Targeting LGSN restores sensitivity to chemotherapy in gastric cancer stem cells by triggering pyroptosis.

Gastric cancer (GC) is notoriously resistant to current therapies due to tumor heterogeneity. Cancer stem cells (CSCs) possess infinite self-renewal potential and contribute to the inherent heterogeneity of GC. Despite its crucial role in chemoresistance, the mechanism of stemness maintenance of gastric cancer stem cells (GCSCs) remains largely unknown. Here, we present evidence that lengsin, lens protein with glutamine synthetase domain (LGSN), a vital cell fate determinant, is overexpressed in GCSCs and is highly correlated with malignant progression and poor survival in GC patients. Ectopic overexpression of LGSN in GCSC-derived differentiated cells facilitated their dedifferentiation and treatment resistance by interacting with vimentin and inducing an epithelial-to-mesenchymal transition. Notably, genetic interference of LGSN effectively suppressed tumor formation by inhibiting GCSC stemness maintenance and provoking gasdermin-D-mediated pyroptosis through vimentin degradation/NLRP3 signaling. Depletion of LGSN combined with the chemo-drugs 5-fluorouracil and oxaliplatin could offer a unique and promising approach to synergistically rendering this deadly cancer eradicable in vivo. Our data place focus on the role of LGSN in GCSC regeneration and emphasize the critical importance of pyroptosis in battling GCSC.

Coexisting Infantile Hepatic Hemangioma and Hepatoblastoma in a Neonate: A Case Report.

Infantile hepatic hemangioma and hepatoblastoma are the most common benign and malignant tumors of the liver in the neonatal and early childhood periods, respectively. However, the simultaneous occurrence of these 2 tumors in the same liver lesion is very rare. We report a case of a newborn infant diagnosed with a liver mass by ultrasound examination 4 days after birth. Serum alpha-fetoprotein (AFP) was elevated for his age (32,881.7 ng/mL). The liver mass was resected. Macroscopically, an externally protruding mass measuring 6 × 4 × 3.5 cm was identified. Microscopically, we observed the coexistence of infantile hepatic hemangioma and epithelial hepatoblastoma components within the tumor. The infantile hepatic hemangioma component was composed of multiple small vascular channels lined by endothelial cells. In the hepatoblastoma component, tumor cells were arranged in a 2- to 3-cell-thick trabecular formation. Immunohistochemistry indicated that the tumor cells in the infantile hepatic hemangioma component expressed CD34, CD31, FLI1, and ERG, and those in the hepatoblastoma component expressed hepatocyte, keratin AE1/AE3 and keratin 8, glypican 3, glutamine synthetase, and AFP. Pathological examination confirmed the presence of an infantile hepatic hemangioma combined with epithelial hepatoblastoma (fetal type). The boy did not undergo chemotherapy after the operation. Regular follow-up through serum AFP levels and liver ultrasound for 16 months to date show that the serum AFP levels decreased continuously to normal levels, with no signs of tumor recurrence or metastasis. The coexistence of infantile hepatic hemangioma and hepatoblastoma is rare. Hepatoblastoma should be considered in neonates with liver tumors and elevated AFP.

Coexistent Kaposi sarcoma and post-transplant lymphoproliferative disorder in the same lymph nodes after pediatric liver transplantation: A case report.

BACKGROUND: Kaposi sarcoma and post-transplant lymphoproliferative disorder have been occasionally reported in post-liver transplant patients. However, the simultaneous occurrence of these two diseases in the same lymph nodes is very rare. CASE SUMMARY: We report the case of a 19-mo-old boy, who presented with intermittent fever and enlarged cervical lymph nodes after liver transplantation. Six cervical lymph nodes were biopsied, and the histopathological examinations revealed multifocal hyperplasia of spindle cells around small blood vessels, extravasated erythrocytes, and heavy infiltration of plasma cells in the cortex and medulla of the lymph nodes. The immunohistochemical analyses of spindle cells revealed positive expression of CD34, CD31, erythroblast transformation-specific-related gene, friend leukemia integration 1, and human herpesvirus-8. The lymphoproliferative lesions expressed CD38, CD138, and multiple myeloma 1. Epstein-Barr encoded RNA in situ hybridization demonstrated Epstein-Barr virus-positive lymphoid cells. Finally, we diagnosed the coexistence of Kaposi sarcoma and post-transplant lymphoproliferative disorder (plasmacytic hyperplasia) in the same lymph nodes. Treatment strategy included anti-CD20 monoclonal antibody (rituximab) and discontinuation of the immunosuppressant therapies. Lymph node biopsies during follow-up examinations revealed lymphoid hyperplasia. CONCLUSION: The rare coexistence of Kaposi sarcoma and post-transplant lymphoproliferative disorder in the same lymph nodes post-liver transplantation possibly associates with immunodeficiency and Epstein-Barr virus and human herpesvirus-8 coinfection.

Torsades de pointes episode in a woman with high-grade fever and inflammatory activation: A case report.

BACKGROUND: QT interval prolongation can induce torsades de pointes (TdP), a potentially fatal ventricular arrhythmia. Recently, an increasing number of non-cardiac drugs have been found to cause QT prolongation and/or TdP onset. Moreover, recent findings have demonstrated the key roles of systemic inflammatory activation and fever in promoting long-QT syndrome (LQTS) and TdP development. CASE SUMMARY: A 30-year-old woman was admitted with a moderate to high-grade episodic fever for two weeks. The patient was administered with multiple antibiotics after hospitalization but still had repeating fever and markedly elevated C-reactive protein. Once after a high fever, the patient suddenly lost consciousness, and electrocardiogram (ECG) showed transient TdP onset after frequent premature ventricular contraction. The patient recovered sinus rhythm and consciousness spontaneously, and post-TdP ECG revealed a prolonged QTc interval of 560 ms. The patient's clinical manifestations and unresponsiveness to the antibiotics led to the final diagnosis of adult-onset Still's disease (AOSD). There was no evidence of cardiac involvement. After the AOSD diagnosis, discontinuation of antibiotics and immediate initiation of intravenous dexamethasone administration resulted in the normal temperature and QTc interval. The genetic analysis identified that the patient and her father had heterozygous mutations in KCNH2 (c.1370C>T) and AKAP9 (c.7725A>C). During the 2-year follow-up period, the patient had no recurrence of any arrhythmia and maintained normal QTc interval. CONCLUSION: This case study highlights the risk of systemic inflammatory activation and antibiotic-induced TdP/LQTS onset. Genetic analysis should be considered to identify individuals at high risk of developing TdP.

A Novel PRRT2 Variant in Chinese Patients Suffering from Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsion.

PRRT2 mutations are the major causative agent of paroxysmal kinesigenic dyskinesia with infantile convulsion (PKD/IC). The study is aimed at screening PRRT2 gene mutations in patients who suffered from PKD/IC in Chinese population. Thirteen Chinese patients with PKD/IC were screened randomly for coding exons of the PRRT2 gene mutation along with 50 ethnically coordinated control people. Nine (2 unaffected) and 4 of the patients showed familial PKD/IC and apparently sporadic cases, respectively. We identified 5 different PRRT2 mutations in 10 individuals, including 8 familial and 2 apparently sporadic cases. However, no mutations were found in the 50 ethnically matched controls. Unknown (novel) NM_145239.2:c.686G>A and previously reported NM_145239.2:c.743G>C variants were identified in two familial and sporadic patients. All affected members of family A showed mutation NM_145239.2:c.650_670delinsCAATGGTGCCACCACTGGGTTA. The previously identified NM_145239.2:c.412 C>G and NM_145239.2:c.709G>A variants are seen in two individuals assessed in family B. Other than the previously identified variants, some of the patients with PRRT2-PKD/IC showed a new PRRT2 substitution variant. Thus, the spectrum of PRRT2 variants is expanded. The possible role and probability of PRRT2 variants involved in PKD/IC are highlighted.

Anticonvulsant and Neuroprotective Effects of Paeonol in Epileptic Rats.

Paeonol is the main active compound in the root bark extract of the peony tree, and it has antioxidative and anti-inflammatory effects. Recent studies have reported the neuroprotective effects of paeonol including its capacity in improving impaired memory. However, the effect of paeonol on epilepsy is yet to be demystified. We aimed to investigate the therapeutic effect of paeonol in epilepsy and its relationship with oxidative stress damage and neuronal loss in the rat brain to reveal the underlying mechanisms of epileptic seizures. A rat model for chronic epilepsy was established, and the seizure scores of the rats in different groups were recorded. The seizure duration and the seizure onset latency were used to evaluate the anticonvulsant effects of paeonol. Terminal deoxynucleotidyl transferase dUTP nick end-labeling staining, Nissl staining and H/E staining were used to evaluate the effects of paeonol on neuronal loss and apoptosis in epileptic rats. The colorimetric assessment of malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, catalase activity and total antioxidant capacity of paeonol were used in assessing paeonol's effect on oxidative stress in epileptic rats. Evaluation of Caspase-3 mRNA and protein expression levels were determined using western blot and quantitative real-time (RT-q)PCR. In this study, we found that paeonol reduced the seizure scores of epileptic rats and attenuated the duration and onset latency of seizures. Paeonol can also increase the activities of total antioxidant capacity, SOD and catalase activity and reduce MDA content as well. This suggests that paeonol can improve the level of oxidative stress in rats. More significantly, paeonol can improve neuronal loss and apoptosis in epileptic rats. These results indicate that paeonol has anticonvulsant and neuroprotective effects in epileptic rats. This effect may be caused by reducing oxidative stress.

Ferulic acid ameliorates pentylenetetrazol-induced seizures by reducing neuron cell death.

To investigate the neuroprotective effect of ferulic acid (FA) in a pentylenetetrazol (PTZ)-induced seizures model in rat, the motor response, spatial learning ability and memory capability of the rats were assessed. Both the antioxidation and anti-apoptosis pathways were also investigated. In this study, male Wistar rats were randomly divided into 3 groups (n = 12 in each group). For 28 days, the rats were administered saline alone (i.p. normal saline, NS group), PTZ (40 mg/kg, i.p., PTZ group) once daily to induce seizures, or FA (i.p. 60 mg/kg) 20 min before being given PTZ (40 mg/kg, i.p., FA + PTZ group) to assess the neuroprotective effect of FA. The motor response of the rats was analysed with the Racine scale. The spatial learning and memory capacity of the rats were assessed by the Morris water maze test. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured, and both in situ staining with the DNA-binding bisbenzimide Hoechst 33258 and TUNEL assays were used to assess apoptosis. Western blotting was used to further analyse the expression of Apaf-1, caspase-9, caspase-3, Bcl-2, Bid, Bax, cleaved caspase-3 and cytochrome c. The results showed that compared to the those of the PTZ group, FA pre-treatment significantly (p < 0.01) reduced the Racine scores starting at day 4, prolonged the latency of the onset of seizure at day 28, reduced the escape latency period starting at day 2, increased the frequency of crossing the platform location, increased the SOD activity, reduced the MDA content and apoptosis percentage, and upregulated the Bcl-2 levels whilst downregulating the Bax, cytochrome c, Apaf-1, caspase-9, caspase-3, cleaved caspase-3 and Bid expression levels. This study demonstrated that pre-treatment with FA exerts strong neuroprotective effects by reducing the motor response and by improving spatial learning ability and memory capacity. The neuroprotective effect may be a result of a reduction in neuron cell death that occurs via the antioxidative and anti-apoptotic pathways.

Acupuncture for hearing loss after traumatic brain injury: A protocol for systematic review of randomized controlled trial.

BACKGROUND: This study aims to systematically assess the effectiveness and safety of acupuncture on hearing loss (HL) after traumatic brain injury (TBI). METHODS: In this study, the following databases will be retrieved from inception up to the May 1, 2019: PUBMED, EMBASE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database. All databases will be retrieved without any language restrictions. Two reviewers will independently carry out article selection, data collection, and risk of bias evaluation. Any disagreements will be solved by a third reviewer through discussion. RESULTS: This study will systematically investigate the effectiveness and safety of acupuncture for treating HL after TBI through evaluating HL assessment, hearing threshold, quality of life, and adverse events. CONCLUSION: The expected findings of this study will provide latest evidence for assessing the effectiveness and safety of acupuncture for HL after TBI. ETHICS AND DISSEMINATION: This study is supposed to be published in a peer-reviewed journal. No ethical approval is needed because this study will based on the literature analysis, but not the individual patient. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019133417.

Neuromuscular electrical stimulation on hearing loss caused by skull base fracture: A protocol for systematic review of randomized controlled trial.

BACKGROUND: This systematic review aims to investigate the effectiveness and safety of neuromuscular electrical stimulation (NMES) on hearing loss (HL) caused by skull base fracture (SBF). METHODS: We will retrieve the following electronic databases of Cochrane Library, PUBMED, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database from the inception to January 1, 2019 for relevant RCTs of NMES for HL caused by SBF. Two experienced authors will independently perform the study selection, data extraction, and methodology quality assessment. A 3rd author will solve any disagreements between 2 authors through discussion. RESULTS: This study will provide a high-quality synthesis of latest evidence of NMES for HL caused by SBF from comprehensive assessments, including hearing loss evaluation, hearing threshold, quality of life, and any relevant adverse events. CONCLUSION: The expected results of this systematic review will provide the up-to-date evidence to assess the effectiveness and safety of NEMS for patients with HL caused by SBF. ETHICS AND DISSEMINATION: The results of this study will be disseminated through publication in a peer-reviewed journal or will be presented at an associated conference meeting. This study will not use individual patient data, thus, the ethical approval is not needed. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019120195.

A CASPR1-ATP1B3 protein interaction modulates plasma membrane localization of Na+/K+-ATPase in brain microvascular endothelial cells.

Contactin-associated protein 1 (CASPR1 or CNTNAP1) was recently reported to be expressed in brain microvascular endothelial cells (BMECs), the major component of the blood-brain barrier. To investigate CASPR1's physiological role in BMECs, here we used CASPR1 as a bait in a yeast two-hybrid screen to identify CASPR1-interacting proteins and identified the ß3 subunit of Na+/K+-ATPase (ATP1B3) as a CASPR1-binding protein. Using recombinant and purified CASPR1, RNAi, GST-pulldown, immunofluorescence, immunoprecipitation, and Na+/K+-ATPase activity assays, we found that ATP1B3's core proteins, but not its glycosylated forms, interact with CASPR1, which was primarily located in the endoplasmic reticulum of BMECs. CASPR1 knockdown reduced ATP1B3 glycosylation and prevented its plasma membrane localization, phenotypes that were reversed by expression of full-length CASPR1. We also found that the CASPR1 knockdown reduces the plasma membrane distribution of the α1 subunit of Na+/K+-ATPase, which is the major component assembled with ATP1B3 in the complete Na+/K+-ATPase complex. The binding of CASPR1 with ATP1B3, but not the α1 subunit, indicated that CASPR1 binds with ATP1B3 to facilitate the assembly of Na+/K+-ATPase. Furthermore, the activity of Na+/K+-ATPase was reduced in CASPR1-silenced BMECs. Interestingly, shRNA-mediated CASPR1 silencing reduced glutamate efflux through the BMECs. These results demonstrate that CASPR1 binds with ATP1B3 and thereby contributes to the regulation of Na+/K+-ATPase maturation and trafficking to the plasma membrane in BMECs. We conclude that CASPR1-mediated regulation of Na+/K+-ATPase activity is important for glutamate transport across the blood-brain barrier.

CXCR1/Akt signaling activation induced by mesenchymal stem cell-derived IL-8 promotes osteosarcoma cell anoikis resistance and pulmonary metastasis.

The loss of appropriate cell adhesion normally induces apoptosis via a process termed anoikis. The aim of this study was to investigate the effects of mesenchymal stem cells (MSCs) in the cancer microenvironment on the anoikis resistance and pulmonary metastasis of osteosarcoma (OS) cells, and to evaluate the critical role of the interleukin (IL)-8/C-X-C chemokine receptor (CXCR) 1/Akt-signaling pathway in these processes. Metastatic OS subtype cells, which did or did not interact with MSC-conditioned medium (MSC-CM) in vitro, were isolated from the pulmonary site and named Saos2-lung-M. Both MSC-CM and IL-8 treatment increased the anoikis resistance of Saos2 cells in vitro. Moreover, exogenous MSC-CM promoted the survival and metastasis of Saos2 cells in nude mice. Saos2-lung-M cells were more malignant and resistant to anoikis than parental cells. MSCs secreted IL-8, thereby protecting OS cells from anoikis. Blocking the IL-8/CXCR1/Akt pathway via CXCR1 knockdown inhibited the pulmonary metastasis of Saos2-lung-MSCs and prolonged the survival of tumor-bearing mice. In conclusion, MSCs enhanced OS cell resistance to anoikis and pulmonary metastasis via regulation of the IL-8/CXCR1/Akt pathway. These findings suggest that MSCs can "select for" OS cells with high metastatic potential in vivo, and highlight CXCR1 as a key target in the regulation of pulmonary metastasis of OS cells.

TIMP3 Overexpression Improves the Sensitivity of Osteosarcoma to Cisplatin by Reducing IL-6 Production.

Osteosarcoma is the most common bone cancer in children and adolescents. Tissue inhibitors of metalloproteinases (TIMPs)-3 inhibit matrix metalloproteinases to limit extracellular matrix degradation. Cisplatin is a widely used chemotherapeutic drug used to cure osteosarcoma. Interleukin (IL)-6 and TIMP3 play important roles in the drug resistance of osteosarcoma; however, their relationship in this process remains unclear. This study aimed to explore the role of TIMP3 in the cisplatin sensitivity of osteosarcoma and its underlying molecular mechanisms in vitro and in vivo. We compared TIMP3 expression levels between patients with cisplatin-sensitive and -insensitive osteosarcoma. TIMP3 was overexpressed or knocked down in the Saos2-lung cell line, which is a Saos2 subtype isolated from pulmonary metastases that has higher cisplatin chemoresistance than Saos2 cells. IL-6 expression, cell proliferation, sensitivity to cisplatin, migration, and invasion after TIMP3 overexpression or knockdown were determined. The same experiments were performed using MG63 and U2OS cells. Subsequently, luciferase-labeled Saos2-lung cells overexpressing TIMP3 were injected into the tibiae of nude mice treated with cisplatin. The results showed that IL-6 inhibited TIMP3 expression in Saos2 and Saos2-lung cells via signal transducer and activator of transcription 3 (STAT3) activation. STAT3 knockdown reversed the effect of IL-6. The expression of TIMP3 was higher in patients with cisplatin-sensitive osteosarcoma than in those with insensitive osteosarcoma. IL-6 expression was downregulated upon TIMP3 overexpression, and upregulated by TIMP3 knockdown. TIMP3 overexpression suppressed cell proliferation and enhanced cisplatin sensitivity by activating apoptosis-related signal pathways and inhibiting IL-6 expression in vitro and in vivo. In conclusion, cisplatin sensitivity correlated positively with TIMP3 expression, which is regulated by the IL-6/TIMP3/caspase pathway. The TIMP3 pathway could represent a target for new therapies to treat osteosarcoma.

Effect of smoking on high-grade cervical cancer in women on the basis of human papillomavirus infection studies.

PURPOSE: We aimed, in the present study, to measure the risk related to the high-grade cervical intraepithelial neoplasia grade 3 (CIN3) or worse (CIN3+) or worse/high-grade squamous intraepithelial lesions with respect to changes in human papillomavirus (HPV) and smoking status. MATERIALS AND METHODS: A structured interview underwent for 7129 women. Then, we obtained their cervical cells and subjected to HPV testing. High-risk HPV infected and "no prevalent" cervical disease infected women were followed for cervical lesions up to 12 years (at baseline; n = 1531). Hazard ratios (HRs) for diagnosis of CIN3 (or worse) or worse/high-grade intraepithelial lesions were calculated along with the corresponding 95% confidence intervals (CIs). RESULTS: Among high-risk HPV-positive women, the conditions of long-term (more than 8 years) smokers and heavy (18 or more cigarettes/day) smokers are highly responsible for the increased risk for CIN3 or CIN3+. In the cases of persistent HPV-infected women, heavy smoking led to a higher risk for CIN3+ than those women who never smoked (HR, 2.31; 95% CI, 1.12-4.16). CONCLUSION: We concluded here that smoking leads to an enhanced risk of high-grade cervical lesions in persistent high-risk HPV-infected women. This makes a good understanding of smoking's role in cervical cancer.

[Clinical Significance of Minimal Residual Disease in Risk Stratification and Prognosis of Childhood B-lineage Acute Lymphoblastic Leukemia].

OBJECTIVE: To explore clinical significance of monitoring the level of minimal residual disease (MRD) at different time point in the risk stratification and prognosis of Childhood B-lineage Acute Lymphoblastic Leukemia. METHODS: Three hundred and eighty cases of children's B-ALL from Augest 2008 to January 2013 in our hospital were enrolled in this study. MRD levels were detected at day 15, day 33 and week 12 after initial chemotherapy. The event-free survival(EFS) and overall survival (OS) were measured on the basis of MRD levels at different stages of chemotherapy and were compared by Kaplan Meier analyses. RESULTS: The patient's age, initial white blood cell count, chromosome, MLL, BCR/ABL, pretreatment reaction, bone marrow MRD at days 33 were closely related with the 5-year EFS rate. Multiparameter flow cytometry showed the marked MRD and unmarked MRD were not significantly different between their 5-year EFS rate(P>0.05), and the every immune phenotype was also no significantly different between the 5-year EFS rate(P>0.05). The children with MRD≥10-2 at day 15(P<0.01), MRD≥10-3 at day 33 (P<0.01) and MRD≥10-3 on week 12(P<0.01) have a decreased 5-year EFS rate and overall survival, which related with poor prognosis obviously. The 5-year EFS rates at the MRD<10-4(negative), 10-4-10-3, 10-3-10-2 and ≥10-2 at day 33 were 86.6±2.7%, 77.5±4.9%, 70.1±8.0%, and 44.8±9.9%(P<0.01) with significant difference respectively; the 5-year OS rate was 89.5±2.7%, 80±4.9%, 76.0±7.8%, and 53.2±10.1% with statistically significant difference(P<0. 01). CONCLUSION: The MRD≥10-2 at day 33 is a high risk factor for significant reduction of the 5-year EFS rate and the 5-year OS rate of children with B-ALL. Thus, dynamic monitoring the MRD level can predict relapse of B-ALL after remission.

Atg7 Regulates Brain Angiogenesis via NF-κB-Dependent IL-6 Production.

The formation of brain vasculature is an essential step during central nervous system development. The molecular mechanism underlying brain angiogenesis remains incompletely understood. The role of Atg7, an autophagy-related protein, in brain angiogenesis was investigated in this study. We found that the microvessel density in mice brains with endothelial-specific knockout of Atg7 (Atg7 EKO) was significantly decreased compared to wild-type control. Consistently, in vitro angiogenesis assays showed that Atg7 knockdown impaired angiogenesis in brain microvascular endothelial cells. Further results indicated that knockdown of Atg7 reduced interleukin-6 (IL-6) expression in brain microvascular endothelial cells, which is mediated by NF-κB-dependent transcriptional control. Interestingly, exogenous IL-6 restored the impaired angiogenesis and reduced cell motility caused by Atg7 knockdown. These results demonstrated that Atg7 has proangiogenic activity in brain angiogenesis which is mediated by IL-6 production in a NF-κB-dependent manner.

[Clinical Features and Prognostic Factors of Children with Acute Lymphoblastic Leukemia in High-Risk Group].

OBJECTIVE: To explore the clinical features and prognostic factors of pediatric acute lymphoblastic leukemia (ALL) in high-risk (HR) group. METHODS: A total of 421 children with ALL in the Children's Hospital of Soochow University from August 2008 to March 2013 were diagnosed and treated according to the Chinese Children Leukemia Group (CCLG)-2008 Protocol. Among different risk-groups, 148 cases were stratified into the low-risk group and 191 cases were included in the moderate-risk group. Eight-two patients of the high-risk group were analyzed retrospectively for their clinical features, 5-year event-free survival (EFS) rate and overall survival (OS) rate. RESULTS: The median follow-up times of 82 patients were 64 months(3.0-76.3 months), 55 patient achieved complete remission(CR) after 1 cycle of induction chemotherapy(CR rate 67.1%), 25 patients relapsed(30.5%) mainly in very early and early relapse phases, significantly different from the low-risk group (P=0.013), 27 pateitns died(32.9%). The 5-year pEFS and pOS were 57.20% and 58.5%, respectively. Ph+ or BCR/ABL+ and MRD>10-2 on the 33rd day in the high-risk group were 2 main factors influencing EFS and OS according to single factor analysis. Ph+ or BCR/ABL+ was an independent prognostic factor, however, the MRD value on the 33rd day was not statistically significant differente by virtue of COX regression analysis. CONCLUSION: The clinical feature of children with ALL in high risk group display low induction CR rate, high recurrence rate and the lower 5-year pEFS. Ph+ or BCR/ABL+ is regarded as an independent factor of poor prognosis.

Bacterial inhibition potential of quaternised chitosan-coated VICRYL absorbable suture: An in vitro and in vivo study.

BACKGROUND/OBJECTIVE: As a widely used absorbable suture with antibacterial property, triclosan- coated polyglactin suture (Vicryl Plus) has been extensively utilized to reduce the occurrence rate of surgical site infections (SSIs) in orthopaedic surgery. However, the potential toxicity and side-effects of triclosan raised increasing concerns about its biological safety. This study aimed to investigate the antimicrobial activity and biocompatibility of quaternised chitosan-coated Vicryl suture (HV) both in vitro and in vivo. METHODS: In this study, a modified chitosan derivate, (hydroxypropyltrimethyl ammonium chloride chitosan, HACC), was coated over the surface of the absorbable Vicryl suture. Two standard bacteria strains, Staphylococcus epidermidis (ATCC35984) and methicillin-resistant Staphylococcus aureus (ATCC43300), were selected to evaluate bacterial adhesion and biofilm formation on the sutures at 6, 24 and 48 h in vitro. Additionally, human skin-derived fibroblasts cells were used to test the cytocompatibility of the sutures. Furtherly, sutures contaminated with methicillin-resistant S. aureus were implanted subcutaneously in SD rats in order to confirm the in vivo antibacterial performance and biocompatibility. RESULTS: We found that HACC-coated Vicryl suture (HV) exhibited significant anti-bacterial effects on the two tested strains. The bacterial attachment and biofilm formation on the surface of the HV sutures were found to be comparable to that of Vicryl Plus sutures (VP). Moreover, all the four tested sutures presented good cytocompatibility with human skin-derived fibroblasts cells. Histology and immunohistochemistry results indicated that the infections and inflammations were significantly inhibited around the HV and VP sutures. CONCLUSION: In general, the present study demonstrated that the quaternised chitosan coating is a flexible and cost-effective alternative strategy to prevent the suture related surgical site infections in orthopaedic practices.

[Clinical and pathologic features of tubulocystic carcinoma of kidney].

OBJECTIVE: To investigate clinicopathological features and differential diagnosis of tubulocystic carcinoma of the kidney. METHODS: The clinical features, histological and immunohistochemical findings were analyzed in 3 cases of tubulocystic carcinoma of the kidney, along with review of the related literatures. RESULTS: Three patients were males with a mean age of 59 years old (range from 44 to 71 years). All presented with no symptom and their tumors were found during routine examination. The tumor size ranged from 1.5 to 5.0 cm in greatest dimension. The tumors were grossly well-circumscribed without capsules and exhibited a spongy cut surface. Microscopically, all three tumors were composed of tubules and cysts of varying sizes separated by thin fibrous septa. The epithelial lining cells were flat, cuboidal and columnar, with often a hobnail-like appearance characterized by abundant eosinophilic cytoplasm with prominent nucleoli. Two cases showed focal clear cytoplasm. One of the three cases coexisted with a papillary renal cell carcinoma. Immunohistochemically, all 3 cases showed positivity for pan-CK, vimentin, CK19, CD10, P504S, and focal positivity for 34ßE12. Two cases showed focal positivity for CK7. CONCLUSIONS: Tubulocystic carcinoma of the kidney is a rare kidney neoplasm and occurs predominantly in males. The tumor is characterized by gross spongy appearance and microscopic cysts and tubules often lined by hobnail-like cells and separated by thin fibrotic stroma. The differential diagnosis mainly includes other lesions of the kidney that have a multicystic growth pattern.

[Clinicopathologic analysis of intestinal follicular lymphoma first presenting with gastrointestinal symptoms].

OBJECTIVE: To study the clinical features, endoscopic findings, pathologic diagnosis and treatment options of intestinal follicular lymphoma first presenting with gastrointestinal symptoms. METHODS: The clinical features, pathologic findings and follow-up data were retrospectively studied in 9 cases of intestinal follicular lymphoma. Immunohistochemical study for CD3, CD5, CD20, CD21, Ki-67, bcl-2, bcl-6, CD10 and cyclin D1 was carried out. RESULTS: Seven of the 9 patients were females and two were males. The age of patients ranged from 5 to 60 years (mean = 44 years). The clinical manifestations included abdominal pain (5 cases), blood in stool (3 cases) and abdominal distension (1 case). The commonest site of involvement was ileocecal region (6/9). Endoscopic examination had been carried out in 6 patients and all showed the presence of multiple polyps. Five cases had undergone endoscopic biopsy. Histologic examination of the endoscopic biopsies showed lymphoma cells located mainly in mucosal layer, forming vague nodules with ill-defined boundaries. Plasma cells and eosinophils were not conspicuous. Immunohistochemically, the tumor cells in all cases diffusely expressed CD20, CD10 and bcl-2. The staining for CD3, CD5 and cyclin D1 was negative. Lymphoid cells with weak CD10-positivity were identified in the interfollicular regions. Four cases were treated with surgical resection and chemotherapy. The other 3 cases received chemotherapy only and the remaining cases were treated conservatively. All of them were still alive on follow up. CONCLUSIONS: Primary intestinal follicular lymphoma affects predominantly elderly patients and has a female predilection. The commonest site of involvement is ileocecal region. Endoscopic examination shows polypoid changes. The disease often runs a relatively indolent clinical course. The prognosis is better than that of primary nodal follicular lymphoma.