Humans ; Severe Combined Immunodeficiency ; therapy

AIM: To explore the influence of Huqi San on the Hedgehog signaling pathway in rats with prehe-patocarcinoma.METHODS: The model of prehepatocarcinoma in the rats was established by a modified solt-farber method.The rats were intragastric administrated with Huqi San solution for 3 d after subtotal hepatectomy.Four weeks after administration of the Huqi San solution, the hepatic damage was observed by histopathological analysis.The protein expression of glutathione S-transferase-π (GST-π), alpha-fetoprotein (AFP), OV6, albumin (ALB) and glioma-associated oncogene homolog 2 (Gli2) was detected by immunohistochemistry and immunofluorescence staining.The expression of Sonic hedgehog (Shh), Smoothened (Smo), Gli2, cyclin D and cyclin E at mRNA and protein levels in the rats was determined by RT-qPCR and Western blot, respectively.The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were assayed using diagnostic kits.RESULTS: Compared with model group, Huqi San decreased the serum levels of ALT, AST and GGT, and alleviated the pathological changes in prehepatocarcinoma rats.Huqi San inhibited the protein expression of GST-π and AFP (P<0.05) in the prehepatocarcinoma rats.Huqi San also promoted the protein expression of OV6 and ALB (P<0.05).Furthermore, Huqi San activated Hedgehog signaling pathway and its downstream targeting molecules such as Shh, Smo, Gli2, cyclin D and cyclin E.In addition, the results in vitro showed that Huqi San may activate Hedgehog signaling pathway and promoted oval cell proliferation.CONCLUSION: Huqi San not only promotes hepatic progenitor cell proliferation, but also induces hepatic progenitor cell differentiation and inhibits prehepatocarcinoma in the rats probably via activating Hedgehog signaling pathway.

Objective To demonstrate the imaging characteristics of pancreatic neuroendocrine neoplasm (P-NEN).Methods The CT and MRI findings of 43 cases of P-NEN confirmed by pathology were analyzed,and compared with pathological results.Results Mean size of 43 lesions in 43 P-NEN patients were (25.00± 1.82)mm.Necrosis cystic degeneration were found in 26 lesions.In CT plain scan,15 lesions were isodense,28 lesions were hypodense.All of 43 lesions were hypointensity signal on T1WI;27 lesions were hypointensity signal,16 cases were isointensity signal on T2WI.Twenty-seven lesions showed envelope;30 lesions showed clear outline.In enhancement images,24 lesions were marked enhancement since arterial phase;8 lesions showed delayed enhancement;5 lesions showed centrality enhancement;6 lesions showed wild enhancement.Conclusion P-NEN has some characteristics on CT and MRI scanning,imaging can play an important role in diagnosis for P-NEN.

Objective:To investigate the significance and mechanism of ten-eleven translocation (Tet1) against Mycobacterium marinum ( Mm) infection in mice. Methods:SPF wild-type C57BL/6 and Tet1-knockout (Tet1KO) mice were injected intravenously with Mm. All mice were monitored and the abscesses formed in tail were observed and quantified. Pathological changes in mouse tail tissues were observed using hematoxylin and eosin (HE) staining and transmission electron microscopy and the differences between the two groups were analyzed. Immunohistochemistry staining was used to detect the expression and distribution of TNF-α and TGF-β in mouse tail tissues. Moreover, mouse tail tissues were cultured on 7H10 plates for bacterial counting. The expression of NF-κBp65 and TGF-β was detected by Western blot. Results:Obvious lesions including abscesses and ulcers were formed in the Mm-infected C57BL/6, but only scattered small abscesses were observed in Mm-infected Tet1KO mice. During Mm infection, the bacterial load was gradually increased in C57BL/6 mice, but decreased in Tet1KO mice. Histopathological examination showed that obvious inflammatory cell infiltration and typical granulomatous lesions were found in Mm-infected C57BL/6 mice, while no significant inflammatory cell infiltration was detected in Mm-infected Tet1KO mice. Immunohistochemistry staining demonstrated that the expression of TNF-α and TGF-β was lower in Mm-infected Tet1KO mice than in Mm-infected C57BL/6 mice. Moreover, the expression of phosphorylated NF-κBp65 and TGF-β was significantly reduced in Mm-infected Tet1KO mice as compared with that in Mm-infected C57BL/6 mice. Conclusions:Deletion of Tet1 could alleviate the inflammatory damage mediated by Mm and enhance the host immune response to bacteria.

OBJECTIVETo investigate the expressions of Engrailed-2 (EN2) and β-catenin in bladder urothelial carcinoma and explore their significance.

METHODSSixty bladder urothelial carcinoma samples of different grades and stages and 10 normal bladder mucosal tissues were examined for expressions of EN2 and β-catenin proteins and mRNA using immunochemistry, Western blotting and RT-PCR. RESULTS Compared to normal bladder mucosa, bladder urothelial carcinoma tissues showed significantly increased expressions of EN2 and β-catenin proteins (P<0.05), and the high-grade carcinoma tissues exhibited significantly stronger expressions than the low-grade ones (P<0.05); the expressions of the proteins increased also significantly with advanced pathological stages of bladder urothelial carcinoma (P<0.05). The expressions of EN2 and β-catenin mRNAs showed a consistent pattern of changes with their protein expressions.

CONCLUSIONThe expressions of EN2 and β-catenin are significantly increased in bladder urothelial carcinoma. EN2 may contribute to the development and progression of bladder urothelial carcinoma by activating Wnt/β-catenin signal pathway.

Adult ; Aged ; Aged, 80 and over ; Carcinoma ; metabolism ; pathology ; Female ; Homeodomain Proteins ; metabolism ; Humans ; Male ; Middle Aged ; Nerve Tissue Proteins ; metabolism ; Urinary Bladder Neoplasms ; metabolism ; pathology ; beta Catenin ; metabolism

OBJECTIVETo evaluate the biomechanical effects of intracellular changes on the voltage-gated sodium channels (VGSCs) on trigeminal ganglion neuron (TRGN).

METHODSTRGN cells were acutely isolated from the neonatal SD rats. The voltage-dependent currents of the VGSCs on these neurons were elicited and analyzed by whole-cell patch-clamp recordings and the intracellular anisotonicity stimuli was established by adjusting the content of pipette solution. The effects of hypo-(260 mOsm) and hypertonic (350 mOsm) osmolarity on the activation and inactivation kinetics of VGSCs on TRGN were evaluated, compared with the normal intracellular environment.

RESULTSThe results demonstrated that intracellular hypotonic stimuli could influence both the activation and inactivation characteristics of VGSCs currents, including the membrane potential at half inactivation (V0.5) of the G-V and inactivation curves had obvious statistics significance (P<0.05) between hypotonicity (260mOsm) and isotonicity (306mOsm). However, only inactivation properties changed under intracellular hypertonic effects, including inactivation rate and k value.

CONCLUSIONIt suggests that the kinetics of VGSCs on TRGN can be modulated both by intracellular hypo- and hypertonic with different characteristics.

Animals ; Cells, Cultured ; Membrane Potentials ; Neurons ; Osmolar Concentration ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Sodium Channels ; Trigeminal Ganglion

Objective To explore the effect of primary exchange reamed nailing (ERN) and augmentation compression plating (ACP) combined with autogenous bone grafting (ABG) on health-related quality of life in patients with dystrophic or atrophic nonunion of femoral shaft after intramedullary nailing. Methods The study used a prospective study method. Sixty- two patients with femoral shaft nonunion after intramedullary nailing from August 2010 to October 2016 were selected, and the patients were divided into ERN group (group A, 32 cases) and ACP group (group B, 30 cases) by random digits table method. In group A, isthmus nonunion was in 18 cases (56.2％), and non-isthmus nonunion in 14 cases (43.8％); in group B, isthmus nonunion was in 16 cases (53.3％), and non-isthmus nonunion in 14 cases (46.7％ ). The health- related quality of life was compared between 2 groups, including physical component summary (PCS) and mental component summary (MCS) in the- 12- item short form health survey (SF- 12), brief pain inventory- severity (BPI- S) and brief pain inventory- interference (BPI- I). Results Fifty-four patients were followed-up for more than 1 year, and the mean follow-up time was 18.3 (13 to 37) months. All patients successfully achieved bone union, and the mean time was 5.8 (4 to 8) months. Significant improvements in terms of SF-12 PCS and SF-12 MCS score were noted after operation for patients with isthmus nonunion in both groups (t=3.148, 2.156, 2.456 and 2.559; P < 0.05), but there were no significant differences before and after operation in group A with non-isthmus nonunion (P >0.05). At the last follow-up, SF-12 PCS and SF-12 MCS in group B were significantly improved compared with those in group A: (45.2 ± 5.8) scores vs. (33.6 ± 4.7) scores and (48.8 ± 6.5) scores vs. (39.4 ± 5.6) scores, and there were statistical difference (P<0.05); SF-12 BPI-S and BPI-I showed obvious relief: (4.6 ± 2.1) scores vs. (6.2 ± 2.5) scores and (5.2 ± 1.9) scores vs. (6.8 ± 2.7) scores, and there were statistical differences (P<0.05); however there were no statistical difference in SF-12 PCS, SF-12 MCS, BPI-S and BPI- I between 2 groups (P>0.05). Conclusions Compared with ERN combined with ABG, ACP combined with ABG can significantly improve the quality of life in patients with dystrophic or atrophic nonunion of femoral shaft after intramedullary nailing. It has greater advantage on the improvement of health-related quality of life, especially for patients with non-isthmus nonunion.

Objective To analyze the related risk factors of re-nonunion after primary revision for femoral shaft nonunion subsequent to failed intramedullary nailing. Methods A retrospective study was performed in 61 patients with femoral shaft nonunion subsequent to failed intramedullary nailing from June 2008 to June.All patients were divided into re-nonunion group(22 cases)and non-re-nonunion group (39 cases) according to diagnostic criteria of bone re-nonunion. Univariate analysis was used to analyze 14 factors that may lead to the occurrence of re-nonunion after revision for femoral shaft nonunion subsequent to failed intramedullary nailing including age, gender, body mass index (BMI), smoking, alcohol abuse, injury reason, fracture types, intramedullary nail types, locking screws technology for intramedullary nail, bone nonunion sites, bone nonunion time, pathological types of bone nonunion, primary revision methods and autologous bone graft or not, and multi-factor logistic regression analysis was performed on the factors showing a significant difference. Results Univariate analysis showed significant difference in smoking (χ2= 6.564, P = 0.036), BMI (χ2= 6.783, P = 0.021), bone nonunion sites(χ2=7.316,P=0.011),primary revision methods(χ2=8.069,P=0.003)and autologous bone graft or not(χ 2=6.668,P=0.027).Logistic regression analysis showed that primary revision methods(OR=1.027,95% CI 0.028-0.463,P<0.05)and autologous bone graft or not(OR=1.024,95% CI 0.006-0.363, P < 0.05) were independent risk factors for re-nonunion after revision of femoral shaft nonunion subsequent to failed intramedullary nailing. Conclusions Primary revision methods and autologous bone graft or not are independent risk factors for re-nonunion after revision of femoral shaft nonunion subsequent to failed intramedullary nailing.By strictly controlling the surgical indications and combining with autogenous bone grafting,it is possible to reduce the occurrence of nonunion after primary revision of the femoral shaft nonunion subsequent to failed intramedullary nailing.

Objective To study the expressions of anaplastic lymphoma kinase (ALK-1) and cytotoxic proteins in primary systemic anaplastic large cell lymphoma (S-ALCL) and their relationship with clinical outcome. Methods 51 S-ALCL cases were collected from Lymphoma Lab of Peking University Health Science Centre & Peking Children's Hospital. The morphologic characteristics were studied under routine microscope, and essential immunohistochemical stainings were performed and reviewed to confirm the diagnosis of S-ALCL. Immunohistochemical stainings for ALK-1 and cytotoxic proteins (TIA-1 & granzyme B) were performed using standard SP method. Patients related clinical data including follow-up materials were collected. Results Survival time of 44 cases with completely clinical follow up materials ranged from 0.5～66months. 36 out of 51 cases(37 %) was positive for ALK-1 protein. While 20 cases out of 47 S-ALCL cases ( 42.55 % ) positive for granzyme B and 22 out of 28 cases (81.48 %) were positive for TIA-1. The prognosis of patients with ALK-1 protein positive and granzyme B negative expression was better, but TIA-1 expression might have nothing to do with clinical outcome (P＞0.05). In addition, multivariate analysis confirmed that ALK-1 protein expression, granzyme B protein expression and Ann-Arbor stage system were possible for prognosis(P＜0.05), Conclusion Expression of ALK-1 and granzyme B protein expression may serve as two independent prognostic predictors in S-ALCL patients.

Objective To explore the value of transvaginal three-dimensional power Doppler ultrasound in evaluation of endometrial receptivity in patients with intrauterine adhesions.Methods Totally 43 patients with intrauterine adhesions confirmed by hysteroscopy were enrolled in this study.According to the hysteroscopy,the patients were divided into mild adhesion group (n=17),moderate adhesion group (n=18) and severe adhesion group (n=8).All the patients were examined with transvaginal three-dimensional power Doppler ultrasonography on the day of ovulation.Endometrial thickness (ED),endometrial volume (EV),endometrial vascular index (VI),endometrial flow index (FI) and endometrial vascular flow index (VFI) were compared among three groups.Results There was significant difference in EV among three groups (P＜0.001).ED,VI and VFI were significantly different between the mild and severe adhesion groups,as well as between moderate and severe adhesion groups (all P＜0.05).Conclusion Transvaginal three-dimensional power Doppler ultrasound provides a safe and noninvasive approach to assess endometrial receptivity of patients with intrauterine adhesions.EV has good predictive value on endometrial receptivity.