,Real Time RT-PCR,CPE indicated that P-specific siRNA could inhibit virus replication at 36 h post-virus infection.In future studies,a combination of siRNAs targeting the NP and L gene may be used as a tool to study NDV replication and antiviral therapy.

Objective To evaluate the correlation between the expression of Survivin、VEGF and MMP 2 and the prognosis of patients with hepatocellular carcinoma Methods Expressions of Survivin、 VEGF and MMP 2 were detected by immunohistochemical S P method in 67 postoperative HCC cases Twelve candidate factors associated with long term survival were analyzed by Kaplan Meier Log rank estimation A multivariative Survival analysis of these individual variables was undertaken using the cumulative survival rate by the COX proportional hazards model Results A multivariative analysis determined three independent significant factors influencing overall cumulative survival including Survivin, VEGF, liver function (Child grade) The three prognostic factors predicted an increased risk of death from HCC Conclusion Survivin, VEGF, liver function, particularly the Child Pugh classification are the most significant prognostic factors for HCC patients undergoing hepatic resection

Objective To investigate clinical effect and safety of eccentric reamer technique foraminoplasty during percutaneous endoscopic lumbar discectomy for the treatment of lumbar lateral recess stenosis.Methods All of 45 cases diagnosed of lumbar lateral recess stenosis between Apr 2010 to Jun 2012 were analyzed in our study.Among these cases,28 cases were male and 17 were female.The age of enrolled cases was 39-62 years old and the average age was 49.23±23.96 years old.All the cases were one-level,25 cases in L4,5 and 20 cases in L5S1.All the patients underwent percutaneous endoscopic lumbar discectomy.During surgery,eccentric reamer technique was applied for foraminoplasty.Perioperative data included surgical segment,surgical duration and blood loss during surgery.Oswestry Disability Index (ODI) and Visual analogue scale (VAS) for lower back and leg pain were recorded for the evaluation of surgical effect.All the data were recorded before surgery,1 day,1 month after surgery and final follow-up.Recurrent lumbar disc herniation,spinal canal hematoma,intervertebral disc infection,nerve root injury and post-operative dysthesia (POD) were recorded for complications.Results All the cases finished surgery and none of the cases was changed to other surgery method and no other electronic drill were used in these patients.Surgical duration was 45-76 min and average time was 61.23± 13.89 min.Blood loss during surgery was 10-25 ml and average blood loss was 15.02±4.33 ml.Post-operative hospitalization days were 1-3 days and 2.80±1.57 days.The follow-up time was 60-84 months and the average time was 73.23±8.47 months.ODI in one-day after surgery was 9.34±6.54％,significantly lower than 68.06±24.14％ before surgery and no statistically change had been observed in one-month after surgery and final follow-up.The VAS for lower back was 1.54±0.97 in one-day after surgery,significantly lower than 3.57±3.12 before surgery.The VAS for leg pain was 1.14±0.79 in one-day after surgery,significantly lower than 6.24±2.35 before surgery.During follow-up,1 case suffered from recurrent lumbar disc herniation (2.22％) and no intervertebral disc infection,spinal canal hematoma and POD was observed.Conclusion Eccentric reamer technique foraminoplasty in percutaneous endoscopic lumbar discectomy is an effective and safe surgical method for the treatment of lumbar lateral recess stenosis.

OBJECTIVETo compare the expressions of hypoxia-inducible factor 1 alpha(HIF-1α) and Semaphorin 4D(Sema4D) in colorectal carcinoma and normal colorectal tissues, and to investigate their correlation and clinical significance.

METHODSThe expressions of HIF-1α and Sema4D were examined in 86 cases of colorectal carcinoma and 52 normal colorectal tissues by SP immunohistochemical staining. Correlation between these two expressions and association of the expressions with clinicopathological characters and prognosis were analyzed.

RESULTSThe positive rates of HIF-1α and Sema4D protein in colorectal carcinoma tissues were significantly higher than those in normal colorectal tissues(58.1% vs. 7.7%, χ(2)=34.624, P<0.01; 60.5% vs. 11.5%, χ(2)=31.839, P<0.01). HIF-1α and Sema4D protein expressions were closely associated with colorectal carcinoma histological types(P=0.003, P=0.010), TNM staging (P=0.003, P=0.017) and lymphatic metastasis (P=0.003, P=0.020), and a significant correlation was observed between the expressions of HIF-1α and Sema4D protein (r=0.567, P<0.01). The 5-year overall survival rate was 37%. Univariate analysis showed that 5-year survival rates of patients with positive and negative HIF-1α protein expression were 24% and 56%(P=0.003), and those with positive and negative Sema4D protein expression were 23% and 59%(P=0.001). Multivariate Cox analysis showed that expression of Sema4D was an independent prognostic factor of colorectal cancer patients(P=0.026), while expression of HIF-1α was not(P=0.501).

CONCLUSIONCombined detection of HIF-1α and Sema4D has the potential to predict the development trend of colorectal carcinoma and prognosis of patients.

Antigens, CD ; metabolism ; Colorectal Neoplasms ; metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Semaphorins ; metabolism ; Survival Rate

Objective To compare the expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and Semaphorin 4D (Sema4D) in colorectal carcinoma and normal colorectal tissues, and to investigate their correlation and clinical significance. Methods The expressions of HIF-1α and Sema4D were examined in 86 cases of colorectal carcinoma and 52 normal colorectal tissues by SP immunohistochemical staining. Correlation between these two expressions and association of the expressions with clinicopathological characters and prognosis were analyzed. Results The positive rates of HIF-1α and Sema4D protein in colorectal carcinoma tissues were significantly higher than those in normal colorectal tissues (58.1% vs. 7.7%, χ2=34.624,P<0.01; 60.5% vs. 11.5%, χ2=31.839, P<0.01). HIF-1α and Sema4D protein expressions were closely associated with colorectal carcinoma histological types (P=0.003,P=0.010), TNM staging (P=0.003,P=0.017) and lymphatic metastasis (P=0.003,P=0.020), and a significant correlation was observed between the expressions of HIF-1α and Sema4D protein (r=0.567, P<0.01). The 5-year overall survival rate was 37%. Univariate analysis showed that 5-year survival rates of patients with positive and negative HIF-1α protein expression were 24% and 56%(P=0.003), and those with positive and negative Sema4D protein expression were 23% and 59%(P=0.001). Multivariate Cox analysis showed that expression of Sema4D was an independent prognostic factor of colorectal cancer patients(P=0.026), while expression of HIF-1α was not(P=0.501). Conclusion Combined detection of HIF-1α and Sema4D has the potential to predict the development trend of colorectal carcinoma and prognosis of patients.

Objective To compare the expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and Semaphorin 4D (Sema4D) in colorectal carcinoma and normal colorectal tissues, and to investigate their correlation and clinical significance. Methods The expressions of HIF-1α and Sema4D were examined in 86 cases of colorectal carcinoma and 52 normal colorectal tissues by SP immunohistochemical staining. Correlation between these two expressions and association of the expressions with clinicopathological characters and prognosis were analyzed. Results The positive rates of HIF-1α and Sema4D protein in colorectal carcinoma tissues were significantly higher than those in normal colorectal tissues (58.1% vs. 7.7%, χ2=34.624,P<0.01; 60.5% vs. 11.5%, χ2=31.839, P<0.01). HIF-1α and Sema4D protein expressions were closely associated with colorectal carcinoma histological types (P=0.003,P=0.010), TNM staging (P=0.003,P=0.017) and lymphatic metastasis (P=0.003,P=0.020), and a significant correlation was observed between the expressions of HIF-1α and Sema4D protein (r=0.567, P<0.01). The 5-year overall survival rate was 37%. Univariate analysis showed that 5-year survival rates of patients with positive and negative HIF-1α protein expression were 24% and 56%(P=0.003), and those with positive and negative Sema4D protein expression were 23% and 59%(P=0.001). Multivariate Cox analysis showed that expression of Sema4D was an independent prognostic factor of colorectal cancer patients(P=0.026), while expression of HIF-1α was not(P=0.501). Conclusion Combined detection of HIF-1α and Sema4D has the potential to predict the development trend of colorectal carcinoma and prognosis of patients.

T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy.However,many challenges remain in extending its application toward the treatment of solid tumors.The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy.One negative regulator of T cell activity is lymphocyte activation gene-3 (LAG-3).We successfully generated LAG-3 knockout T and CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture.LAG-3 knockout CAR-T cells displayed robust antigen-specific antitumor activity in cell culture and in murine xenograft model,which is comparable to standard CAR-T cells.Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing.

Objective: To study the incidence and clinicopathological features of intermediate fibroblastic/myofibroblastic tumors(IF/MFT) in infants and the young children. Methods: All available cases with soft tissue tumors in infants and children were retrieved from the files of Women and Children′s Hospital Affiliated to Qingdao University, from January 2012 to December 2017.The incidence rate of IF/MFT was observed.Cases of IF/MFT were identified and investigated by light microscopy and immunohistochemistry by reviewing the related literature. Results: Among 290 soft tissue tumors, 15 cases(5.2%) were IF/MFT, accounted for 88.2%(15/17 cases) of borderline soft tissue tumors.Twelve cases were male, 3 cases were female, the median age was 8 months, and 4 cases were congenital.Clinically, 11 cases were presented with slow-growing painless masses located in the trunk or extremities.According to histopathology, 9 cases(60.0%) were categorized as infantile fibromatosis(IFM), including 5 cases(33.3%) desmoid-type and 4 cases(26.7%) diffuse-type; 3 cases(20.0%) as lipofibromatosis(LFM); 2 cases(13.3%) as infantile fibrosarcoma(IFS) and 1 case(6.7%) as giant cell fibroblastoma(GCF). All 15 tumors were characterized by the presence of spindle fibroblasts and myofibroblasts with infiltration of the surrounding structures.Immunohistochemically, all the 15 cases were diffusely positive for Vimentin(Vim), but negative for Myogenin, MyoD1, Desmin and S-100.Smooth muscle actin(SMA), β-catenin and Bcl-2 were positive in some cases to a certain degree.The Ki-67 proliferation index was higher in diffuse-type IFM and IFS, the former was 5.0%-20.0%, and the latter was about 20.0%, however, the other cases showed Ki-67 <5.0%.The main clinical treatment was complete or extensive excision. Conclusions IF/MFT accounts for a high proportion of intermediate soft tissue tumors in infants and young children, mostly seen in male children, and IFM and LFM are the main types.The clinical signs and symptoms associated with these tumors are often nonspecific, and their histopathologic manifestations may overlap.The final diagnosis of IF/MFT must depend on the characteristics of age, location, histopathologic changes and immunohistoche-mical findings.