ORTHOPOD: Linking ambulatory future trauma injury distribution from fragility proximal femur fracture caseload.

INTRODUCTION: The age of those experiencing traumatic injury and requiring surgery increases. The majority of this increase seen in older patients having operations after accidents is in fragility proximal femur fractures (FPFF). This study designed a model to predict the distribution of fractures suitable for ambulatory trauma list provision based on the number of FPFF patients. METHODS: The study utilized two datasets which both had data from 64 hospitals. One derived from the ORTHOPOD study dataset, and the other from National Hip Fracture Database. The model tested the predictability of 12 common fracture types based on FPFF data from the two datasets, using linear regression and K-fold cross-validation. RESULTS: The predictive model showed some promise. Evaluation of the model with mean RMSE and Std RMSE demonstrated good predictive performance for some fracture types, although the r-squared values showed that large variation in these fracture types was not always captured by the model. The study highlighted the dominance of FPFFs, and the strong correlation between these and numbers of ankle and distal radius fractures at a given unit. DISCUSSION: It is possible to model the numbers of ankle and distal radius fractures based off the number of patients admitted with hip fractures. This has great significance given the drive for increased day case utilisation and bed pressures across health services. While the model's current predictability was limited, with methodological improvements and additional data, a more robust predictive model could be developed to aid in the restructuring of trauma networks and improvement of patient care and surgical outcomes.

[Mammary myofibroblastoma: a clinicopathological analysis of fifteen cases].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of breast myofibroblastoma. Methods: The clinicopathological data and prognostic information of 15 patients with breast myofibroblastoma diagnosed at the Department of Pathology of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from 2014 to 2022 were collected. Their clinical characteristics, histological subtypes, immunophenotypes and molecular characteristics were analyzed. Results: There were 12 female and 3 male patients, ranging in age from 18 to 78 years, with a median and average age of 52 years. There were 6 cases in the left breast and 9 cases in the right breast, including 12 cases in outer upper quadrant, 2 cases in inner upper quadrant and 1 case in outer lower quadrant. Most of the cases showed a well-defined nodule grossly, including pushing growth under the microscope in 13 cases, being completely separated from the surrounding breast tissue in 1 case, and infiltrating growth in 1 case. Among them, 12 cases were classic subtype and composed of occasional spindle cells with varying intervals of collagen fiber bundles; eight cases had a small amount of fat; one case had focal cartilage differentiation; one case was epithelioid subtype, in which epithelioid tumor cells were scattered in single filing or small clusters; one case was schwannoma-like subtype, and the tumor cells were arranged in a significant palisade shape, resembling schwannoma, and one case was invasive leiomyoma-like subtype, in which the tumor cells had eosinophilic cytoplasm and were arranged in bundles, and infiltrating into the surrounding mammary lobules like leiomyoma. Immunohistochemical studies showed that the tumor cells expressed desmin (14/15) and CD34 (14/15), as well as ER (15/15) and PR (15/15). Three cases with histologic subtypes of epithelioid subtype, schwannoma-like subtype and infiltrating leiomyoma-like subtype showed RB1 negative immunohistochemistry. Then FISH was performed to detect RB1/13q14 gene deletion, and identified RB1 gene deletion in all three cases. Fifteen cases were followed up for 2-100 months, and no recurrence was noted. Conclusions: Myofibroblastoma is a rare benign mesenchymal tumor of the breast. In addition to the classic type, there are many histological variants, among which the epithelioid subtype is easily confused with invasive lobular carcinoma. The schwannoma-like subtype is similar to schwannoma, while the invasive subtype is easily misdiagnosed as fibromatosis-like or spindle cell metaplastic carcinoma. Therefore, it is important to recognize the various histological subtypes and clinicopathological features of the tumor for making correct pathological diagnosis and rational clinical treatment.

Frail patients having vascular surgery during the early COVID-19 pandemic experienced high rates of adverse perioperative events and amputation.

BACKGROUND: Frailty predicts adverse perioperative outcomes and increased mortality in patients having vascular surgery. Frailty assessment is a potential tool to inform resource allocation, and shared decision-making about vascular surgery in the resource constrained COVID-19 pandemic environment. This cohort study describes the prevalence of frailty in patients having vascular surgery and the association between frailty, mortality and perioperative outcomes. METHODS: The COVID-19 Vascular Service in Australia (COVER-AU) prospective cohort study evaluates 30-day and six-month outcomes for consecutive patients having vascular surgery in 11 Australian vascular units, March-July 2020. The primary outcome was mortality, with secondary outcomes procedure-related outcomes and hospital utilization. Frailty was assessed using the nine-point visual Clinical Frailty Score, scores of 5 or more considered frail. RESULTS: Of the 917 patients enrolled, 203 were frail (22.1%). The 30 day and 6 month mortality was 2.0% (n = 20) and 5.9% (n = 35) respectively with no significant difference between frail and non-frail patients (OR 1.68, 95%CI 0.79-3.54). However, frail patients stayed longer in hospital, had more perioperative complications, and were more likely to be readmitted or have a reoperation when compared to non-frail patients. At 6 months, frail patients had twice the odds of major amputation compared to non-frail patients, after adjustment (OR 2.01; 95% CI 1.17-3.78), driven by a high rate of amputation during the period of reduced surgical activity. CONCLUSION: Our findings highlight that older, frail patients, experience potentially preventable adverse outcomes and there is a need for targeted interventions to optimize care, especially in times of healthcare stress.

[Interpretation of Chinese expert consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis associated with lymphoma (2022)].

Chinese expert consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis (HLH) associated with lymphoma was revised on the basis of evidence-based medical evidence in combination with domestic and international research progress. It added the classification of "according to the difference in the causes of HLH". For the first time, the revised version included the classification of lymphoma-associated HLH induced by immunotherapy. The contents of genetic background defects and central nervous system involvement in lymphoma-associated HLH were also supplemented. This article gives a detailed interpretation of the updated content in the consensus.

miR-34a-5p plays an inhibitory role in hepatocellular carcinoma by regulating target gene VEGFA.

OBJECTIVE: The objective of this research is to determine the role of miR-34a-5p in the occurrence and development of HCC by targeting VEGFA. METHODS: The expression of miR-34a-5p in HCC cell lines and tumour tissue was detected by qRT-PCR; the effect of miR-34a-5p on the invasive ability of HCC cells (SMMC7721 and MHCC97H) were detected by Transwell invasion assay; VEGFA is predicted as a potential target gene of miR-34a-5p by TargetScan, and validated with dual-luciferase reporter gene assay, qRT-PCR and western blot. VEGFA expression in HCC cell lines and tumour tissue was detected using qRT-PCR; the regulation and influence of miR-34a-5p and VEGFA on the proliferation, invasion, migration and the S-phase cell of HCC cells with different invasive abilities were detected by CCK8, Transwell assay, wound healing assay, and flow cytometry. The effect of miR-34a-5p on the growth of tumour was detected by constructing a xenograft model of nude mice with HCC. RESULTS: It was found that the expression of miR-34a-5p in HCC cells and tumour tissue was significantly decreased. Up-regulating miR-34a-5p expression could reduce the invasion ability of HCC cells. MiR-34a-5p could inhibit the mRNA and protein expression level of VEGFA via combining with the 3'-UTR of VEGFA. VEGFA was highly expressed in HCC cells and tumour tissues. The miR-34a-5p inhibited the proliferation, invasion, migration and S-phase arrest of HCC cells, but this inhibition effect could be neutralised by VEGFA; miR-34a-5p exerted the inhibitory effect on HCC cell proliferation and tumour growth in the HCC xenograft model of nude mice. CONCLUSION: These results suggest that miR-34a-5p could inhibit the occurrence and development of HCC by targeting VEGFA.

[High-flow nasal cannula oxygen therapy can reduce occurrence of hypoxia in elderly patients during anesthesia recovery].

OBJECTIVE: To explore the effect of high-flow nasal cannula (HFNC) oxygen therapy in elderly patients during anesthesia recovery. METHOD: A total of 178 elderly patients undergoing elective non-cardiac surgeries were randomly assigned into HFNC oxygen therapy group (group H) or nasal cannula oxygen therapy group (group N), with 89 patients in each group.All the patients were admitted in postanesthesia care unit (PACU) after the surgery for recovery following the routine procedure.After trachea extubation, the patients in group H received HFNC oxygen therapy and those in group N had nasal cannula oxygen therapy.In both groups, arterial blood gas analysis was performed at 10 min after oxygen inhalation and the respiratory parameters were recorded.During oxygen inhalation, the occurrence and frequency of hypoxia (oxygen saturation < 90%), trachea reintubation and adverse events (unplanned admission to ICU, vomiting, aspiration, etc.) were recorded. RESULTS: All the patients recovered safely from anesthesia in the PACU and subsequently received routine care, and only 1 patient in group N required trachea reintubation.Compared with those in group N, that patients in group H had a significantly lower incidence of hypoxia (3.4% vs 11.2%, P=0.044), a higher arterial partial pressure of oxygen (161.96±51.21 vs 114.35±43.60 mmHg, P < 0.001), and a higher oxygenation index(398.76±231.86 vs 324.10±194.16, P=0.021).The mean respiratory rate, arterial partial pressure of carbon dioxide and blood oxygen saturation were all comparable between the two groups. CONCLUSION: HFNC oxygen therapy during anesthesia recovery is safe and effective in elderly patients and can reduce the occurrence of hypoxia after tracheal extubation and improve arterial partial pressure of oxygen and oxygenation.

Sentinel lymph node biopsy with carbon nanoparticle suspension after neoadjuvant chemotherapy for breast cancer patients.

INTRODUCTION: The aim of the study was to explore the feasibility of performing sentinel lymph node biopsy (SLNB) using a carbon nanoparticle suspension (CNPS) after neoadjuvant chemotherapy in breast cancer patients. METHODS: Some 152 patients diagnosed with primary breast cancer (cT1-3N0-2M0) were recruited. Patients were divided into two groups according to axillary lymph node (ALN) status after four to six cycles of neoadjuvant chemotherapy. All patients received a CNPS injection, after which SLNB and axillary lymph node dissection (ALND) were performed. RESULTS: Sentinel lymph nodes (SLN) of 143 patients were identified; with an accuracy rate of 94.4% and a false-negative rate of 9.9%. Group A included 67 patients, and the detection, accuracy and false-negative rates within this group were 95.5%, 96.9% and 6.7%, respectively. The corresponding rates for group B (85 patients) were 92.9%, 92.4% and 11.8%, respectively. CONCLUSIONS: CNPS is an ideal tracer for improving the detection rate of SLN and can be used to determine SLN status following neoadjuvant chemotherapy.

[Cytological analysis of lymphoblastic lymphoma/acute lymphoblastic leukemia in serous effusion].

Objective: To study the diagnostic clues and significance in serous effusion cytology associated with lymphoblatic lymphoma/acute lymphoblastic leukemia (LBL/ALL). Methods: Forty-five serous effusion specimens with final diagnosis of LBL/ALL were collected from August 2011 to December 2019 at the First Affiliated Hospital of Zhengzhou University. All cases were reviewed for their clinical profiles, cytomorphologic features and ancillary studies. Cell blocks and immunocytochemistry were prepared in 22 cases; flow cytometric immunophenotyping was performed in three cases and gene rearrangement analysis (T-cell recepter, TCR and immunoglobulin, Ig) was performed in five cases. Results: Among the 45 cases, there were 35 males and 10 females with male to female ratio of 3.5∶1.0. The median age was 15 years. Mediastinal mass was the initial presentation in 39 patients (86.7%) and high LDL level were observed in 34 patients (75.6%). Microscopically, the majority of the specimens (86.7%) were hypercellular. The smears demonstrated dispersed lymphoblasts that were predominantly small to intermediate in size with scanty basophilic cytoplasm and irregular or convoluted nuclei with fine chromatin condensation and inconspicuous nucleoli. Mitoses were frequently observed. Karyorrhexis and apoptosis were seen in all cases. By immunophenotyping, TdT was expressed in 19 cases (86.4%) and CD99 in 20 cases (90.9%). Ki-67 expression varied from 65% to 95%. Flow cytometry in three cases demonstrated positivity for TdT, CD2, CD3 and CD7. Monoclonal TCR gene rearrangement was found in 4 of 5 cases, and both monoclonal TCR and Igκ gene were found in 1 case. Conclusions: In LBL/ALL, primary diagnosis could be made basing on clinical features (younger male patients with a mediastinum mass) and cytomorphology (monotonous, small to medium sized lymphoid cells with prominent irregular nuclei, fine chromatin and frequent mitoses, karyorrhexis and apoptosis). If immunocytochemistry and other ancillary studies are performed, the accuracy and reliability of the results could be improved.

[Clinical study of haploidentical hematopoietic stem cell transplantation on 15 cases of adult-onset primary hemophagocytic lymphohistiocytosis].

Objective: This study was designed to evaluate the efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for adult-onset primary hemophagocytic lymphohistiocytosis (HLH) . Method: A retrospective study was carried out to analyze the clinical data of 15 adult patients with primary HLH who received haplo-HSCT from January 2013 to October 2019 in Beijing Friendship Hospital, Capital Medical University, Beijing, China. Results: Among the 15 patients included in the study, ten were males and five were females, with a median age of 21 years old (18-52) . Eight of the patients had familial hemophagocytic lymphohistiocytosis type 2 (FHL-2) , four had FHL-3, one had Griscelli syndrome type 2 (GS-2) , one had X-linked lymphoproliferative disease type 1 (XLP-1) , and the other had XLP-2. The median time from HLH diagnosis to transplantation was 7 months (2-46 months) . Seven patients were treated with Bu/Cy condition regimen prior to transplantation. Meanwhile, the other eight cases were treated with TBI/Cy. The median concentration of mononuclear cell (MNC) infusion was 12.6 (9.2-20.3) ×10(8)/kg and CD34(+) cells was 4.91 (2.51-8.37) ×10(6)/kg. The median time of leukocyte engraftment was on day 13 following transplantation (10-23 days) , and the platelet engraftment was on day 12 (9-36) . Graft failure (GF) finally occurred in two patients (one primary GF and one secondary GF) . The cumulative incidence of acute graft-versus-host-disease (GVHD) grades 2 to 4 was 71.4% (10/14) and chronic GVHD was 30.8% (4/13) , respectively. The five-year overall survival (OS) for all 15 cases of primary HLH was 65.5% (95% CI, 34.9%-73.3%) and the transplant-related mortality (TRM) was 26.7% (4/15) . The five-year OS was 87.5% (95% CI, 38.7%-66.3%) in eight patients who received haplo-HSCT subsequent to initial therapy and 42.9% (95% CI, 8.5%-65.2%) in patients seven patients who needed salvage therapy prior to haplo-HSCT (χ(2)=2.387, P=0.122) . The five-year OS was 85.7% (95% CI, 50.4%-89.8%) in eight patients who achieved complete response before haplo-HSCT and 42.9% (95% CI, 6.4%-53.0%) in seven patients with partial response (χ(2)=3.185, P=0.074) . Conclusion: The results indicated that haplo-HSCT is a promising method for the treatment of primary HLH in adults.

MicroRNA-15a inhibits inflammatory response and apoptosis after spinal cord injury via targeting STAT3.

OBJECTIVE: To clarify the function of microRNA-15a in the spinal cord injury (SCI) and its potential mechanism. PATIENTS AND METHODS: The plasma levels of microRNA-15a and signal transducer and activator of transcription 3 (STAT3) in SCI patients were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the expressions of microRNA-15a and STAT3 was analyzed. The in vitro SCI model was established in H2O2-induced C8-D1A and C8B4 cells, and in vivo SCI model was established in mice by hitting T10. The mRNA and protein expressions of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) were detected in the SCI model. The apoptosis was examined by flow cytometry or TUNEL staining, respectively. The motor function of mouse hindlimb was evaluated using the Basso Beattie Bresnahan (BBB) standard scale. The target gene of microRNA-15a was predicted by bioinformatics and further verified by dual-luciferase reporter gene assay. The expression changes of target genes in C8-D1A and C8B4 cells with microRNA-15a overexpression or knockdown were examined by qRT-PCR and Western blot. Finally, rescue experiments were performed to evaluate the regulatory effects of microRNA-15a and STAT3 on cell apoptosis. RESULTS: MicroRNA-15a was lowly expressed in plasma of SCI patients, while STAT3 was highly expressed with a negative correlation to microRNA-15a. Identically, microRNA-15a was lowly expressed in H2O2-induced C8-D1A and C8B4 cells, and STAT3 was highly expressed. MicroRNA-15a overexpression downregulated mRNA and protein levels of TNF-α and IL-6 in C8-D1A and C8B4 cells. BBB score was markedly low in SCI mice relative to controls. SCI mice injected with microRNA-15a mimics had higher BBB score than those injected with negative control. Besides, SCI mice with microRNA-15a overexpression had downregulated expressions of STAT3, TNF-α, and IL-6 in the impaired spinal cord tissues, as well as lower apoptotic rate. Through bioinformatics, we found binding sites between STAT3 and microRNA-15a. Their binding conditions were further verified by dual-luciferase reporter gene assay. Moreover, STAT3 expression was negatively regulated by microRNA-15a. Finally, rescue experiments showed that STAT3 overexpression could reverse the regulatory effects of microRNA-15a on expressions of TNF-α and IL-6, as well as apoptosis. CONCLUSIONS: MicroRNA-15a expression decreases in the SCI model, which participates in the process of SCI by regulating inflammatory response and cell apoptosis via targeting STAT3.

Effect of RhoC silencing on multiple myeloma xenografts and angiogenesis in nude mice.

In this study, we investigated the expression of RhoC in the multiple myeloma (MM) cell line RPMI- 8226, as well as the effects of silencing RhoC on the growth of tumor xenografts and tumor-induced angiogenesis in nude mice with MM. For this purpose, we transduced RPMI-8226 cells with lentiviral particles overexpressing short hairpin RNAs (shRNA) targeting RhoC. Tumor xenografts were generated by subcutaneously injecting nude mice with RPMI-8226 cells overexpressing control shRNA [negative control (NC) group] or the RhoC shRNA [the experimental (S) group], respectively. RhoC protein and mRNA levels in the tumor xenografts were measured. Nude mice were also subcutaneously inoculated with Matrigel mixed with vascular endothelial growth factor, and CD31 and KI67 levels in the tumor xenografts were measured by immunohistochemistry. Similarly, we assessed tumor xenograft growth and angiogenesis in Matrigel implants in the mice of both groups. We found that RhoC levels, microvessel density, and CD31 labeling index were more reduced in the S group than in the NC group. However, there was no significant difference in the size of tumor xenografts between the 2 groups. The number of new vessels and the neovascular length in the Matrigel implants were significantly lower in the S group than in the NC group. Therefore, we concluded that RhoC expression in myeloma xenografts has important effects on the induction of angiogenesis.

CircRNA UBAP2 promotes the progression of ovarian cancer by sponging microRNA-144.

OBJECTIVE: This study aims to elucidate the regulatory effect of circular RNA UBAP2 (circUBAP2) on the progression of ovarian cancer (OC). PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expressions of circUBAP2, microRNA-144 and CHD2 in OC tissues and adjacent normal tissues. The correlation between the expression levels of circUBAP2 and microRNA-144 with pathological parameters of OC patients was analyzed. Subcellular distribution of circUBAP2 was detected by chromatin fractionation assay. After overexpression of circUBAP2 in OC cells, changes in proliferative and migratory abilities were evaluated by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. In addition, the Dual-Luciferase reporter gene assay was used to verify the binding of circUBAP2 and microRNA-144, and the binding of CHD2 to microRNA-144. RESULTS: QRT-PCR results showed that circUBAP2 was highly expressed in OC tissues, and its expression was negatively correlated with TMN stage and five-year survival of OC patients. CircUBAP2 was mainly distributed in the cytoplasm. Overexpression of circUBAP2 significantly promoted the proliferative and migratory abilities of OC cells. The Dual-Luciferase reporter gene assay demonstrated that circUBAP2 could bind to microRNA-144. Meanwhile, circUBAP2 negatively regulated microRNA-144 expression in OC cells. Besides, the promotive effects of circUBAP2 on the proliferation and migration of OC cells were reversed by microRNA-144 overexpression. MicroRNA-144 was lowly expressed in OC tissues, which was negatively correlated with TNM stage of OC patients. The Dual-Luciferase reporter gene assay confirmed the binding condition between CHD2 and microRNA-144. CHD2 expression was negatively regulated by microRNA-144 in OC cells. Moreover, CHD2 could bind to microRNA-144 and partially inhibited its activity, thereby promoting the proliferative and migratory abilities of OC cells. CONCLUSIONS: CircUBAP2 promotes the progression of ovarian cancer by adsorbing microRNA-144.

Transarterial chemoembolization with raltitrexed-based or floxuridine-based chemotherapy for unresectable colorectal cancer liver metastasis.

PURPOSE: To evaluate and compare the efficiency and safety of raltitrexed- or floxuridine (FUDR)-based transarterial chemoembolization (TACE) in patients with unresectable colorectal cancer liver metastasis (CRCLM). METHODS: We conducted a retrospective analysis of 81 patients with unresectable CRCLM who failed systemic chemotherapy and were treated with TACE in our department from Oct 2014 to Oct 2017. Of these, 61 patients received TACE using raltitrexed, oxaliplatin, and pirarubicin (raltitrexed group), and 20 received TACE using FUDR, oxaliplatin, and pirarubicin (FUDR group). The objective response rate (ORR), disease control rate (DCR), overall survival (OS, from the first TACE), progression-free survival (PFS, from the first TACE), and adverse reactions were evaluated and compared between the two groups, and prognostic factors for OS were analyzed. RESULTS: The ORRs of the raltitrexed group and FUDR group were 67.2 and 45.0%, respectively (P = 0.076), and the DCRs were 86.9 and 80.0%, respectively (P = 0.452). The median OS (from first TACE) was 14.0 months in the raltitrexed group and 13.0 months in the FUDR group (P = 0.556). The median PFS (from first TACE) was 2.1 months in the raltitrexed group and 2.4 months in the FUDR group (P = 0.878). Univariate and multivariate analyses showed that the primary tumor site, Child-Pugh class, and combination with local ablation (RFA or CRA) were independent significant factors affecting survival. There were no significant differences in adverse reactions between the two groups (P > 0.05), and no treatment-related death occurred in either group. CONCLUSION: TACE treatment based on raltitrexed or FUDR is an efficient and safe alternative choice for treating unresectable CRCLM.

Long non-coding RNA ZEB1-AS1 promotes glioma cell proliferation, migration and invasion through regulating miR-577.

OBJECTIVE: Long non-coding RNA ZEB1-AS1 (ZEB1-AS1) was reported to be implicated and aberrantly expressed in multiple cancers. However, the potential mechanism and clinical significance of ZEB1-AS1 in the carcinogenesis of glioma remain unclear. PATIENTS AND METHODS: RT-PCR was performed to determine the expression of ZEB1-AS1 in glioma tissues and cell lines. The association between ZEB1-AS1 expression and clinical features and prognosis were statistically analyzed. MTT and transwell assays were used to test the proliferation, invasion, and migration of glioma cells. Luciferase report assay was used to detect the correlation between ZEB1-AS1 and miR-577 in glioma. RESULTS: Compared with normal brain tissues and cells, ZEB1-AS1 in glioma tissues and cell lines was shown to be expressed at high levels. Clinical association analysis indicated that ZEB1-AS1 expression was closely associated with tumor size (p = 0.014), KPS (p = 0.004) and WHO grade (p = 0.001). In addition, it was observed that high expression level of ZEB1-AS1 was remarkably associated with overall survival and could be an independent prognostic indicator of glioma using univariate and multivariate analysis. Functional experiments demonstrated that down-regulation of ZEB1-AS1 suppressed the proliferation, invasion, and migration of glioma cell in vitro. In the mechanism, we found that ZEB1-AS1 acted as a competing endogenous RNA to sponge miR-577. Moreover, miR-577 could reverse the tumor-promotive role of ZEB1-AS1 on glioma cells. CONCLUSIONS: Our findings demonstrated that ZEB1-AS1 might play an oncogenic role in glioma and was a poor prognostic factor. The ZEB1-AS1/miR-577 axis might be a potential target for the development of effective glioma therapy.

Knockdown of PLK1 inhibits invasion and promotes apoptosis in glioma cells through regulating autophagy.

OBJECTIVE: Polo like kinase 1 (PLK1), an oncogene, is a ubiquitously expressed serine/threonine protein kinase. We aimed at investigating the role of PLK1 in glioma. PATIENTS AND METHODS: Clinical glioma specimens were obtained from Zhejiang Hospital (Hangzhou, Zhejiang, China). The mRNA and protein levels of PLK1 in glioma tissues and different glioma cells were analyzed by Real-time PCR and Western blot, respectively. The expression of PLK1 protein in glioma tissues was also determined by immunohistochemistry staining. Then, the effect of PLK1 on cell proliferation and apoptosis of U251 and U87 cells was analyzed by using CCK-8 assay and Annexin V/PI staining, respectively. Furthermore, the migration and invasion of glioma cells were examined by transwell assay. Finally, the protein levels of autophagy indicators LC3-II, ATG5 and p-p70 S6 in U251 and U87 cells were detected by Western blot, and the expression of E-cadherin, vimentin and MMP9 and apoptosis associated indicators Bax, cleaved caspase-3 and Bcl-2 in U251 cells were also determined using Western blot. RESULTS: PLK1 was upregulated in glioma tissues and cells. Knockdown of PLK1 significantly inhibited cell proliferation, migration, invasion, and induced apoptosis of U87 and U251 glioma cells. Furthermore, the data demonstrated that knockdown of PLK1 significantly elevated expression of cleaved caspase-3, BIM, BAX, and E-cadherin, and reduced expression of MMP9, ATG5 and LC3-II in U251 and U87 cells. Additionally, we found that knockdown of PLK1 can inhibit autophagy in glioma cells. CONCLUSIONS: Knockdown of PLK1 can inhibit the glioma development by suppressing the autophagy and enhancing the apoptosis of glioma cells. PLK1 may be a potential therapeutic target in gliomas.

MRPL33 and its splicing regulator hnRNPK are required for mitochondria function and implicated in tumor progression.

MRPL33 gene encodes a large mitoribosomal subunit protein, which may be involved in mitochondrial translation. Although two splice variants of MRPL33 have been described, its splicing regulation remains elusive. Here we observed that inclusion of alternative exon 3 was greatly promoted in a panel of human cancer cells. Depletion of the exon 3-containing long isoform of MRPL33 (MRPL33-L) led to impaired proliferation and increased apoptosis in cancer cell lines and in a xenograft model. MRPL33-L knockdown could also induce mitochondrial dysfunction including increased accumulation of reactive oxygen species, decreased ATP production and 16 S rRNA levels. We further showed that alternative splicing of MRPL33-L pre-mRNA is regulated by hnRNPK and that knocking down hnRNPK could phenocopy MRPL33-L depletion. More importantly, overexpression of MRPL33-L could increase tumorigenic potential of hnRNPK-depleted cancer cells, likely indicating that hnRNPK mediates tumorigenesis through splicing regulation of MRPL33 pre-mRNA. Finally, we found that inclusion of MRPL33 exon 3 was promoted in human colorectal cancer tissues and this was correlated with hnRNPK levels. In summary, our findings underscore the biological significance of MRPL33-L and hnRNPK in the tumor formation and identifies hnRNPK as a critical splicing regulator of MRPL33 pre-mRNA in cancer cells.

Cockroach is a major cross-reactive allergen source in shrimp-sensitized rural children in southern China.

BACKGROUND: Little is known about the prevalence of food allergy (FA) in China. The aim of this study was to investigate the disparity of FA between urban and rural areas in southern China. METHODS: EuroPrevall questionnaire responses were obtained from 5542 school-age children in urban Guangzhou and 5319 in rural Shaoguan. A case-control study enrolled 190 children with adverse reactions (ARs) after food intake as cases and 212 controls in Guangzhou, whereas 116 cases and 233 controls in Shaoguan. These subjects underwent skin prick test (SPT) and serum IgE measurements to food and inhalant allergens. Allergen extracts from shrimp, house dust mite (HDM), and cockroach were prepared for IgE cross-reactivity testing in 23 Guangzhou and 20 Shaoguan shrimp-sensitized subjects. RESULTS: The prevalence of ARs to shrimp was higher in Guangzhou than in Shaoguan children (3.5% vs 1.4%, P < .001). However, sensitization rate to shrimp (SPT: 3.7% vs 11.2%, P = .015; IgE: 12.6% vs 36.2%, P < .001) and cockroach (SPT: 5.3% vs 33.5%; IgE: 2.6% vs 27.6%, P < .001) was lower in Guangzhou. A significant correlation between shrimp and HDM/cockroach IgE was found in Shaoguan children. The proportions of positive IgE to tropomyosin (Pen a 1, Der p 10) were lower than 7.4% in both areas. Cockroach allergen has a significantly higher inhibition rate of binding to IgE to house dust mite allergens in Shaoguan sera. CONCLUSION: Shrimp is a common allergic food in southern China. Higher proportion of shrimp sensitization in rural subjects could be explained by cross-reactivity to cockroach. Tropomyosin was not a major allergen responding to the cross-reactivity.

A 4-miRNAs signature predicts survival in glioblastoma multiforme patients.

BACKGROUND: Although O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation status is an important marker for glioblastoma multiforme (GBM), there is considerable variability in the clinical outcome of patients with similar methylation profles. OBJECTIVE: We examined whether a MicroRNA (miRNA) signature can be identified for predicting clinical outcomes and helping in treatment decisions. METHODS: The differentially expressed miRNAs were evaluated in 6 pairs of short- (⩽ 450 days) and long-term survivors (> 450 days) by using microarray. Real time quantitative PCR (qRT-PCR) was applied to further verify screened miRNAs with a greater number of samples (n= 48). Meanwhile, functional interpretation of miRNA profile was carried out based on miRNA-target databases. In addition, MGMT promoter methylation status was tested by means of pyrosequencing (PSQ) testing. RESULTS: Six miRNAs were upregulated in the long-term survival group (fold change ⩾ 2.0, P< 0.05). The further verification by qRT-PCR indicated that the increase in let-7g-5p, miR-139-5p, miR-17-5p and miR-9-3p level in long-term survivors was statistically significant. Kaplan-Meier survival analysis showed that high expression of a prognostic 4-miRNA signature was significantly associated with good patient survival (p= 0.0012). The signature regulated signaling pathways including Calcium, MAPK, ErbB, mTOR and cell cycle involved in carcinogenesis from glial progenitor cell to primary GBM. CONCLUSIONS: The 4-miRNA signature was identified as an independent prognostic biomarker that identified patients who have a favorable outcome.

Downregulation of long non-coding RNA LINC01133 is predictive of poor prognosis in colorectal cancer patients.

OBJECTIVE: This study aims to investigate long non-coding RNA LINC01133 (LINC01133) expressions in colorectal cancer (CRC) patients, and discuss its correlation with CRC clinicopathological features and prognosis. PATIENTS AND METHODS: qRT-PCR was performed to measure expression levels of LINC01133 in CRC tissues. The chi-square test was used to assess LINC01133 expression with respect to clinicopathological parameters. Kaplan-Meier analysis and the log-rank test were performed to identify survival differences in CRC patients. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. RESULTS: LINC01133 was significantly down-regulated in CRC tissues compared to normal tissue samples (p < 0.001), and a low expression of LINC01133 was found to be significantly associated with lymph node metastasis (p = 0.004), distant metastasis (p = 0.043), N classification (p = 0.022) and TNM stage (p = 0.011). Moreover, Kaplan-Meier survival analysis revealed that high LINC01133 expression predicted significantly better overall survival (p = 0.0093). Finally, multivariate analysis results indicated that LINC01133 was an independent prognostic factor in CRC. CONCLUSIONS: Our results indicated that reduced LINC01133 expression contributed to CRC metastasis and poor prognosis. Thus, LINC01133 might serve as a promising biomarker for prognosis of CRC.